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[Use of loading tests to detect silent myocardial ischemia]. A total of 74 patients with postinfarct cardiosclerosis (PC) and stable angina (SA) were examined by Holter monitoring, bicycle ergometry, echocardiography and 201Tl chloride myocardial scintigraphy and loading tests (transesophageal cardiac pacing and isometric hand exercise test). The detection rate for silent myocardial ischemia (SI) was found to be 57.1% with Holter monitoring, 52.3% by bicycle ergometry, 62.5% with echocardiography, 100% with myocardial scintigraphy with loading test and 88.8% with that without the loading test. The detection rate for PC was 33.9, 32.0, 64.7, 81.8, and 56.7%, respectively. Higher SI detection rates in postinfarct patients were more frequently observed when echocardiography and myocardial scintigraphy in combination with loading tests in patients with PC without angina. The efficiency of SI detection in patients with various coronary heart disease increases when loading tests are employed. The loading tests in echocardiography and myocardial scintigraphy ensure the most complete detection of SI in postinfarct patients without angina.

[Catalase inactivation during storage in solution and its stabilization by polysaccharides of microbial origin]. It has been experimentally shown that the rate of inactivation of pure catalase in solution does not obey the kinetics of the first order. The kinetics of denaturation taking into account partial stabilization of catalase due to the formation of intermolecular complexes of native molecules with denatured molecules has been derived. Using the equation, the rate of catalase inativation during storage in pure solutions has been calculated from the experimental data. Polysaccharides of microbial origin can also stabilize catalase. The kinetics of catalase inactivation in the system where the enzyme and polysaccharide forms a reversibly dissociating complex has been described.

Aspirin, cyclophosphamide, and dexamethasone effects on experimental secondary herpes simplex uveitis. The effects of aspirin, cyclophosphamide, and dexamethasone on secondary herpes simplex uveitis were studied in rabbits. Neither daily treatment with aspirin (rectal suppositories, 650 mg begun 24 hours before challenge) nor cyclophosphamide injections every two days (80 mg begun eight days before challenge) had any effect on the severity of the uveitis, on the rise in intraocular pressure (IOP), or on the host's immune responses. As in the control animals, infectious herpes simplex virus (HSV) could not be isolated from iris tissues of either aspirin- or cyclophosphamide-treated rabbits. On the other hand, twice-daily treatment with topical dexamethasone (0.1% drops begun 24 hours before challenge) lessened the severity of the uveitis appreciably and suppressed the rise in IOP, but iris tissues yielded infectious HSV in two of ten eyes. Although the dexamethasone had no effect on the neutralizing-antibody or macrophage migration inhibition factor, it markedly suppressed the chemotactic activity of the aqueous humor for both polymorphonuclear leukocytes and macrophages.

Phosphorylation of casein by the lactating mammary gland: a review. The lactating mammary gland synthesizes and secretes large amounts of phosphoproteins that mainly are associated with the casein fraction of milk. The free amino acids and inorganic phosphate of blood serve as building materials for casein, and the final product appears in milk as a colloidal-sized particle, the casein micelle. According to our present concept, the biosynthesis of casein occurs in two steps: synthesis of the polypeptide chain, followed by phosphate addition. Phosphate groups are transferred to the nascent casein by a protein kinase localized in the Golgi apparatus. The enzyme uses adenosine 5'-triphosphate as the phosphate donor and requires divalent cations. Neighboring amino acids may be important in determining which serine residues in casein are phosphorylated. This review discusses historical and current research on the phosphorylation of casein.

Central noradrenergic inhibition of gastric motility in rats. The roles of central noradrenergic mechanisms in the regulation of gastric motility were investigated in urethane-anesthetized rats in whom an intragastric balloon had been placed. Noradrenaline 100 nmol administered intracerebroventricularly (i.c.v.) significantly decreased spontaneous contractions of the stomach and this decrease in gastric motility was not observed in bilaterally vagotomized animals. Intracisternally administered (i.c.) noradrenaline (10 nmol) induced a decrease in gastric motility comparable to that elicited by noradrenaline 100 nmol i.c.v. Phentolamine 10 nmol i.c. but not the same dose of propranolol i.c. significantly antagonized the noradrenaline (10 nmol)-induced inhibition of gastric motility. These results suggest that alpha-adrenoceptor-mediated noradrenergic mechanisms in the brain stem are involved in the inhibitory regulation of gastric motility.

Presence of VIP fibers of sensory origin in the rat trachea. The presence of vasoactive intestinal peptide (VIP) immunoreactive nerve fibers (LI) in the respiratory tract of mammals is well documented. These fibers are known to originate from parasympathetic postganglionic neurons and to be associated with blood vessels, submucosal glands, and with smooth muscle. We found that, in addition to this, the epithelial layer of the rat trachea also contains VIP-LI fibers. Vagotomy or ligation of the cervical portion of the vagus nerve resulted respectively in a decrease of VIP-LI fibers within the epithelium or in the accumulation of VIP in axons proximal to the site of transection or ligation, whereas no changes were seen in other parts of the trachea. On the other hand, capsaicin pretreatment also caused similar changes to the surgical procedures. These findings indicate that VIP-LI fibers in the tracheal epithelium of the rat are supplied by the sensory ganglia of the vagus nerve.

Quinolinate neurotoxicity and glutamatergic structures. Neurotoxic properties of quinolinic acid following intracerebroventricular application were investigated in the hippocampal formation of 12- and 30-day-old rats. Quinolinic acid neurodegenerative potency was found to depend on the survival time, the dose applied and the developmental stage of the animal. Pretreatment with kynurenic acid and ketamine as well as the transection of the perforant path were noted to protect major parts of the hippocampal cell layers from quinolinic acid-induced degenerative effects. The results are interpreted in view of a putative dependence of quinolinic acid neurotoxicity on the presence of established synaptic, in particular glutamatergic, processes which play a major role in the hippocampal formation and mature during the first postnatal weeks. For comparison, we studied local effects of quinolinic acid on superior cervical and dorsal root ganglia in which glutamate inputs obviously do not occur; no signs of neuronal vulnerability were seen.

Piericiden A sensitivity, site 1 phosphorylation, and reduced nicotinamide adenine dinucleotide dehydrogenase during iron-limited growth of Candida utilis. It has been reported that cells of Candida utilis, grown in continuous culture under iron-limited conditions, develop site 1 phosphorylation, without the appearance of piericidin sensitivity and without changes in the iron-sulfur centers of NADH dehydrogenase, on aeration in the presence of cycloheximide, as well as on increasing the supply of iron during growth. These findings were reinvestigated in the present study. The parameters and properties followed during these transitions were sensitivity of NADH oxidation to piericidin, presence or absence of coupling site 1, EPR signals appearing on reduction with NADH or dithionite, the specific activities of NADH oxidase, NADH-ferricyanide reductase, and NADH-5-hydroxy-1,4-naphthoquinone (juglone) reductase, and the kinetic behavior of NADH dehydrogenase in the ferricyanide assay. Monitoring the rates of oxidation of NADH in submitochondrial particles with artificial oxidants, observing the kinetics of the ferricyanide assay, and measuring the concentration of iron-sulfur centers elicited by EPR permitted ascertaining the type of NADH dehydrogenase present and its relative concentration in different experimental situations. It was found that on gradually increasing the concentration of iron during continuous culture (transition from ironlimited to iron- and substrate-limited growth), as well as on aeration of iron-limited cells, coupling site 1, piericidin sensitivity, NADH-ferricyanide activity, and iron-sulfur centers 1 and 2 increased concurrently, with concomitant decline of NADH-juglone reductase activity. Cycloheximide prevented all these changes. Iron-sulfur centers 3 plus 4 underwent relatively little increase during these transitions. It is concluded that in both of these experimental conditions a replacement of the type of NADH dehydrogenase present in exponential phase cells by that characteristic of stationary phase cells occurs and that the appearance of site 1 phosphorylation, piercidin sensitivity, and iron-sulfur centers 1 plus 2, all associated with the latter enzyme, is a consequence of this replacement. No evidence was found for the development of coupling site 1 without the appearance of piericidin sensir th

[Beta adrenergic receptors and experimental left ventricular hypertrophy]. The effects of sinoaortic denervation (SAD) on the development of left ventricular hypertrophy (R: heart weight/total body weight; LVT : left ventricular thickness), myocardial beta-adrenergic receptivity ([125I]CYP binding; adenylate cyclase activity) and plasma catecholamine levels (HPLC) were investigated in both normotensive (group 1) and hypertensive dogs evaluated (group 2) 1 and 18 months (group 3) after SAD. Noradrenaline (NA) and adrenaline (A) plasma levels were 461 +/- 54 and 85 +/- 45 pg/ml in controls, 861 +/- 185 and 191 +/- 23 pg/ml in group 2 (P < 0.05) and were normal in group 3 (426 +/- 132 and 110 +/- 16 pg/ml). R and LVT values were higher (p < 0.05) in SAD dogs (R = 7.7 +/- 0.1 and 7.8 +/- 0.2; LVT = 13.6 +/- 1.3 and 14.2 +/- 0.9 mm in groups 2 and 3 respectively) than in group 1 (R = 6.7 +/- 0.1, LVT = 9.3 +/- 0.8 mm). In group 1, the total number of beta-adrenoceptors (beta-AR) was 37 +/- 11 and 29 +/- 6 fmol/mg prot in left ventricule (LV) and right auricle (RA) respectively. Bmax was significantly lower in group 2 (LV: 10 +/- 3; RA: 13 +/- 2 fmol/mg prot, p < 0.05) than in group 1 but was normal in group 3 (LV: 37 +/- 3 and RA: 31 +/- 3 fmol/mg prot).(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of factor XIIIa-positive dermal dendrocytes to Kaposi's sarcoma. The histogenesis of Kaposi's sarcoma (KS) has been the subject of controversy, much of which has centered around whether the spindle cells of KS are derived from vascular endothelium or from lymphatics. Recently, some investigators have speculated that the spindle cells of KS are derived from dermal dendrocytes, a population of mononuclear dendritic cells normally present in the papillary and upper reticular dermis. These cells have been shown to proliferate in response to a variety of stimuli and have been reported to express the plasma proenzyme factor XIIIa. We examined immunohistochemically sections fixed in formaldehyde solution and embedded in paraffin from 20 tumor-stage, 15 patch-stage, and 15 plaque-stage lesions of KS with antibodies directed against factor XIIIa, factor VIII-related antigen, Ulex europaeus lectin, and LN3 (anti-HLA-DR) to investigate the relationship of dermal dendrocytes to KS in general and to try to clarify the histogenesis of this tumor. Our results revealed that the dermis of patch- and plaque-stage KS lesions contains an increased number of factor XIIIa-positive dermal dendrocytes compared with normal dermis and that some of these cells are spindle shaped. Many of the spindle cells in patch- and plaque-stage lesions of KS, however, are negative for factor XIIIa. The cells lining the slitlike spaces and some spindle-shaped cells in close proximity to the vascular spaces stain for factor VIII-related antigen and for Ulex europaeus lectin. LN3 labeled many cells resembling macrophages within the lesions and in papillary dermis. Less than 25% of the dendritic cells within the lesions and in the adjacent dermis expressed both factor XIIIa and LN3. Tumor-stage lesions showed focal but unequivocal staining of the spindle cells for factor VIII-related antigen and Ulex europaeus lectin. Tumor spindle cells were negative for factor XIIIa. Factor XIIIa-positive dendrocytes were plentiful in the uninvolved dermis and were aggregated around the periphery of the tumor nodules. The expression of factor VIII-related antigen and Ulex europaeus lectin by the spindle cells of nodular KS, and their lack of expression of factor XIIIa, suggests that the spindle-shaped tumor cells in all stages of KS are derived from endothelial cells and not from dermal dendrocytes. Dermal dendrocytes appear to undergo hyperplasia in response to KS of all stages. In patch- and early plaque-stage KS lesions, dermal dendrocytes are near factor VIII-related antigen-positive spindle cells and tumor vessels. The mechanism reactive dermal dendrocyte hyperplasia in KS remains obscure.

[Lysosomal enzymes and natural killer activity]. The natural killer activity (NKA) of human mononuclear cells and the activity of the lysosomal enzymes of these cells (arylsulfatase, acid phosphatase and beta-glucuronidase) has been studied in norm and under human lung cancer. The mononuclear cells were isolated from peripheral blood of 10 healthy donors and 20 patients with lung cancer of II-III stages. Under the action of mononuclear cells on the target cells (human erythroleukosis cells K-562 labeled with 3H-uridine) the NKA of mononuclear cells of patients was seen to decrease (cytotoxic index = 54.8 +/- 6.4%), in comparison with that of healthy donors (cytotoxic index = 65.1 +/- 4.5%). Simultaneously a decrease in arylsulfatase activity (0.05 +/- 0.01 nmoles/10(6) cells/min) was found in comparison with the control value (0.11 +/- 0.01 nmoles/10(6) cells/min). In 2-3 weeks after the operation the NKA value (cytotoxic index = 50.2 +/- 5.8%) was restored and arylsulfatase activity (0.09 +/- 0.02 nmoles/10(6) cells/min) was increased. There was no correlation between the NKA value and the activities of acid phosphatase and beta-glucuronidase. The parallelism observed between changes in NKA value and arylsulfatase activity may suggest a possible participation of this enzyme in the killing mechanism at the stage of cerebroside sulfate ester degradation of the target cell membrane to initiate the lytic events.

Insulin resistance and acanthosis nigricans. Report of a case with antibodies to insulin receptors. A 64-year-old black man presented with the syndrome of acanthosis nigricans and insulin-resistant diabetes mellitus requiring up to 3000 units of insulin per day. The patient's plasma contained circulating antibodies to insulin receptors thought to be responsible for the insulin resistance. The marked insulin resistance, the manifestations of acanthosis nigricans, the evidence of immunologic dysfunction by the absence of expected circulating antibodies to insulin, and the demonstration of circulating antibodies to insulin receptors put this patient in Kahn's category B of insulin resistance and acanthosis nigricans. There was no evidence of malignancy, lipodystrophy, or endocrine abnormality. The occurrence of acanthosis nigricans with insulin resistance due to binding of cell membrane insulin receptors by antibodies has been reported exclusively in women. This case report is the first description of a male patient with the syndrome of insulin resistance and acanthosis nigricans and focuses attention on features that might mislead one to suspect other causes of insulin resistance.

Intraamniotic infection in patients with intact membranes and preterm labor. The purpose of this review was to determine the frequency of intraamniotic infection in women with preterm labor and intact membranes and to assess the need for amniocentesis in these patients. We reviewed reports in the English language literature from the past 10 years in which the frequency of intraamniotic infection was determined by transabdominal amniocentesis. The 16 studies reviewed demonstrated frequencies of positive cultures that varied from 0 to 61 per cent. This extreme variability seems to be the result of diverse patient populations, dissimilar microbiologic techniques, and different definitions of preterm labor. Advanced cervical dilation and poor response to tocolytic agents were two factors associated with a higher frequency of intraamniotic infection. We conclude that each institution must determine the frequency of intraamniotic infection associated with preterm labor in their patient population. In populations with a high frequency of infection, amniocentesis for microbiologic evaluation is recommended for management of preterm labor, especially in patients who have advanced cervical dilatation or who are unresponsive to tocolytic therapy.

Modeling the relations of attributional style, expectancies, and depression. Structural modeling techniques were used to assess relations of attributional style, expectancies, and depression. According to an initial theoretical model, attributions are directly related to expectancies, and expectancies are directly related to depression, but attributions are only indirectly related to depression by means of their relation to expectancies. The results of Study 1 indicated that this model was flawed in 2 respects: (a) Attributions for positive and negative events did not form a single latent variable, and (b) attributions for negative events both were indirectly related to depression by means of expectancies and were directly related to depression. Attributions for positive events only were indirectly related to depression by means of expectancies. The model derived in Study 1 was replicated in Study 2. Discussion centers on the interpretation of this modified model and on issues in the measurement of attributional style.

Lung biopsy: methods, value, complications, timing, and indications. Six methods of lung biopsy are discussed on the basis of literature reports: 1. Aspiration biopsy by fine needle, 2. split needle biopsy (Vim-Silverman), 3. cutting needle biopsy (Travenol), 4. trephine biopsy by rotating needle, 5. transbronchial biopsy, 6. open biopsy. Because of the high risk, biopsies with thick needles (methods 2--4) should be abandoned. Transbronchial biopsy is renounced because reliable results are only achieved in sarcoidosis which can be clearly diagnosed in high percentage of cases by other less dangerous procedures. In solitary tumors which could not be diagnosed by any other means aspiration biopsy is indicated because of its low risk and its diagnostic accuracy of more than 80%. In disseminated pulmonary disorders which cannot be diagnosed by any other means open lung biopsy is the most reliable method. The lung specimens can be taken under eye control. They should contain tissue from the transitional zone between diseased and unchanged areas, however. The specimens are usually big enough for additional electron and fluorescence microscopic examinations as well as dust analyses. The pathologist must be aware of all clinical data including X-ray pictures, laboratory findings, case history, and history of occupational and nonoccupational dust exposure. If these conditions are fulfilled and adequate methods are applied, lung biopsy provides diagnosis and prognosis, makes causal therapy possible, and amplifies the medical knowledge of pulmonary diseases.

Phenotypic analysis of skin infiltrates in comparison with peripheral blood lymphocytes, spleen cells and thymocytes in early avian scleroderma. University of California at Davis line 200 (UCD-200) chickens develop a hereditary connective tissue disease characterized by severe lymphocytic infiltration, vascular occlusion and fibrosis of skin and internal organs. To identify cellular immunological abnormalities in the acute inflammatory disease stage of this animal model for progressive systemic sclerosis (PSS) we investigated the phenotypic characteristics and function of peripheral blood lymphocytes (PBL), spleen cells and thymocytes in comparison with skin infiltrating cells. Immunofluorescence and immunohistochemical analysis using monoclonal antibodies revealed the overwhelming majority of skin infiltrating mononuclear cells in the deeper dermis and subcutaneous tissue to be T cell receptor alpha/beta (TcR2)+/CD3+/CD4+/class II+ cells, a small portion (5-10%) of which were interleukin 2 (IL-2) receptor positive. In contrast, the inflammatory infiltrate in perivascular areas of the papillary dermis was constituted of mainly TcR gamma/delta (TcR1)+/class II- lymphocytes. Only few B cells (T/B cell ratio greater than 5) were detected. These diseased chickens showed significantly reduced percentages and numbers of circulating peripheral T cells exhibiting TcR1, TcR2, CD3, CD4 or IL-2-receptor, probably owing to an increased influx into lymphoid organs and affected tissues. In contrast to healthy chickens, the thymi of UCD-200 animals revealed fewer cells expressing TcR1, TcR2 and class II antigen, suggesting an altered intrathymic maturation of the T cell lineage. Functional in vitro studies showed a significantly decreased T cell mitogen-induced proliferation rate associated with a decreased capacity to produce IL-2 and to express IL-2 receptors. In contrast to the deficient in vitro IL-2 production the sera of UCD-200 chickens contained significant levels of IL-2 bioactivity. The alteration of T lymphocyte physiology in UCD-200 chickens adds, at least in part, to the parallels between this animal model and its human counterpart. These data confirm our hypothesis that the PSS-like disease of UCD-200 chickens includes a numeric and/or functional alteration of peripheral T cell subsets, especially of TcR1 positive cells, in contrast to the pronounced accumulation in the afflicted tissues.

Experimental and clinical studies on toxicity of xenogeneic tumor-specific immune ribonucleic acid. To learn the toxicity of xenogeneic tumor-specific immune ribonucleic acid (I-RNA), experimental and clinical studies were carried out. Experimentally, doses of 30 mg/kg, 15 mg/kg, 7.5 mg/kg or 3.75 mg/kg of xenogeneic I-RNA extracted from lymphoid tissues of rabbits sensitized with 105,000 Xg sediments of human gastric carcinoma tissue were injected intraperitoneally into Wistar rats once a day for 30 days. During the period of the study, changes of physiological and biochemical values were examined. In addition, pathological study was made for each organ after the I-RNA administration. There was no death during the study. In the groups of high dose administration, there were poor increase in the body weight, elevation of GOT, GPT and LDH, findings of vacuolar degeneration of hepatic cells, and increase of mesangial matrix and polynuclear glomerulus. Throughout the experiment, the groups given 7.5 mg/kg and 3.75 mg/kg of I-RNA showed no significant difference from control groups. Clinically, 31 cases treated with passive immunotherapy with allogeneic lymphocytes, preincubated with xenogeneic I-RNA, were examined retrospectively for the difference in hematological and biochemical data before and after the therapy. One case showed a transient mild febrile reaction after the therapy. There was no significant difference in hematological and biochemical data. Pathological findings in 3 autopsies after the treatment were reported.

Reversible myeloneuropathy of nitrous oxide abuse: serial electrophysiological studies. Detailed electrophysiological studies were performed in 4 patients with myeloneuropathy induced by abuse of nitrous oxide for 1 to 4 years. All presented with paresthesias, weakness, and Lhermitte's phenomena, and exhibited signs of sensorimotor polyneuropathy, ataxia, and arreflexia. Two had subnormal serum vitamin B12 levels. Baseline electrophysiologic testing revealed reduced motor unit potentials, prolonged F wave latencies, absent H reflexes, denervation potentials, and delays in motor and sensory conduction. Three had peripheral and nuchal delay after median nerve stimulation. All were reevaluated after 3 to 12 months' abstinence and treatment with vitamin B12, and all showed substantial clinical improvement. Parallel improvement in electrophysiologic findings occurred, but residual minor conduction delays, loss of H reflexes, electromyographic evidence of denervation, or abnormalities of posterior tibial SEP were noted. These findings confirm the reversibility of myeloneuropathy of nitrous oxide abuse and describe the profile of electrophysiologic recovery in subjects who abstain from further neurotoxic exposure.

Ketotifen inhibits PAF-induced actin polymerization in a human eosinophilic leukaemia cell line, EoL-1. The inhibitory effect of ketotifen on platelet activating factor (PAF)-induced actin polymerization in a human eosinophilic leukaemia cell line, EoL-1, was examined by flow cytometry with the use of reagents specific for the filamentous form of actin (F-actin). Actin polymerization has been considered to be essential for locomotion of cells, chemotaxis and chemokinesis, and thus it reflects the chemotactic reaction of EoL-1 cells stimulated by PAF. Unstimulated EoL-1 cells showed little PAF-induced actin polymerization, whereas EoL-1 cells cultured for 9 days with the supernatant of a human ATL cell line, HIL-3 (HIL-3 sup), showed marked actin polymerization when stimulated with PAF. The actin polymerization in EoL-1 cells induced by PAF was seen in a dose-dependent manner at concentrations of 10(-10) M to 10(-6) M of PAF, and the maximum effect was seen at 10(-7) M of PAF. CV-3988, a specific antagonist of PAF, inhibited 80% of the actin polymerization in EoL-1 cells induced by PAF at a concentration of 10(-5) M. Ketotifen inhibited up to 40% of the PAF-induced actin polymerization of EoL-1 cells in a dose-dependent manner at concentrations of 10(-9) M to 10(-5) M. These results suggest that ketotifen may play an important role in the prevention of eosinophil-induced inflammation in allergic disorders by inhibiting PAF-induced chemotaxis of eosinophils.

Turbulent flow effects on NMR imaging: measurement of turbulent intensity. A general expression has been derived for the NMR signal from a fluid in steady but turbulent flow in a magnetic field gradient. The precise dependences of the spin echo amplitude on both flow and experimental parameters are described in terms of the temporal autocorrelation function for velocity fluctuations in the fluid. The correlation function width determines whether a diffusion model of turbulent eddies is valid, and for physiological flow in large vessels in NMR imaging a more appropriate measure is the turbulent intensity of velocity fluctuations. The theoretical predictions have been verified in experiments using gradient echo images of flowing water. The theory also predicts that even echo rephasing phenomena may still occur in MR imaging of turbulent flows.

One-year outcome after cerebral infarction in whites, blacks, and Hispanics. Little is known about outcome after cerebral infarction for different ethnic groups. Of 590 stroke patients hospitalized from 1983 to 1986 at the Neurological Institute, cerebral infarction over age 39 years occurred in 135 whites, 177 blacks, and 82 Hispanics. Outcome after cerebral infarction differed by ethnicity. The 1-month mortality rate was similar in whites and blacks and least in Hispanics. Whites had a slightly greater risk of recurrent stroke or death than blacks or Hispanics until 6 months after infarction, when their risk stabilized, while the risk in blacks and Hispanics continued to rise for the entire year of follow-up. By 1 year, the rate of recurrent stroke or death was 34.8 +/- 4.2% in whites, 31.1 +/- 3.6% in blacks, and 21.4 +/- 4.8% in Hispanics (p = 0.04). Differences were found in the distribution of various stroke risk factors in the three ethnic groups. A Cox proportional hazards model demonstrated that the ethnic differences in stroke risk factors and infarct subtype were responsible for the ethnic differences in outcome. An abnormal first electrocardiogram was a risk factor for stroke recurrence or death in all three ethnic groups, while a nonlacunar infarct subtype and a history of diabetes were significant only in Hispanics. Understanding the associations of stroke determinants with ethnicity may lead to more focused secondary prevention of recurrent stroke.

Kinetic analysis of the interaction of nitric oxide with the membrane-associated, nickel and iron-sulfur-containing hydrogenase from Azotobacter vinelandii. The effects of nitric oxide (NO) on the membrane-associated form of the nickel and iron-sulfur-containing hydrogenase from Azotobacter vinelandii have been investigated. In the presence of H2 and an electron acceptor (turnover conditions), NO acts as a noncompetitive inhibitor vs. methylene blue (Ki = 12 microM). There is no element of competition between NO and H2, implying that the site of NO action is not the H2-activating site of the hydrogenase. When the membrane-associated hydrogenase is incubated under non-turnover conditions, the enzyme is irreversibly inactivated by NO in a time-dependent process. The inactivation is a non-saturable, pseudo-first-order process which is consistent with a direct chemical reaction between NO and the hydrogenase. Kinetic evidence is presented which is compatible with an interaction between NO and a redox-active component other than the H2-activating site on the enzyme. The complex inhibition pattern of NO has been interpreted in terms of two distinct interactions of NO with iron-sulfur centers of the hydrogenase.

Isolation and characterization of four peptide hydrolases from the brush border of rat intestinal mucosa. Peptide hydrolases (EC 3.4.-.-) were solubilized from purified brush borders of rat intestinal mucosa by papain digestion. Three peptide hydrolases, I, II, and III, with different substrate specificities were isolated by means of DEAE-cellulose chromatography and preparative acrylamide gel electrophoresis. On repeat preparative acrylamide gel electrophoresis under slightly different conditions, enzyme II was resolved into two proteins, IIa and IIb, with vary similar, possibly identical, substrate specificities. Efforts to discover additional brush border peptide hydrolases revealed none. Studies using more than 50 substrates showed that enzyme I was most active against Met-Met, Met-Ala, and Met-Phe while enzyme II was most active against Phe-Gly, Phe-Ser, and Leu-Gly-Gly, and enzyme III most rapidly hydrolyzed Gly-Leu, Leu-Gly, and Met-Gly. Efforts to discover substrates which are highly discriminating for each enzyme were partly successful. Thus, a number of substrates including leucine amide, leucyl-beta-naphthylamide and Phe-Asp were hydrolyzed almost exclusively (95% or more) by enzyme II while Gly-Leu was similarly specific for enzyme III. No substrate highly discriminating for enzyme I was discovered. Ion-exchange chromatography resulted in increases in specific activity of 10- and 120-fold for enzymes II and III, respectively. By sequential use of ion-exchange chromatography and preparative acrylamide gel electrophoresis, each of the three enzymes was partially purified to the point that they were free of contaminating disaccharidases and enzymes I and II gave single dense bands on analytical acrylamide gel electrophoresis while enzyme III gave a single dense band plus one additional faint protein band. Under appropriate conditions, analytical gel electrophoresis also resolved enzyme II into two bands with enzyme activity. The three enzymes were isolated from intestinal brush borders of germ-free rats indicating that none of the enzymes is of bacterial origin. With Phe-Gly as substrate, pH optima for enzymes I, II, and III were 8.0, 8.0, and 8.5, respectively. Molecular weights determined by gel filtration were 283 000, 284 000, and 134 000, respectively. Studies of activation by metal ions and inhibition by metal ion chelators suggested that the activity of each of the enzymes is dependent on a relatively tightly bound metal cofactor. Peptide hydrolases of the intestinal mucosa play an essential role in protein digestion. The studies presented here help to clarify the total number and substrate specificities of these enzymes in the rat brush border.

Effects of amfonelic acid and GBR 12909 on the haloperidol- and clozapine-induced activation of dopamine neurons. The purpose of the present study was to establish the extent to which dopamine uptake inhibitors, for example, amfonelic acid (AFA) and GBR 12909, differentially affect the haloperidol- and clozapine-induced activation of dopamine neurons. In the striatum and nucleus accumbens, the haloperidol-induced increases in dopamine synthesis and metabolism, as well as striatal dopamine release, were either potentiated or unaffected by AFA or GBR 12909. In contrast, AFA or GBR 12909 markedly attenuated the clozapine-induced increases in dopamine synthesis, metabolism, and release. However, the clozapine-induced increase in dopamine synthesis within tuberoinfundibular dopamine neurons was not significantly altered by AFA treatment. AFA and GBR 12909, appear to differentially affect the haloperidol- and clozapine-induced activation of nigrostriatal and mesocorticolimbic dopamine neurons. However, the inhibitory effect of AFA on the clozapine-induced activation of dopamine neurons does not extent to the stimulatory effect of clozapine on tuberoinfundibular dopamine neurons.

Development and survival of Anopheles pharoensis and An. multicolor from Faiyum, Egypt. Adults of Anopheles pharoensis and An. multicolor were held under cycling environmental conditions in the laboratory to examine the duration of the gonotrophic cycles, survival and life expectancy, and to examine the life table characteristics of F1 larvae. The first gonotrophic cycle took 6.14 and 7.37 days for An. pharoensis and An. multicolor, respectively. Subsequent gonotrophic cycles for the 2 species were shorter. Daily survival rates of An. pharoensis and An. multicolor in the laboratory were 0.95 and 0.93, respectively. The parity rate of field-collected females and estimates of the duration of the gonotrophic cycle yielded daily survivorship estimates of 0.89 and 0.80 for An. pharoensis and An. multicolor, respectively. Mean life expectancy at emergence was 19.0 days for An. pharoensis compared with 17.9 days for An. multicolor. Survivorship from egg eclosion to adult emergence and development time were similar for both species. Both the duration of gonotrophic cycles and mean life expectancies indicated that An. pharoensis had a greater potential to serve as a malaria vector than An. multicolor.

Severity of imported falciparum malaria: effect of taking antimalarial prophylaxis. To investigate the effects of antimalarial chemoprophylaxis and other variables on the severity of falciparum malaria. Review of consecutive malaria cases between 1987 and 1991. The Hospital for Tropical Diseases, London. 250 consecutive cases of mild and 51 consecutive cases of severe falciparum malaria. Prophylaxis was taken in 52.4% (131/250) of the cases of mild malaria and 21.6% (11/51) of cases of severe malaria. Severe malaria was more common in white patients than in those of African origin and was also seen more commonly in people returning from central, southern, and east Africa than in those returning from west Africa. Patients with severe malaria presented sooner than patients with mild malaria. Prior chemoprophylaxis led to a reduction in the severity of falciparum malaria. Ethnic origin, time to presentation, and sex were also associated with the severity of malaria.

Associations between the total fluoride content of dental plaque and individual caries experience in Australian children. Individual caries experience (DMFT) and the total fluoride content of dental plaque were determined for 72 schoolchildren, aged 9.7-13.0 years, lifelong residents in one of three New South Wales towns, where the fluoride levels of the reticulated water supplies were: Katoomba, less than 0.1 parts/10(6); Sydney, 1.0 parts/10(6) for 4 years; and Yass, 1.0 parts/10(6) for 16 years, prior to sampling. The mean fluoride content of plaque in Sydney (22.6, s.d. = +/- 16.8 parts/10(6)) and Yass (25.6, s.d. = +/- 16.4 parts/10(6)) differed significantly (t = 2.27, P less than 0.05 and t = 3.30, P less than 0.02, respectively) from that in Katoomba (13.5, s.d. = +/- 8.3 parts/10(6)). Significant inverse associations were demonstrated between total plaque fluoride and individual caries experience (DMFT) in Sydney (r = -0.45, P less than 0.025) and overall (r = -0.28, P less than 0.010). Inverse trends were established between plaque quantity (dry weight of plaque collected) and fluoride levels. No associations could be demonstrated between fluoride treatment (dentifrice, tablets or topical application) and plaque fluoride, DMFT or plaque quantity.

Measurement of gonadotrophins, testosterone, delta4 androstenedione and dihydrotesterone in idiopathic oligospermia. Basal concentrations of FSH, LH, testosterone, delta4 androstenedione and dihydrotestosterone, together with FSH and LH responses to single injections of LHRH were determined in eighty-four patients with oligospermia and in twenty-seven normal men. LHRH responses were heterogeneous and indicate that various disorders might cause this syndrome. In six cases there appeared to be an isolated deficiency in spermatogenesis, as indicated by an increased FSH response, whilst the LH response was normal as were the concentrations of the testicular hormones. In twenty cases a concomitant disorder of Leydig cell function and spermatogenesis is suggested as indicated by increased FSH and LH responses and decreased concentrations of testosterone and delta4 androstenedione (six) or concentrations at the lower limit of normal (fourteen). Furthermore, in five cases a hypothalamic and/or pituitary disturbance may be accepted on the basis of normal or decreased basal concentrations decreased and responses to LHRH with decreased concentrations of testosterone and delta4 androstenedione. Finally, in thirty-seven cases, oligospermia was not associated with any modification basal gonadotrophin concentrations or response to LHRH when compared with normal subjects.

Fetal ovarian cysts: prenatal ultrasonographic detection and postnatal evaluation and treatment. Ovarian cysts were diagnosed by antenatal ultrasonographic examination in 15 fetuses between 19 and 37 weeks' gestation. In six cases there was ultrasonographic evidence of torsion. Intracystic flocculation, which typically was deposited on the sloping part of the cyst, gave a characteristic liquid interface that was regarded as ultrasonographic evidence of torsion. All cases with evidence of torsion were managed surgically post partum, and in all patients this complication was confirmed. The remaining nine cases were followed up by repeated ultrasonograms, and in all patients disappearance of the cyst was documented within the first 6 months of life. The mean size of cysts with evidence of torsion was 5.41 +/- 0.25 cm, and the mean size of those without torsion was 4.33 +/- 0.3 cm (p less than 0.01). Histologic examination of the surgical specimen in the cases with evidence of torsion revealed follicular cysts in three cases and necrotic ovarian cysts with no specific epithelial findings in the remaining three. We recommend continuous ultrasonographic assessment of antenatally diagnosed cysts and believe that the choice of treatment depends on the appearance of the cyst and its evolution throughout pregnancy.

[Synthesis of spaced trisaccharides with blood group A and B specificity, their fragments, and structural analogs]. Trisaccharides GalNAc alpha 1----3(Fuc alpha 1----2)Gal and Gal alpha 1----3(Fuc alpha 1----2)Gal, which are the determinant fragments of the human blood group specific antigens A and B, respectively, were synthesized as R-glycosides (R = beta-OCH2CH2CH2NHCOCF3). 4,6-BdGal-R was acetylated selectively at 3-OH, the 3-O-acetate was alpha-fucosylated and then deacetylated to give a protected H-disaccharide bearing a free 3-OH. The disaccharide was alpha-glycosylated with 2-azido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-galactopyranosyl chloride (GCl) or 2,3,4,6-tetra-O-benzyl-alpha-D-galactopyranosyl bromide (GBr) to give protected spacered trisaccharides A and B, respectively. Disaccharides GalNAc alpha 1----3Gal-R and Gal alpha 1----3Gal-R were synthesized in two ways. 1. Hydrogenolysis followed by benzylidenation of Bzl3-2-O-Ac-Gal-R gave 4,6-Bd-2-O-Ac-Gal-R, which was alpha-glycosylated with GCl and GBr. 2. The required disaccharides were isolated from the mixture of di- and trisaccharides which was obtained by selective glycosylation of 4,6-Bd-Gal-R with GCl and GBr. Synthesis of GalNAc alpha 1----3(GalNAc alpha 1----2)Gal and Gal alpha 1----3(Gal alpha 1----2)Gal, non-natural analogues of A and B trisaccharides, is also described. Deprotected R-glycosides were converted to OCH2CH2CH2NH2 (R1) derivatives, N-biotinyl derivatives were synthesized from GalNAc alpha 1----3(Fuc alpha 1----2)Gal-R1 and Gal alpha 1----3(Fuc alpha 1----2)Gal-R1 glycosides. The oligosaccharides, their macromolecular forms, and affinity sorbents obtained from them were used in the epitope specificity studies of the monoclonal antibodies and blood group typing.

Processes of change across five stages of smoking cessation. A cross-sectional design with 190 smokers and exsmokers selected by random digit dialing was used to determine differences in processes individuals use to modify behavior across five stages of smoking cessation. Five stages of cessation are: precontemplation, contemplation, recent quitting, long-term quitting, and relapse. Ten processes of change (POC) or ways individuals modify behavior were assessed. Examples of POCs are: consciousness raising, self-liberation, reinforcement management, and stimulus control. Biochemical validation of smoking abstinence was performed on a random subset of exsmoker subjects. Individuals in five stages of smoking cessation used processes of change differently as reflected by a significant MANOVA, F (40,590) = 5.02, p = .0001. It is important to assess an individual's stage of smoking cessation when planning interventions related to POCs.

Preliminary studies on vaccination of rhesus monkeys with irradiated sporozoites of Plasmodium knowlesi and characterization of surface antigens of these parasites. Studies were conducted to develop an effective method of inducing protection against sporozoite-induced malaria in a primate system and to obtain information regarding the surface membrane antigens of sporozoites. Immunization of rhesus monkeys was performed with gamma-irradiated sporozoites of Plasmodium knowlesi. Levels of antisporozoite antibodies were monitored by immunofluorescence, sporozoite neutralization, and the circumsporozoite precipitate reaction, and appeared to correlate well with protection. Only the intravenous route was effective in inducing both protection and antisporozoite antibodies. Immunization with sporozoites mixed with Freund's complete adjuvant failed completely to induce protection and resulted in a minimal antibody response. Mechanisms of resistance to sporozoites probably involve the interaction of the host's immune system with the parasite's surface antigen(s). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of surface-labelled, partially purified sporozoites followed by autoradiography revealed the presence of a small number of labelled proteins in the extract. Immunoprecipitation with specific antisera to P. berghei detected primarily one of these membrane components, with an apparent molecular weight of 41 000. The molecular weight of this main surface antigen in sporozoites of P. berghei was different from that in sporozoites of P. knowlesi.

Evaluating the patient with coronary artery disease. The evaluation of patients with suspected or known CAD involves a comprehensive diagnostic workup. Careful analysis of pain and the factors that influence it is a key factor in differentiating CAD from other cardiovascular and noncardiac diagnoses. The assessment of pain also serves as an important guide for the identification of appropriate diagnostic tests. An evaluation of lifestyle patterns is helpful in identifying behaviors associated with a high risk of CAD. FHP serves as a useful categorization for documentation and provides data that are complementary to the physician's traditional review of systems. The ECG is the most common initial diagnostic test; however, cardiac catheterization remains the most definitive source for the diagnosis of CAD. The sequence and use of diagnostic tests proceeds according to the patient's physiologic stability, with consideration to the risks and benefits to the individual patient. The nurse has an important role in the evaluation for CAD. The initial encounter provides an opportunity to promote the patient's full participation in treatment as well as to establish a commitment to ongoing evaluation. The nurse must be prepared to explain not only the process for the evaluation but also the sometimes unclear results to the patient. In this way, patients can be better prepared to meet the challenges of daily living with CAD.

Cellular models of macrophage tumoricidal effector mechanisms in vitro. Characterization of cytolytic responses to tumor necrosis factor and nitric oxide pathways in vitro. The recently described L-arginine-dependent nitric oxide (NO) pathway has been proposed to interact synergistically with the TNF pathway in murine macrophage-mediated tumor cytotoxicity in vitro. We have employed an experimental construct in which these two pathways were independently expressed by two different effector cell populations. The TNF-dependent pathway was committed by murine 3T3 cells transfected with the cDNA encoding human pro-TNF. The NO pathway was executed by the murine EMT-6 mammary adenocarcinoma cell line treated with murine rIFN-gamma and LPS. Controls for the TNF pathway committed by the transfectant included lysis of the TNF-sensitive murine L929 cell in coculture, secretion of TNF, and absence of nitrite synthesis. For the NO pathway controls included lysis of the murine P815 mastocytoma cocultured with activated EMT-6 cells that had been pretreated with murine rIFN-gamma and LPS, production of nitrite by this activated effector cell, and an absence of TNF secretion. The target cell panel included L929, EMT-6, P815, and murine B16 melanoma and TU-5 sarcoma cell lines. All targets on this panel were susceptible to lysis by LPS-triggered murine bacillus Calmette-Guérin-activated macrophages. The 3T3 transfectant caused significant lysis of cocultured L929 and TU-5 targets. The EMT-6 effector cell only caused significant lysis of the P815 target. When both effector cells were cocultured with these target cells, lysis of the P815 target was observed to be additive or superadditive; however, for all the other targets, cytotoxicity was comparable with or subadditive compared with that seen with the 3T3 transfectant effector cell alone. Thus, these two pathways do not appear to account for the broad, potent tumoricidal activity observed for activated macrophages in vitro.

Management of testicular seminoma at Westmead Hospital from 1980 to 87. Testicular seminoma comprises fewer than 1% of male cancers but is a relatively common malignancy in young men. The management and outcome of 73 consecutive patients with testicular seminoma were reviewed. Median follow-up was 51 months (range: 15-109 months). Their median age was 37 years (range: 21-67 years). There was a history of testicular maldescent in 5.5% of patients. Beta-human chorionic gonadotropin was elevated in 22% of patients prior to orchidectomy and in 5% post-surgery. The majority of patients had stage I (78%) or stage II (19%) seminoma after clinical staging. One patient (2%) with stage I seminoma relapsed, while two patients (14%) with stage II seminoma relapsed. The latter two were salvaged with further therapy. One of two patients treated for stage III seminoma died. A residual mass after radiotherapy was commonly observed in patients with stage II seminoma, but did not represent viable tumour. These results reflect the high cure rates that are achievable in seminoma with radiotherapy for early stage and non-bulky abdominal disease and, more recently, with cisplatin-based chemotherapy for bulky abdominal or disseminated disease.

Studies on the immunopotentiating effects of a streptococcal preparation, OK-432. I. Enhancement of T cell-mediated immune responses of mice. The effects of the anti-tumour agent OK-432 on the immune response to hamster erythrocytes (HRBC) and nucleated chicken erythrocytes (CRBC) were studied in inbred SL mice. Mice were treated repeatedly with OK-432 before immunization with erythrocytes in saline. The cytotoxicity of CRBC-primed spleen cells, as demonstrated by 51Cr release from labelled CRBC, was markedly increased by treatment with OD-432. The delayed footpad reaction to CRBC was significantly augmented by treatment with OK-432. These results in mice indicate that OK-432 can enhance the cellular immune responses which require the contribution of T cells. Such an activation of T cells by OK-432 was observed in the humoral immune response to a trinitrophenyl group. Augmentation of anti-hapten antibody production, suggesting the enhancement of helper T cell activity by OK-432, was noticed after immunization with trinitrophenyl conjugated to erythrocytes. Furthermore, this enhancement of helper T cell activity by OK-432 was confirmed by utilizing an adoptive transfer system. These results support the possibility that T cell activation may be one of the important effects of OK-432 as an immunopotentiator.

Intrahepatic arterial infusion of combination of mitomycin-C and 5-fluorouracil in treatment of primary and metastatic liver carcinoma. Improvement in drug response and reduction of toxicity were observed after continuous intrahepatic arterial infusion of mytomycin-C (MMC) and 5-fluorouracil (5-FU) in 15 of 26 patients with primary or metastatic carcinoma of the liver. Serum bilirubin values of 10 mg/100 ml absence of ascites, extreme cachexia and impending hepatic failure were used as the criteria for admission of these patients into the study. The patients were given MMC in a dose of 0.08 mg/kg on day 1,5-FU in a dose of 8-10 mg/kg on days 2-5, and MMC on day 6. This schedule was reinitiated on days 8 and 15 for total mean duration of 18 days. Maintenance therapy was carried out by the administration of these drugs at induction dosage alternated each week as a single 24 hourly intravenous infusion. Objective response to combination therapy was defined as decrease of at least 50% in the liver size and in the abnormal levels of serum alkaline phosphatase and glutamic oxaloacetic transaminase (SGOT), and near normal levels of serum bilirubin for a minimum period of 2 months. The duration of objective response ranged from 3-16 months with a median of 8.2 months. The median survival time for the responders was 7.2 months for patients with primary carcinoma and 9.4 months for patients with metastatic carcinoma of the liver as compared to 2 months for patients who failed to respond to the treatment. Five out of 12 patients who were refractory to MMC or 5-FU by intravenous infusion responded to the present combination drug therapy. Of four patients who died during induction therapy, three had liver failure and the fourth suffered pulmonary embolism. These studies provide evidence that combination therapy with MMC and 5-FU increases the survival time of patients with hepatic cancer, presumably due to the synergistic action of these drugs which permits the use of a low dosage schedule and has less toxic effects.

Increasing maternal participation in the hospitalization of young children. In an attempt to reduce the harmful emotional effects of separation for young children, hospitals in recent years have liberalized visiting hours, but parents have not taken advantage of their new privileges. The study described here sought to increase mothers' participation in their children's hospitalization by overcoming some of the psychological barriers believed to exist. The mothers of 48 children aged 1 to 5, to be admitted for elective surgery to a large, metropolitan pediatric hospital, constituted the primary sample and were divided into experimental and control groups. Mothers in the experimental group had an extra half-hour session in a pre-admission interview focusing on visiting, and specific suggestions were made about frequency and timing of visits, as well as the role of the mother during her visits. During the experimental period weekly meetings were held with the nursing staff to enlist their support for this change in visiting patterns. Results indicate that duration of visits, timing of visits, and behavior during them were all significantly modified for the experimental group of mothers. In contrast, the nurses did not significantly change their relationship with the mothers or the children. Clinical possibilities and limitations of such a program are discussed.

Calcium stimulation of gastrin and gastric acid secretion: effect of small doses of calcium carbonate. Oral calcium carbonate (0-5 g, pH 9-4) increased serum gastrin and gastric acid output with slight but insignificant change in serum calcium. A similar rise in serum calcium during an intravenous infusion of calcium gluconate failed to increase serum gastrin and gastric acid output. Both intragastric calcium actions were abolished by acidification of the calcium carbonate solution (pH 1-0). The increase in serum gastrin and gastric acid output after intragastric calcium carbonate was not affected, however, by a simultaneous intraduodenal acid load. Equivalent neutralising doses of magnesium hydroxide (pH 9-4) did not increase serum gastrin and gastric acid output above basal levels, whereas antral acidification with 20 ml 0-1 N HCl resulted in a slight decrease in serum gastrin. Intraduodenal calcium carbonate (pH 3-0) also increased serum gastrin and gastric acid output, whereas an equivalent volume of intraduodenal saline (pH 3-0) had no effect. These findings indicate that calcium increases serum gastrin by local stimulation of antral and duodenal mucosa. They also suggest that the action of calcium on gastric secretion is partly mediated by gastrin.

Hepatic siderosis in alcoholics. In a population of 157 (120 males, 37 females) predominantly British alcoholics with liver disease, the incidence of some degree of hepatic siderosis, as estimated by stainable parenchymal iron, was 57.3%. The incidence of significant siderosis (grades III and IV) was 7%, and was similar for both sexes. In the female alcoholics there was a significant correlation between age and the degree of siderosis (P less than 0.05)--four of the five females with significant siderosis being premenopausal. In the male alcoholics there was a significant inverse relationship between the grams of ethanol consumed per day and the degree of siderosis (P less than 0.05) and a significant correlation between the percentage saturation of iron-binding protein and the degree of siderosis (P less than 0.05). The mean daily iron intake from alcoholic beverages was 1.5 mg; there was no relationship between the amount of iron ingested in the alcohol and the degree of siderosis. In this population of alcoholics the incidence of significant siderosis in both sexes was low.

Potential and polarization measurements in vivo of oral galvanism. Galvanic currents within the oral cavity may have harmful effects on biological tissues. In the present work 16 patients with different kinds of oral and other discomfort and pain which they attributed to oral galvanism were investigated. The potential and polarization of each metal restoration within reach of a platinum probe were measured versus a reference electrode. A recording of these measured values permits a calculation of the currents which may pass between the teeth. A control group of patients with no subjective symptoms of galvanism in the oral cavity was also investigated. The results of the electrochemical measurements showed that conditions for oral galvanism existed within the individuals of the patient group as well as within the control group. One remarkable observation was that the metallic restorations often consisted of different electrically isolated areas with different electrochemical properties. This and other factors influencing oral galvanism are discussed.

[Appendectomy with intraoperative celioscopy in children. 465 cases]. The authors report a retrospective series of 465 appendectomies with intraoperative celioscopy in children under age 16. The technical issues and the indications are discussed. The results are the following: No death, 3.6% intraoperative incidents of no consequence, 3% postoperative complications, including 1.3% requiring second surgery or celioscopy. These results are better than those obtained with conventional surgery. The advantages of appendicectomy with intraoperative celioscopy are the following: easy, quick search for the appendix, whatever its location, exploration of the entire abdominal cavity, possibility to perform a complete peritoneal washing, suppression of parietal complications, and almost no skin scar, definite reduction in the number of intraperitoneal residual abscesses, and likely reduction of postoperative adhesions, which are a cause of obstruction, of chronic pain and of infertility in girls, rapid resumption of transit and of all activities, including sports.

Effect of ferric and ferrous iron chelators on growth of Bacteroides fragilis under anaerobic conditions. Growth of Bacteroides fragilis under anaerobic conditions in the presence of either haemin or protoporphyrin IX was inhibited by the ferrous iron chelator bipyridyl. The ferric-iron chelator desferrioxamine inhibited growth in the presence of protoporphyrin but not haemin, suggesting that even under anaerobic conditions Fe3+ is involved in uptake of non-haem iron, which is required in the absence of haemin. However, the ferric iron chelators 1,2-dimethyl-3-hydroxy-pyrid-4-one (L1) and pyridoxal isonicotinoyl hydrazone (PIH) were only weakly inhibitory. Apotransferrin, which also binds Fe3+, inhibited growth, but this was not simply due to binding of iron in the medium, as under the reducing conditions present, transferrin was unable to bind iron. This study suggests that even under anaerobic conditions, uptake of non-haem iron by B. fragilis may involve conversion of Fe2+ to Fe3+.

Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. Patients with congestive heart failure have a high mortality rate and are also hospitalized frequently. We studied the effect of an angiotensin-converting-enzyme inhibitor, enalapril, on mortality and hospitalization in patients with chronic heart failure and ejection fractions less than or equal to 0.35. Patients receiving conventional treatment for heart failure were randomly assigned to receive either placebo (n = 1284) or enalapril (n = 1285) at doses of 2.5 to 20 mg per day in a double-bind trial. Approximately 90 percent of the patients were in New York Heart Association functional classes II and III. The follow-up averaged 41.4 months. There were 510 deaths in the placebo group (39.7 percent), as compared with 452 in the enalapril group (35.2 percent) (reduction in risk, 16 percent; 95 percent confidence interval, 5 to 26 percent; P = 0.0036). Although reductions in mortality were observed in several categories of cardiac deaths, the largest reduction occurred among the deaths attributed to progressive heart failure (251 in the placebo group vs. 209 in the enalapril group; reduction in risk, 22 percent; 95 percent confidence interval, 6 to 35 percent). There was little apparent effect of treatment on deaths classified as due to arrhythmia without pump failure. Fewer patients died or were hospitalized for worsening heart failure (736 in the placebo group and 613 in the enalapril group; risk reduction, 26 percent; 95 percent confidence interval, 18 to 34 percent; P less than 0.0001). The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions.

Immunohistochemical positivity for neuron-specific enolase and Leu-7 in malignant mesotheliomas. The discovery of immunostaining for neuron-specific enolase (NSE) and Leu-7 in a small cell mesothelioma prompted us to study some putative immunohistochemical markers of neuroendocrine differentiation in malignant mesotheliomas and to examine any diagnostically important immunohistochemical distinctions or similarities between malignant mesothelioma and other histologically similar lung tumours. Most mesotheliomas were positive for NSE (96 per cent) and Leu-7 (70 per cent) and positivity for these two markers was also found in small cell carcinomas (NSE 25 per cent, Leu-7 81 per cent) and adenocarcinomas (NSE 28 per cent, Leu-7 28 per cent) but carcinosarcomas were positive for only NSE (44 per cent). Chromogranin A positivity was found only in occasional small cell carcinomas (6 per cent) and adenocarcinomas (6 per cent). No tumour was positive for bombesin. The high incidence of NSE and Leu-7 positivity in mesotheliomas is an important original observation because it guards against the unjustified exclusion of mesothelioma from a differential diagnosis on the basis of positivity for these two markers.

An examination of the relationships among three outcome scales in schizophrenia. The functioning of 94 schizophrenic subjects was rated using the Global Assessment Scale, the Strauss and Carpenter Outcome Scale, and the Role Functioning Scale. The convergent validity among the scales was quite modest and highly variable. Solid empirical convergence only occurred when two of the scales each measured social and vocational dimensions of functioning. It is argued that these findings strongly illustrate the need for conceptual and operational consensus in this area. The findings also support the notion of outcome in schizophrenia as a set of distinct, yet linked, dimensions. Other implications of the findings for the definition and measurement of outcome in schizophrenia when using global and multidimensional scales are discussed.

[From epidemiology to social epidemiology in dentistry. The example of caries]. Today, we know the caries aetiology and prevention rather well. We also know that caries-related levels of dental health are inequitably distributed among social classes: on the average, disadvantaged people experience higher DMFS then privileged people. This difference can be explained by a differential access to health care, which can be shown by the study of components of the DMFS index: proportion of filled surfaces (F/DMFS), proportion of missing surfaces (M/DMFS), and proportion of recurrent caries (secondary caries/filled surfaces). Though we are able to describe the social distribution of levels of dental care, we cannot "explain" the differences we observe. The explanation of those differences defines the field of social epidemiology. This consists in determining the social aetiology of diseases, starting from social determinants of attitudes and behaviors influencing health.

Antimicrobial effect of root canal débridement in teeth with immature root. A clinical and microbiologic study. The aim of present investigation was to compare the antibacterial effect of biochemical root canal cleansing in permanent non-vital upper incisors with immature with those with mature root. The material comprised three groups made up of 34, 46 and 28 teeth in which the mechanical cleansing was accompanied by flushing with sterile saline and sodium hypochlorite solutions giving 0.5 or 5.0% active chloride, respectively. Samples were taken in root canals initially after removal of necrotic tissue and after completed cleansing, transferred to solid and liquid media for aerobically and anaerobically and incubated until growth appeared or up to 10 days. The microorganisms were identified by biochemical tests and gas-chromatographic analysis. The antibacterial effect of mechanical cleansing with sterile saline was very low (9%) and limited to the teeth with mature root. The flushing with sodium hypochlorite increased the antibacterial effect to about 25%. No statistical difference was found in the antibacterial effect between flushing with 0.5 % or 5.0% sodium hypochlorite solutions. The antibacterial effect was, however, irrespective of the sodium hypochlorite concentrations, less good in teeth with immature root at the statistically significant 5% level. It was concluded that mechanical cleansing of root canals in teeth with immature root with the instruments now available is inadequate. This inadequacy cannot be compensated for by use of highly concentrated solution, with dissolving effect on necrotic tissue, for flushing. The use of such substances which also have toxic effect on the tissue should be avoided.

Improving the safety of topically applied timolol in the pigmented rabbit through manipulation of formulation composition. The objective of this study was to compare the efficiency of various formulations in maximizing the ratio of ocular to systemic absorption of topically applied timolol in the pigmented rabbit. Formulations of various pHs, tonicities, and concentrations of benzalkonium chloride, EDTA, poly(vinyl alcohol), poly(vinylpyrrolidone), hydroxypropylcellulose, and Na hyaluronate were tested. Ocular absorption was determined by monitoring the timolol concentration in various anterior segment tissues 30 min after instillation of timolol solution, while systemic absorption was determined by monitoring the time course of timolol concentration over 120 min. Timolol was assayed by reversed-phase HPLC. Lowering the solution tonicity to 80 mosmol kg-1 and incorporating polymers into the formulation were the only approaches that promised to improve the safety of topically applied timolol, since they afforded the desired increase in ocular absorption and reduction in systemic absorption. Lowering the solution pH to 6.4 and increasing the tonicity of the solution to 600 mosmol kg-1 reduced systemic absorption but caused either no change or a decrease in ocular absorption. Raising the solution pH to 8.4 and incorporating 0.025% benzalkonium chloride and 0.5% EDTA into the formulation led to an undesirable increase in systemic absorption although ocular absorption was also increased. In the final analysis, the net effect of formulation changes on the ratio of ocular to systemic absorption depended on the interplay of changes in solution drainage; permeability of the cornea, conjunctiva, and nasal mucosa; and fraction of drug in the preferentially absorbed form.

Intracoronary C5a induces myocardial ischemia by mechanisms independent of the neutrophil: leukocyte filters desensitize the myocardium to C5a. Activation of the complement cascade with the generation of anaphylatoxins accompanies the inflammatory response elicited by acute myocardial ischemia and reperfusion. Although complement is activated in the interstitium during acute myocardial ischemia, we have studied mechanisms whereby complement might exacerbate ischemia by using a model employing intracoronary injection of C5a in nonischemic hearts. Intracoronary injection of complement component C5a induces transient myocardial ischemia, mediated through the production of the coronary vasoconstrictors thromboxane A2 and peptidoleukotrienes (LTC4, LTD4), and causes sequestration of polymorphonuclear leukocytes (PMN) in the coronary vascular bed. To further investigate the role of the PMN in the C5a-induced vasoconstriction, the left anterior descending coronary artery (LAD) in pigs was perfused at constant pressure and measurements of coronary blood flow, myocardial contractile function (sonomicrometry), arterial/coronary venous blood PMN count, and thromboxane B2 (TxB2) levels were performed. The myocardial response to intracoronary C5a (500 ng) was determined before, during, and after perfusion with blood depleted of PMNs using leukocyte filters (Sepacell R-500, Pall PL-100). In additional animals, the myocardial response to the PMN chemotactic agent, LTB4, and the effects of intracoronary C5a during constant flow perfusion were measured. Control intracoronary injection of C5a decreased flow (41% of baseline) and contractile function (39% of baseline), PMNs were trapped (5.1 x 10(3) cells/microliters), and TxB2 concentration increased in coronary venous blood. The response to C5a during coronary perfusion with arterial blood depleted of PMNs with Sepacell or Pall filters (less than 0.1 x 10(3) cells/microliters) was greatly blunted, with flow and contractile function falling by less than 14 and 8%, respectively, from baseline, and release of TxB2 was greatly attenuated. However, the myocardial ischemia and TxB2 release remained depressed in response to C5a after removal of the filters and perfusion with either arterial blood containing normal levels of PMNs or stored arterial blood never exposed to filters. In contrast, the repeat C5a challenge resulted in equivalent myocardial extraction of PMNs, thus indicating a dissociation of PMN sequestration from the acute ischemic response and release of TxB2. In separate experiments, the intracoronary injection of LTB4 also resulted in a pronounced myocardial extraction of PMNs (8.6 x 10(3) cells/microliters) greater than during C5a, but did not depress coronary flow or function. Perfusion at constant flow greatly diminished the ischemic response to C5a, indicating that vasoconstriction and resultant ischemia is the main cause of the contractile dysfunction. These data indicate that leukocyte filters inhibit the myocardial ischemia and release of TxB2 induced by C5a via mechanisms not related to PMN depletion.(ABSTRACT TRUNCATED AT 400 WORDS)

Hepatitis C virus infection in post-transfusion hepatitis. An analysis with first- and second-generation assays. The causes of post-transfusion non-A, non-B hepatitis are still not fully defined, nor is it clear how accurate the tests are that are used to screen blood donors for hepatitis C virus (HCV) and to diagnose post-transfusion hepatitis caused by infected blood. We used two first-generation enzyme-linked immunoassays (EIAs) and one second-generation immunoassay to test for anti-HCV antibodies in serum samples collected between 1976 and 1979 in the Transfusion-Transmitted Viruses Study (from 1247 patients who underwent transfusion and 1235 matched control subjects who did not receive transfusions). We tested serum collected before and after infection from the patients in whom non-A, non-B hepatitis developed, serum from their blood donors, and serum from 41 of the control subjects who had hepatitis unrelated to transfusion. Of the 115 patients in whom post-transfusion non-A, non-B hepatitis developed, the initial serum samples of 111 were anti-HCV-negative; after hepatitis developed in these 111 patients, the first-generation EIAs detected anti-HCV in 51 (46 percent), and the second-generation assay detected anti-HCV in an additional 16 (14 percent), for a total of 60 percent. Of 40 controls, 37 were anti-HCV-negative initially, and none seroconverted after hepatitis developed. If the 3 percent rate of non-A, non-B, non-C hepatitis among the controls (37 of 1235) was applied to the 1247 transfusion recipients, only 74 of the 111 cases of hepatitis were attributable to the transfusion. Thus, 91 percent (67 of 74) of the cases of post-transfusion hepatitis were caused by HCV. Of the 99 donors, 60 were HCV-positive (9 on second-generation tests only) and 39 were not. Nearly all cases of non-A, non-B post-transfusion hepatitis are caused by HCV. Screening with a second-generation assay improves the rate of detection of HCV infection in patients with post-transfusion hepatitis and in blood donors. The use of this test showed a 3.6 percent risk of non-A, non-B, non-C hepatitis, which was not significantly different from the rate in the controls (3.0 percent).

Gingival response to silk, cotton, and nylon suture materials. Silk, cotton, and nylon suture materials were implanted in the tunica propria of the gingiva in seven adult rhesus monkeys. The histologie study of twenty-four biopsy specimens indicated that there was neither an increase in the vascular permeability nor a leukocytic margination and migration into the tissues adjacent to the suture materials. However, there was a variable histiocytic reaction, with multinucleated cell formation. This reaction was quite intense with cotton, less intense with silk, and practically absent with nylon. The greater cellular response to cotton was probably due to its more active capacity for modifying the internal biologic medium of the gingvia.

Uptake of infarct-imaging agents in reversibly and irreversibly injured myocardium in cultured fetal mouse heart. We studied the specificity of uptake of infarct-imaging agents for reversibly or irreversibly injured myocardium independently of blood flow by using intact beating fetal mouse hearts in organ culture. Reversible injury resulted from deprivation of oxygen and glucose for 4 hours at 37 degrees C; irreversible injury, from similar deprivation at 42 degrees C. At the end of the insult, uptake of 99mTc(Sc)-labeled pyrophosphate, glucoheptonate, or tetracycline was markedly increased in irreversibly damaged and, to a lesser degree, in reversibly injured hearts. After 24 hours of recovery, necrotic hearts accumulated even more pyrophosphate and tatracycline but less glucoheptonate. Uptake of radioiodinated tetracycline increased only in irreversibly injured hearts. Pyrophosphate uptake was not reduced in hearts cultured in calcium-free medium. These finding suggest that 99mTc(Sn)-labeled pyrophosphate, tetracycline, and glucoheptonate preferentially localize in irreversibly damaged myocardium; the 99mTc(Sn) complex modifies the specificity of uptake; and the uptake of 99mTc(Sn)-pyrophosphate appears unrelated to calcium uptake.

Post-extrasystolic potentiation of ischemic myocardium by atrial stimulation. The response of acutely ischemic myocardium to post-extrasystolic potentiation (PESP) was evaluated in 11 mongrel dogs. Mercury-in-silastic length gauges were sutured to the epicardial surface of the left ventricle; left ventricular pressure was determined via an apical large-bore catheter-transducer system and controlled by volume manipulation. The anterior descending coronary artery was then ligated, and single premature atrial contractions were introduced via an external stimulator. Thirty minutes after occlusion, shortening during ejection had decreased an average of 81 +/- 8 per cent, from 1.30 +/- 0.29 to 0.32 +/- 0.05 mm. PESP initially induced a marked restoration toward normal segmental contraction as systolic shortening increased significantly to 1.14 +/- 0.23 mm. Additionally, paradoxic systolic expansion, when present, reverted to a normal pattern of contraction during PESP. Responsiveness to PESP deteriorated progressively with time over 3 hours following occlusion until the muscle became essentially totally unresponsive to this stimulus. It is concluded that a single premature atrial beat may be used to induce PESP and provides an effective stimulus for contractile reserve of acutely dysfunctional ischemic myocardium. Loss of responsiveness to PESP may represent the progression to nonviability following acute ischemia.

Chimeric HU-IHF proteins that alter DNA-binding ability. Chimeric proteins between Escherichia coli histone-like HU and IHF were constructed by genetic engineering, in which part of the arm region was replaced by the corresponding region of IHF alpha (designated as HupANhimA) or IHF beta (HupANhimD); alternatively, an alpha-helix 2-beta 1 region was replaced by the corresponding region of IHF alpha (HupAXhimA) or IHF beta (HupAXhimD) (symbols N and X indicate NotI and XhoI junctions). These proteins were synthesized in a hupA-hupB double-deletion mutant. HupANhimA exhibited marked reduction in nonspecific DNA binding in vitro, and a drastic loss of HU activity in replicative transposition of Mu phage in vivo. HupANhimD also showed a significant reduction in the ability for DNA binding, though this protein supported Mu phage development. In contrast, the other two chimeric HU proteins showed only slight changes in nonspecific DNA-binding ability: they retained activities for transposition of Mu phage in vivo. These observations confirm that the flexible arm of HU-2, a domain proposed for DNA binding [Tanaka et al., Nature 310 (1984) 376-381; Goshima et al., Gene 96 (1990) 141-145], plays an important role in the physiological function of this protein. The results indicate that a unique conformation of the arm structure of HU protein, particularly the N-terminal half of a two-strand antiparallel beta-ribbon of the structure, is important for the DNA-binding ability of this protein.

Characteristics of the contractile response of rabbit aorta produced by cromakalim in calcium-free solution. 1 The effect of potassium channel opening compounds has been investigated in the smooth muscle of rabbit aorta under Ca-free conditions. Examination of the characteristics of the response has been performed using cromakalim as the prototype compound. 2 In order of potency, Ro 31-6930, cromakalim, minoxidil sulphate and pinacidil each produced a contraction in rabbit aortic strips bathed in Ca-free MOPS-buffered physiological salt solution (PSS). In contrast, forskolin, glyceryl trinitrate and nifedipine each failed to increase tension under identical conditions. Cromakalim also evoked contraction of bovine trachealis muscle bathed in Ca-free PSS. 3. The contractile response to cromakalim in rabbit aortic strips was of delayed onset (15-20 min) and reached a plateau after approximately 120 min (1.8 g maximum with 1 microM cromakalim). No cromakalim-induced tension changes were observed in either 1 mM or 2.5 mM Ca-containing PSS. 4. Raising the [KCl] of the Ca-free PSS to 65.9 mM fully inhibited the cromakalim-induced contraction in rabbit aortic strips. In addition, pretreatment of aortic strips with the sulphonylurea glibenclamide antagonized the subsequent mechanical response to cromakalim. 5. In Ca-free PSS, cromakalim (1 microM) stimulated 42K-efflux with a time-course corresponding to the contractile event. Glibenclamide (1 microM) inhibited this cromakalim-induced 42K-efflux. 6. In sharp microelectrode studies in bovine trachealis, cromakalim (10 microM) produced a sustained membrane hyperpolarization in normal PSS. In contrast, the cromakalim-induced hyperpolarization in Ca-free PSS was not sustained. The fading of the hyperpolarization was temporally correlated with the increase in tension under these experimental conditions. 7. It is concluded that the K-channel opener-induced smooth muscle contractile response revealed in Ca-free PSS is the consequence of K-channel opening. The nature of the detailed mechanism which underlies this contractile phenomenon remains to be determined.

Purified factor XII has a higher specific activity than the parent molecule in plasma. The specific clot promoting activity of factor XII (F XII) in plasma samples from 50 healthy adults was between 30 and 48 U/mg, whereas the specific activity of purified F XII ranged from 55 to 66 U/mg. This difference was neither due to partial proteolytic activation during purification of F XII nor to the influence of plasma protease inhibitors. Purified F XII showed normal size and charge, as demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing, respectively. The increase of the specific F XII activity during the purification process mainly occurred after anion exchange chromatography on DEAE-Sephadex and after the final gel filtration step. Upon dextran sulfate activation, proteolytic cleavage of F XII and generation of kallikrein-like amidolytic activity was faster in F XII deficient plasma containing purified F XII than in F XII deficient plasma containing a corresponding amount of pooled normal plasma (NHP). The binding to kaolin was similar for both, purified F XII and plasma F XII. In conclusion, purification alters the properties of F XII in an unknown way, resulting in an increased specific clot promoting activity.

Insulin receptor binding and action in human adipocytes. A critical approach to methods, correlations with receptor binding to other cell types, and relations between insulin binding and action. Since the beginning of the seventies, studies of the cellular mechanisms behind insulin resistance in man have included studies of insulin receptor binding and insulin action in isolated cells. In the first studies, only measurements of insulin binding to circulating blood cells (mononuclear cells and erythrocytes) were possible. In these studies it was thus necessary to anticipate that insulin binding to these cells was representative for binding to target cells for insulin (adipocytes, hepatocytes, muscle cells). Later, studies of the human adipocyte became available. In the isolated human adipocyte it was possible to measure both insulin binding and the action of insulin on glucose transport and on the intracellular glucose processing. Immediately, it was observed that receptor binding to the different cell types was not always comparable. Moreover, the relationship between fat cell insulin binding and action was not always straightforward. Because fat tissue is only responsible for a small fraction of total glucose uptake, it is not possible to know whether changes in insulin binding and action in this tissue is representative for changes in the total organism. In the present review these problems have been elucidated by studies of patients with insulin-dependent and non-insulin-dependent diabetes mellitus. In chapter one, the methods used in the clinical studies are reviewed. The precision (intraassay variability) and reproducibility (intraperson variability) has been measured for all insulin receptor assays. It was found that the earlier used assay for mononuclear cells was improved by using a pure monocyte assay, because precision as well as reproducibility was improved. On the other hand, these values were considerably poorer than those found for the other cell types. The precision was 0.09, 0.04, and 0.04 for monocytes, erythrocytes and adipocytes, respectively. The reproducibility was 0.19, 0.06 and 0.11. In order to be able to measure comparability between insulin binding to the above mentioned cell types and hepatocytes, methods for measurement of insulin binding to these cell types from swine have been developed. These studies showed that insulin binding to swine cells have many similarities to that of human cells whereas several dissimilarities were seen between insulin binding to rat and human cells. Thus, it is surmised that swine cells are more suitable than rat cells concerning insulin receptor binding and action studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Ultrastructural investigation of granulation tissues on the osteoarthritic femoral head. A scanning electron microscopic and transmission electron microscopic study. From the femoral heads of nine cases of advanced osteoarthritis of hip joint, three categories of granulation tissues with different colors (bright red, dark-red and white granulation tissues) and texture were obtained. After processing, the specimens were observed under scanning electron microscope and transmission electron microscope. With transformation of the granulation tissues from bright red to white, the collagen fibers therein contained gradually changed from fine to thick ones. Nevertheless, the cellular components in these three types of granulation tissues always possessed the characteristics of both fibroblasts and chondrocytes, i.e., fibroblastic configuration with pericellular Type I collagen fibrils bearing 64 nm periodicity; and chondrocytic scallop-shaped cytoplasmic membrane with intracytoplasmic fat droplets and glycogen granules and pericellular Type II collagen fibrils. All these indicated that in osteoarthritis of hip joints, the granulation tissues of the femoral heads transformed eventually into fibrocartilage, irrespective of their color and texture.

Pharmacodynamics of propofol in female patients. Although the clinical properties of propofol have been studied extensively, the pharmacodynamics have not yet been described fully. We studied the propofol concentration-effect relationships for loss of eyelash reflex, loss of consciousness, and hemodynamic changes in 18 female patients, ASA physical status 1, aged 20-49 yr. Propofol was given by computer-controlled infusion. The initial target concentration of 0.5-1 microgram/ml was increased every 12 min by 0.5-1 microgram/ml until the patients lost consciousness. Every 3 min, loss of eyelash reflex and loss of consciousness were tested and an arterial blood sample was taken for analysis of the blood propofol concentration. The concentration-response relationships for loss of eyelash reflex and loss of consciousness were defined by fitting a sigmoid Emax function (where Emax = the maximum effect that can be reached; i.e., 100% of the patients showing loss of eyelash reflex or loss of consciousness) to the response/no response data versus the propofol concentration, using nonlinear regression. The effect of propofol on hemodynamic parameters was analyzed by linear regression. The propofol concentrations at which 50% and 90% of the patients showed loss of eyelash reflex were 2.07 and 2.78 micrograms/ml, respectively. The corresponding values for loss of consciousness were 3.40 and 4.34 micrograms/ml. The systolic and diastolic blood pressure decreased with increasing blood propofol concentration. The correlation coefficients for the decrease in systolic and diastolic blood pressure versus the blood propofol concentration were r2 = -0.663 and r2 = -0.243, but heart rate did not change. In conclusion, propofol concentrations inducing loss of eyelash reflex are less than those inducing loss of consciousness.

Psoriasis and human immunodeficiency virus infection. Psoriasis associated with human immunodeficiency virus (HIV) infection has been reported to be severe and perhaps associated with decreased survival. Our purpose was to document the natural history, response to therapy, and effect of psoriasis and its treatment on survival in HIV-infected patients with psoriasis. This was an observational cohort study of 50 persons with psoriasis and HIV infection followed up during a 2-year period. In one third of the patients the psoriasis appeared before 1978, the year when HIV seroconversion began in San Francisco (group I). In two thirds psoriasis developed after 1978 (group II). Group I had a lower mean age of onset (19 vs 36 years) and more commonly had a family history of psoriasis. Palmoplantar and inverse psoriasis were more common in group II. Severe psoriasis occurred in one fourth of this group (12 of 50 patients). The median survival in this group after diagnosis of acquired immunodeficiency syndrome (AIDS) was 19 months, which is comparable to the median survival for all AIDS patients diagnosed in San Francisco between 1984 and 1990. Psoriasis in the setting of HIV disease may be mild, moderate, or severe. Standard therapies and zidovudine are effective in management. Survival does not seem to be adversely affected by the presence of psoriasis or its therapy.

[Lectin-induced chemiluminescence of peripheral blood neutrophils in patients with ischemic heart disease before and after blood irradiation with helium-neon laser]. The blood taken from 35 patients with coronary heart disease and 30 healthy donors was irradiated with He-Ne laser, which resulted in a decrease in its count of segmented neutrophilic granulocytes. Lectins bound to various carbohydrate determinants onto the neutrophil surface were shown to affect changes occurring after luminol-depended chemiluminescence irradiation in patients and healthy persons in different ways. The patients' neutrophils contained lower levels of radiommunologically detectable leukotriene B4. Thromboxane B2 levels also dropped following the irradiation. The laser irradiation induced elimination of some less resistant cells from blood flow, i.e. "rejuvenation" of a cell population of neutrophilic granulocytes. The remaining cells differed in the composition and reactivity of surface lectin receptors and in the content of biologically active substances, which is likely to play the key role in the mechanism responsible for the therapeutical effect of He-Ne laser.

[The economic consequences of breaches of hygienic standards]. Economic detriment due to the main occupational diseases diagnosed in 1990 forms a sum of 2.58 billion roubles. Careful assess of economic losses concerning only a deficiency in supply due to an increased morbidity of workers gave a total amount of 20 billion roubles a year in prices of 1987. Privilege pensions connected with hazardous working conditions and based on lists N1 and 2 are considered as an occult legalization of the hygienic norms breaking. Contents of the lists trend to expand. By the end of 1987 the privilege pensions payments covered 6.6 billion roubles, but in 1991 that sum reached 7.3 billion roubles.

Ca2+ depletion from the photosynthetic water-oxidizing complex reveals photooxidation of a protein residue. A new intermediate in the water-oxidizing reaction has been observed in spinach photosystem II (PSII) membranes that are depleted of Ca2+ from the site which is conformationally coupled to the manganese cluster comprising the water-oxidizing complex (WOC). It gives rise to a recently identified EPR signal (symmetric line shape with width 163 +/- 5 G, g = 2.004 +/- 0.005), which forms in samples inhibited either by depletion of Ca2+ [Boussac, A., Zimmerman, J.-L., & 28, 8984-8989; Sivaraja, M., Tso, J., & Dismukes, G.C. (1989) Biochemistry 28 9459-9464] or by substitution of Cl- by F- (Baumgarten, Philo, and Dismukes, submitted for publication). Further characterization of this EPR signal has revealed the following: (1) it forms independently of the local structure of the PSII acceptors; (2) it arises from photooxidation of a PSII species that donates an electron to Tyr-Z+ or to the Mn cluster in competition with an exogenous donor (DPC); (3) the Curie temperature dependence of the intensity suggests an isolated doublet ground state, attributable to a spin S = 1/2 radical; (4) the electron spin orientation relaxes 1000-fold more rapidly than typical for a free radical, exhibiting a strong temperature dependence of P1/2 (half-saturation power approximately T3.4) and a broad inhomogeneous line width; (5) it yields an undetectable change in the magnetic susceptibility upon formation by a laser flash; (6) it disappears in parallel with release of Mn during reduction with NH2OH, indicating that it forms only in the presence of the modified Mn cluster. (ABSTRACT TRUNCATED AT 250 WORDS)

Pathway of ultrasound waves in the equine third metacarpal bone. The velocity of ultrasound waves through bone has been used widely as a non-invasive method for assessing bone quality. Accurate measurement of velocity depends on accurate assessment of the distance travelled by the sound wave. It has been argued that the sonic pathway is deflected around the marrow cavity and so does not follow a straight line through the bone; therefore, correction factors have been developed to account for the extra distance travelled. This hypothesis was examined in vitro using sections from the equine third metacarpal bone. Two 1 MHz transducers used with the transmitting transducer energized by a 600 V electrical spike generator produced a 0.1 microsecond pulse width and the received signal was recorded on a delayed time-base oscilloscope, from which the velocity was calculated. Two distinct peaks were apparent in the received signal, corresponding to a direct cortical transmission wave and a direct medullary transmission wave. This observation was confirmed quantitatively using models of the third metacarpal made from homogeneous materials that allow accurate determination of the transit times of each component of the signal. Perspex was used to mimic cortical bone, with water as the mimic for the contents of the medullary canal; these materials were chosen because they have transmission velocities similar to the materials they were mimicking. The results confirmed that the pathway went straight through the bone with a time lag in the medullary wave due to the slower transmission velocity of the marrow. To ensure that the cortical wave is always received, transducers larger than the medullary width should always be used.

Effect of intracerebroventricular administration of thyrotropin-releasing hormone upon the electroenteromyogram of rat duodenum. Electroenteromyographic activity (EMG) of the duodenum was recorded in pentobarbital-anesthetized rats. TRH intraventricularly administered to rats produced changes in EMG such as increased amplitude, decreased frequency of slow waves and the association of bursts of spike potentials with nearly every cycle of the basal electric rhythm (BER). The effect was selectively prompt and marked in the EMG of proximal duodenum. The response was abolished by vagotomy or atropine injection and no response was elicited in the neonatally 6-OHDA-treated rat. Hypophysectomy, cord-transection or acute i.v. injection of 6-OHDA did not block the response. In the brain, TRH seems to stimulate the neuronal system controlling the vagus efferents involved in the regulation of the duodenal enteric nervous system which in turn modulates the myogenic excitability of the duodenum.

The foramen meningo-orbitale and its relationship to the development of the ophthalmic artery. The incidence of the foramen meningo-orbitale is reported from a sample of 50 adult dried skulls. The foramen meningo-orbitale is not an inconsistent finding, being identifiable in half of the samples studied. Multiple foramina may exist. Although the location of the foramen meningo-orbitale is not fixed, it lies along or near the suture leading superolaterally from the superior orbital fissure. The foramen represents the remnant of an embryonic conduit for the supraorbital division of the stapedial artery en route to the orbit and the developing ophthalmic artery. An alternative, more medial, pathway exists through the superior orbital fissure. The embryonic anastomosis that occurs between the internal and external carotid systems does not occur at the level of this foramen, but closer to the optic nerve as a portion of the primitive 'ring' artery. The term 'stapedial-ophthalmo-lacrimal' foramen is proposed to proclaim the embryonic significance of this foramen.

Ketoconazole, an oral antifungal: laboratory and clinical assessment of imidazole drugs. Miconazole, a parenterally administered imidazole antifungal agent has been shown to produce responses in systemic fungal infections in man. Ketoconazole, an analogue, can be given by mouth. It is inhibitory in vitro at low concentrations to most fungi. Blood levels after oral administration to animals and man greatly exceed these inhibitory concentrations for several hours. The efficacy of this drug has been demonstrated in animal models. Initial clinical evaluation has produced responses to therapy with 200-400 mg/day in 13 of 16 evaluable patients with systemic and superficial fungal infections, involving 10 fungal pathogens. No toxicity has been noted to date in these human studies. Ketoconazole is a promising agent needing further extensive evaluation.

Caulobacter crescentus cell envelope: effect of growth conditions on murein and outer membrane protein composition. The murein and membrane protein compositions of Caulobacter crescentus strains CB13B1a and CB15 have been characterized, and the influence on cell envelope constituents of culture conditions which affect morphogenesis have been studied. Amino acid and sugar analysis of murein sacculi revealed a simple A1gamma murein configuration typical of gram-negative bacteria. The membranes of C. crescentus had low levels of 2-keto-3-deoxyoctonate relative to enteric bacteria, in addition to the absence of lipid A components (Shapiro et al., Science 173:884-892, 1971; Chow and Schmidt, J. Gen. Microbiol, 83:369-373, 1974). Nevertheless, C. crescentus membranes could be fractionated into inner and outer membrane components by sucrose density gradient centrifugation procedures developed for Escherichia coli. The proteins of the outer membrane were distributed between three major (I, II, and III) and two minor (IV and V) protein classes. Class I proteins were greater than or equal to 74,000 daltons and constituted the primary proteins of the outer membrane. Class I proteins were separated into approximately 50 polypeptides by two dimensional gel electrophoresis; the protein composition of thi s class was affected by culture conditions in both CB13B1a and CB15. Class II (47,000 to 39,000 daltons) and III (20,000 to 11,500 daltons) proteins differed in each strain in composition and response to culture conditions.

Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin. The purpose of this study was to compare the effects of low-to-high doses of aspirin on platelet aggregability determined by different methods and on the metabolism of thromboxane A2 and prostacyclin. We administered increasing doses (40, 320, and 1,280 mg/day) of aspirin to 19 poststroke patients and studied the differences in 1) the changes in platelet aggregability depending on the methods of evaluation and 2) the concentrations of prostaglandin metabolites in the blood and urine. Aggregation of platelet-rich plasma induced by a strong stimulus (10 microM ADP) was significantly reduced after 40 mg/day aspirin (p less than 0.005), and this reduction was similar to that after higher aspirin doses. In contrast, aggregation of platelet-rich plasma induced by weaker stimuli (1 and 5 microM ADP) decreased less significantly after 40 mg/day aspirin compared with that after higher aspirin doses. The serum thromboxane B2 generated after ex vivo incubation was reduced significantly (by 85%) after 40 mg/day aspirin and decreased further after 320 mg/day (by 96%) and 1,280 mg/day (by greater than 99%) of aspirin. The urinary 11-dehydro-thromboxane B2 concentration decreased less significantly after 40 mg/day aspirin (by 42%) compared with that after 320 mg/day (by 78%) and 1,280 mg/day (by 91%) aspirin doses. The urinary concentration of 2,3-dinor-6-keto-prostaglandin F1 alpha did not decrease after 40 mg/day aspirin but decreased significantly after higher doses of aspirin. These findings suggest that different doses of aspirin may be necessary to prevent thrombogenesis induced by different triggers of different strengths and that 40 mg/day aspirin is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.

Squamous cell carcinoma of the penis. Squamous cell carcinoma of the penis (CA Penis) is not a rare disease in P.R. We have reviewed all cases of CA penis diagnosed in our institution from Jan. 79-Jan. 89. Pathology and hospital records were audited. The survival data on all patients was updated via telephone or record review up to May 89. A total of 18 pts were seen in the last decade. Of these 11. (61%) were seen in the last four years. Four of 18 patients were excluded from analysis due to lack of staging and therapy data. The median age 54.9 y (range 23-82y). The following risk factors were identified: phimosis 12/14 (86%) p = .05, leukoplakia 8/14 (57%); prior venereal disease 1/14 (7%). The primary lesion appeared in the prepuce 8/14 (57%) and glans 6/14 (43%). TNM staging was done in all pts. Most pts presented with T3 or T4 disease 10/14 (71%) and palpable regional adenopathy (N1-N3) 9/14 (64%). Of the nine pts with palpable adenopathy, in 5 (56%) microscopic malignant disease was confirmed. A correlation between T3 or T4 disease and the presence of palpable adenopathy was seen (80%). The Stage at diagnosis of the 14 pts: I: 0/14 (29%), II: 5/14 (7%), III: 3/14 (21%), IV: 6/14; (43%). All pts were treated with partial penectomy and 7/14 had unilateral or bilateral inguinal lymphadenectomy. Long term survivors (LTS), greater than 12 mo., were seen 3/4 pts with Stage II disease, 1/3 Stage III, and 2/5 in Stage IV. The most important prognostic factor for LTS was malignant involvement of regional lymph nodes with 0/5 in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Mutation generating a fragment of the major heat shock-inducible polypeptide in Drosophila melanogaster. Drosophila melanogaster tissues carrying a third chromosome with the deletion Df(3R)Kar(D2) make a 40,000-dalton (Dal) heat shock protein not made by wild type. The unusual polypeptide was inducible in every tissue examined. Tryptic peptide fingerprints showed it to include part of the 70,000-Dal major heat shock protein. Mapping experiments placed the mutation responsible for the 40,000-Dal protein at or close to the kar(D2) deletion. One break point of the deletion is in subdivision 87A, close to or at a heat shock locus that codes for the 70,000-Dal protein. The results are consistent with the possibility that this break point is within a gene for the 70,000-Dal protein, leaving only the initial portion of its coding sequence. This would specify the direction of transcription of the mutant gene as proximal to distal on the normal chromosome. The 87A heat shock locus should contain at least two genes for the 70,000-Dal protein, because embryos homozygous for the kar(D2) deletion and lacking the heat shock locus at 87C, which also codes for the 70,000-Dal protein, nevertheless produced both the 40,000-Dal and the 70,000-Dal proteins upon temperature elevation. Using the presence of the 40,000-Dal protein to monitor chromosome segregation, we found that embryos homozygous for deletions of the heat shock puff site at 93D exhibited a normal electrophoretic pattern of heat shock proteins.

Effect of sialoadenectomy on stomach lesions induced by indomethacin and ethanol in relation to gastric vascular permeability, the gastrin level and HCl secretion in rats. Stomach lesions induced by indomethacin (20 mg.kg-1 i.p.) and ethanol (1 ml 95% intragastrically) were studied after a 24 hour fast in rats which had undergone sialoadenectomy. The size of the lesions was correlated with gastric HCl secretion, with gastric vascular permeability (determined from the Evans blue concentration in the stomach tissue after its i.v. administration) and with the serum gastrin level. These parameters were also studied in sialoadenectomized rats and in animals given epidermal growth factor (EGF) (50 lg.kg-1). It was found that sialoadenectomy significantly (p < 0.01) raised the incidence of stomach lesions after the administration of indomethacin and also after ethanol (p < 0.05). A significant increase in both basal and stimulated HCl secretion was found after sialoadenectomy. Both indomethacin and ethanol also increased gastric vascular permeability in rats not subjected to sialoadenectomy, but sialoadenectomy raised it significantly compared with the non-sialoadenectomized group. The serum gastrin levels fell after sialoadenectomy and the decrease was significant after the subsequent administration of indomethacin or ethanol. The administration of EGF to sialoadenectomized rats lowered the incidence of stomach lesions, inhibited HCl secretion and reduced vascular permeability. The lowered susceptibility of the gastric mucosa to the formation of lesions in sialoadenectomized rats given indomethacin or ethanol can be regarded as the outcome of the uptake of EGF.

Adenosine receptors in cortical-derived vesicles of the rat: studies on binding sites and accumulation of cyclic AMP. A vesicular preparation derived from the cerebral cortex of the rat was used to obtain, under the same experimental condition, binding parameters and stimulation data for cyclic AMP. Two analogues of adenosine were employed in the binding studies: [3H]NECA, a mixed A1/A2 agonist and [3H]CHA, a more selective A1 agonist. The [3H]CHA seemed to bind to a single high affinity site (Kd = 1.31 nM, Bmax = 0.327 pmol bound); saturation data for [3H]NECA were resolved for the presence of a high and a low affinity binding site (Kd1 = 3.08 nM, Bmax1 0.115 pmol bound; Kd2 = 204 nM, Bmax2 1.59 pmol bound), but only when calcium ions were omitted from the incubation medium. At 0 degree C, [3H]NECA bound to a single, low affinity site; the presence of calcium ions (1 mM) significantly reduced the affinity of [3H]NECA (Kd 419 nM), with respect to the absence of calcium (Kd 208 nM), without affecting the Bmax value. The influence of calcium ions was also investigated on the binding of [3H]CHA and a reduction of the Bmax value (36%) was found. Regardless of the presence or the absence of calcium ions, NECA stimulated accumulation of cyclic AMP in a dose-dependent way with an EC50 of 2.79 microM; this value did not correlate with the Kd of the low affinity binding site for [3H]NECA. Thus, the purpose of establishing a correlation between binding sites for analogues of adenosine and the site in the cerebral cortex through which the accumulation of cyclic AMP is induced, was not achieved. It is concluded that the stimulatory effect of analogues of adenosine on adenylate cyclase might not be a receptor-mediated effect. The complex influence of calcium ions on affinity and binding capacity of analogues of adenosine is discussed.

Memory accessibility and probability judgments: an experimental evaluation of the availability heuristic. Consistent with Tversky and Kahneman's (1973, 1974) availability heuristic hypothesis, the current study found a negative correlation between recall latency for past events and the perceived future probability of similar events. Furthermore, when the relative accessibility of memories of positive and negative events was experimentally manipulated using the Velten mood-induction procedure, the perceived future probabilities of similar events also changed in a manner consistent with the availability heuristic account. Reductions in recall latencies resulting from the mood manipulations were, as predicted, related to increases in perceived probability, and vice versa. Partial correlations indicated that this association between the observed patterns of changes in recall latencies and probability judgments could not be accounted for by the existence of independent associations between each of these effects and the magnitude of mood change.

Effects of temperature and acid-base state on hippocampal population spikes in hamsters. Previous studies have shown that changes in temperature, within the range encountered by hamsters entering hibernation, alter the evoked response of hippocampal pyramidal cells to stimulation of an afferent pathway. The present study was designed to determine whether these alterations are due to changes in the acid-base status of the neural tissue brought about by changes in temperature. Extracellular-evoked responses were recorded from hamster hippocampal slices after Schaffer collateral stimulation. The pH was changed by varying the concentration of CO2 aerating the bathing medium. Buffers contained either 26 or 40 mM bicarbonate ion. The width of the population spike (the synchronous firing of pyramidal cells) was measured as pH was varied between 7.5 and 7.1, with slice temperature set at either 25 or 20 degrees C. There was a significant increase in spike width as temperature was lowered to 20 degrees C, but no significant change in spike width or amplitude as pH or bicarbonate was varied. The effect of temperature (20 degrees C for half-maximal stimulation, and from 20 to 25 degrees C for just maximal stimulation) on spike width and amplitude thus does not appear to be due to pH- or bicarbonate-induced changes.

Cellular retinoic acid binding protein type II was preferentially localized in medium and posterior parts of the progress zone of the chick limb bud. The expression and distribution of cellular retinoic acid binding protein II (CRABP II) was examined in chick limb buds. CRABP II was detected in the limb buds at Hamburger and Hamilton (1) stage 21 and the amount of CRABP II was gradually increased during stages 21-27 and thereafter decreased. CRABP II was mainly located in the progress zone, and the dorsal and ventral premuscular mass in the proximal region of the limb buds at stage 23. CRABP II was preferentially localized in the medium and posterior parts rather than the anterior part of the progress zone; The content of CRABP II in the medium and posterior parts was 8-9 times more than that in the anterior part.

Modified MacConkey medium which allows simple and reliable identification of Providencia stuartii. This work describes a modified MacConkey medium (MCP medium) enabling the simple identification of Providencia stuartii, an emerging nosocomial pathogen. A total of 813 strains, belonging to the families Enterobacteriaceae and Pseudomonadaceae, were tested on MCP medium; all P. stuartii strains were phosphatase positive, as were 97.5% of Morganella morganii strains, in contrast with all other tested organisms. A simple discriminating test, such as the ornithine or citrate test, allowed identification of strains of these species. We have also compared the reliabilities of P. stuartii identification by commercial kits (API 20E system) by using a standard MacConkey or MCP medium. Sixteen and three-tenths percent of P. stuartii strains were misidentified by using the former procedure, while with the latter all strains were correctly identified. Finally, the MCP medium was used over a 6-month period in our routine clinical laboratory. Of a total of 1,278 seeded urine samples from elderly patients, we isolated 103 P. stuartii strains which were all correctly identified by coupling MCP medium and the API 20E system. Seventeen and one-half percent of these strains were misidentified when the API 20E system was used in combination with standard MacConkey medium.

The natural history of the perforated duodenal ulcer treated by suture plication. This retrospective study of 174 patients with proven duodenal ulcer perforation was undertaken to delineate the natural history of those patients primarily managed by suture plication. During this 25-year period, 122 patients (70%) were treated with suture plication and 52 (30%) underwent a definitive procedure. There were 13 deaths in the overall group (7.4%) of which the mortality was 6.5% in the plicated group and 9.6% in the definitive group. Of the 122 patients treated with suture plication, 48% either 1) died of ulcer complications later, 2) required reoperation for ulcer disease, or 3) were under active treatment for ulcer symptoms. The reperforation rate in the entire series was 9% and the reoperation rate 32%. Suture plication is a time-honored, life-saving procedure, however, definitive surgery is a superior form of long-term management of the perforated duodenal ulcer patient.

Possibilities of immunization against cholera and related enterotoxic enteropathies. Scientifically controlled field studies have established that parenterally administered killed vibrio vaccines or somatic antigen preparations offer only limited degrees of protection in certain population groups and have made it obvious that new approaches to the immunoprophylaxis of cholera are needed. It has now also been established that the symptoms of cholera result from the action of the cholera enterotoxin (choleragen) on the epithelial cells of the small intestine. Immulogically related enterotoxins have been incriminated in other newly recognized diarrheal diseases (e.g., those caused by Escherichia coli and "non-agglutinable" (NAG)vibrios). Additionally, volunteer studies have shown that induced cholera results in rather solid and lasting immunity against homologous re-challenge thus proving that immunity against cholera is feasible. Although numerous studies have demonstrated the efficacy of purely antitoxic immunity in experimental animal models, the protective effect of parenterally administered glutaraldehyde treated toxoid in man has shown to be limited, at best. The protection attained following an attack of cholera suggests that local immune mechanism may be of predominant importance. Immunity has been stimulated, experimentally in mice, by toxin antigen administered per os on a single occasion. Choleragenoid, which is non-toxic but binds to the same receptors as cholera toxin, has been shown to provide immediate resistance as well as later immunity to toxin challenge. More ideal, however, would be a colonizing mutant of V. cholerae which elaborates a non-toxic cross-reactive material (CRM) like choleragenoid and which could stimulate local antitoxic as well as anti-vibrio immune mechanisms. A tox-mutant of V. cholerae which is avirulent for man has been shown to elicit substantial immunity in man but the ideal CRM-mutant has yet to be found.

Role of CD4+ T lymphocytes and interleukin-5 in antigen-induced eosinophil recruitment into the site of cutaneous late-phase reaction in mice. Previous studies suggested that the eosinophil recruitment into the site of cutaneous late-phase reaction (LPR) was dependent on IgE antibody and mast cells. In this study, we determined the role of CD4+ T cells and CD8+ T cells in causing antigen-induced eosinophil recruitment of LPR in mouse skin. Eosinophil infiltration into the subcutaneous tissue of ovalbumin (OVA)-sensitized BALB/c mice was biphasic, reaching the first peak at 6 h after the subcutaneous challenge with OVA and the second peak at 24 to 48 h. The in vivo depletion of CD4+ T cells by pretreatment with anti-L3T4 monoclonal antibody (mAb) significantly decreased the second peak (at 24 h and 48 h), but not the first peak (at 6 h), of OVA-induced eosinophil infiltration into the skin of OVA-sensitized mice. However, the depletion of CD8+ T cells by pretreatment with anti-Lyt-2 mAb had no significant effect on either the first peak or second peak of OVA-induced cutaneous eosinophilia. Pretreatment with anti-murine interleukin-5 (IL-5) mAb also decreased the second peak, but not the first peak, of OVA-induced cutaneous eosinophilia. In contrast to the inhibitory effects of depletion of CD4+ T cells and of anti-IL-5 mAb on the second peak of antigen-induced cutaneous eosinophilia, disodium cromoglycate and a selective antagonist for platelet activating factor (PAF) CV-6209 decreased the first peak of OVA-induced cutaneous eosinophilia in the mouse. These results indicate that CD4+ T cells, but not CD8+ T cells, cause the second peak of antigen-induced eosinophil recruitment of cutaneous LPR and that IL-5 mediates this eosinophil recruitment. In contrast, the first peak of antigen-induced eosinophil recruitment of cutaneous LPR is mediated by mast cells and PAF.

Dynamic redistribution of major platelet surface receptors after contact-induced platelet activation and spreading. An immunoelectron microscopy study. The authors used an immunogold labeling procedure to investigate the redistribution of platelet receptors and their ligands on the surface of contact-activated adherent platelets before and after thrombin stimulation. During the initial stage of platelet adhesion, a typical segregation of receptors occurred. Gold particles identifying glycoprotein (GP) Ib (CD42b) and GPIIb-IIIa (CD41a) remained distributed over the entire platelet surface, whereas gold particles identifying GPIa-IIa (CDw 49b) and GPIV (CD36) were found essentially overlying the granulomere; p24 (CD9) was present at the peripheral platelet rim and over the cell body. An increased labeling of GPIIb-IIIa, GPIV and p24 was also observed on pseudopods, with GPIIb-IIIa and GPIV concentrated at the enlarged extremities and at sites of contact between two platelets, whereas GPIb was absent from pseudopods. After thrombin stimulation of adherent platelets, GPIb underwent a relocation to the cell center, in contrast to GPIIb-IIIa which still remained randomly distributed over the cell body. To investigate whether ligand distribution paralleled this receptor segregation, platelet released von Willebrand factor (vWF), fibrinogen (Fg) and thrombospondin (TSP) were visualized. During the early stages of platelet activation, surface labeling for all three adhesive proteins was minimal and almost undetectable. Occasionally, intragranular Fg and vWF was accessible to gold-coupled antibodies, with vWF exhibiting the typical eccentric alpha-granular localization. At later stages of activation and especially after thrombin stimulation, no surface labeling for vWF was observed, whereas immunogold particles identifying vWF were still present inside enlarged clear vacuoles. In contrast, labeling of Fg and TSP was increased over the granulomere and extended to the cell periphery and the pseudopods, but was absent from the hyalomere, despite the presence of GPIIb-IIIa molecules. Double labeling experiments showed colocalization of Fg and TSP, GPIV and TSP, as well as Fg and GPIIb-IIIa, although no typical coclustering of GPIIb-IIIa and GPIV or GPIIb-IIIa and p24 was apparent. Our results further suggest that 1) on surface activated adherent platelets, not all GPIIb-IIIa molecules become competent to bind Fg, 2) GPIa-IIa is not anchored to the platelet membrane skeleton, and 3) during the early stage of platelet activation, a communication exists between the alpha granules and the platelet surface.

Changes in pancreatic exocrine secretion with age: pancreatic exocrine secretion does decrease in the elderly. Pancreatic exocrine secretion was estimated in 180 normal control patients, free of abdominal and pancreatic disease, aged from 16 to 83 years. Duodenal juice was collected in two 15-min fractions after a single intravenous injection of 1 U/kg secretin + 3 U/kg CCK. Volume, maximal concentration and output of bicarbonate, lipase, phospholipase and chymotrypsin were estimated as well as minimal concentration and output of chloride and calcium. Each parameter was plotted against age, either individually or after separation into two age groups. Volume linearly increased up to the 3rd decade, and thereafter linearly decreased. Bicarbonate secretion paralleled fluid secretion and also decreased after the 3rd decade. The changes in chloride and calcium concentrations were different: concentrations linearly increased after the 3rd decade. Calcium concentration linearly increased with age (p less than 0.02) while chloride output was unchanged. The three enzymes that were studied linearly decreased in concentration as well as in output with age from the 3rd decade (p less than 0.02). Protein secretion decreased before water and bicarbonate secretion. One can conclude that pancreatic secretion changes in humans with age. Aging alters pancreatic secretion, through a decrease in flow rate, bicarbonate and enzyme secretion while calcium concentration is enhanced. Although not requiring substitutive therapy in the whole population, individual cases of pancreatic exocrine insufficiency might be explained by aging, without malnutrition.

Nucleic acids: interaction with solar UV radiation. Atmospheric pollutants that reduce the amount of ozone in the stratosphere may markedly increase the flux of intermediate-wavelength solar ultraviolet (UV) radiation that reaches the Earth's surface. Like short-wavelength germicidal UV radiation (less than 280 nm), these intermediate UV wavelengths (280-315 nm) can promote photochemical reactions in nucleic acids, leading to the appearance of such products as cyclobutadipyrimidines and single- and double-strand breaks. These photochemical reactions strongly affect the biological activities of the nucleic acids. Computer techniques are now available for predicting the chemical and biological effects of increased in vitro irradiation of purified nucleic acids. However, the effect of increased UV irradiation in vivo is complicated by the presence of sensitizing agents in cells and by the action of nucleic acid repair processes. There is strong evidence that in vivo damage to nucleic acids injures irradiated cells and tissues, but further research is needed to predict quantitatively the physiological consequences of increases in solar UV.

An evaluation of the hydrogen sulphide water screening test and coliform counts for water quality assessment in rural Malaysia. The H2S water screening test and the membrane filtration faecal coliform count were compared with Escherichia coli counts for water samples collected from household water sources and domestic drinking water in rural Malaysia. Water samples were taken from 151 wells, 44 taps supplying water from the treated municipal supply and 192 domestic stored water supplies. E. coli were detected in 20% of the samples (42% of wells, 7% of tap water and 6% of drinking water). Excellent correlation (Spearman's rank correlation rs = 0.93) was found between the faecal coliform and E. coli counts for all sample types. The H2S method was poorly correlated whether read at 18 or 30 h. False positive rates were highest for well water, and false negative rates were highest for both well and drinking water samples, with low E. coli counts. The faecal coliform test was an excellent predictor of the presence of E. coli in these water samples, while the H2S test was very inadequate.

Frequency-domain localization of intracerebral dipolar sources. A frequency-domain localization of intracerebral dipolar sources can be carried out basically in the same way as a time-domain localization, since the minimization problems to be solved in the two cases have exactly the same structure. The quantity to be minimized can be interpreted as a sum of residual variances of independent linear minimization problems. In the time domain there is one linear problem per sampling time, whereas in the frequency domain there are two linear problems per frequency. It is demonstrated that algorithms readily available for the solution of the time-domain inverse problem can also be used for the solution of the frequency-domain inverse problem. In this way it is not only possible to localize multiple dipoles, but also to combine information from different epochs and from different frequencies.

Gallbladder sepsis after stent insertion for bile duct obstruction: management by percutaneous cholecystostomy. Of 364 patients undergoing insertion of a biliary endoprosthesis in 1989, six (1.6 per cent) developed gallbladder sepsis. Three patients had cholangiocarcinoma, two had carcinoma of the pancreas and one had a benign biliary stricture. Two of the five patients with malignancy had gallbladder stones, and the patient with a benign stricture developed stones after 3 years of stenting. Three patients developed gallbladder sepsis early after endoprosthesis insertion (less than 6 days), while in the other three it occurred late (greater than 6 months). All six patients failed to respond to antibiotics and were successfully managed by percutaneous cholecystostomy; the patient with a benign biliary stricture also had cholecystolithotomy. The gallbladder drainage tubes were removed or became dislodged at intervals varying from 2 weeks to 6 months without complications. Percutaneous cholecystostomy is the treatment of choice for gallbladder sepsis unresponsive to antibiotics in patients with a biliary endoprosthesis in situ.

H-2-linked genetic control of murine T-cell-mediated lympholysis to autologous cells modified with low concentrations of trinitrobenzene sulfonate. Spleen cells from B10.BR and C57BL/10 (B10) mice were compared for their ability to generate primary in vitro cytotoxic responses to syngeneic cells modified with different concentrations (from 10 to 0.031 mM) of trinitrobenzene sulfonate (TNBS) (TNP-self). Although both strains generated effector cells to TNP-self in the range of 10-0.25 mM TNBS modification, effector activity of B10 cells was weaker than that of B10.BR cells. B10 spleen cells did not respond to syngeneic stimulating cells modified at 0.1 mM or lower, whereas B10.BR cells generated effector activity even when stimulated by TNP-self modified with as low as 0.031 mM TNBS. Fluorescence analysis of the modified cells using the FACS II indicated that equivalent quantities of TNP were conjugated to the surfaces of B10.BR and B10 spleen cells for any given concentration of TNBS modification. Similar strain-dependent differences were observed when the TNP was diluted out in the cultures by reducing the number of stimulating cells modified with 10 mM TNBS. These response patterns were verified by stimulating cultures of B10.BR and B10 spleen cells either with TNP conjugated to bovine serum albumin or bovine gamma globulin (B10.BR but not B10 cells responded to TNP-conjugated proteins) or with TNBS-modified glass-adherent spleen cells. The strain-dependent differences could also be detected at the effector phase, because optimally stimulated B10.BR, but not B10 effector cells, could lyse 0.1 mM TNBS-modified syngeneic target cells. The genetic parameters associated with the response and nonresponse patterns of B10.BR and B10 mice were further investigated by comparing the cytotoxic responses to low doses of TNP-self of spleen cells from the following strains: (a) C3H/HeJ (H-2k) and C3H.SW (H-2b); (b) BALB.K (H-2k) and BALb.b (h-2b); and (c) B10.A (H-2a) and B10.D2 (H-2d). The H-2k and H-2a, but not the H-2b and H-2d, strains generated cytotoxic responses to TNP-self when the syngeneic stimulators were modified with 0.1 mM TNBS. Further studies using (B10 X B10.BR)F1 responding cells and parental or F1-modified stimulating cells, indicated that the F1 cells generated cytotoxic activity to low doses of TNP in association with H-2k but not in association with H-2b self products. The results of this study indicate that H-2-linked genetic factors, expressed in the target as well as in the responding and/or stimulating cell populations, control the ability of inbred mouse strains to generate cytotoxic effector cells to low doses of TNP-self. Such dose-dependent genetic effects may be important in the regulation of immune responses activated in vivo by chronic exposure to infectious agents.

Programs developed from concerns for women in medicine. Since the Medical College of Pennsylvania, formerly the Woman's Medical College of Pennsylvania, became coeducational in 1969, there has been a continued effort to maintain the commitment of the institution to its heritage of women in medicine. An office has the role of coordinating and stimulating the establishment and maintenance of programs relevant to women in medicine throughout the institution. These programs are now available to men as well but particularly serve women's needs. They include the Summer Premedical Program, the Summer Health Policy Program, a restraining program for inactive physicians, a demonstration child care project, archives and special collections related to women in medicine, a women in medicine oral history project, and a bibliography of the literature on women physicians. The Medical College of Pennsylvania will continue its interests in the present and future needs of women physicians.

Spontaneous Fanconi syndrome in the dog. Three dogs with spontaneous renal tubular defects similar to idiopathic Fanconi syndrome are characterized. Renal clearance studies revealed a fractional reabsorption of glucose ranging from 31% to 82%. Abnormal glucose thulium values were present in all dogs. A generalized aminoaciduria occurred in two dogs while one had aminoaciduria characteristic of canine cystinuria. Fractional reabsorption of phosphate ranged from 47% to 79%. In vitro uptake of alpha-methyl-D-glucoside was significantly depressed (p less than 0.001). In vitro uptake of amino isobutyric acid was similar to controls. Renal biopsy revealed nonspecific interstitial change in two dogs and normal histology in the other. These animals represent a useful new model for the study of renal tubular transport defects.

[Prognostic factors in stage Ia-IIb invasive cervix cancer after radical hysterectomy with special reference to stroma reaction]. 158 cases of invasive carcinoma of the uterine cervix stages Ia to IIb were analysed with respect to the following prognostic criteria: histological stage, presence of nodal metastases, vascular space invasion and inflammatory stromal reaction at the periphery of the tumor. The assessment of these criteria was correlated to the prevalence of tumor recurrence. In cases with absent nodal metastases, a significant increase of tumor recurrence in stage IIb compared to other stages was noted. A constant increase of the recurrence rate was found, when nodal metastases were present, although the incidence of positive lymph nodes was approximately equal in stages Ic, IIa and IIb. The involvement of the parametrium therefore appears to be a significant parameter for the poor prognosis in stage IIb. Vascular space invasion proved to be a significant parameter with regard to lymph node involvement. When no vascular space invasion was obvious, 94% of the cases showed tumor-free lymph nodes. Overall, heavy inflammatory infiltration at the tumor periphery correlated with a good prognosis. In cases of heavy inflammatory stromal reaction, the risk of nodal metastases and tumor recurrence was significantly lower, independent of the histological stage. The incidence of heavy inflammatory infiltration was significantly higher in microinvasive carcinomas than in clinically invasive tumors. Therefore, the extent of inflammation appears to be an additional useful prognostic index to identify a group of patients at high risk for recurrence and reduced chance of survival.

Cecropia immunoresponsive factor, an insect immunoresponsive factor with DNA-binding properties similar to nuclear-factor kappa B. The immune genes in Hyalophora cecropia contain an upstream sequence that is homologous to the binding site of the mammalian nuclear-factor kappa B (NF-kappa B). These genes are strongly induced by bacteria, lipopolysaccharides and 4 beta-phorbol 12-myristate 13-acetate. Induction of the immune genes involves the activation of a DNA-binding protein complex that we have named Cecropia immunoresponsive factor (CIF). CIF specifically recognizes the kappa B-like DNA sequences in the promoter regions of the Cecropia immune genes. The DNA binding activity of CIF correlates well with the transcriptional induction of the immune genes. Competition assays show that CIF has a DNA binding specificity similar to mammalian NF-kappa B. The two factors also share other characteristics, including the pattern of induction and the migration on the native gel.

Hepatic dysfunction accompanying acute cocaine intoxication. We identified 39 patients with acute cocaine intoxication and rhabdomyolysis over an 8-year period. Twenty-three of the patients (59%) demonstrated biochemical evidence for hepatic dysfunction. Sixteen of these patients had severe liver injury as defined by an alanine aminotransferase (ALT) of greater than 400 U/l (group A). Seven had an ALT between 36-399 U/l (group B) and 16 showed no evidence of liver injury (group C). In contrast to those with normal ALT, the clinical course of the group A patients was more often accompanied by profound hypotension (44 vs. 0%, p less than 0.025), disseminated intravascular coagulation (50 vs. 0%, p less than 0.005), hyperpyrexia (75 vs. 25%, p less than 0.025) and acute renal failure (81 vs. 0%, p less than 0.001). Seven of the group A patients expired (44%). Histologic examination of liver tissue obtained from post-mortem samples demonstrated extensive centrilobular and midzonal necrosis in three cases and panlobular necrosis in two others. A mild lymphocytic infiltrate with bile duct proliferation was present in each specimen. We conclude that cocaine intoxication can be accompanied by liver dysfunction which is most likely multifactorial; the presence of severe dysfunction identifies a patient with potentially significant morbidity and mortality.

Two-step cloning and expression in Escherichia coli of the DNA restriction-modification system StyLTI of Salmonella typhimurium. The StyLTI restriction-modification system is common to most strains of the genus Salmonella, including Salmonella typhimurium. We report here the two-step cloning of the genes controlling the StyLTI system. The StyLTI methylase gene (mod) was cloned first. Then, the companion endonuclease gene (res) was introduced on a compatible vector. A strain of S. typhimurium sensitive to the coliphage lambda was constructed and used to select self-modifying recombinant phages from a Res- Mod+ S. typhimurium genomic library in the lambda EMBL4 cloning vector. The methylase gene of one of these phages was then subcloned in pBR328 and transferred into Escherichia coli. In the second step, the closely linked endonuclease and methylase genes were cloned together on a single DNA fragment inserted in pACYC184 and introduced into the Mod+ E. coli strain obtained in the first step. Attempts to transform Mod- E. coli or S. typhimurium strains with this Res+ Mod+ plasmid were unsuccessful, whereas transformation of Mod+ strains occurred at a normal frequency. This can be understood if the introduction of the StyLTI genes into naive hosts is lethal because of degradation of host DNA by restriction activity; in contrast to most restriction-modification systems, StyLTI could not be transferred into naive hosts without killing them. In addition, it was found that strains containing only the res gene are viable and lack restriction activity in the absence of the companion mod gene. This suggests that expression of the StyLTI endonuclease activity requires at least one polypeptide involved in the methylation activity, as is the case for types I and III restriction-modification systems but not for type II systems.

Ultrastructure of the frontal cap of monotactic forms of Amoeba proteus. The frontal cap of the monotactic form of Amoeba proteus is separated from other cell components by a continuous structure defined as the "membrane-like envelope" (MLE). It originates from the membranes of cytoplasmic vesicles and vacuoles. The border zone between the cap and the cytoplasm is strongly vacuolized. Structural differences between frontal caps, depending on the degree of their development, indicate that the growing cap gradually fills up the whole tip of an advancing pseudopodium, and at the front it reduces the cortical layer in the interstice between the MLE and the outer cell membrane, up to its eventual disrupture. This is probably the efficient cause of the specific morphological and motory pattern of monotactic amoebae. These results and conclusions are supported by an ultrastructural analysis of the artificial frontal caps obtained by injecting oil droplets into polytactic cells, a procedure transforming polytactic forms into forms morphodynamically analogous to the natural monotactic amoebae.

Growth comparison between children with cleft lip and/or palate and controls. General growth from birth to 2.5 years of age of 45 children with a solitary, nonsyndromic cleft lip and/or palate (CL/P) was compared to that of 50 controls. Weight, height, and head circumference were studied in relation to possible influencing factors. Growth of children with CL/P was found to be similar, to a large extent, to that of the control sample, with the exception of growth measured by height. Whereas males in the control group are generally taller than females, the reverse is seen for the CL/P group. Feeding difficulties and intestinal disorders, airway infections, and cleft restoring operations do not account for differences among the groups with CL/P and the control group as was suggested in the literature. Feeding difficulties and intestinal disorders between 12 and 18 months of age and airway infections between 0 and 3 months of age were identified as having a negative influence on growth, measured by weight and height, though not on head circumference.

Drosophila segmentation: supercomputer simulation of prepattern hierarchy. Spontaneous prepattern formation in a two level hierarchy of reaction-diffusion systems is simulated in three space co-ordinates and time, mimicking gap gene and primary pair-rule gene expression. The model rests on the idea of Turing systems of the second kind, in which one prepattern generates position dependent rate constants for a subsequent reaction-diffusion system. Maternal genes are assumed responsible for setting up gradients from the anterior and posterior ends, one of which is needed to stabilize a double period prepattern suggested to underly the read out of the gap genes. The resulting double period pattern in turn stabilizes the next prepattern in the hierarchy, which has a short wavelength with many characteristics of the stripes seen in actual primary pair-rule gene expression. Without such hierarchical stabilization, reaction-diffusion mechanisms yield highly patchy short wave length patterns, and thus unreliable stripes. The model yields seven stable stripes located in the middle of the embryo, with the potential for additional expression near the poles, as observed experimentally. The model does not rely on specific chemical reaction kinetics, rather the effect is general to many such kinetic schemes. This makes it robust to parameter changes, and it has good potential for adapting to size and shape changes as well. The study thus suggests that the crucial organizing principle in early Drosophila embryogenesis is based on global field mechanisms, not on particular local interactions.

[Causes of death of patients with breast cancer (according to the materials of the Oncological Research Center of the USSR AMS for the period 1953-1975)]. The article presents results of investigations of 207 case records and protocols of autopsies of deceased patients who suffered from breast cancer, covering the period from 1953 to 1972 (materials of the USSR AMS Oncological Research Centre). It was established that in 154 patients (74.4%) the cause of death was the progress of the main disease, the most common and "typica" causes of death being pulmonary-cardiac, renal insufficiency (as a result of metastatic lesions of the above mentioned organs) and complications associated with metastases of breast cancer in to the brain and its meninx. In 39 patients (18.8%) the cause of death was directly associated with therapy complications, 14 patients died of diseases not connected with carcinoma of the mammary gland. The structure of causes in the group of deceased patients who when alive suffered from cancer of the mammary gland and who survived 10 and more years from the moment of establishing the diagnosis and carrying out primary treatment (11 observations) was found to be the same as that for the whole group of observations.

Effects of cyclophosphamide in newly hatched chickens after inoculation with avian nephritis virus. Effects of immunosuppression were compared in newly hatched chickens given cyclophosphamide (CY) after inoculation with avian nephritis virus (ANV). All CY-treated infected chickens died within 13 days after inoculation of the virus and had heavy urate deposits throughout the body. However, non-CY-treated infected, CY-treated noninfected, and non-CY-treated noninfected control chickens survived through the observation period. In a chronologic study, the value of serum uric acid in CY-treated infected chickens was more than 3 times higher than that in non-CY-treated infected chickens, and more than 9 times higher than in noninfected chickens. Serum uric acid values were coincident with the positive degree of ANV antigen in the tubular epithelial cells in the kidneys and with the severity of renal degeneration. Serologic and immunohistologic examinations did not reveal detectable antibody and IgG- and IgM-containing cells in the spleen and kidneys of CY-treated infected chickens. However, non-CY-treated infected chickens had an increased number of IgM- and IgG-containing cells and antibody against ANV on postinoculation day 6. These findings demonstrated that CY treatment enhanced the susceptibility of chickens to ANV infection.

Correlations between plasma renin activity, angiotensin II, and aldosterone. To obtain more information about the relationships of the components of the renin-angiotensin-aldosterone system, we measured plasma renin activity (PRA) and the concentrations of plasma angiotensin II (AII) and aldosterone (PA) in 36 healthy 19-22-yr-old students, both after a night's bed rest and after 2 h of ambulation. The correlations of these parameters were calculated. PRA, AII, and PA were determined by RIAs. The values of AII after rest correlated positively both with PRA (r = 0.80; P less than 0.001) and with PA (r = 0.51; P less than 0.01). AII also showed a good correlation with PRA (r = 0.77; P less than 0.001) and with PA (r = 0.67; P less than 0.01) after ambulation. The latter correlation was higher than that after rest. Positive correlations were also found between the increases in PRA and AII and between AII and PA. Further, a multiple regression analysis was carried out to calculate the regression equations for these parameters. The results support the view that PRA and AII parallel each other in normal physiological circumstances. They also seem to indicate that AII has an important role in the basal as well as in the posture-stimulated secretion of aldosterone in normal man.