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Age-related modification of average volume and anisotropy of vascular smooth muscle cells. The aim of this study was to determine what changes in the arterial wall are related to age. In two groups of rabbits, one young and one adult, the aorta and carotid were studied using a morphometric approach based on stereological axioms and planimetric morphometry. The problem of anisotropy of smooth muscle cells is discussed in detail. Two forms of anisotropy must be distinguished, that of single cell and that due to the histological pattern of the smooth muscle cells in the arterial wall. Our results show in adult animals, as compared to the young ones, statistically significant decrease in anisotropy of the cell pattern which tends to become more regular. Moreover, in aorta and carotid of young and adult animals there is an increment of 95.39% and 80% of the absolute cell volume, respectively. We suggest that there may be a direct relationship between aging and phenotypical modulation of the smooth muscle cells and that the modification of the architectural cell pattern with age may represent an adaptive event related to the change in forces acting upon the arterial wall.

The effects of continous irradiation on histological picture and deoxyribonucleoprotein content in spleen of rats. The histological picture and deoxyribonucleoprotein (DNP) content in the spleen of the white male Wistar rats continuously irradiated with the daily dose rates 9.57 mGy (1 R), 95.7 mGy (10 R), 478.5 mGy (50 R) and 657.0 mGy (100 R) were studied. The animals were examined within the day until 60 of irradiation. The number of lymphocytes permanently decreased at the daily dose rates 95.7 mGy and higher ones. The increased activity of reticulum with the simultaneous multiplication of the erythroid cells in the red pulp of spleen was observed at day 10 and 60 of irradiation with 9.57 mGy and 95,7 mGy. Simultaneously DNP content in spleen increased in accordance with the increased activity of reticulum and extramedullar erythropoiesis. The significant decrease in DNP content alter the onset of irradiation with the daily dose rates 478.5 mGy and 957.0 mGy was caused mainly by the fall of lymphocytes. The incidence of eosinophilic leukocytes increased from day 40 irradiation with the daily dose rates 9.57 mGy, 95.7 mGy and 478.5 mGy and decreased with the daily dose rate 957.0 mGy. The plasma cells tended to increase in accordance with the increasing accumulated dose of irradiation with all daily dose rates.

Localized mast cell degranulation induced by concanavalin A-sepharose beads. Implications for the Ca2+ hypothesis of stimulus-secretion coupling. Concanavalin A (Con A) covalently linked to Sepharose 4B beads induced localized degranulation of sensitized rat peritoneal mast cells in regions of contact between beads and cells. This degranulation was Ca2+ dependent and was not seen when sensitized mast cells bound to beads conjugated with a nonstimulating lectin, wheat germ agglutinin, or when unsensitized mast cells bound to Con A-Sepharose. The finding that sensitized mast cells which had adhered to Con A-Sepharose beads degranulated in regions of the cell away from the area of bead contact if exposed to soluble Con A excluded the possibility that the localized release was due to a redistribution of the IgE receptors or putative Ca2+ channels to the region of bead contact. The results suggest that, if an influx of Ca2+ is the mechanism for initiating mast cell degranulation, then the opening of Ca2+ channels in the plasma membrane of activated mast cells is a localized event and that Ca2+ acts locally within the cell to initiate exocytosis.

Transhiatal and transthoracic esophagectomy for adenocarcinoma of the esophagus. Adenocarcinoma of the esophagus is no longer rare and is treated by resection. To determine whether the approach used for resection influences outcome, we studied 88 patients who underwent resection; 14 had stage I or II disease, 74 had stage III, and 40 had stage IV. One third of those with Barrett's esophagus were noted on screening endoscopy to have potentially curable disease; the others were diagnosed with stage III or IV disease. Transhiatal esophagectomy was performed in 63 patients; 24 patients underwent transthoracic esophagectomy. We found no difference in survival or morbidity between transhiatal and transthoracic esophagectomy. Overall 5-year survival for stage I and II disease was 86%. For stage III and IV disease, 5-year survival was 14.5%. Aggressive surveillance of Barrett's esophagus facilitates the discovery of early disease. Esophagectomy for adenocarcinoma can result in cure of early cancers and improved palliation of more advanced disease.

Prognostic factors in acquired aplastic anemia. A study of 352 cases. The prognostic factors of short- and long-term survival have been studied in 352 patients with aplastic anemia of all grades of severity. This group was homogeneous with regard to the clinical and laboratory survey, and the treatment used [high-dose androgen therapy]. The "hierarchy" of the individual prognostic parameters has been established: current severe infection, granulocyte count, percentage of the nonmyeloid cells on the bone marrow slides, platelet count, reticulocyte count, 59Fe utilization, and stromal disorganization on the bone marrow biopsy specimen. As these parameters are interrelated, a multiparametric analysis enables us to define groups of patients with different short-term evolution and to derive a prognostic index from these data. The use of such an index, however, allows a correct prediction in only 73 per cent of the cases, better in the milder than in the more severe cases. It is possible that the short-term evolutive tendency (improvement or worsening during the first six weeks of therapy) may contribute supplementary information useful for prognosis and the choice of treatment. After the first three months critical period, the mortality rate no longer depends on the initial severity of the disease but exclusively on the clinical and hematologic improvement. Thus, comparing the hematologic data obtained initially and after three months of androgen therapy allows us to correctly predict the long-term evolution.

The effect of time of introduction of a high-fructose, low-copper diet on copper deficiency in male rats. The purpose of the present study was to compare the time of introduction of the high-fructose low-copper diet on the expression of copper (Cu) deficiency. Weanling male rats were randomly assigned to either a diet containing 62.7% fructose or starch, and 6.0 (F+Cu) or 0.6 (S-Cu) microgram Cu/g diet, respectively, for either 1, 2, or 3 wk before being transferred to a diet containing fructose and inadequate in copper (F-Cu). At week 10, body weight and relative heart size of rats initially consuming the F + Cu diet was inversely related to the week placed on the F-Cu diet, but not for those initially consuming S-Cu. Hematocrit, hepatic Cu concentration and RBC superoxide dismutase activity were significantly lower in rats initially consuming S-Cu when compared to those fed F + Cu. Mortality was greatest in rats switched to the F-Cu diet at weeks 1 and 2 when compared to those switched at week 3 regardless of the type of diet initially consumed. Plasma cholesterol, triacylglycerols, and blood urea nitrogen concentrations were not significantly altered by the type of diet initially consumed or by the time of introduction of the F-Cu diet. It was concluded that changing rats to a F-Cu diet at 1, 2, or 3 wk after weaning did not significantly improve some of the characteristic signs associated with Cu deficiency, but the later that the F-Cu diet was introduced after weaning the greater the chances for survival.

[Inpatient and partial hospitalization facilities for child and adolescent psychiatry in the unified Germany, 1991]. First results of the project "Surveys regarding the structure of psychiatric institutions for children and adolescents in the Federal Republic of Germany" are described. On July 1, 1991 there were 111 in-patient institutions with a total capacity for 6363 children and youths. The contributing shares of each state (Bundesland) vary enormously. The number of accommodations per 100,000 residents is between 2.1 and 19. One reason for this discrepancy lies in the fact that the services of the institutions are called upon without regard to the state borders. More important though is the fact that in the new states the psychiatric institutions for children and youths also treat young patients who are psychologically or mentally handicapped with neuropsychiatric complications to a greater extent than comparable institutions in the old states.

Identification and analysis of antisense RNA target regions of the human immunodeficiency virus type 1. Antisense RNA, transcribed intracellularly from constitutive expression cassettes, inhibits the replication of the human immunodeficiency virus type 1 (HIV-1) as demonstrated by a quantitative microinjection assay in human SW480 cells. Infectious proviral HIV-1 DNA was co-microinjected together with a fivefold molar excess of plasmids expressing antisense RNA complementary to a set of ten different HIV-1 target regions. The most inhibitory antisense RNA expression plasmids were targeted against a 1 kb region within the gag open reading frame and against a 562 base region containing the coding sequences for the regulatory viral proteins tat and rev. Experimental evidence is presented that the antisense principle is the inhibitory mechanism in this assay system.

[The pulsatile LH fluctuation (spiking) dependent on the circulating prolactin. Studies during physiological (puerperium), functional pathological and TRH induced hyperprolactinemia]. The magnitude and frequency of episodic LH-fluctuations have been observed to change during the different phases of the menstrual cycle. A hypothalamic control center appears to be responsible for these variations. Disturbances of the hypothalamus often make themselves known through a lack of LH-episodes. Ahypothalamic derangement in women with functional amenorrhoea can result in a disregulation of gonadotropins as well as prolactin, thereby leading to hyperprolactinemia. One finds an inverse relationship between high prolactin secretion and cessation of or decreased pulsatile LH-secretion (spiking). LH-spiking was tested in physiological post partum, functional pathological and TRH-induced hyperprolactinemias. No LH-episodes were observed post partum after the end of HCG clearance although prolactin had returned to normal levels at 12 days p.p. The mode of LH-secretion in a group of functionally amenorrhoic patients was changed by a TRH-induced prolactin increase: the previously observed LH-spikes in these women could no longer be seen. Normal cycling women, however, were not affected. In patients with hyperprolactinemic anovulatory syndromes, prolactin suppressed LH-fluctuations reappeared after administration of 2-Bromo-alpha-ergocryptin. The inhibitory influence of hyperprolactinemia on the function of the gonadostat will be discussed. High plasma prolactin levels influence the cyclic and tonic hypothalamic function. Furthermore, prolactin appears to have a peripheral inhibitory influence on ovarian gonadotropin stimulation. Post partum anovulation and amenorrhoea can be caused by an antigonadotropic and antigonadic effect of prolactin.

Leukemia inhibitory factor is expressed in cartilage and synovium and can contribute to the pathogenesis of arthritis. This study reports on leukemia inhibitory factor (LIF) in human articular connective tissues. Biologically active LIF is present in synovial fluids from patients with osteoarthritis and at higher titers in samples from patients with rheumatoid arthritis. Cultured human synoviocytes and articular chondrocytes produced biologically active LIF and synthesized and secreted LIF proteins that migrated in SDS PAGE at approximately 43 kD. This was increased after stimulation with IL-1 beta. Chondrocytes in serum-containing cultures expressed the 4.2-kb LIF mRNA. IL-1 beta, LPS, and to a lesser extent tumor necrosis factor-alpha induced LIF gene expression. LIF autoinduced its mRNA and this provides evidence for an effect of this cytokine on function of joint tissue cells. Among a series of growth factors tested, transforming growth factor (TGF beta), including the isoforms TGF-beta1, TGF-beta 2, and TGF-beta 3, platelet-derived growth factor, basic fibroblast growth factor, and insulin-like growth factor induced this cytokine gene but differed with respect to the duration of their effects. Cultured synoviocytes expressed the LIF gene in response to the same set of peptide regulatory factors. Analysis of signal transduction pathways showed that PMA increased LIF mRNA, whereas calcium ionophore and cAMP had no detectable effects. Cycloheximide was a potent LIF mRNA inducer and dexamethasone inhibited LIF induced by PMA or IL-1 beta. Cartilage organ cultures and synovial tissues stimulated with IL-1 expressed high levels of LIF mRNA as demonstrated by in situ hybridization. These results identify LIF as a new cytokine that is produced by joint tissue cells and is overexpressed in arthritis. The induction of this cytokine by factors that are present during joint inflammation and the effects of LIF on connective tissue cells suggest that LIF is a mediator that can contribute to the pathogenesis of arthritis.

Functional innervation of spinal cord tissue by fetal neocortical grafts in oculo: an electrophysiological study. The ability of fetal neocortex transplants, to functionally innervate maturated cervical spinal cord grafts in oculo, was investigated in rats. We found that a neocortex co-graft will grow and develop in contact with a spinal cord graft, and will generate a functional input to maturated spinal cord tissue which can be activated by electrical stimulation of the neocortex graft. Our data suggest that orthodromic stimulation of this pathway causes short latency, transient excitations of spinal graft neurons. These appear to be mediated by an excitatory amino acid receptor since the response was noncompetitively antagonized by kynurenic acid. Kynurenic acid also noncompetitively antagonized the excitatory effects of glutamate superfused over single spinal cord grafts. The mechanism of the excitation probably does not involve an NMDA (N-methyl-D-aspartate) receptor since APV (2-amino-5-phosphonovalerate) did not alter the spinal graft neuronal responses to neocortical co-graft stimulation. These data suggest that fetal neocortex can functionally innervate maturated cervical spinal cord in the in oculo graft preparation. The in oculo spinal cord graft model may thus provide a unique test system for studies of the influence of drugs and other manipulations that might alter cortico-spinal pathway development as well as influence reestablishment of neuronal pathways after spinal cord injury.

An examination of dietary intakes and nutritional status of chronic healthy spinal cord injured individuals. To examine the nutritional composition of the dietary intake of chronic healthy spinal cord injured (SCI) individuals, 33 subjects affiliated with 3 SCI rehabilitation centers logged their food consumption for 7 days. Prior to record keeping, subjects were trained by a registered dietitian on the accurate recording of their standard food choices and portion size, and were provided with scales to weigh food accurately. Dietary macro and micronutrients were analyzed with a computer software package, with nutritional analysis compared to the recommended daily allowances (RDA) of the Food and Nutrition Board of the National Academy of Sciences. Analysis showed caloric intake to be 75% of that recommended for able bodies persons, with a high reliance on fat for calories. Fat intake accounted for 37.9% of calories, well above the recommended level of 30%, but typical of the American diet. The ratio of polyunsaturated to saturated fat was approximately one half the recommended level, with carbohydrate calories averaging 16.5% below optimal RDA. Protein consumption was within normal range, but average dietary fiber was only 25% of recommended levels. Micronutrient analysis showed deficiencies in both water and fat-soluble vitamins, with suboptimal intake of multiple minerals. Given the apparent reliance on a high-fat and low-carbohydrate diet, this research shows that nutritional intervention and education of SCI persons are needed, and that a registered dietitian should be included in the SCI health care team.

[Destroyed lung (author's transl)]. The expression of "destroyed lung" is, now, accepted to designate the large destructions of the lung, secondary to pulmonary and essentially infectious diseases, the cure of which is obtained but with important sequelae. The main cause remains tuberculosis, cured by chemotherapy. Some large pulmonary suppurations, treated by antibiotics, can lead to the same sequelae. These "destroyed lungs" can keep an asymptomatic form. But often, about ten years after the initial disease, they cause several troubles such as progressive dyspnea leading to irreversible respiratory insufficiency, repeated pulmonary infectious episodes and hemoptysis, the risk of which is increased by aspergillosis. The radiological aspect of these "destroyed lungs" is made of opacities with multiple cavities or with one unique large cavity. The mechanism of hemoptysis has been understood recently: all destructive lesion of the pulmonary tissue produces as a consequence a development of the systemic blood circulation, bronchial or parietal, with reverse blood circulation from systemo-pulmonary anastomoses-which can produce capillary dilatations-into the pulmonary artery. All these complications can lead to a surgical treatment. Embolization of bronchial arteries is a less aggressive method when hemoptysis is the main symptom. These acquires "destroyed lungs" can be compared to those caused by extensive pseudokystic bronchiectases. For both cases clinical aspects and therapeutic methods are similar, though the lesions are fixed and likely congenital in the last form.

Suicidal behaviors in young adolescents. A two-stage epidemiologic study investigated the frequency of suicidal behavior in children 12-14 years of age. In the first stage, the Center for Epidemiologic Studies Depression Scale, a three-item suicide scale, a life-event schedule, and a family environment scale were administered during 1986 to a southeastern US community sample of 1,542 seventh and eighth grade students. In the second stage, 226 mother-child pairs were interviewed utilizing the Schedule for Schizophrenia and Affective Disorders in School Age Children (K-SADS). Subjects interviewed included students with high depression scores and a random sample of the remaining students. Prevalence estimates for moderate to severe suicidal ideation (K-SADS score greater than or equal to 4) were 4.0% (95% confidence interval (CI) 0.6-16.4%) in males and 8.7% (95% CI 2.4-23.3%) in females. The prevalences of suicide attempts were 1.9% (95% CI 0.0-13.2%) in males and 1.5% (95% CI 0.6-12.7%) in females. Significant relations were found between major depression and both suicide ideation (odds ratio = 6.19, 95% CI 1.53-24.94) and suicide attempts (odds ratio = 9.80, 95% CI 1.89-50.86). The undesirable life-events score was also a significant predictor of suicide ideation and suicide attempts.

Enhanced basal and stimulated PMN chemiluminescence activity in children with atopic dermatitis: stimulatory role of colonizing staphylococci? In adults, intense staphylococcal skin colonization and hyperactivity of polymorphonuclear leukocyte (PMN) oxidative metabolism are characteristic features of atopic dermatitis. Precise data on childhood atopic dermatitis are lacking. In a prospective study we analysed the PMN chemiluminescence activity with special reference to staphylococcal stimuli in 19 children (mean age 6.2 years) with mild to moderate atopic dermatitis. Staphylococcus aureus was isolated from 17/19 (90%) of children with atopic dermatitis and 13/45 (29%) of healthy age-matched controls (p less than 0.001). The mean (SEM) chemiluminescence activity of unstimulated atopic dermatitis-PMN was 0.34 (0.009) (controls: 0.092 (0.003) x 10(6) cpm/10(6) PMN/min (p less than 0.02). Staphylococcal antigens (S. aureus, S. epidermidis, S. haemolyticus) induced a 1.9-3.1-fold higher peak chemiluminescence response in children with atopic dermatitis than in controls (p less than 0.05). The time interval until peak chemiluminescence activity was considerably shorter for all stimuli in atopic dermatitis. We conclude that PMN of children with atopic dermatitis are "primed", showing enhanced release of reactive oxygen metabolites even in the "resting" state, and are easily stimulated by staphylococcal antigens present on the skin of patients with atopic dermatitis from early childhood on. We speculate that PMN hyperreactivity may contribute to chronic skin damage in atopic dermatitis.

Chemical determination of protein neighbourhoods in a cellular organelle. Experimental procedures developed for the identification of near-neighboring proteins in a complicated organelle are described in this paper. The specific system studied here is the ribosome of Escherichia coli; however, the techniques and reagents described should have a wide range of applications. We have used three kinds of cross-linking agents: noncleavable maleimide reagents which react with free SH groups; noncleavable diimidoesters which react with free amino groups, and cleavable diazide agents that also react with free amino groups. The combination of immunological and isotopic labelling techniques used to identify proteins cross-linked by noncleavable reagents, as well as the special electrophoretic techniques used with the cleavable reagents are described. We show that the neighborhoods detected by the crosslink technology are functionally meaningful ones, and also discuss the ambiguities inherent in the structural interpretation of such protein neighborhoods.

Plasmin inhibitors in the prevention of systemic effects during thrombolytic therapy: specific role of the plasminogen-binding form of alpha 2-antiplasmin. To delineate the role of plasmin inhibitors, especially the two molecular forms of alpha 2-antiplasmin (that is, the plasminogen-binding and the nonplasminogen-binding forms), in the control of systemic effects during thrombolytic therapy, the consumption of plasmin inhibitors and the degree of fibrinogen breakdown were studied in 35 patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) or streptokinase. At a low degree of plasminogen activation (in six patients treated with rt-PA), plasminogen-binding alpha 2-antiplasmin was consumed first. At a higher degree of plasminogen activation (in 20 patients), plasminogen-binding alpha 2-antiplasmin became exhausted (less than 20%) and other plasmin inhibitors (that is, nonplasminogen-binding alpha 2-antiplasmin and alpha 2-macroglobulin) were consumed. After extensive plasminogen activation (in nine patients treated with streptokinase), plasminogen-binding alpha 2-antiplasmin consumption was complete and nonplasminogen-binding alpha 2-antiplasmin and alpha 2-macroglobulin were consumed to about 30% to 50% of the pretreatment level. No significant C1-inactivator consumption occurred, even at extreme degrees of plasminogen activation. Fibrinogen breakdown as a marker for systemic effects correlated strongly with consumption of plasminogen-binding alpha 2-antiplasmin. Fibrinogen breakdown did occur, but only when the amount of plasminogen-binding alpha 2-antiplasmin was decreased to less than 20% of the pretreatment level. The other plasmin inhibitors could not prevent fibrinogen breakdown. These results were confirmed by in vitro studies. It is concluded that plasminogen-binding alpha 2-antiplasmin is the most important inhibitor of plasmin in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

[State of humoral and cellular immunity in experimental amyloidosis]. On a model of caseine amyloidosis in 52 rabbits it was shown that in the preamyloid phase the humoral immunity was stimulated, but as soon as the first deposits of amyloid appeared, it was inhibited. The cellular immunity was inhibited starting from the 20th day of the experiment. On the 40th day of the experiment the cellular immunity was found to be less inhibited in the animals with initial deposits of amyloid as compared with the animals with no amyloidosis; on the 60--80th day in progressing of amyloidosis differences in the degree of inhibition of the cellular immunity were obliterated. The degree of fixation of IgG in amyloid was directly dependent on its content in the blood serum and on the "age" of amyloid.

Improvement in mammography interpretation skills in a community radiology practice after dedicated teaching courses: 2-year medical audit of 38,633 cases. The authors conducted a complete audit of results of 38,633 mammographic examinations performed by 12 general radiologists during a 2-year period with a computerized reporting system. During this period, 11 group members attended 17 dedicated mammography courses. Audit results were analyzed for each radiologist and the entire group. In the 2nd year, the number of breast cancers diagnosed increased 50% (from 121 to 181), with a 6.5% increase in patient volume. Sensitivity increased from 80% to 87%, and there was no change in the positive predictive value of 32%. Median tumor size and node positivity decreased. Most major variables of population and technical factors were unchanged. Diagnostic approach was altered during the 2nd year, as shown by a 50% increase in the use of spot compression, magnification views, and sonography. Analysis of each radiologist's performance before and after attending mammography courses showed similar changes. These data suggest that dedicated mammography courses can help improve radiologists' performance and alter their interpretive approach.

The Child Behavior Checklist nonclinical standardization samples: should they be utilized as norms? The Child Behavior Checklist (CBCL) is an extensively standardized parent-completed checklist of competencies and behavior problems of children and adolescents. Clinicians and researchers frequently assume that the published scale scores for the CBCL nonclinical sample are stable even across demographically heterogeneous populations. The present study, a school-based postal questionnaire survey, was designed to compare the CBCL nonclinical sample with a different community sample collected in the U.S. The parents of 530 children, 6 to 10 years of age (73% of the eligible sample), attending one public school system in northern New Jersey were recruited. Mean total behavior problem scores for both sexes in the school sample were dramatically higher than the CBCL nonclinical sample even after removing clinically referred cases from the analyses. Additionally, in contrast to the manual, marked race/ethnicity effects were found in the male subsample. These results, in conjunction with those from other studies, raise serious questions about the common practice of using the CBCL norms as a yardstick for sample comparisons.

Primary endodermal sinus (yolk sac) tumor of the liver. First reported case. A primary endodermal sinus (yolk sac) tumor of the liver occurring in an 18-month-old boy is described. Although several examples of extragonadal endodermal sinus tumors have occurred in other sites, this is believed to be the first reported instance of origin in the liver. An additional important feature was the detection of alpha-fetoprotein in a preoperative serum sample. Although no metastases were identified at the time of celiotomy, widespread metastases developed, and he died 6 1/2 months after an extended right hepatectomy was performed. Neither triple chemotherapy nor radiation therapy appeared to deter progressive spread of the neoplasm, although the metastases exhibited some radiosensitivity.

The intestinal phase of gastric secretion. The intestinal phase hormone, elaborated by the jejunum in response to an intestinal meal or simple distension, produces profound gastric hypersecretion when it escapes hepatic degradation through a portacaval anastomosis. The hormone is released within 30 min of the application of the stimulus and rapidly reaches peak concentration in the portal blood. Intravenous infusion into a donor dog of active portal plasma from a shunted, intestinally fed dog stimulates gastric acid secretion after a delay of approximately 1 h, and requires a mean 1 1/2 h to stimulate peak secretion, which suggests that intermediate steps may be necessary before the hormone can effectively stimulate the parietal cell mass. The pig develops portacaval-shunt-related gastric acid hypersecretion in response to food comparable to that observed in the dog and in man. Porcine jejunal mucosa is thus an appropriate source for isolation of the intestinal phase hormone. Pig intestinal mucosal extract contains a heat-stable acidic peptide which is a potent stimulator of gastric acid secretion. Administration of crude intestinal mucosal extract elicits gastric acid secretion after a brief delay, again indicating that some intermediate reactions occur before the target organ--the parietal cell mass--is stimulated.

GABAergic neurons and circuits in the pretectal nuclei and the accessory optic system of mammals. Two classes of GABAergic cell bodies have been described. They probably can be divided into GABAergic local interneurons and GABAergic projection neurons. GABAergic cell bodies receive few terminals which is in contrast to non-GABAergic somata, which receive many synaptic contacts. GABAergic dendrites that originate from GABAergic cell bodies, however, receive numerous terminals, both GABAergic and nonGABAergic. It can therefore be concluded that somatic inhibition is not present on GABAergic neurons, but does occur on nonGABAergic neurons. Furthermore, dendrites traverse large parts of the NOT/DTN forming a complex network that enables sampling and integration from a wide area. The projection to the IO is not GABAergic itself, but cells projecting to the IO receive a substantial GABAergic input, that probably originates in part from the MTN. Further investigation on the distribution of this input over a completely identified neuron would provide the quantitative data that are required to verify the above mentioned hypothesis. A GABAergic projection that originates in the pretectal nuclei is directed towards the superficial layers of the SC in the cat (Appell and Behan, 1990) and rat (Van der Want et al., 1991). A second GABAergic projection derives from the pretectum and reaches the LGN (Cucchiaro et al., 1991). Whether this projection originates from the same GABAergic cell bodies that project to the SC and the LGN or is derived from different populations remains to be determined. The ultrastructural studies of the NOT/DTN complex have shown that GABAergic terminals with different morphological characteristics are present and that the GABA positive F and P terminals are widely distributed over somata and the adjacent neuropil. The P terminals probably originate from dendrites of GABAergic interneurons while the F types originate from GABAergic projection and interneurons (Van der Want and Nunes Cardozo, 1988). One of these sources is located in the MTN differ from the intrinsic GABAergic terminals with respect to their relation to R terminals. GABAergic MTN terminals were never observed to receive R terminal input. This is in contrast with other GABAergic terminals which frequently do receive direct contact from R terminals. Within glomeruli triadic arrangements, formed by a single retinal terminal, a dendritic profile and second axonal profile dendritic profile and second axonal profile synapsing with the dendrite, were frequently encountered in the OPN (Campbell and Lieberman, 1985), but only occasionally in the NOT/DTN (Nunes Cardozo and Van der Want, 1987).(ABSTRACT TRUNCATED AT 400 WORDS)

Detection of Pseudomonas aeruginosa in sputum from cystic fibrosis patients by the polymerase chain reaction. A DNA amplification procedure using heat stable Taq polymerase and the polymerase chain reaction is described for the detection of Pseudomonas aeruginosa in specimens from cystic fibrosis patients. A set of primers was selected on the basis of the nucleotide sequence of the algD gene encoding GDP mannose dehydrogenase, a major enzyme in the biosynthesis of alginate by P. aeruginosa. Using this set of primers in conjunction with the polymerase chain reaction, P. aeruginosa could be specifically detected, with a sensitivity approximating 10 bacteria, in sputum harbouring large numbers of other respiratory pathogens, including Staphylococcus aureus and Haemophilus influenzae. These results suggest that amplification of specific sequences within the algD gene by the polymerase chain reaction may provide a highly sensitive and specific tool for the detection of P. aeruginosa in the early stages of pulmonary colonization.

[Criteria for a pathogenetic approach to antiarrhythmic therapy in paroxysmal supraventricular reciprocal tachycardia]. An electrophysiological study using programmed transesophageal atrial pacing was performed in 106 patients with abnormalities in the myocardial conduction system, of whom 102 suffered from paroxysmal supraventricular reciprocal tachycardia and/or paroxysmal atrial fibrillation. The electrophysiological properties of the myocardial conduction system were demonstrated to be labile. The factors determining the frequency and length of palpitations were outlined. The conditions for an onset of supraventricular reciprocal tachycardiac paroxysm and for existence of a reentrant chain were found to be minimal in the effective refractory period of the accessory pathway, which was less or equal to the effective refractory period of the atrioventricular junction. An approach to antiarrhythmic therapy was proposed, which was based on modifying the ratio of the effective refractory periods of normal and abnormal excitation pathways.

Factors influencing the response and survival of patients with liver metastases from breast cancer receiving OK-432-combined adoptive immunotherapy. The response and survival of 26 patients with liver metastases from breast cancer, who received OK-432-combined adoptive immunotherapy from 1984 to 1990, were evaluated. OK-432-combined adoptive immunotherapy was comprised sequential treatment via the hepatic artery with a streptococcal preparation, OK-432 (1-5 KE), and adoptive transfer of lymphocytes expanded in T-cell growth factor and sonicated tumor extract antigen. Seventeen (65%) patients responded to the therapy. The median survival time of all patients after treatment was 13 months (range, 2-63 months). Of the 20 prognostic factors analyzed, performance status (PS) alone was related to response (P less than 0.01). The response rate of the patients with a PS of 0-2 was 83% but only 25% in those with a PS of 3 or 4. In univariate analysis, 11 factors significantly influenced the survival: tumor response; size of primary tumor; menopausal status; PS; serum bilirubin, albumin, lactate dehydrogenase and glutamate-oxalate transaminase (aspartate aminotransferase); the extent of liver involvement; and the number and the proliferation rate of transferred lymphocytes. The MST was 22.8 months for the responders versus 2.8 months for the nonresponders (P less than 0.01). In multivariate analysis, the most important factor associated with survival was the tumor response, as well as PS, liver involvement, lactate dehydrogenase and albumin. These results suggest that OK-432-combined adoptive immunotherapy can be considered a candidate for a randomised control study and these factors should be used for stratification.

[Continuous intra-arterial infusion chemotherapy in colorectal cancer patients with nonresectable metastatic liver cancer]. Five colorectal cancer patients with nonresectable metastatic liver cancer underwent continuous intraarterial chemotherapy in our institute from January to December 1991. Patients included four rectal cancers and one colonic cancer. 5-fluorouracil (5-FU) was infused continuously through an Infuse-A-Port; 360 mg/m2/day for one week after operation, and 180 mg/m2/day for the following three weeks. Since the fifth week after operation, two weeks without infusion and two weeks of infusion (180 mg/m2/day) were alternated as long as possible. Total periods of 5-FU infusion therapy were from one to 11 months and total doses of 5-FU ranged from 8,750 mg to 25,650 mg. Three patients showed partial response (PR) and two patients progressive disease (PD) (response rate; 60%). In three cases of PR, lengths of infusion therapy and total doses of 5-FU before PR was first observed was 8 weeks, 10,750 mg, 6 weeks, 9,250 mg, and 4 weeks, 8,750 mg, respectively. Four patients presented nausea, appetite loss or abdominal pain, which were considered to be side effects of 5-FU. In one of these four patients, infusion could not be continued because symptoms were so severe. However, catheter troubles were not noticed among all cases.

Abolishment of bradykinin-induced calcium oscillations in ras-transformed fibroblasts by the expression of 80 kDa diacylglycerol kinase. Our previous study showed bradykinin-induced periodic Ca2+ changes (Ca2+ oscillations) in v-Ki-ras-transformed NIH/3T3 (DT) cells in which protein kinase C (PKC) activity is partially down-regulated by a sustained high level of 1,2-diacylglycerol (DAG) [FEBS Lett. (1991) 281, 263-266]. In the present study, DAG kinase with 80 kDa mass (80K DGK) has been successfully transfected in DT cells, which exhibited enhanced cellular DAG kinase activities, decreased cellular DAG contents, and increased PKC activities compared to the control vector-transfected cells. Furthermore, these DGK-transfectants showed strong inhibition in bradykinin-induced Ca2+ oscillations. The results suggest that the sustained DAG increase down-regulates the PKC activity, thereby leading to the induction of Ca2+ oscillations in DT cells.

Immunoglobulin class specificity of non-agglutinating antibody produced in cattle following Brucella abortus 45/20 vaccination. The immunoglobulin class specificity of non-agglutinating antibody produced following vaccination with Br. abortus 45/20 vaccine was determined using the antiglobulin test. In previously unvaccinated cattle it was found that most of the non-agglutinating antibody was associated with the IgG1 immunoglobulin class. In cattle sensitised to Brucella antigens by prior vaccination with Brucella abortus strain 19 the majority of antibody was also associated with the IgG1 immunoglobulin class, but a significant amount of IgG2 antibody was also present. The results indicate that the significance of levels of IgG2 antibody would be difficult to determine in cattle repeatedly exposed to Brucella antigens.

Acceleration of H+ extrusion via Na(+)-H+ exchange in guinea-pig ventricular papillary muscle under intracellular acidic condition. We investigated mechanisms by which intracellular pH was regulated under intracellular acidic condition in resting guinea-pig ventricular papillary muscles in vitro. Intracellular sodium ion activity (aiNa), intracellular and surface pH (pHi and pHs) were measured with Na(+)- and H(+)-selective microelectrodes and resting tension was measured. By exposure to 0 mM K solution aiNa and resting tension increased progressively while pHi decreased but reached the steady level of pH 6.95. pHs which was lower than external bulk pH (pHo) decreased progressively by exposure to 0 mM K solution. In 4 mM K solution, amiloride (1 mM), an inhibitor of Na(+)-H+ exchange, induced a reversible decrease in both aiNa and pHi, and an increase in pHs. Changes in pHi and pHs induced by application of amiloride in 0 mM K solution were larger than those in 4 mM K solution. The rate of decrease in pHi induced by amiloride became larger at longer exposure to 0 mM K solution. Lowering pHo from 7.4 to 6.4 induced a larger decrease in pHi in 0 mM K solution than that in 4 mM K solution. Lowering pHo from 7.4 to 5.4 reversed the difference between pHs and pHo. These results suggest that in guinea-pig papillary muscle, Na(+)-H+ exchange is active to regulate intracellular H+ under resting condition and under intracellular acidic condition, H+ extrusion via the Na(+)-H+ exchange would be accelerated not only by the net thermodynamic driving force for Na+ and H+ but also by other factors.

Altered hemolysin production in urine-grown uroisolates of Escherichia coli. Fifteen uroisolates of E. coli were studied for both cell-free and cell-bound hemolysin production. Estimations were done in Trypticase soy broth (TSB, providing iron-replete medium) TSB + 2,2'-bipyridine (providing experimentally created iron-depleted conditions) and pooled normal human urine (providing natural iron-depleted growth medium). In TSB 40% of strains showed no detectable cell-free hemolysin, they were able to produce it in the presence of 2,2'-bipyridine and more so when grown in urine. The cell-bound hemolysin was produced by all the strains in TSB, but in the presence of 2,2'-bipyridine and urine an insignificant increase was observed. All the strains when given 2nd and 3rd passage in urine, were found to elaborate significantly more cell-free as well as cell-bound hemolysin.

Embryonic loss and progesterone metabolism in rats fed a high energy diet. To elucidate the mechanism of the reduction of embryonic loss due to an increase of dietary protein level in rats fed a high energy diet, the relationship between embryonic loss and progesterone metabolism was investigated in rats fed high energy diets (digestible energy: about 5 kcal/g) differing mainly in casein and starch contents. The embryonic loss was minimum in rats fed a relatively high protein-low starch diet (30% protein-19% starch) and maximum in rats fed a very high protein-very low starch diet (39.9% protein-2.5% starch). On the basis of measuring urinary pregnanediol and in vivo conversion from progesterone to urinary pregnanediol and in vivo conversion from progesterone to urinary pregnanediol in each group, the production of progesterone in the body was shown to vary. In vitro studies showed that the mechanism responsible may involve inhibition of progesterone synthesis by the ovary in the presence of a very high protein-very low starch diet.

Twin imitation for antisocial behavior: implications for genetic and family environment research. When twin pairs influence each other's behavior, observed variance is greater for MZ twins than for DZ twins under at least 1 of 2 conditions: (a) the trait has some heritability and (b) MZ twins influence each other more than do DZ twins. Applied to a trait that has an underlying continuous distribution but is measured as a dichotomy, the presence of reciprocal twin influence predicts that if the base rate for the trait is not exactly 50%, then the prevalence of the trait should differ in MZ and DZ twin pairs. This prediction held for registered criminality in a large twin cohort. Methods of analysis that permit reciprocal twin interaction not only provide better statistical fits to the data but also yield estimates of heritability that agree with adoption data. The results suggest that the genetic influence on registered criminality may be more modest than previously thought.

Interindividual variation in carcinogen metabolism and bladder cancer risk. Epidemiological studies indicate that subjects of the genetically based slow acetylator phenotype may be at higher risk for bladder cancer than fast acetylators, particularly when they are exposed to carcinogenic arylamines: N-acetylation is a detoxification step in the metabolism of some arylamines. We describe two collaborative studies on tobacco smoking, in which markers of internal dose (arylamine-hemoglobin adducts) and markers of genetically-based metabolic polymorphism have been coupled. In the first investigation, we found that hemoglobin adducts formed by mononuclear arylamines have high reciprocal correlation coefficients, as do adducts from binuclear arylamines. This tendency of adducts with structurally similar arylamines to correlate reciprocally explains a large proportion of the residual variance seen after controlling for smoking habits (number and type of cigarettes). In the second study, the concentration of 4-amino-biphenyl-hemoglobin adducts varied according to three independent determinants: number of cigarettes, type of tobacco (air or flue cured), and acetylator phenotype (slow and fast). The dose-response relationship between the amount of tobacco smoked and level of 4-aminobiphenyl-hemoglobin adducts in the slow acetylators (with an immediate steep increase of the adducts) was different from that in the fast acetylators (with a more regular increase). These findings from "molecular epidemiology" may contribute to an understanding of the role of metabolic polymorphism in human carcinogenesis.

Data-based interventions for cancer control in Texas. The percentage of excess mortality based on the ratio of the race-ethnic-sex-specific regional rate to the state rate was used to identify regions with differing risks of lung, breast, and cervical cancer. Mortality maps show wide variation in mortality risks for these cancers not only by race and ethnicity but also by geographic region. Cancer-staging information from the State Cancer Registry indicated that excess mortality for breast and cervical cancers in black and Mexican-American women results largely from the later detection of these cancers. Together with geographic mapping of data on cancer mortality, data on the prevalence of tobacco use and on the use of Papanicolaou's tests and mammograms can be used to select and direct interventions to specific regions and to the highest risk populations. Evaluation of routinely collected cancer data, particularly in state health departments, is a primary step in implementing programs to control and prevent cancer in Texas.

Acetylcholinesterase in human amniotic fluid: An index of fetal neural development? Acetylcholinesterase (AChE) activity was detected in amniotic fluid either sampled by amniocentesis at 14--23 weeks gestation or collected at normal parturition. Activity ranged from 0.2 to 8.9 u/l in the earlier samples and from 0.2 to 4.2 u/l in the later samples. Since the fetal but not the maternal serum contained AChE activity, we suggest that the AChE in the amniotic fluid is derived from the fetus. AChE is released from both neural and nonneural tissues, and the release of the enzyme from both sources may diminish as the nervous system matures. The amount of AChE found in amniotic fluid may be affected by abnormalities of the nervous system. Amniotic fluid from two fetuses with spina bifida contained AChE activity: one, with a gestational age of 21 weeks, was in the upper levels of the normal range (4.5 u/l), whereas the other, at 36 weeks, contained 1.9 times more activity than the next highest sample. In a 20-week fetus with anencephaly, the AChE activity in the amniotic fluid was increased 2.8-fold over the activity of the highest "normal" sample.

Treatment of small cell carcinoma of the lung using methyl-CCNU (NSC-95441) combined with cyclophosphamide (NSC-26271) and vincristine (NSC-67574) in a 3-week schedule. Twenty-six patients with small cell carcinoma of the lung were treated with a combination of methyl-CCNU (75 mg/m2 orally), cyclophosphamide (750 mg/m2iv), and vincristine (1.4 mg/m2iv) once every 3 weeks and followed for 2-56 weeks (mean, 24 weeks). An average of seven treatments were given per patient. Myelotoxicity was mild to moderate with no white blood cell count (wbc) less than 1000 cells/mm3 and no platelet count less than 25,000 cells/mm3. Six patients (23%) had a wbc of 1000-2000 cells/mm3 and two (8%) had a platelet count of 25,000-75,000 cells/mm3. Sixty-eight persons of the projected dose of methyl-CCNU was given. Fourteen of 22 patients with measurable disease (54%) responded. Of 14 patients who had received no prior treatment 64% responded with a median survival duration of 40 weeks. Complete responses occurred only in patients without prior radiation therapy or chemotherapy. We conclude that methyl-CCNU may be given with an acceptable level of toxicity in an every 3-week schedule and that the combination of cyclophosphamide, methyl-CCNU, and vincristine warrants further evaluation in the treatment of small cell carcinoma of the lung.

Structural and enzymatic characterization of a purified prohormone-processing enzyme: secreted, soluble Kex2 protease. The prohormone-processing Kex2 protease of the budding yeast Saccharomyces cerevisiae can be converted from an intracellular membrane protein to a soluble, secreted, and active form by deletion of the transmembrane domain and C-terminal tail. One such molecule was purified to near homogeneity from the culture medium of an overexpressing yeast strain. Amino acid sequence analysis revealed that the N terminus of mature Kex2 protease is created by a potentially autoproteolytic cleavage at Lys108-Arg109, prior to the domain homologous to subtilisin, followed by trimming of Leu-Pro and Val-Pro dipeptides by the Ste13 dipeptidyl aminopeptidase. Kinetic parameters were examined using fluorogenic peptidyl-methylcoumarin amide substrates. Initial burst titration indicated that the preparation was entirely active. Measurements of dependence of activity on pH yielded a simple curve suggesting titration of a single ionizable group. Activity was half-maximal at pH 5.7 and nearly constant from pH 6.5 to 9.5. Discrimination between substrates was as great as 360-fold in Km and 130-fold in kcat. Substrates with a Lys-Arg dipeptide preceding the cleaved bond were preferred, having kcat/Km values up to 1.1 x 10(7) sec-1.M-1. The enzyme cleaved substrates having Arg-Arg, Pro-Arg, Ala-Arg, and Thr-Arg with increased Km but with unchanged kcat. In contrast, the enzyme displayed a dramatically lower kcat for a Lys-Lys substrate with a smaller increase in Km. Thus the two residues preceding the cleaved bond may play distinct roles in the selectivity of binding and cleavage of prohormone substrates.

Effect of prolonged feeding with chenodeoxycholic acid on bile in patients with and without gallstones. Nineteen patients who received chenodeoxycholic acid 750 mg/day for six months had duodenal bile aspirated before and after treatment. In five patients with hypertriglyceridaemia but no gallstones cholesterol saturation was reversed in every case, the mean cholesterol saturation index (SI +/- standard deviation) changing from 1-38 +/- 0-31 to 0-68 +/- 0-06 (P less than 0-005). In 14 patients with gallstones there was also an improvement in bile cholesterol content, but this was not sufficient to produce mean unsaturation, saturation index changing from 1-55 +/- 0-52 to 1-13 +/- 0-43 (P less than 0-05). Only seven of 14 patients with gallstone achieved cholesterol unsaturation. In four patients with hypertriglyceridaemia and gallstones, mean unsaturation was produced and the saturation index changed from 1-70 +/- 0-45 to 0-86 +/- 0-47 (P less than 0-05). When all nine patients with hypertriglyceridaemia were grouped, the mean saturation index fell from 1-52 +/- 0-40 to 0-76 +/- 0-30 after therapy (P less than 0-001). In contrast the 10 patients without hypertriglyceridaemia showed no significant fall in saturation index which was 1-50 +/- 0-54 before and 1-24 +/- 0-40 after therapy. The ability of chenodeoxycholic acid feeding to improve bile saturation with cholesterol correlated with the presence of hypertriglyceridaemia whether or not gallstones were present. It did not correlate with gallstone dissolution or body weight.

Increased soluble CD4 and decreased soluble CD8 molecules in patients with Sjögren's syndrome. A new enzyme-linked immunosorbent assay for soluble CD4 (sCD4) and soluble CD8 (sCD8) molecules has been developed. We estimated the concentrations of these molecules in patients with Sjögren's syndrome and in patients with systemic lupus erythematosus (SLE) serving as a control population for non-Sjögren's inflammatory disease, since several findings suggestive of an aberration of immunocompetent cells have been reported in these autoimmune diseases. The study population consisted of 41 patients with Sjögren's syndrome (28 cases of the primary form and 13 cases of the secondary form), 66 patients with SLE, and 43 normal individuals. Serum samples and clinical and laboratory data were collected from each patient and control. Assays of the sCD4 and sCD8 molecules were performed using an enzyme-linked immunosorbent kit developed by T Cell Science Inc., Cambridge, MA. The concentration of sCD4 was significantly increased in patients with both primary and secondary Sjögren's syndrome as compared with that in the control subjects. In contrast, sCD8 was significantly decreased in patients with primary disease but not in patients with secondary disease. A low or high concentration of sCD8 was significantly correlated with the presence of anti-SS-A antibody or hypocomplementemia, respectively. A similar significant correlation was noted between an increased sCD4 concentration and increased serum IgG level. In patients with SLE, the levels of both sCD4 and sCD8 were significantly increased. These observations represent the first evidence of an increased level of the sCD4 molecule and a decreased level of the sCD8 molecule and an association with immunologic abnormalities in Sjögren's syndrome. The increased and decreased levels of these soluble molecules observed may play a pathologic role in patients with Sjögren's syndrome.

The QRS phasic characteristics of right ventricular hypertrophy in precordial leads. The QRS apparent phase in some electrocardiograms (ECGs) progresses in opposite directions in the two halves of the precordial leads. The genesis of the waveforms leading to such bidirectional phase properties may be given in terms of the particular shapes of the horizontal vector loops. Such phasic properties associate themselves with right ventricular hypertrophy (RVH) of type A and type C although the reverse is not necessarily true. Schematic diagrams are generally used in this article for clarity in illustration, but the method has been tried on some well-documented cases of RVH, reported by Chou and Helm, 3 with promising results.

Chemotactic potency of recombinant human neutrophil attractant/activation protein-1 (interleukin-8) for polymorphonuclear leukocytes of different species. In order to establish the species cross-reactivity of the human neutrophil attractant/activation protein-1 (interleukin-8, NAP-1/IL-8) and find which experimental species are responsive to the human cytokine, blood polymorphonuclear leukocytes (PNMLs) were isolated from chicken, dog, goat, guinea-pig, monkey, mouse, pig, rabbit, and rat and their in vitro migration in response to this cytokine was investigated. PMNLs from all of the tested species migrated in response to recombinant human NAP-1/IL-8 (rhNAP-1/IL-8). The potency of rhNAP-1/IL-8 for the PMNLs of different species varied and was considerably lower than its potency for human cells. The morphological study combined with the leukocyte enumeration in the intradermal rhNAP-1/IL-8 injection sites established an in vivo proinflammatory potency of rhNAP-1/IL-8 for rabbit and rat that was comparable to the observed in vitro chemotactic potency of rhNAP-1/IL-8 for neutrophils of these species.

Bioavailability and disposition of metoprolol and hydrochlorothiazide combined in one tablet and of separate doses of hydrochlorothiazide. 1. The plasma levels and the urinary excretion of hydrochlorothiazide (HCT) have been studied after administration of single doses of 12.5 and 25 mg of the drug in solution and in combination with 100 mg of the selective beta 1-adrenoreceptor antagonist metoprolol in a rapidly dissolving tablet. 2. Metoprolol did not significantly influence the bioavailability or the time-course of HCT. 3. HCT had no significant effect on the time-course or the plasma levels of metoprolol. The average half-life, 4.4 +/- 0.9 h, is about the same as previously observed for separate doses of this drug. 4. It seems unlikely that repeated doses of the combination product studied will lead to biopharmaceutic or pharmacokinetic interactions of clinical importance.

Utility of bronchoalveolar lavage in the assessment of diffuse pulmonary infiltrates in nonAIDS immunocompromised patients. The efficacy of bronchoscopy with bronchoalveolar lavage for diagnosing 32 episodes of diffuse pulmonary infiltrates was studied in 30 nonAIDS immunocompromised patients. Bronchoalveolar lavage had an overall diagnostic yield of 84% (27 of 32 episodes). Bronchoalveolar lavage was noncontributive in five episodes of pneumonitis: drug induced in one, nonspecific in three and pneumonitis of unestablished etiology in one. Overall, the procedure is safe and did not miss diagnoses for which conventional treatment was available. Our data support the use of bronchoscopy with bronchoalveolar lavage as the primary diagnostic procedure in immunocompromised patients with diffuse pulmonary infiltrates.

[Effect of semipermissive conditions on recombination involving the early genes of bacteriophage T4 in amber-mutants. I. Effect of amber-mutation in gene 43]. Recombination frequencies between rII markers of bacteriophage T4 under conditions of partial inhibition of several early functions of the phage by amber mutations have been studied. Mutations in genes 33, 42 and 45 did not affect significantly recombination frequencies. Mutations in genes 32, 44 and 46 inhibited it. It has been found that effects of double mutations in pairs of genes: 43 and 30; 43 and 52; 43 and 33; 43 and 46; 43 and 32 were consistent with theoretically expected additive effects of corresponding single mutations. The presence of double mutations in pairs of genes: 43 and 41; 43 and 42, 43 and 44, 43 and 45 caused evident deviations from additivity. These deviations could reflect specific interactions of respective pairs of genes products under phage T4 recombination. Possible mechanisms of some of the effects observed are discussed.

A galactosyl(alpha 1-3)mannose epitope on phospholipids of Leishmania mexicana and L. braziliensis is recognized by trypanosomatid-infected human sera. An immunoglobulin M antibody reactive with galactosyl(alpha 1-3)mannose [Gal(alpha 1-3)Man] residues present on phospholipids extracted from Leishmania mexicana and L. braziliensis was found to be present in high titer in the serum of every normal individual studied. Periodate oxidation, acid hydrolysis, or acetylation suppressed immunoreactivity, suggesting that an oligosaccharide chain was responsible for antibody binding. Interaction occurs only with alpha-Gal terminal residues, since treatment of purified glycophospholipids with alpha-galactosidase but not with beta-galactosidase abolished it. Antibody bound to galactosyl(alpha 1-3)galactose-linked synthetic antigens but did not bind to the same residues present in rabbit, rat, and guinea pig erythrocytes or in murine laminin. Antigen-antibody binding was strongly blocked with Gal(alpha 1-3)Man and Gal(beta 1-4)Man. These results plus inhibition studies with several oligosaccharides suggest that they are indeed different from antibodies against the galactosyl(alpha 1-3)galactose residue. Anti-Gal(alpha 1-3)Man antibody values were significantly elevated in 89% of patients with diffuse cutaneous leishmaniasis, 84% of patients with localized cutaneous leishmaniasis, 69% of patients with mucocutaneous leishmaniasis, and 44 and 62% of patients with Trypanosoma cruzi or T. rangeli infection, respectively, but not in patients with 15 other different infectious and inflammatory diseases. Anti-Gal(alpha 1-3)Man antibody readily absorbed to American Leishmania and Trypanosoma culture forms, suggesting a surface membrane localization of reactive epitope. Gal(alpha 1-3)Man-bearing glycophospholipid was easily extracted from American Leishmania promastigotes and T. cruzi trypomastigotes as well as from American Trypanosoma culture forms. The possibility that this antibody arises against parasitic glycophospholipid-linked Gal(alpha 1-3)Man terminal residues is proposed.

Ultrastructural demonstration of the importance of crystal size of bioceramic powders implanted into human periodontal lesions. Stages in bone formation were studied ultrastructurally after the implantation of the following 3 bioceramic powders into human periodontal lesions: (1) beta-tricalcium phosphate whitlockite (Synthograft) consisting of particles with a mean length of 229 +/- 87 microns in SEM and appearing in TEM as crystals with a mean diameter 488 +/- 192 nm; (2) an hydroxyapatite (Bioapatite) which consisted of particles with a mean length of 283 +/- 87 microns in SEM and of crystals with a mean diameter of 146 +/- 47 nm in TEM; and finally (3), a microsized hydroxyapatite consisting of elongated platelets with a mean length of 32 +/- 4 microns in SEM, composed of small crystals with a mean diameter of 38 +/- 16 nm in TEM. In a preliminary experiment in rats, it appeared that the microsized hydroxyapatite implanted into the alveolar region after first molar extraction exhibited biocompatibility. In 6- and 12-month biopsies, it appeared that bone formation in association with the 3 bioceramics tested in human periodontal lesions occurred through similar mechanisms at the ultrastructural level. After the appearance of peripheral fibroblast-like or osteoblast-like cells with an interposed layer reminiscent of an osteoid tissue, collagen fibrils were observed in the intercrystalline spaces. These spaces subsequently underwent mineralization, with deposition of bone apatite crystals followed by the peripheral deposition of a thin inner bone layer with a granular appearance and an outer normal bone layer of either woven bone, lamellar bone or bone with parallel calcified collagen fibrils. These bone nodules, however, formed around the bioceramic particles at highly variable time intervals. Bone formation was observed around Synthograft and Bioapatite implants only in 12-month biopsies, and thicker layers of peripheral bone were observed with the latter hydroxyapatite implant. With microsized hydroxyapatite, a significant amount of peripheral bone formation had already occurred by 6 months, strongly suggesting an important effect of crystal size on bone formation.

Psychoneuroimmunology: where are we, where are we going? We have reviewed briefly the current status of research on central nervous system-immune system interactions, focusing attention on the neural and humoral pathways by which CNS and IS communicate and interact and on the effects of stress and psychiatric illness on immune function. It is evident that CNS-IS communication occurs by direct innervation of lymphoid organs and by means of hormones, neuropeptides and cytokines. There is also clear evidence that humoral substances each of which were thought to be the product of one specific cell type are elaborated and secreted by a variety of cell types. This observation suggests a new unified concept of CNS-IS interactions with mediators of these interactions being produced ubiquitously and acting on cells of the two systems. In examining the effects of stress on IS it has become apparent that stress of various types can have a depressive effect on immune functions, primarily at the level of T lymphocytes and NK cells. This suggests that the defense mechanisms affected by stress are those which are responsible for cytotoxic effector responses. These findings are interesting in that they support older studies implicating stress in the pathogenesis and/or the clinical course of neoplastic diseases. Further support for a role of stress-induced immunodepression in morbidity comes from a very interesting, recent prospective study showing that stress will affect susceptibility to viruses. Finally, exploration of the mechanisms of stress-induced immunodepression, suggests that a variety of mediators which regulate lymphocyte interactions and activation may be affected, perhaps at the level of gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Disseminated Kaposi's sarcoma not associated with HIV infection in a bisexual man. We report a 42-year-old white bisexual man with disseminated Kaposi's sarcoma limited to the skin and gastrointestinal tract. Results of several serum tests for human immunodeficiency virus (HIV) antibodies have been negative. The CD4/CD8 ratio has remained normal, and his Kaposi's sarcoma has had a benign clinical course during 30 months of follow-up. Similar reports of disseminated Kaposi's sarcoma with a benign clinical course in homosexual or bisexual men without demonstrable HIV infection are reviewed. Some cellular immune impairment that might be more prevalent in the homosexual population may be implicated in the pathogenesis of this type of Kaposi's sarcoma.

Effects of recording speed on precision of time-based polycardiographic measurements. Optimal paper speeds for measuring points and intervals. Optimal paper speeds have not been established for all time-based measurements of the cardiac cycle by appropriately designed observer performance studies. In 10 subjects (5 normals and 5 cardiac patients) carotid pulse, phonocardiogram, and electrocardiogram were recorded on magnetic tape for measurement of all fiducial points for systolic time intervals, the systolic time intervals themselves, the pulse transmission time, cycle length (RR), qR time, and R-to-point versus q-to-point measurements at recording speeds of 25, 50, 75, 100, and 200 mm/s. Tracings were coded numerically and randomised. Three observers measured all points and calculated intervals in a sequence determined by individual tables of random numbers. Left ventricular ejection time was the only calculation that could be made at 25 mm/s statistically equally well as at all other speeds. The smallest numerical observer differences occurred uniformly at 100 mm/s paper speed when all recording speeds were considered. However, after excluding the 25 mm/s speed there were no significant differences among point measurements. Measurements of points from R (rather than q) reduced observer variability. We conclude that for point measurements, for systolic time intervals, pulse transmission time, and RR interval, recording speed between 50 and 200 mm/s showed no statistical differences, though smallest numerical differences occurred at 100 mm/s. For LVET, 25 mm/s was satisfactory.

[Changes in myocardial enzyme activity of patients with dilated cardiomyopathy and the relationship of these parameters to disturbed myocardial contractility and coronary atherosclerosis]. Endomyocardial biopsies from 20 patients with dilated cardiomyopathy (DCMP) were studied histochemically. The decrease of the mitochondrial enzyme activity and increase of the activity of lysosomal and hydrolytic enzymes were found. These alterations reflect degenerative processes in cardiomyocytes followed by activation of their degradation and utilization. This results in the decrease of the myocardium contractile volume and its contractile function damage. There was no correlation between the level of the enzyme activity in the myocardium and the degree of the contractile function activity. There was a tendency to the increase of the above changes in patients with early signs of coronary atherosclerosis.

Isolation, phenotyping, and functional analysis of lymphocytes from human liver. The isolation of mononuclear cells from human liver tissues was achieved by a simple method consisting of enzymatic and mechanical dissociation, density gradient centrifugation, and adherence to plastic. The method was optimized to obtain a nearly complete recovery of different lymphoid subpopulations. The mononuclear cells recovered from "normal" liver tissues consisted of 33 +/- 9% (mean +/- SD) small lymphocytes, 44 +/- 6% large granular lymphocytes, 9 +/- 2% monocytes/macrophages, 9 +/- 3% granulocytes, and 5 +/- 2% other cells as determined by microscopic analysis of May-Grünwald-Giemsa-stained cytocentrifuge smears. Phenotypic analysis of the liver-infiltrating lymphocytes (LIL) by two-color flow cytometry showed that CD3-CD56+ NK cells represented 43 +/- 6% (mean +/- SD), CD3+CD56- T cells, 30 +/- 9%, and CD19+ B cells 3 +/- 1%. The predominant phenotype of the liver-infiltrating NK cells was CD3-CD56+CD16- in contrast to that of circulating NK cells, which are largely CD3-CD56+CD16+. The alpha/beta TCR+ T cells were 42 +/- 14% and gamma/delta T cells were infrequent (4 +/- 4%). The proportions of the three major lymphoid populations (T, NK, and B cells) recovered from liver tissues of 10 patients with different liver diseases were altered. Tissue sections from the same specimens were stained by the immunoperoxidase method to compare the in situ cellular composition with that determined by flow cytometry. LIL recovered from normal (control) and virally infected (non-A, non-B hepatitis) liver tissues had high NK activity (up to 1,000 LU/10(7) cells) as measured against K-562 targets in 4-hr 51Cr-release assays. NK activity was significantly lower (P less than 0.05) in LIL recovered from other liver diseases. LIL had spontaneous cytotoxicity against NK-resistant Daudi targets which was significantly higher (P less than 0.05) in control and virally infected than in other liver tissues. Our results indicated that human LIL recovered from normal and diseased liver tissues contained a high proportion of functionally active NK cells and that NK and lymphokine-activated killer activities but not the percentages of CD56+ cells were decreased in end-stage primary biliary cirrhosis and primary sclerosing cholangitis. In contrast, the proportions of NK cells and NK activity remain high in non-A, non-B hepatitis.

Production of auxins by bacteria isolated from the roots of pine seedlings (Pinus silvestris L.). Qualitative and quantitative studies were carried out on the production of auxins by Coryneform bacteria, the only bacterial types isolated from roots of pine seedlings. Almost all isolates were capable of producing auxins in tryptophan containing media. In media without this amino acid only trace or no auxins were produced. Most of the bacteria studied synthesized auxins located on the chromatograms run with isopropanol, ammonia, water (10:1:1 v/v) at Rf 0.3--0.5. Moreover substances with Rf values 0.05--0.2 and 0.8--1.0 were produced by some strains. No plant growth inhibitors detected with the Avena coleoptiles biotest were produced by the bacteria studied.

Fosfomycin, antimicrobial activity in vitro and in vivo. Antibacterial activities of fosfomycin were investigated both in vitro and in vivo for the purpose of comparative evaluation on its fundamental properties with other antimicrobial agents. The MIC was determined with nutrient agar (Difco) inoculated with one loopful of 1,000-fold dilution (about 10(6) cells/ml) of bacterial suspension cultured overnight in nutrient broth. This substance showed antibacterial activity to most gram-positive and gram-negative bacteria, being strongest to Enterobacteriaceae with a peak of the MIC at 1.56 mug/ml in Salmonella. It was also active against P. aeruginosa with a peak of the MIC at 6.25 mug/ml in its sensitivity distribution. Intravenous and subcutaneous fosfomycin Na salt and oral fosfomycin Ca salt were given to 5-week-old ddN strain male mice challenged with clinical isolates of P. aeruginosa, E. coli and P. mirabilis. Therapeutic effect was observed in all these test organisms. In P. aeruginosa, it was more effective than carbenicillin.

The effect of depolarizing potassium concentrations on the efflux of GABA from rat dorsal medulla in vivo and from slices and synaptosomes. The efflux of [3H]GABA from the dorsal surface of adult rat medulla overlying the dorsal column nuclei (DCN) was found not be influenced by increasing the concentration of potassium in the superfusing solution to 40 mequiv. Similarly, raised potassium was found not to influence the efflux from slices of the dorsal region of the caudal medulla containing the dorsal column nuclei. This lack of effect of raised potassium is not thought to be due to lack of GABAergic terminals in this region because there is good pharmacological evidence for their presence and bacause both electrical stimulation and 100 microM veratridine increased the efflux of [3H]GABA from such slices. Also, 40 mequiv potassium was found to increase the efflux of both endogenous and [3H]GABA from crude synaptosome preparations of this region without influencing the efflux of [14C]sucrose or [3H]leucine. This release of [3H]GABA was calcium-dependent, and was similar whether produced by 20, 40 of 60 mequiv potassium and occurred whether eos or AOAA was used to inhibit GABA metabolism. Release from synaptosomes could also be induced with 100 microM veratridine. Raised potassium was additionally found to prevent the increased efflux from slices produced by electrical stimulation and to increase the efflux from slices prepared from the brains of rats 14 days old. It is suggested that the astrocytic swelling produced by raised potassium concentration restricts the diffusion of GABA away from depolarized terminals.

Crystal structure of calf eye lens gamma-crystallin IIIb at 2.5 A resolution: its relation to function. The crystal structure of gamma-crystallin IIIb (gamma C) from calf eye lens has been refined at 2.5 A resolution. The molecule of about 21 kDa consists of two similar domains. Each domain is composed of two motifs with the 'Greek key' topology which form a pair of four-stranded beta-sheets with an antiparallel packing. The molecule has three hydrophobic cores: one within each domain and one between them. Six of the eight functionally important cysteines are located within the N-domain, and only two in the C-domain. Several large clusters of charged residues are at the surface of the molecule. Surface residues Val 101, Met 103 and Leu 155 are important for packing of molecules in crystal medium and possibly in the lens. Features of the gamma-crystallin IIIb molecule which may be related to its function in the vertebrate eye lens are briefly discussed. An attempt has been made to correlate molecular characteristics with some general properties of the eye lens such as high density and refractive index gradients and strong stability of the lens during an organism's lifetime.

Differences in activities of thromboxane A2 receptor antagonists in smooth muscle cells. Thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors were characterized in rat vascular smooth muscle cells (VSMC). The specific binding of [3H]SQ 29,548 was inhibited by KW-3635, a novel non-prostanoic TXA2 antagonist, SQ 29,548 and BM-13505 (daltroban). SQ 29,548 showed a single class of binding sites with a Ki value of 1.6 nM. The inhibition patterns were better fit to two-component curves for KW-3635 (Ki values of 0.45 nM and 42 nM) and BM-13505 (2.3 nM and 20 nM). U46619, a TXA2 agonist, induced an increase in intracellular calcium concentration ([Ca2+]i), which was inhibited by these antagonists. KW-3635 and SQ 29,548 did not induce any increase in [Ca2+]i, whereas BM-13505 was found to induce a smaller increase in [Ca2+]i. The BM-13505-induced increase in [Ca2+]i was also inhibited by pretreatment with KW-3635, SQ 29,548 and BM-13505. The results demonstrate that BM-13505 has partial agonistic activity on TXA2/PGH2 receptors, and KW-3635 and SQ 29,548 do not. SQ 29,548 and BM-13505 inhibited both U-46619- and BM-13505-induced increases in [Ca2+]i to a similar degree. Alternatively, KW-3635 inhibited a U46619-induced increase in [Ca2+]i more effectively than a BM-13505-induced increase. These results suggest the heterogeneity of functional binding sites or subtypes of TXA2/PGH2 receptors present in VSMC.

Contrasting effects of hypoglycemia on plasma renin activity and cyclic adenosine 3',5'-monophosphate (cyclic AMP) in low renin and normal renin essential hypertension. Insulin-induced hypoglycemia previously has been shown to provoke a beta-adrenergic response that normally results in an increase in plasma renin activity (PRA). In our study, hypoglycemia induced definite increases in PRA in a group of five patients with normal renin essential hypertension but failed to do so in a group of six patients with low renin essential hypertension. In both groups, plasma cyclic adenosine 3',5'-monophosphate (cyclic AMP; cAMP) increased more than 2-fold during hypoglycemia, but the response in the low renin group was significantly less than that previously observed in normal subjects under the same conditions. Plasma cortisol increased to an equal extent in both groups of hypertensive patients during hypoglycemia. Infusion of the phosphodiesterase inhibitor, theophylline, resulted in definite increases of PRA in patients with normal renin hypertension but not in patients with low renin hypertension. Because changes in the level of plasma cAMP during hypoglycemia have been thought to reflect adrenal catecholamine release, our finding of a blunted increase in plasma cAMP during hypoglycemia in patients with low renin hypertension may suggest that there is a generalized alteration in adrenergic responsiveness in this condition.

Preliminary characterization of Pseudomonas aeruginosa peptide chemotactins for polymorphonuclear leukocytes. In a previous report, we showed that supernatants of Pseudomonas aeruginosa cultures exhibit chemotactic activity for polymorphonuclear leukocytes (PMNL). In this study, P. aeruginosa chemotactins were isolated, purified, and partially characterized. The organisms were cultured in Vogel-Bonner defined medium, and cultures were stopped in late log phase. Chemotactins withstood heating, remained unaltered after acid or alkali treatment in a pH range from 4 to 10, and resisted digestion by trypsin or carboxypeptidase, but chemotactic activity was decreased by 73% after incubation with pronase. Only 2% of the total chemotactic activity of culture supernatants could be extracted with chloroform. Chemotactins with molecular sizes less than 3 kDa constituted the largest contribution to the chemotactic activity of culture supernatants. Pretreatment of PMNL with 10(-5) M formylmethionyl-leucyl-phenylalanine (FMLP) inhibited chemotaxis towards FMLP and P. aeruginosa culture supernatants but not towards complement component C5a. In conclusion, the total chemotactic activity for PMNL of P. aeruginosa culture supernatants was due, almost exclusively, to chemotactins that have properties similar, if not identical, to those exhibited by formylmethionyl peptides.

Nonsteroidal anti-inflammatory drug toxicity: increased risk in the elderly. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the therapy of rheumatic diseases, especially in older patients. The toxicity profile of NSAIDs includes gastrointestinal (GI) toxicity, renal dysfunction and hepatic disease. Altered drug pharmacology in older patients may be a factor in their increased risk for drug toxicity. Elderly patients appear to be at greatest risk for symptomatic GI toxicity, including ulceration and even major GI bleeding. Central nervous system toxicity, characterized by dizziness, headaches, mood alteration and confusion, and renal dysfunction have also been reported to occur more commonly among elderly patients. Hepatic dysfunction is a rare NSAID-induced toxicity, but older patients are often at greatest risk for serious hepatic disease. Understanding the patient's underlying physiologic condition, concomitant drug therapy and the kinetics of the NSAID being used is critical to the safe administration of these agents to elderly individuals.

Pulmonary rehabilitation. Any COPD patient with symptoms is a candidate for pulmonary rehabilitation. A careful assessment of the individual to determine the patient's precise disease process and needs is essential to outlining an appropriate treatment program. Following the sequence described in the ATS Statement on Pulmonary Rehabilitation included in the appendix to this article provides the best potential for successfully returning the patient to the highest level of function possible. An increase in the availability of pulmonary rehabilitation programs should allow more COPD patients to participate in this process, resulting in an enhanced ability to carry out daily activities, an improved quality of life, and a reduction in the long-term costs of caring for such individuals.

[Experiment with rats on a 22-day flight on the "Kosmos-605" biological satellite (objectives and methods)]. In 1974 a rat experiment was carried out onboard the Cosmos-605 biosatellite. Inflight Wistar rats were kept unrestrained in small cages. The cages were equipped with a feeder, water supply, light source and a ventilation device. The state of the animals was assessed with respect to their motor activity. The flight experiment was preceded by a number of preparatory runs and testinns that were completed with an end-to-end experiment in a biosatellite mockup. The flight experiment was paralleled by the ground-based synchroneous experiment which simulated almost entirely the flight profile. For each experiment rats were selected and trained during a month's observation. Postflight rats were exposed to clinical, physiological, morphological, cytochemical and biochemical investigations. Tissue examinations were performed on the 2nd-3rd day (20 rats) and 26-27th day (12 rats) after flight. Four rats were kept to study remote aftereffects.

Effect of manganese (II) bis(glycinate)dichloride on Ca2+ channel function in cultured chick atrial cells. Manganese (II) bis(glycinate)dichloride (Mn(glycinate)2) is a coordination complex of manganese with application as a contrast enhancement agent for magnetic resonance imaging in the heart. To determine the cardioactivity of the manganese ion in this chelation cage, the effects of Mn(glycinate)2 on Ca channel function in the cultured chick atrial cell was studied. Mn(glycinate)2 decreased amplitude of contraction in chick atrial cells from embryos 14 days in ovo with complete inhibition of beating at 1 mM and half-maximal effect at 0.1 mM. Under control conditions, Bay K 8644, a Ca channel activator increased amplitude of contraction by 86% with a half maximal effect at 3.2 x 10(-7) M. In the presence of 0.025 mM Mn(glycinate)2, a concentration which had no effect on the amplitude of contraction, the maximum response to Bay K 8644 was decreased to 31%. Mn(glycinate)2 had no effect on the EC50 for the response to Bay K 8644, 1.7 +/- 0.1 x 10(-9) M (S.E.M., n = 4) in control cells compared to 2.2 +/- 0.4 x 10(-9) M (S.E.M., n = 4) in cells incubated with Mn(glycinate)2. 45Ca2+ uptake over 5 min in cultured chick atrial cells decreased from 2.0 nmol/mg protein in control cells to 1.5 nmol/mg protein in the presence of 10(-5) M PN200-110, a Ca2+ channel blocker, a decrease of 28%. 45Ca2+ uptake decreased to 0.94 nmol/mg protein (53%) in the presence of 1 nmol Mn(glycinate)2. Effects of Mn(glycinate)2 and PN200 were not additive. These data demonstrate that Mn(glycinate)2 exerts its negative inotropic effect, at least partially, by interfering with the function of the L-type Ca channels at high concentrations.

Characterization of descending facilitation and inhibition of spinal nociceptive transmission from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. 1. Descending influences produced by focal electrical stimulation in the nuclei reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha) on spinal nociceptive transmission and the dorsoventral region of spinal white matter mediating stimulation-produced modulation were examined in pentobarbital sodium-anesthetized, paralyzed rats. Spinal units studied responded to mechanical stimuli and noxious heating (50 degrees C) of cutaneous receptive fields confined to the glabrous skin of the ipsilateral hind foot. Recording sites were located in laminae I-VI of the L3-L5 spinal segments. 2. Electrical stimulation in the NGC or NGC alpha produced both facilitation and inhibition of responses of spinal units to noxious heating of the skin. At 33 of 57 stimulation sites in the NGC and NGC alpha, electrical stimulation produced biphasic effects, facilitating responses at lesser intensities (5-25 microA) and inhibiting responses at greater intensities (50-100 microA). At 21 other sites in the NGC and NGC alpha, electrical stimulation (5-100 microA) only inhibited, and at 3 sites stimulation (5-100 microA) only facilitated responses of spinal units to noxious heating of the skin. 3. Electrical stimulation in the NGC or NGC alpha contralateral to the spinal recording site produced the same magnitude of facilitation/inhibition or inhibition of spinal nociceptive transmission as did stimulation in the ipsilateral NGC and NGC alpha. 4. The latencies to descending facilitation and inhibition of spinal nociceptive transmission from the NGC and NGC alpha were estimated by a cumulative sum technique to be 232 and 80 ms, respectively. 5. Responses of spinal units to graded heating (42-50 degrees C) of the skin exhibited positively accelerating stimulus-response functions (SRF) throughout the temperature range tested. Electrical stimulation at lesser, "facilitating" intensities produced a parallel, leftward shift of the SRF, whereas stimulation at greater, "inhibitory" intensities significantly decreased the slope of the SRF without affecting the threshold for response. 6. To determine whether activation of cell bodies in the NGC or NGC alpha were capable of replicating the effects of electrical stimulation, L-glutamate was microinjected into sites where electrical stimulation facilitated at lesser and inhibited at greater intensities the responses of spinal units to 50 degrees C heating of the skin. L-Glutamate (5 nmol) produced a rapid onset, short-lasting and reproducible facilitation of nociceptive transmission; glutamate microinjection into the same site at a greater dosage (50 nmol) inhibited responses of the same spinal units.(ABSTRACT TRUNCATED AT 400 WORDS)

Organization of cat striate cortex: a correlation of receptive-field properties with afferent and efferent connections. The purposes of this study were 1) to relate the receptive-field characteristics of area 17 cells to their afferent and efferent connections, and 2) to obtain quantitative data from area 17 neurons for later comparison with area 18 cells. Intra- and extracellular recordings were obtained in paralyzed preparations which were anesthetized with nitrous oxide. The connectivities of the recorded cells were determined from responses to electrical stimulation of afferent and efferent pathways. In parallel to the classification of units as simple and complex cells, the receptive fields were grouped in four classes according to the spatial arrangement of on- and off-areas; class I, fields with exclusive on- or off-areas; class II, fields with spatially separate on- and off-areas; class III, fields with mixed on-off areas; class IV, fields which could not be mapped with stationary stimuli. The results from electrical stimulation suggest two major classes of cells: cells in the first group are driven mainly or exclusively by LGN afferents. They rarely receive additional excitation from intrinsic or callosal afferents and rarely possess corticofugal axons. Cells in the second group receive either converging inputs from LGN afferents and further intrinsic afferents or only from intrinsic afferents. They frequently received additional input from callosum and from recurrent collaterals of corticofugal axons. They project subcortically more often than cells in the first group. Cells in both groups can be driven either by X- or Y-type afferents. Cells in the first group have mainly class I and class II fields or simple fields, whereas the neurons in the second group have mainly class III and class IV fields or complex fields. Thus, simple and complex cells differ in their connectivity patterns, but the discriminative parameter is neither the selective connection to the X- or the Y-system nor, in a strict sense, the synaptic distance from subcortical input. From the combined consideration of receptive-field properties and connectivity patterns it is concluded that class I and class II cells or simple cells are concerned mainly with the primary analysis of subcortical activity, whereas class III and class IV cells or complex cells perform a correlative analysis between highly convergent activity from extrinsic and intrinsic afferents.

Two rat models of hepatic fibrosis. A morphologic and molecular comparison. We present a morphologic and molecular comparison of two models of hepatic fibrosis. Immune complexes are the source of insult in one model. In the other model, CCl4 induces fibrosis. For the immune complex model, rats were immunized intraperitoneally over the course of 4 weeks with human albumin, then injected through a tail vein three times a week for at least 5 more weeks with the same albumin. Seventy-five percent of all treated animals developed fibrosis characterized by fine collagen bands. There was a mild degree of hepatocyte trapping and necrosis as well as some bile duct hyperplasia and tissue eosinophilia. However, there was no significant Kupffer cell hyperplasia or inflammatory reaction. Quantification of specific mRNA species was determined by Northern blot hybridization analysis of total RNA. In comparison with CCl4-induced fibrosis in rats, a hepatotoxin-mediated model with a much greater inflammatory response, this immune complex model showed a less pronounced increase in type I procollagen mRNA, but a relatively greater increase in types III and IV procollagen mRNA. Whereas transforming growth factor-beta 1 mRNA levels were markedly increased in CCl4-induced fibrosis, there was only a slight increase in this cytokine, known to stimulate type I collagen synthesis, in the immune complex model. A comparison of the two model systems indicates that a variety of mechanisms may be involved in the process of hepatic fibrogenesis. It appears that an inflammatory response and elevated transforming growth factor-beta 1 levels are associated with a marked increased synthesis of type I collagen in a hepatotoxin model while other, as yet undefined, mediators may be responsible for the increase in types III and IV procollagen mRNA species found in the immune complex model.

Three species of polyoma virus tumor antigens share common peptides probably near the amino termini of the proteins. Detergent extracts of polyoma virus-infected mouse cells contain three major proteins of approximately 100,000--108,000 (100K), 55,000 (55K) and 21,500 (22K) daltons, which react with sera obtained from rats carrying tumors induced by the virus. A comparison of the 35S-methionine-, 3H-leucine- and 3H-proline-labeled tryptic peptides of each of these proteins by cation-exchange chromatography followed by descending paper chromatography has shown that: at least five peptides are shared by all three T-reactive proteins; at least three peptides are shared by the 55K and 22K proteins, but not by the 100K protein; at least three peptides are found only in the 22K protein; at least six peptides are found only in the 55K protein; and at least sixteen peptides are found only in the 100K protein. The results are consistent with the hypothesis that the polypeptide chains of the 100K, 55K and 22K dalton tumor antigens of polyoma virus share a common virus-coded amino terminal region. The data also suggest that there is a portion of the polypeptide chains (probably immediately adjacent to the common amino terminal region of the molecules) that is shared by the 55K and 22K proteins, but not by the 100K protein (perhaps because this portion of the genetic information is spliced out of the messenger RNA coding for the 100K protein). The facts that all the peptides common to the 100K and 55K proteins are also found in the 22K protein and are thus assigned to the common amino terminal region of the molecules, and that there are several peptides unique to the 100K protein, as well as several peptides unique to the 55K protein, suggest that the presumed carboxy terminal portion of the polypeptide chain of the 100K protein is considerably, if not entirely, different from that of the 55K protein.

[Irritable colon and ulcerative colitis. Alternative treatment is used frequently]. A questionnaire investigation was undertaken to compare the employment of alternative treatment in patients with irritable colon (CI) and ulcerative colitis (CU) as compared with a control group of appendectomized (A). A total of 430 questionnaires were sent out. The percentage of replies was 83 without significant difference between the patient groups. Alternative therapists were consulted more frequently by the CI group than the two other groups which did not differ from one another in this respect. Both CI and CU had employed "natural medicine" more frequently than the control group. Women and younger patients were the most frequent employers of the alternative system. The effect of alternative treatment was frequently experienced in the form of headache and discomfort in the locomotor system. The average expense of treatment was 1,000 Danish crowns (approximately 83 pounds). 23% of the CU group and 41% of the CI group experienced aggravated or unchanged abdominal symptoms compared with their complaints during the period of hospitalization 1-10 years prior to the current investigation. No correlation could be demonstrated between a favourable course and employment of the alternative system.

Effect of phosphoenolpyruvate on metabolic and morphological recovery of red cells after prolonged liquid storage and subsequent freezing in glycerol medium. The present study was designed to determine the effects of (i) phosphoenolpyruvate (PEP) treatment of red blood cells (RBCs) previously cold stored for a prolonged period in a liquid medium and (ii) the freezing of these treated cells in glycerol. RBCs stored for 21 days at 4 degrees C were incubated for 30 min at 37 degrees C with rejuvenant solution containing 50 mM PEP, 60 mM mannitol, 30 mM sodium chloride, 25 mM glucose, and 1 mM adenine, pH 6.0, and then frozen at -80 degrees C for 4 weeks. Red cell recovery as frozen and thawed red cells (FTRCs) after deglycerolization was increased to 80 +/- 4% compared to 43 +/- 9% in units without rejuvenation; the percentage of PEP-treated FTRCs was similar to the percentage of FTRCs recovered from fresh RBCs within 5 days after donation. Incubation of RBCs with PEP solution restored ATP and 2,3-DPG to levels seen in fresh RBCs, and also facilitated transformation of crenated RBCs to discocytes. These results indicate that maximum recovery of viable RBCs can be attained when FTRCs are processed from cells stored in the frozen state after they had been rejuvenated with PEP even after prolonged liquid storage.

Endothelins are more sensitive than sarafotoxins to neutral endopeptidase: possible physiological significance. Incubation of endothelins (ETs) with bovine kidney neutral endopeptidase (NEP) resulted in a selective two-step degradation with loss of biochemical activity. The Km of the enzyme indicated high-affinity binding, and hydrolysis was completely inhibited by phosphoramidon. The first step was nicking of the Ser5-Leu6 bond, followed by cleavage at the amino side of Ile19. The nicked peptide exhibited biochemical activities comparable to those of the intact peptide--i.e., binding to the ET receptor, induction of inositol phospholipid hydrolysis, and toxicity. The twice-cleaved product was inactive. The sarafotoxins (SRTXs) were more resistant than the ETs to NEP: for example, the half-time for ET-1 was approximately 1 hr, while it was approximately 4 hr for SRTX-b and even higher for SRTX-c. These in vitro findings may indicate a regulatory role of NEP (or similar enzymes) in the physiological inactivation of ETs. They might also help to explain why under certain physiological conditions ETs may be less toxic than SRTXs.

Radiation therapy of squamous carcinoma of the floor of mouth and the lower alveolar ridge. Treatment for 139 patients with squamous carcinomas in the floor of mouth and the lower alveolar ridge, which accounted for one-third of all patients with intra-oral cancer, are evaluated and classified after UICC and AJC's TNM recommendations retrospectively, for cancer staging and End Result Reporting. The figures include 50% women with tumours and in lower alveolar ridge. Two treatment schemes: external cobalt irradiation and external irradiation in combination with intra-oral radium-mould have been used in spite of primary bone invasion. 30% had remnant tumours and 22% recurred locally. 70% of the recurrences were discovered within a year after treatment. The total crude survival for all patients was 32%, identical for both groups. Lymph node metastases lower the survival significantly. Less than one-third had difficulties in mucous healing after treatment and 9% developed osteoradionecrosis, but only half of those patients had symptoms.

Preparation of asialofetuin-labeled liposomes with encapsulated human interferon-gamma and their uptake by isolated rat hepatocytes. The selective delivery of human recombinant interferon (IFN)-gamma to isolated rat hepatocytes was studied with asialofetuin (AF)-labeled liposomes. AF-liposomes containing buffer solution were initially prepared by the detergent removal method, and IFN-gamma was subsequently encapsulated by the freeze-thawing method without loss of activity. Virtually no free [32P]IFN-gamma was internalized into isolated rat hepatocytes, whereas AF-liposomes containing [32P]IFN-gamma were taken up to a significant degree. Liposomal binding to the hepatocytes (estimated at 4 degrees C) was one-fifth of the uptake (estimated at 37 degrees C). Since the uptake was inhibited by the addition of free AF, AF-liposomes may be taken up by the action of galactose-binding protein on the hepatocytic cell surface. The liposome preparation method reported in this paper provides a useful means for the encapsulation of unstable macromolecules into AF-liposomes. AF-liposomes were found effectively to carry IFN-gamma into hepatocytes in vitro.

Antinuclear antibodies: a simplified classification of the nuclear immunofluorescent patterns. The key to a simplified classification of the nuclear immunofluorescent patterns is to separate out only two patterns, the speckled and nucleolar, from the nonhomogeneous particulate group (showing stained particles). There are only six categories divided into two major groups: nonparticulate and particulate. The nonparticulate group consists of the (1) peripheral, (2) homogeneous, and (3) leukocyte specific patterns. The particulate group is divided into (1) nucleolar, (2) speckled, and (3) "other particulates." The major diagnostic and prognostic values of of the test are retained by the simple expedient of separating out only two morphologically distinct and diagnostically important patterns from the particulate group, the nucleolar and speckled patterns, seen mainly in scleroderma but not in lupus erythematosus.

Maintenance of feedback regulation of filtration dynamics in the absence of divalent cations in the lumen of the distal tubule. In the present experiments we have studied the hypothesis that the feedback responses of glomerular capillary pressure and glomerular filtration rate to elevated distal fluid delivery depend to some extent on the luminal concentration of calcium or magnesium [1]. Loops of Henle were therefore perfused with the following solutions which were designed to yield wide variations of distal divalent cation concentration: 1. Ringer, 2. 140mM NaCl, 3. 125mM NaCl + 10mM CaCl2, 4. 125 mM NaCl + 10 mM MgCl2, 5. 125 mM NaCl + 10 mM Na citrate, and 6. 125 mM NaCl + 10 mM EDTA. During orthograde perfusion with these solutions stop flow pressure (SEP) and early proximal flow rate (EPFR) were measured in each nephron at perfusion rates of 0, 15, 30, and 45 nl/min. We found that perfusion with solutions 2 to 6 did not significantly modify the flow induced change of SFP or EPFR observed during Ringer perfusion. To expose the macula densa cells to chemically well defined solutions loops of Henle were retrogradely perfused from the distal tubule and EPFR was measured in a given nephron with and without perfusion. Identical reductions of EPFR were induced by retrograde perfusions with 140 mM NaCl, 125 mM NaCl + 10 mM CaCl2, and 125 mM NaCl + 10 mM EDTA. Furthermore, an almost complete blunting of the feedback response was noted during retrograde perfusion with 25 mM NaCl. Addition of 5 mM CaCl2 failed to restore the feedback reaction. These results do not support the concept that luminal divalent cations participate in the initiation of tubulo-glomerular feedback responses.

[Computer tomographic findings after resection of the rectum (author's transl)]. Computed tomography findings in the pelvis after resection of the rectum, obtained from 48 patients primarily suspected of recurrent carcinoma, are represented. Compared with conventional radiographic methods CT demonstrates directly in most cases the presence of a pelvic mass, its extension and relationship to adjacent soft tissue. In some cases this is advantageous for further diagnostic procedures, but also for treatment and further check-up. False conclusions are discussed. The distinction between recurrent carcinoma and retroperitoneal fibrosis in the pelvis, frequently enhanced by retarded healing of the sacral cavity, remains a problem. Progress in the early diagnosis of recurrence of pelvic mass could be made by regular CT check-up during the first two years after resection of the rectum, to increase the value of palliative radiotherapy treatment indicated in any case. As CT, however, is expensive and not always available, this demand cannot be met and the value of conventional radiographic methods remains at present unquestioned.

Beta-1-3-glucanase and dimorphism in Paracoccidioides brasiliensis. Mycelial and yeast forms of P. brasiliensis were tested for several glucohydrolases. In addition to high levels of beta-glucanases, low amounts of alpha-glucanase, chitinase and maltase were found. Tests for invertase, amylase and lactase were negative. The levels of beta-1,3-glucanase were higher in the mycelial form. The shift to the mycelial phase correlated with an increase in the levels of beta-1,3-glucanase. The enzyme was present in the cytoplasm, cell wall and culture medium. The extracellular enzyme was purified 42 fold by ammonium sulphate precipitation and gel filtration. Maximal activity was obtained at 60 degrees C and pH of 5.0 (acetate buffer or pH 6.0 (phosphate buffer). Its Km was 0.205 mg/ml. The cell wall-bound enzyme showed a higher temperature optimum. Optimum pH and Km were also slightly different. Following treatment of the cell walls with chitinase, beta-1,3-glucanase was released into the medium.

Urethritis due to Chlamydia trachomatis. Ninety-five men suffering from gonococcal urethritis were treated and observed. Forty-nine developed postgonococcal non-specific urethritis (PGU). Seventeen men were demonstrated to be free from PGU after careful observation; these formed a control group. Chlamydia trachomatis was isolated from urethral material from 26 (53%) of the PGU group but from none of the controls. This difference was highly significant (P less than 0-001). It confirms that C. tachomatis is a pathogen in the urethra. The presence of specific IgM antibody to C. trachomatis in serum from some men developing PGU, from whom that organism was isolated, suggests that the infection was recent in those cases. Ureaplasma urealyticum (T strain mycoplasma) was isolated from urethral material taken from 22 (45%) of the 49 men in the PGU group, and from 12 (71%) of the 17 in the control group. Mycoplasma hominis was isolated from 10 (20%) of the 49 men in the PGU group, and from four (24%) of the 17 men in the control group. Thus, no evidence was obtained that mycoplasmas (U. urealyticum, M. hominis) are patogenic in the urethra.

Maternal nutrition and lactation. The present recommended dietary interpretation of the effects of both maternal nutritional status and diet on the yield and composition of milk is complicated by disparities between the methods of sampling, collection of samples and analysis in these studies. The effect of breast-feeding on the growth of the neonate and the desirable period during which unsupplemented breast-feeding can be safely given are discussed. Well coordinated studies worldwide on the effect of lactation on maternal and infant health and on the nutrient requirements of infants are urgently needed in view of recent developments regarding the true protein value of breast milk. The let-down reflex must be considered. Three main strategies, including supplementary feeding of the mother, for improving breast-feeding potential among mothers who want to suckle their infants are outlined.

Palliation of esophageal carcinoma with intraluminal tubes: experience with 30 patients. Between 1968 and 1978, 26 patients with carcinomas of the thoracic esophagus and 4 with adenocarcinomas involving the esophagogastric junction were treated by the insertion of indwelling intraluminal (endoesophageal) tubes. Four different types of tube were inserted by the pull-through technique. Thirteen of the 30 patients died in the hospital within 30 days. However, among the 20 patients who did not have neoplasms of the upper third of the thoracic esophagus or who had not had a prior resection, only 5 died. The principal cause of death was aspiration pneumonia. Survival averaged 2.5 months. Four patients survived 5 to 7 months. Deglutition was adequate in most patients but was not as satisfactory as after esophagogastrectomy. Our best results were obtained in patients with carcinoma of the middle or lower third of the esophagus, with or without an esophagorespiratory fistula, who had not had a previous resection.

Rapid measurement of leucine-specific activity in biological fluids by ion-exchange chromatography and post-column ninhydrin detection. Commonly used methods for the measurement of leucine-specific activity use either high-performance liquid chromatography (HPLC) and pre-column derivatization or conventional ion-exchange chromatography. These are time-consuming, labor-intensive, relatively costly procedures, requiring high concentrations of radioactivity for accuracy. The present paper describes a method for the measurement of plasma leucine-specific activity using HPLC equipment, a large-bore ion-exchange column and post-column ninhydrin detection. With this method, determination of leucine concentration and leucine radioactivity was found to be linear (r2 greater than 0.999) over physiological ranges for both standards and deproteinized plasma. The intra- and inter-assay coefficients of variation for leucine concentrations were 1.4 and 2.7%, respectively. The intra- and inter-assay coefficients of variation for leucine-specific activities were 1.5 and 1.9%, respectively. The automated method is relatively fast (injection to injection time approximately 45 min), economical and capable of accurately assessing relatively small amounts of radioactivity.

Morphological observations in the nervous system of prenatal mucopolysaccharidosis II (M. Hunter). Light and electron microscopic finding in the nervous system of a 23-week-old fetus are reported, in which MPS II was diagnosed prenatally. The degrees of myelination and neuronal differentiation were similar as in a normal fetus of the same age. A storage of mucopolysaccharides in typical vacuolar inclusion bodies was present throughout the peripheral and central nervous system, mainly in cells of mesenchymal origin. "Zebra" bodies and granulo-membranous bodies, which are thought to represent secondard ganglioside accumulation were only found in the well developed neurons of the spinal cord and spinal ganglia, but not in the poorly developed neurons of the cerebellar and cerebral cortex. Mucopolysaccharide storage in endothelial cells of cerebral bood vessels precedes the appearance of lipid storgae in cerebral neurons.

Urinary excretion of ephedrine after nasal application in healthy volunteers. The urinary excretion of ephedrine after intranasal administration of the drug was studied in 8 healthy volunteers. Ephedrine (6 drops of a commercial 0.75% nasal ephedrine solution in each nasal cavity) was administered 4 times at intervals of 2 h (total amount applied equivalent to approximately 14 mg ephedrine), and urine was collected each hour for 10 h; the volunteers exercised on a bicycle ergometer at 50% of their VO2max for 2 h after the last ephedrine application. Ephedrine was detected in all urine samples. The urinary ephedrine concentration ranged from 0.9 to 16.5 micrograms mL-1; the number of urine samples with an ephedrine concentration exceeding 5 micrograms mL-1 ranged from 1/10 (volunteer 2) to 9/10 (volunteers 1 and 3). The mean percentage of dose recovered within 10 h was 33% (range 23-50%). There was a weak but significant negative correlation between urinary pH and amount of ephedrine in the urine; exercise did not consistently influence the urinary amount. These results illustrate the systemic availability of ephedrine upon intranasal administration and show that the therapeutic use of a nasal ephedrine formulation by an athlete on the day of a competition can lead to a urinary ephedrine concentration above 5 micrograms mL-1, which is considered positive in current doping regulations of the International Union of Cyclists.

[Morphological characteristics of the destructive and reparative changes in tuberculosis in those dying of nontubercular diseases]. The evolution of destructive and restorative alterations was morphologically followed up in 82 tuberculotics that died of non-tiberculous diseases. In the majority of the deceased, the restorative alterations were observed with manifested mesenchymal and immunologic reactions with morphological peculiarities as in the treated with anti tuberculous remedies. The destructive alteration are clearly manifested and the restorative manifestations are depressed in tuberculotics with non-treated diabetes and osteomyelitis treated with cortison. In a negligible part of the patients died of non-tuberculous diseases, a reactivation of the foci developed around the fibrocaseous lung foci, tracheobronchial lymph nodes, kidneys and suprarenals, manifested with filamented neutrophyils in the calcified and caseous matter, fresh necrosis, tubercula, specific granular tissue, friable capsule with appearance of lymphoid cells and specific granular tissue.

Clinical diagnosis of congestive heart failure in patients with acute dyspnea. The validity and utility of physical examination maneuvers were determined in diagnosing congestive heart failure (CHF) in patients with acute dyspnea. Fifty one patients presented to the emergency room with the chief complaint of shortness of breath. History and physical examination were obtained independently, and the physical examination included hepatojugular reflux and the Valsalva maneuver. The diagnosis of CHF was made by predetermined criteria, and was compared with the diagnosis of the emergency room (ER) physician and with the response to bedside maneuvers. The hepatojugular reflux and Valsalva maneuvers were valid in the diagnosis of congestive heart failure in acutely dyspneic patients. Although these maneuvers rarely added to the routine assessment of patients in this study, they may provide a useful, noninvasive adjunct to clinical diagnosis in problematic cases.

Diurnal variations in the motor activity of the rat: effects of inhibitors of the catecholamine synthesis. The effects of the inhibitor of the tyrosine-hydroxylase H 44/68 and the inhibitor of the dopamine-beta-hydroxylase FLA 63 on the diurnal variations of the motor activity was studied in male Wistar rats, which were kept under standardized conditions of light and darkness (L:D = 12:12 h). The motor activity was continuously registered in groups of 5 rats using a two-channel Animex motimeter. During light FLA 63 (40 mg/kg, s.c.) greatly increased motor activity on acute application and during darkness the physiological elevation in motor activity was further but slightly increased. H 44/68 (200 mg/kg, i.p.) also increased motor activity during light, but in contrast to FLA 63 greatly reduced motor activity during darkness. The results indicate that though dopamine and noradrenaline are involved in the regulation of behavioural components, one or the other catecholamine may play a predominant role at different times of the day. Thus, it seems worthwhile to study the effects of drugs separately during light and during darkness.

In vivo action of activin-A on pituitary-gonadal system. Activin, a dimer of the beta-subunits of inhibin, has been found to stimulate FSH secretion from the cultured pituitary cells. However, in vivo action of activin is poorly elucidated. Daily sc injections of 40 micrograms activin-A over a period of 1-3 days to intact immature female rats caused a significant increase in serum FSH, inhibin, estradiol, uterine weight, and ovarian FSH receptors. Daily sc injections of 5 micrograms or 20 micrograms activin-A for 6 days caused a marked increase in ovarian weight and the development of large ovarian follicles. However, daily sc injections of 20 micrograms activin-A to hypophysectomized immature female rats for 3 days induced no significant changes in ovarian and uterine weight, serum inhibin, estradiol, and progesterone levels. Simultaneous injections of both activin-A and 5 IU PMSG induced a significant increase in ovarian and uterine weight, serum inhibin, and estradiol levels, compared to simultaneous injections of both vehicle and PMSG in the hypophysectomized immature female rats. These results demonstrate that activin-A induces not only an increase of FSH secretion from the pituitary but also a direct autocrine or paracrine ovarian stimulation resulting in an increase of the number of ovarian FSH receptors and ovarian and uterine weight, as well as an increase in the level of inhibin and estradiol secretion from the ovary.

Diagnosis of cervical spine injury in motor vehicle crash victims: how many X-rays are enough? As delay in diagnosing unstable cervical spine injuries unnecessarily exposes patients to risk of neurologic injury, it is often recommended that complex radiologic investigations be performed on alert patients with neck pain, tenderness, or neurologic deficit despite normal plain radiographs. The optimal investigation of patients unable to reliably provide such information is less clear. How many X-rays are enough to clear the cervical spine? In order to answer this question, a retrospective review of 775 motor vehicle crash (MVC) victims was conducted. Ninety-two (12%) sustained cervical spine injury. Sixteen of these injuries were missed initially and, in a further 18 cases, the lateral cervical spine X-ray was wrongly interpreted as positive. Fifty-five per cent of patients with cervical injury had a Glasgow Coma Score (GCS) of less than 15 on admission. Lateral radiographic visualization of the complete cervical spine (including a swimmer's view as required) had a sensitivity of 83% and a specificity of 97%. The addition of open mouth (OM) and anteroposterior (AP) views detected all patients with unstable fractures except one man with a head injury who was unable to provide clinical clues to the diagnosis, but who suffered no additional harm as a result. A single lateral X-ray of the cervical spine is inadequate to exclude cervical spine injury in severely traumatized patients and the addition of OM and AP views still failed to identify unstable fractures in one of 385 patients in this series of MVC victims with GCS less than 15.(ABSTRACT TRUNCATED AT 250 WORDS)

[Conceptual evolution regarding the pathogenesis of biliary lithiasis due to cholesterol calculi]. In the recent 5 years, several important conceptual changes in the understanding of cholesterol gallstone formation have occurred. This article discusses the molecular basis of the disease, as we understand it today. The discovery of a vesicular carrier of biliary lipids and the metabolic regulation of biliary cholesterol secretion have markedly modified our understanding of the pathogenesis of cholelithiasis, giving more emphasis to molecular and cell biology aspects, rather than to physicochemistry, as occurred in the late seventies (micellar theory). The critical step in gallstone formation is cholesterol crystallization and it occurs after vesicle aggregation and fusion. This process is probably dependent of hepatic glycoproteins secreted into bile, presumably associated to the vesicular carrier of biliary cholesterol. Risk factors such as sex, obesity, sexual hormones, and diet seem to modify either biliary cholesterol secretion, and/or nucleation (crystallization) in the gallbladder, and/or gallbladder motility. It seems most likely that gallstones is a multifactorial disease, dependent of an interactions between environmental and genetic, or ethnic, factors.

Genetic analysis of a new mutation conferring cysteine auxotrophy in Saccharomyces cerevisiae: updating of the sulfur metabolism pathway. We have identified a mutation in a gene of Saccharomyces cerevisiae, STR1, that leads to a strict nutritional requirement for cysteine. The str1-1 mutation decreases to an undetectable level the cystathionine gamma-lyase activity. This enzyme catalyzes one of the two reactions involved in the transsulfuration pathway that yields cysteine from homocysteine with the intermediary formation of cystathionine. The phenotype induced by this mutation implies that, in S. cerevisiae, the sulfur atom of sulfide resulting from the reductive assimilation of sulfate is incorporated into a four carbon backbone yielding homocysteine, which, in turn, is the precursor of the biosynthesis of both cysteine and methionine. This also reveals that the direct synthesis of cysteine by incorporation of the sulfur atom into a three carbon backbone as found in Escherichia coli does not occur in S. cerevisiae. The study of the meiotic progeny of diploid strains heterozygous at the STR1 locus has shown that the str1-1 mutation undergoes a particularly high frequency of meiotic gene conversion.

[Public vocational integration: a new method for integrating psychiatrically handicapped patients into occupational life?]. Suitable conditions of employment represent a central factor in the rehabilitation of mentally ill people. In this case both the normality of the job--as felt by the individual--and adequate instrumental and social working conditions are determining factors. According to the ideas of the Workshop for the Handicapped (Werkstatt für Behinderte) and the movement for the Self-help Firms, the integration of the mentally ill into normal jobs is an important step in the right direction. Appropriate preparations (i.e. assessment of patients' working capabilities and the drawing up of expectation profiles, work-preparation measures) and well-organized follow-up care are required to achieve this. Statutes which make access easier must be created in the fields of both labour and social law in order to make integration into the labour market possible. In this respect the non profit-making provision of employees (Gemeinnützige Arbeitnehmerüberlassung) represents a model. The procedure has been described and first experiences with its realization have been reported upon.

Growth hormone-dependent serum stimulation of DNA synthesis in chick embryo fibroblasts in culture. We have investigated the role of GH in the serum requirement for the multiplication of chick embryo fibroblasts (CEF-S) in culture . Serum from hypophysectomized (hypox.) rats is much less effective than normal serum in stimulating the incorporation of (3H-methyl]thymidine into DNA. More importantly, bovine GH(bGH) treatment of the hypox. rat restores 60% or more of the activity in the 3H-thymidine incorporation assay. Bovine GH is inactive when tested directly in the assay. Mixing experiments show that the decreased activity of hypox. serum is not due to the presence of an inhibitor in the hypox. serum. The GH is dependent factor is nondialysable and stable to Boiling at pH5.5. boiling the normal, hypox. and bGH treating hypox. rat sera results not only in enhancement of the activity but also a more linear dose response curve in the 3H-thymidine incorporation assay. The thesis because measurements of cell numbers show the CEFs multiply less well in boiled normal rat serum and bGH treatment of the hypox. rat restores approximately half of the multiplication stimulating activity of normal boiled rat serum. CEFs in culture may provide a satisfactory in vitro system for the study of the mechanism of action of the growth hormone dependent anabolic factors found in serum.

Plasma levels of unconjugated estetrol and estriol and of total estriol in normal human pregnancy. The course of normal pregnancy in 54 patients was monitored by weekly assays of Unconjugated Estriol (E3U), Total Estriol (E3T) and Unconjugated Estetrol (E4U). These subjects were divided into two groups: one of those patients who delivered a fetus with a weight above the 50th percentile and the other of those who delivered a fetus with a weight below the 50th percentile. No significant difference was found between these two groups and it is not therefore possible to have information regarding the weight of the fetus, starting from the weekly values of these hormones. Analogous variations of the three hormones were found as pregnancy progresses. However, the rate of increase for E4U was higher than for E3T and E3U.

Further findings on the inhibitory effect of estradiol benzoate on the circulation and on 45Ca and 3H-proline incorporation in rat bones. Various aspects of the effect of estradiol benzoate (EB, Agofollin Depot, Czechoslovakia, usually in a s.c. dose of 5 mg/kg body weight once a week), on the local circulation (the uptake of 85Sr-microspheres), the incorporation of 45Ca and 3H-proline, bone density and ash weight related to bone volume were studied in six experiments in the tibia and distal femur of 224 rats. 1. The dose-response. In rats treated four weeks with doses of 0.5, 1.0, 1.5 and 2.0 mg EB per rat once a week, a significant correlation with the uptake of 85Sr-microspheres (r = -0.56), the blood flow (r = -0.56), the incorporations of 45Ca (r = -0.89) and 3H-proline (r = -0.35) and body weight (r = -0.71) was demonstrated. 2. The time course of changes after 1, 2, 4 and 8 weeks administration of EB. Circulatory values were not significantly lowered until after four weeks, 45Ca incorporation and body weight were significantly lower after only one week and 3H-proline incorporation did not fall until after eight weeks. The course of the uptake of 85Sr-microspheres and the incorporation of 45Ca were very similar. 3. Comparison of males and females. EB reduced circulatory values and 45Ca and 3H-proline incorporation and increased bone density and bone ash weight in both males and females. Conclusions. The decrease in the local bone blood flow after EB showed a significant dose-effect correlation; the decrease in circulatory values, on using the given administration method, is significant after four weeks. The inhibitory effect of EB on the bone blood flow is not sex-specific.(ABSTRACT TRUNCATED AT 250 WORDS)

Phenol sulphotransferase and uridine diphosphate glucuronyltransferase from rat liver in vivo and vitro. 2,6-Dichloro-4-nitrophenol as selective inhibitor of sulphation. Microsomal UDP-glucuronyltransferase and cytosolic sulphotransferase share many substrates, such as phenols and hydroxamic acids. In a search for a selective inhibitor of sulphation, several phenolic compounds were tested. 2,6-Dichloro-4-nitrophenol is introduced as a selective inhibitor of sulphation in vivo, having no effect on UDP-glucuronyltransferase activity. As substrate for both conjugating enzymes the phenolic drug harmol (7-hydroxy-1-methyl-9H-pyrido[3,4-b]indole) was used. In the rat in vivo 2,6-dichloro-4-nitrophenol caused almost complete inhibition of harmol sulphation after a single intraperitoneal injection (26mumol/kg) for 48h; the percentage of harmol sulphated decreased from 75% in controls to 5% in the treated rats. The percentage of harmol glucuronidated increased from 25 to 95%. Pentachlorophenol was equally effective but also highly toxic. Salicylamide had only a very-short-lasting inhibitory effect on sulphation. In vitro, 2,6-dichloro-4-nitrophenol inhibited sulphation of harmol by a rat liver postmitochondrial supernatant completely at 1mum, whereas even at 100mum it had no effect on glucuronidation of harmol. It is concluded that 2,6-dichloro-4-nitrophenol is a selective inhibitor of sulphation and, further, that its long duration of action makes it suitable for studies on the regulatory role of sulphation in some biological processes.

Rapid epidemiologic analysis of cytomegalovirus by using polymerase chain reaction amplification of the L-S junction region. A technique based on polymerase chain reaction (PCR) amplification was developed to facilitate the study of the epidemiology of cytomegalovirus (CMV). Consensus oligonucleotide primers from repetitive DNA sequences were designed to amplify interspersed repetitive sequences in an area of heterogeneity within the L-S junction region of the CMV genome, and PCR products were detected by gel electrophoresis. Purified CMV DNAs from 25 CMV isolates, 13 from members of five families in which person-to-person transmission was documented, 9 random clinical isolates of CMV, and 3 laboratory reference strains of CMV (Towne, Davis, and AD169), were analyzed. The gel electrophoretic patterns of DNA bands, or PCR profiles, produced by amplification with the L-S primers were unique for epidemiologically unrelated strains and laboratory reference strains, yet similar patterns were observed for epidemiologically related strains isolated from members of the same family. This method of rapid fingerprinting of CMV DNA within the hypervariable L-S junction region by PCR to produce strain-specific, variably sized PCR products should simplify the molecular epidemiologic analysis of CMV.

A kinetic investigation of phosphoenolpyruvate carboxylase from Zea mays. The reaction catalyzed by phosphoenolpyruvate carboxylase from Zea mays has been studied kinetically. Results of initial velocity patterns and inhibition studies indicate that phosphoenolpyruvate carboxylase has a random sequential mechanism in which there is a high level of synergism in the binding of substrates. The preferred order of addition of reactants is Mg2+, phosphoenolpyruvate, and bicarbonate. The binding of Mg2+ is at equilibrium. Values for the various kinetic parameters are KiMg = 2.3 +/- 0.4 mM, KPEP = 3.6 +/- 0.6 mM, KiPEP = 0.2 +/- 0.07 mM, and Kbicarbonate = 0.18 +/- 0.04 mM. In addition, double inhibition experiments have been performed to examine the nature of the active site interactions with the putative intermediates, carboxy phosphate and the enolate of pyruvate. Highly synergistic inhibition of phosphoenolpyruvate carboxylase was observed in the presence of oxalate and carbamyl phosphate (alpha = 0.0013). However, an antisynergistic relationship exists between oxalate and phosphonoformate (alpha = 2.75).

Inhibition of Ca-activated K+ channels from renal microvillus membrane vesicles by amiloride analogs. The effect of the K(+)-sparing diuretic amiloride and two of its hydrophobic analogs, methylisobutyl amiloride (MIA) and ethylisopropyl amiloride (EIPA), on Ca-activated K+ channels from renal microvillus membrane vesicles incorporated into planar lipid bilayers was investigated. Amiloride did not inhibit currents through Ca-activated K+ channels. MIA and EIPA, however, inhibited channel currents when added to both the internal and external solutions in concentrations between 10 and 250 microM. Furthermore, when dose-response data for channel inhibition were examined using Hill plots, Hill numbers of approximately 1.5 were found for both blockers from both sides, suggesting that the mechanism of block involves multiple inhibitory binding sites. A simple kinetic scheme is proposed that can account for the results.

Methotrimeprazine versus meperidine and dimenhydrinate in the treatment of severe migraine: a randomized, controlled trial. To compare the effectiveness of IM administration of methotrimeprazine, a non-narcotic, nonaddicting phenothiazine derivative, with that of a combination of meperidine and dimenhydrinate in the treatment of severe migraine. Double-blind, randomized, controlled trial. University hospital emergency department. Consecutive adult patients with migraine who met eligibility criteria. Random allocation to receive IM injections of either 37.5 mg methotrimeprazine (Levoprome, Nozinan) or 75 mg meperidine (Demerol) combined with 50 mg dimenhydrinate (Dramamine, Gravol). The 37 patients in each group who completed the study were similar in all demographic and clinical characteristics. There were no statistical differences in pain intensity one hour after treatment, change in pain intensity, or pain relief as measured on a visual-analog scale; need for additional analgesia; persistence of nausea or vomiting; adverse effects; or follow-up status, except for prolonged drowsiness, in the group receiving methotrimeprazine. Methotrimeprazine is comparable to meperidine with dimenhydrinate for treating severe migraine and may be considered an effective, nonaddicting, IM alternative to narcotics for the management of this problem.

Erythrocyte volume and count: a linear relation descriptive of population differences. In a sample of 215 adult males the mean red cell volume decreases linearly with increasing red cell concentration. The mean corpuscular volume and the red cell count are found uncorrelated with age of subject. Of these subjects 69 are identified as smokers and 114 as nonsmokers. Linear regression analysis shows negative linear relation for the smoking-defined groups, with slopes judged to be no different. When the regression lines are constrained to be parallel the line for smokers is displaced upward by 2.7 fl. No difference is found in mean corpuscular haemoglobin concentration or reticulocyte count. Haematocrit, haemoglobin, mean corpuscular haemoglobin are also reported. Viscosity of blood is greater in smokers. Optical determination of cell volume and area confirms the linear relation of volume and count.

Permeability of cellulosic and non-cellulosic membranes to endotoxin subunits and cytokine production during in-vitro haemodialysis. The possibility of endotoxin transfer across haemodialysis membranes remains a controversial issue. Additional concern has arisen because of the recent introduction in clinical practice of highly permeable, synthetic dialysis membranes and of bacteria-contaminated bicarbonate concentrate with potential short-term and long-term hazards for haemodialysis (HD) patients. Therefore, we performed experiments in an in-vitro dialysis recirculation system using three different types of HD membranes, namely standard regenerated cellulose (Cuprophan, CU), polyacrylonitrile AN-69 (PAN), and polysulphone F-60 (PS). When radiolabelled lipopolysaccharide (125I M-LPS) from E. coli, together with 10 micrograms/ml unlabelled LPS, was added to the recirculating solution in the dialysis compartment, radioactivity could be detected in the blood compartment after 15 min and increased progressively with time up to respectively 6.7% (CU), 10.3% (PAN), and 10.3% (PS) of initial activity on the dialysate side. The addition of albumin to the solution on the blood side led to a decreased permeability of radioactivity (7.3% vs 10.3%), compared to the absence of albumin (tested only for PS membrane). Furthermore, 73% of 125I M-LPS transferred across the PS membrane in the presence of albumin was TCA-precipitable. In contrast, free iodine (Na 125I) incubated in an albumin-containing solution did not precipitate with albumin after the addition of TCA (precipitation of only 0.6%). Moreover, kinetics of transmembranous transfer of Na-125I were strikingly different from that of 125I M-LPS. Analysis by the method of sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of the blood side solution, after LPS addition in the dialysis solution and 30 min of back-filtration, revealed the presence of several silver-stainable and autoradiographic bands of low-molecular-weight range, probably LPS fragments. Finally, the presence of LPS in the dialysate compartment led to a moderate increase in interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF) concentrations in plasma as well as in monocyte culture supernatants after isolation from recirculating normal human whole blood exposed to CU, PAN, or PS membrane. In conclusion, our study provides evidence for the permeation of low-molecular-weight LPS subunits across cellulosic and non-cellulosic HD membranes. The clinical significance, if any, of such a transfer has, however, still to be demonstrated.