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Does glycemic control of type II diabetes suffice to control diabetic dyslipidemia? A community perspective. To assess the extent to which glycemic control by itself results in satisfactory control of diabetic dyslipidemia. A population-based case series consisting of 386 Mexican Americans and 94 non-Hispanic whites with non-insulin-dependent (type II) diabetes was studied. All subjects answered questions about their medical history and care received and underwent a standardized oral glucose tolerance test and measurements of fasting serum lipid and lipoprotein concentrations. Three definitions of dyslipidemia were used: total cholesterol greater than 6.20 mM (240 mg/dl), triglyceride greater than 2.82 mM (250 mg/dl), and high-density lipoprotein cholesterol less than 0.90 mM (35 mg/dl). Despite having removed subjects receiving lipid-lowering drugs, diabetic subjects who had been previously diagnosed and were under medical care exhibited a lower prevalence of hypertriglyceridemia than those who were newly diagnosed at the time of their survey visit, suggesting that conventional management was associated with a reduced frequency of this dyslipidemia. Among previously diagnosed cases, the prevalence of dyslipidemia rose with worsening glycemic control but there was little association with type of therapy (diet only, oral agents, or insulin) or frequency of physician visits. In general, the prevalence of dyslipidemia in diabetic subjects remained higher than in nondiabetic subjects, despite hypoglycemic therapy. The results suggest that glycemic control by itself does not suffice to control diabetic dyslipidemia and that significant numbers of diabetic subjects will need direct lipid management. Clinical trials are urgently needed to define the optimum management strategy for diabetic dyslipidemia.

Assessment of different methods to detect increased autochthonous production of immunoglobulin G and oligoclonal immunoglobulins in multiple sclerosis. The formulae for immunoglobulin G (IgG) synthesis rate, IgG(loc), IgG index, and IgG extended index in determining increased autochthonous production (intra-blood-brain barrier synthesis) of IgG was assessed in 50 chronic progressive multiple sclerosis patients. The results of all four formulae clearly show elevated intra-blood-brain barrier IgG synthesis in 35 patients, 94% of whom had oligoclonal immunoglobulins detected by the method of isoelectric focusing with immunofixation and silver staining (IEF-IS). The results from the four formulae are all normal in seven patients (none have oligoclonal immunoglobulins by IEF-IS) and are discordant in eight patients (five have oligoclonal immunoglobulins by IEF-IS). Whenever intra-blood-brain barrier synthesis of IgG is suspected, IEF-IS should be used to assay for oligoclonal immunoglobulins because this method is more sensitive than agarose electrophoresis with either Coomassie blue dye or silver stain (94% vs. 74% vs. 54%).

[Veterinary pathology: a vital specialism within veterinary medicine]. Pathology is by definition an entity of major importance in medical science. Within medical care, pathologists are involved in cytopathological, histopathological and post mortem examinations. The value of post mortem examinations is discussed with reference to the value of the autopsy within human medical science. In veterinary medicine, veterinary pathology has to be incorporated in highly qualified veterinary medical care, has to participate in the quality assessment and the quality control of veterinary medical care, and has to be involved in the required continuing education of veterinarians. In addition, veterinary pathology is involved in basic research and research with regard to human health control.

The role of extracellular material in chick neurulation. II. Surface morphology of neuroepithelial cells during neural fold fusion. Changes in cell surface morphology of the neuroepithelium during fusion of neural folds in the chick were studied. As the folds were about to meet, a thick extracellular coat material (ECM) appeared between the two leading edges. Cell membranes forming the fusion area were relatively smooth and heavily coated with ECM. By contrast, the apical surface of most cells lining the wall of the neural tube was folded with much less ECM. During the contact of neural folds, ECM was displaced from the space between the two leading edges, leaving a thin, closely adherent "typical" cell surface coat. Trypsin and concanavalin A inhibited proper alignment and fusion of apposing neural folds by modifying the surface of developing neuroepithelium. Results of this study support a hypothesis that ECM may serve temporarily as an adhesive to bind together the leading edges of neural folds until establishment of more intimate contacts (junctional complexes).

Antiandrogenic effects of the pineal gland and melatonin in castrated and intact prepubertal male rats. In castrated prepubertal rats, pinealectomy enhanced the testosterone-induced growth response of the seminal vesicles and melatonin inhibited this effect in a dose-related manner. In entire animals, the serum concentration of LH was increased after pinealectomy with no significant changes in other parameters. Administration of melatonin to intact, pinealectomized rats did not affect the serum concentrations of LH or testosterone but caused a dose-related decrease in the weight of the seminal vesicles. The highest dose of melatonin tested reduced the weight of the ventral prostate gland and the uptake of radioactivity by both the ventral prostate gland and the testes after injection of [5-3H]uridine. It is suggested that the pineal gland and melatonin may exert an antagonistic effect on the biological activity of androgens administered to castrated rats and that melatonin can reduce the growth of the accessory sex organs of intact, pinealectomized rats, in spite of a high concentration of LH in the serum. The well-known inhibitory influence of systemically administered melatonin on the accessory sex organs in male rats may be due to its antagonistic effect at a peripheral level.

Characterization of the multiple catalytic activities of tartrate dehydrogenase. Tartrate dehydrogenase (TDH) has been purified to apparent homogeneity from Pseudomonas putida and has been demonstrated to catalyze three different NAD(+)-dependent reactions. TDH catalyzes the oxidation of (+)-tartrate to form oxaloglycolate and the oxidative decarboxylation of D-malate to form pyruvate and CO2. D-Glycerate and CO2 are formed from meso-tartrate in a reaction that is formally a decarboxylation with no net oxidation or reduction. The steady-state kinetics of the first two reactions have been investigated and found to follow primarily ordered mechanisms. The pH dependence of V and V/K was determined and indicates that catalysis requires that a base on the enzyme with a pK of 6.7 be unprotonated. TDH activity requires a divalent and a monovalent cation. Kinetic data suggest that the cations function in substrate binding and facilitation of the decarboxylation of beta-ketoacid intermediates.

Routes of formation and toxic consequences of lipid oxidation products in foods. Lipid oxidation in foods is initiated by free radical and/or singlet oxygen mechanisms which generate a series of autocatalytic free radical reactions. These autoxidation reactions lead to the breakdown of lipid and to the formation of a wide array of oxidation products. The nature and proportion of these products can vary widely between foods and depend on the composition of the food as well as numerous environmental factors. The toxicological significance of lipid oxidation in foods is complicated by interactions of secondary lipid oxidation products with other food components. These interactions could either form complexes that limit the bioavailability of lipid breakdown products or can lead to the formation of toxic products derived from non-lipid sources. A lack of gross pathological consequences has generally been observed in animals fed oxidized fats. On the other hand, secondary products of lipid autoxidation can be absorbed and may cause an increase in oxidative stress and deleterious changes in lipoprotein and platelet metabolism. The presence of reactive lipid oxidation products in foods needs more systematic research in terms of complexities of food component interactions and the metabolic processing of these compounds.

Alterations in the beta-adrenergic receptor system after hypothermic ischemia in hearts with preischemic beta-receptor desensitization. Although hypothermic cardioplegic arrest is a basic method of myocardial protection in cardiac surgery, the beta-adrenergic receptor (BAR) system has been little investigated in the heart subjected to hypothermic ischemia. Additionally, although the hypothermic arrest is often induced in hearts with preischemic desensitization of the BAR system by preceding congestive heart failure, the functional state of the BAR system after ischemia has not been studied in these hearts. We investigated alterations in the BAR system after hypothermic ischemia in normal rat hearts and in those with preischemic desensitization of the BAR system produced with isoproterenol (ISP: 400 micrograms/kg/hr for 24 hr). Both normal and BAR-desensitized hearts were isolated and subjected either to 40 min of hypothermic (10 degrees C) global ischemia followed by 40 min of reperfusion or subjected to time-matched aerobic perfusion with modified Krebs-Henseleit solution. At the end of perfusion (1) BAR binding properties with [3H]CGP-12177 and adenylate cyclase activity were measured in crude membrane fraction and (2) the inotropic response to ISP (delta LV + dP/dtmax) was evaluated in an isovolumetric contracting heart preparation. Following reperfusion, normal hearts without desensitized BAR showed a higher Bmax value than those of nonischemic time-matched hearts (41.8 +/- 3.1 vs 35.4 +/- 2.4 fmole/mg protein, P less than 0.05), whereas the Kd value was in a similar range in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet-activating factor stimulates eicosanoid production in cultured feline tracheal explants. Eicosanoids have been shown to be major mediators of airway inflammation. Platelet-activating factor (PAF), a potent bronchoconstrictor and stimulator of respiratory mucous secretion, may mediate some of its effects via eicosanoid production. To explore eicosanoid generation by cultured feline tracheal explants, eicosanoids were measured following PAF stimulation. After labeling the explants with [3H]arachidonic acid, supernatant from control and PAF treated explants was fractionated by reverse phase high-performance liquid chromatography (HPLC). The resulting elution pattern suggested the release of arachidonic acid (AA), 15-hydroxyeicosatetraenoic acid (HETE), leukotriene (LT)B4, C4, prostaglandin (PG) D2/E2/F2 alpha, and 6-keto-PGF1 alpha. Radioimmunoassay (RIA) following HPLC resolution confirmed that PAF induced a significantly increased release of peptido-leukotrienes, PGD2, PGE2, PGF2 alpha, LTB4, and 5-HETE, as well as thromboxane (TX) B2. The most remarkable increase was LTC4/D4/E4 (15 x control) and PGD2 (4 x control). The PAF antagonist Ro 19-3704 had an inhibitory effect on the PAF-stimulated release of peptido-leukotrienes. We conclude that PAF stimulates the production of a variety of lipoxygenase and cyclooxygenase pathway metabolites in feline airways.

Chronic copper poisoning in sheep grazing pastures fertilized with swine manure. Several pregnant ewes developed an acute hemolytic crisis and died. Liver and kidney copper concentrations were high, confirming chronic copper poisoning as the cause of death. Feed and water samples that the affected ewes had been consuming did not contain excess copper. Because swine manure slurry had been applied to the pasture where the sheep had grazed, a copper analysis was conducted on soil and forage samples from this field. High copper concentrations were detected in the soil and forage samples from the slurry pasture. Most sheep producers are aware of the catastrophic consequences that result when feeds containing copper and insufficient amounts of molybdenum are fed to sheep. However, producers and veterinarians often are unaware of some of the subtle sources of copper. Most of the copper that is added to swine and poultry feeds as growth promotants passes through the gastrointestinal tract unabsorbed and remains in the waste material. Pastures that have copper-containing waste material, but no molybdenum applied, can produce the same fatal results as giving sheep feed supplemented with copper but containing no molybdenum.

[Liver resection in children. Experience in 10 cases]. The authors report their experience with ten major hepatic resections; six on the right lobe and four on the left. Six of the resected masses were hepatoblastomas, two were hamartomas, was a hemangioma, and the last one a pheochromocytoma of the right adrenal gland with invasion to the liver next from the affected site. The four patients with major hepatic resection of the left lobe are at present alive, ranging from two months to two years after surgery. Of the six patients with major resection of the right lobe, three died during surgery, another one died late post-operatively and one died a year after surgery from generalized metastasis of an hepatoblastoma. The sixth patient is alive with no complications, four months after surgery. The authors used two types of hepatic resections and they make some recommendations for achieving better results in this type of operation.

[Proof of the effectiveness of compression by nuclear medicine, plethysmography and venous pressure measurement]. 1) In a lying down position a) immediately and under rapid compression, one observes a reduction in muscle flow as well as a reduction of the perfusion of the foot and of the systolic pressure of the big toe. After disinfiltration of the leg by compression, the muscular flow more than doubles (clearance with Xenon 133). b) a reduction in the venous blood volume of the limb by about 1/3. c) an increase in the venous circulation speed by about 1.5 times (tracer in a vein of the back of the foot). The degree of change is depending from the pressure of the compressive bandage (in a lying down position, between 20 mmHg and a maximum of 40 mmHg). 2) while walking a) shortening of the pathological refluxes in the veins of the lower limbs (directional Doppler). b) improvement of the pump output (increase inthe volume of blood pumped upwards), and a variable influence of the peripheral venous pressure (simultaneous methods of plethysmography of the foot and the venous pressure). c) reduction of edema, improvement of the disturbed lymphatic flow (plethysmography, lymphotropic tracers with radioactive marking).

Complete amino acid sequence of subunit e of rat liver mitochondrial H(+)-ATP synthase. Subunit e of H(+)-ATP synthase from rat liver mitochondria was isolated from the purified enzyme by reverse-phase high-performance liquid chromatography. The amino acid sequence of the subunit was determined by automated Edman degradation of the whole protein and derived peptides. The nucleotide sequence of the import precursor of subunit e of rat liver H(+)-ATP synthase was determined from a recombinant cDNA clone isolated by screening a rat hepatoma cell line H4TG cDNA library with a probe DNA. The sequence was composed of 289 nucleotides including a coding region for the import precursor of subunit e and noncoding regions on the 5'- and 3'-sides. The possible import precursor of subunit e and its mature polypeptide deduced from the open reading frame consisted of 71 and 70 amino acid residues with molecular weights of 8254 and 8123, respectively. Subunit e is a basic hydrophilic protein with an isoelectric point of 9.78. The sequence of the rat subunit e is highly homologous with that of subunit e of bovine heart, but has no homology with any subunit of bacterial or chloroplast H(+)-ATP synthase. The function of subunit e is unknown. However, a homology search in the database of the National Biomedical Research Foundation revealed that residues 34-65 of subunit e are homologous with residues 90-117 of troponin T, and with residues 529-561 of h-caldesmon and residues 289-319 of l-caldesmon, which are the homologous sequences corresponding to the Ca(2+)-dependent tropomyosin-binding region of troponin T.

Prolapsing right atrial myxoma: clinical and heamodynamic considerations. A 22-year-old woman with a right atrial myxoma prolapsing to the right ventricle is described. The haemodynamic findings were similar to those of cases of prolapsing myxoma of the left atrium; a notching on the ascending limb of the right ventricular pressure curve, and an initial negative, irregular deflection on the pulmonary artery pressure curve with a pronounced rise in the mean right atrial pressure (18 mmHg) were found. On deep inspiration there was a significant deepening of the y descent from 12 mmHg to 2 mmHg, indicating a changing, dynamic obstruction of the right ventricle inflow tract. These haemodynamic features can be helpful in the diagnosis of prolapsing right atrial myxoma.

Flunitrazepam, a new benzodiazepine compound in general anaesthesia. Clinical and statistical considerations on the first thousand cases. Flunitrazepam, a derivative of benzodiazepine was used for induction and maintenance of anaesthesia in 933 patients. The induction dose was from 1,786 to 2,053 mg. The total dose of 2-2.66 mg was sufficient for maintenance of hypnosis for about 2 hours. The undesirable side effects were very rare. The average time of hypnosis after a single dose of flunitrazepam was 50.1 sec. The sedative action of the drug lasted for some time after regaining of consciousness. In most patients there was no need for administration of analgetics during first 24 hours after the operation. The authors believe that surgical anaesthesia will greatly benefit from this drug.

[Serotoninergic and adrenergic factors influencing the ovulation and reproduction in the rat]. The action of 5-hydroxytryptamine (5-HT) on ovulation and reproduction in female rats with unique or repeated treatments of p-chlorophenylalane (p-CPA) was studied under different conditions of illumination. Histological studies were carried out on the tube and ovaries, controls of the ovarian cycle and of inseminations produce by vaginal deposits. An evaluation has been made of the insemination, fecundation, number of embryos, ovarian cycle and in anothers series hypothalamic determinations of 5-HT were carried out. In one group of rats the effect of intracerebrally administration (n. accumbens septi) 6-hydroxydopamine (6-OH-DA) (250 mug) on ovulation was studied. The administration of a unique doses of p-CPA (300 mg/Kg) induces an inhibition of the reproductive cycle in all its phases and in all the rats. Which repeated doses (100 mg/Kg) reproduction was inhibited in rats maintained under continuous illumination and under continuous darkness. Ovulation studies revealed that follicle rupture, was inhibited with a unique dose of p-CPA (300 mg/Kg). The histological study showed, marked luteinitation of ovaries. The ovarian cycle after a unique dose of p-CPA showed continuous diestrus phases. The results may indicate that a decrease of cerebral 5-HT producing a hormonal change which leads to the disappearence of the oestrogenic phase, with consequent inhibition of rupture and decrease in receptivity of the female rat. The administration of 6-OH-DA in the n.accumbens septi inhibited follicle rupture giving rise to manifest lutteynitation. A further study on the degeneration of nerve fibres, suggests the posssibility of adrenergic influence in ovulation of septal structures.

Visual target acquisition and tracking performance using a helmet-mounted sight. Experiments have been conducted on human subjects to assess the efficiency with which a helmet-mounted sighting system can be used to locate and track target sources in the horizontal plane. In the first experimental condition, in which the sight was aligned with discrete stationary target sources, the latency between target presentation and final target location was in the 2-4 s range, dependent upon the amplitude of target offset and the rate of head movement. In the second condition, subjects were instructed to track a sinusoidally oscillating visual image with the sight. Tracking performance was found to be impaired when the frequency of oscillation was increased beyond 0.8-1.0 Hz. Recording of eye movement during both experimental conditions indicated that the impairment of performance could, in part, be attributed to involuntary eye movements consequent upon stimulation of the vestibulo-ocular reflex by the head turning movements.

Plasma lipid abnormalities in the miniature poodle with progressive rod-cone degeneration. The miniature poodle with progressive rod-cone degeneration (prcd) is a model for human retinitis pigmentosa (RP). Since previous studies from several laboratories have shown abnormalities in plasma lipids in human RP, we examined the plasma lipids of prcd-affected animals. Fasting blood was drawn on three separate occasions from affected and control miniature poodles and on one occasion from normal Irish setters and those affected with a different inherited retinal degeneration (rod-cone dysplasia). Plasma phospholipids from prcd-affected animals had significantly lower levels of docosahexaenoic acid (22:6 omega 3) and cholesterol, compared to control miniature poodles. No differences were observed in plasma levels of phospholipids, vitamin E, or vitamin A, and no lipid differences were found between control and affected Irish setters. The ratios of 22:5 omega 3 to 22:6 omega 3 and of 22:4 omega 6 to 22:5 omega 6 were significantly elevated in prcd-affected poodles compared to controls. Since the conversion of 22:5 omega 3 to 22:6 omega 3 and of 22:4 omega 6 to 22:5 omega 6 is catalysed by a delta 4-desaturase, these results are consistent with a defect in desaturase activity in the prcd-affected poodle.

The microtubule-associated protein tau forms a triple-stranded left-hand helical polymer. High resolution transmission electron microscopy (TEM) has shown that bovine tau are 2.1 +/- 0.2-nm diameter filaments which are triple-stranded left-hand helical structures composed of three 1.0 +/- 0.2-nm strands. The reported amino acid sequence of human and bovine tau have been computer processed to predict secondary structure. Within the constraints imposed by the images, the secondary structure models and other structural information have been used to calculate tau's maximum and minimum length. The length calculations and secondary structure form the basis for image interpretation. This work indicates that each approximately 1.0-nm strand is a tau polypeptide chain and that the approximately 2.1-nm filament is composed of three separate tau chains (tau3). Bovine tau length measurements indicate that tau trimer filaments are generally longer than a fully extended tau monomer. These measurements indicate that each trimer, tau3, is joined with other trimers to form long tau polymers, (tau3)n. An inverse temperature transition has been found in the circular dichroism spectrum of tau indicating that its structure is less ordered below 20 degrees C and more ordered at 37 degrees C. The implications of this phenomenon with respect to tau's temperature-dependent ability to reconstitute microtubules is discussed and a mechanism for the possible abnormal aggregation of tau into neurofibrillary tangles in Alzheimer's disease is proposed.

Seasonal study of the adrenal gland of some Indian avian species. Adrenal glands of eight Indian species of birds, namely Columba livia, Passer domesticus, Corvus splendens, Acridotheres tristis, Acridotheres ginginianus, Milvus migrans, Francolinus pondicerianus and Bubulcus ibis were examined during the sexually active and inactive phases of their annual reproductive cycles. Excepting A ginginianus and M. migrans, among members of either sex of the remaining six species the weight of the adrenal gland increases during the period of sexual activity. Histologically, the interrenal tissue of these birds could be divided into a peripheral subcapsular zone and a central zone. The cytochemical content of these two zones varies between sexual activity and inactivity. In sexually active birds of both sexes, interrenal cells of the central zone exhibit an increased concentration of alkaline phosphatase, glycogen, acid mucopolysaccharides and gross lipids, while in the subcapsular interrenal cells there is a prominent increase of ascorbic acid content. Cytochemical contents of chromaffin cells remain unchanged except acid phosphatase, which increases during the sexually active phase.

[Clinical pattern of malignant brain tumors in patients over 50 years of age]. On the basis of a material of 180 cases from a hospital department of neurology the clinical course of malignant brain tumours in patients aged over 50 years was outlined. In 154 cases the clinical diagnosis was confirmed by histological investigations. The study showed that intracranial raised pressure syndrome was rather infrequent in this age group (5% in this material), with the exception of headaches. The most frequent manifestations were psychic changes and neurological deficit signs (hemiparesis). The course of the disease was frequently acute with rapid increase in the intensity of symptoms and signs. The cases unrecognized clinically accounted for 14.4% of this material. From the admission to the hospital a very rapid progression of manifestations was observed which seemed to be connected with association of blood flow disturbances.

Localization of catecholamines in the eyes and other tissues of Aplysia. A green fluorescence indicative of catecholamines (CA) was localized in the secondary cells (nonreceptor neurons), neuropile and optic nerve of the eye and other tissues in Aplysia by using the formaldehyde-induced fluorescence method for the demonstration of biogenic amines. The specificity of the induced fluorescence was confirmed by its absence in tissue not exposed to formaldehyde vapor, relatively rapid decay upon exposure to UV light and its chemical reduction by sodium borohydride. The fluorescence was greatly reduced in eyes treated with reserpine (depletes serotonin and catecholamines). Furhter confirmation that the green fluorescence in the eye was due to a CA and not to serotonin was obtained by showing that it was decreased or eliminated by alpha-methyl-para-tyrosine (an inhibitor of catecholamine synthesis), increased by incubation in dopamine and exhibited a peak emission (470 nm) characteristic of CA fluroescence. CA fluorescence was also observed in the neuropiles of the cerebral, pedal, pleural and parieto-visceral ganglia and in cells in the pedal ganglion, statocyst, mantle, anterior tentacles and siphon. The finding of CA in secondary neurons of the eye was unusual since CA-containing cells have not been observed in other gastropod eyes. The distribution of CA in Aplysia, in tissue other than the eye, is similar to that of other gastropod molluscs.

Identification of residues in VP2 that contribute to poliovirus neutralization antigenic site 3B. Amino acid substitutions were placed at residues 74, 243, and 246 in capsid protein VP2 of poliovirus serotype 1, using site-specific mutagenesis methods. The proximity of these residues to those previously identified in neutralization site 3B suggests that these residues may also contribute to neutralization site 3B and potentially be under antibody selective pressure to mutate. However, sequence analyses of independent serotype 1 isolates indicate high sequence conservation at these residues, suggesting selective pressures are present within the virus to maintain sequences within these loop regions. All viable mutants display partial or complete resistance to neutralization by the site 3B neutralizing monoclonal antibodies. Cross-neutralization data with the site-specifically generated viral mutants confirm that these residues do indeed contribute to forming neutralization site 3B and also identify the participation of a new loop region within site 3B. However, many amino acid substitutions generate nonviable virus mutants and even conservative amino acid substitutions produce growth-compromised virus mutants. These data suggest that previous definition of neutralization antigenic sites by isolation of neutralization resistant mutants favors detection of viable mutant viruses with more normal growth characteristics and is inherently biased against detection of neutralization antigenic sites formed by residues critical for other stages of virus replication.

Ultrastructural similarities between epidermal Langerhans cell Birbeck granules and the surface-connected canalicular system of EDTA-treated human blood platelets. Birbeck granules characterize under the electron microscope epidermal Langerhans cells. These distinctive pentalaminar organelles are indeed not detectable in the possible precursors of human Langerhans cells and tend to disappear in cultured human Langerhans cells. The mechanisms that lead to the appearance of Birbeck granules in epidermal Langerhans cells and to their later disappearance still remain unknown. In the present study we show that the more or less dilated elements of the surface-connected canalicular system of human blood platelets collapse after EDTA treatment. Made up of two parallel limiting membrane and central irregular striated density, these elements show great ultrastructural similarities with the Birbeck granules of human epidermal Langerhans cells. These platelet morphologic changes i) are directly dependent on the EDTA-induced dissociation of the glycoprotein GP IIb-IIIa, the platelet-specific calcium-dependent heterodimer complex, member of the beta 3 integrin subfamily (alpha IIb beta 3) and ii) apparently result from a cross-linking of the dissociated glycoproteins. These findings lead us to propose that in the same manner cells of the Langerhans lineage, on reaching the epidermis, will find themselves in contact with an epidermal specific ligand. Interactions between this epidermal ligand and Langerhans cell receptors could then induce, all along the circuit taken by the ligand-receptor complexes, morphologic modifications, i.e., appearance of structures of Birbeck granule type.

[Incidence of myocarditis in patients with dilated cardiomyopathy]. We performed right ventricular endomyocardial biopsies in 23 patients with dilated cardiomyopathy aged 45 +/- 14 years. All patients had congestive heart failure of unknown etiology dating up to one year before the procedure (57% less than 3 months). NYHA functional class was II in 5, III in 12 and IV in 6 patients. All patients had evidence of systolic dysfunction and a dilated left ventricle (LV diastolic dimension 68 +/- 11 and systolic dimension 55 +/- 11). Definite evidence of myocarditis, based on findings of inflammatory infiltrate and cellular damage, was found in 6 patients (26%), borderline myocarditis in 9 and abnormalities consistent with dilated cardiomyopathy in 8. The incidence of myocarditis here reported is lower than previously figures based on findings of more than 5 lymphocytes per high power field. In this series, clinical and functional aspects of heart failure did not differ in patients with or without evidence of myocarditis.

Non-selective and selective beta-1-adrenoceptor blocking agents in the treatment of hyperthyroidism. Treatment for one month with propranolol or atenolol, a selective beta-1-adrenoceptor blocking agent, was evaluated in 20 hyperthyroid patients. The patients improved to the same extent on either drug, as shown by a clinical diagnostic index. Basal metabolic rate decreased by 11% during both treatments, while it was unchanged in seven untreated hyperthyroid controls. Thyroxine concentration did not change during any treatment. During propranolol treatment T3 decreased from 4.6 to 3.9 nmol/l, while no changes were observed during atenolol treatment or in the control group. No significant changes were seen in free T4, free T3 or rT3 concentrations on any treatment, although free T3 was observed to decrease slightly during propranolol treatment. Thus, the improvement of the clinical symptoms of hyperthyroidism cannot be explained by diminished thyroid hormone concentrations in serum, since the reduction was small during propranolol and absent during atenolol treatment.

Lifetime occupational physical activity and prostate cancer risk. The authors compared the lifetime occupational physical activity of 452 prostate cancer cases identified through the population-based Hawaii Tumor Registry and 899 population controls interviewed from 1981 to 1983. Each job reported was classified into one of five levels of physical activity using published sources. Among men aged 70 years or older, a negative association was found between prostate cancer risk and proportion of life spent in jobs involving only sedentary or light work. Compared with men never employed in such jobs, men who spent more than 54% of their life in these jobs had an odds ratio of 0.5 (95% confidence interval 0.3-0.9). This negative association was dose-dependent, consistent across ethnic groups, and unrelated to socioeconomic status, dietary risk factors, or job-related chemical exposures. The findings for younger men were less clear, but not inconsistent with those for older men. Surprisingly, no association was found with years spent in moderately active or very active jobs in either age group. Although inconclusive, these results suggest that physical activity may be positively associated with the risk of prostate cancer, but this association is likely to be weak and indirect.

Characterization of anti-Z-DNA antibody binding sites on Z-DNA by nuclear magnetic resonance spectroscopy. Two monoclonal anti-Z-DNA antibodies, Z22 and Z44, were shown to bind to the oligonucleotides, d(CG)2 and d(CG)3, and to interact with different parts of the helix. 1H nuclear magnetic resonance spectroscopy showed that Fab fragments stabilize an ordered structure in the tetranucleotide d(CG)2. Nuclear Overhauser effects measured in the presence of Z22 Fab indicate a syn conformation of guanine residues of d(CG)2. Intermolecular transfer of saturation between the Fabs and bound d(CG)3 was detected by a saturation of the protein spectrum and observation of changes in the DNA spectrum. Antibodies with deuterated aromatic amino acids were prepared to eliminate the protein aromatic resonances and thereby allow a more detailed analysis of the transfer to the DNA base protons. The greatest transfer with Z44 was to the dC-5 protons although all of the base protons interact with this antibody. Little, if any, transfer to the DNA base protons was observed with Z22. These results are consistent with a Z44 binding site on the convex surface of the Z-helix (analogous to the major groove of B-DNA) and a Z22 binding site on the sugar-phosphate backbone.

[A new device for phototherapy of neonatal jaundice]. The effectiveness of a new device for phototherapy in the treatment of nonhemolytic hyperbilirubinemia (Wallaby Phototherapy System) was evaluated. 46 healthy term infants, appropriate for gestational age and with serum bilirubin > 12 mg/dl in the first 3 days of life or > 15 mg/dl after 3rd day were randomly assigned to a treatment group (24 hours of light exposure with Wallaby Phototherapy System) and to a control group (any treatment for hyperbilirubinemia). Body temperature, weight, feeding and hydration were recorded during the study period. Serum bilirubin and haematocrit were done every 12 hours in all babies. In the treated group we found a decrease of 5.1% and of 7.8% at 12 and 24 hours, while an increase of 3.37% and of 2.9% at 12 and 24 hours was found in the control group. After 24 hours the serum bilirubin level was significantly lower in the treated group than in the control group (p < 0.05). No newborn of the treated group needed conventional phototherapy versus 4 control infants (17.4%). The conclusion of our study is that the Wallaby System is useful in the treatment of neonatal nonhemolytic hyperbilirubinemia even if its effectiveness for higher bilirubin levels has still to be tested.

Stabilisation and development of the hip after closed reduction of late CDH. We used ultrasound to investigate the anatomy and stability of the hip during the phase of joint stabilisation after closed reduction of unilateral late CDH in 15 infants aged from two to 15 months. Conservative treatment by splintage in abduction led to complete stability in all hips in from three to 13 weeks. Immediately after reduction, interposed soft tissue caused lateralisation of the femoral head, but this progressively disappeared, and the initially smaller femoral head on the dislocated side regained normal size. Ultrasonic evaluation of the hip in late CDH is a valuable and safe tool; it reduces the need for radiographic examination and improves treatment by visualising the actual pathology. The more frequent use of ultrasound can reduce the need for open reduction in the age group that we studied.

[From pseudopregnancy to anorexia nervosa]. Translated in the primeval environment where humanization evolved during millions of years (man's environment of evolutionary adaptation, according to Bowlby), the characteristic behaviours of anorectics and bulimics do not look unfavourable but on the contrary adaptive, helping to the survival of the group or kinship (hyperactivity, altruistic feeding, etc.). Analogies, indeed homologies, exist in many animal species, distant or closely related to us (social insects, birds, mammals including primates) observed in nature. It concerns altruistic behaviours described among individuals, for the most part females, referred to as allomothers (aunts) or helpers (co-operative breeding) in ethological terms. From this evolutionary perspective, a biological genetic basis would exist in anorexia and bulimia, as a component of a phylogenetic inheritance of the K-selection strategy of reproduction. At the present time, anorexia would be a pathological extreme of this strategy, whereas pseudocyesis would be, on the contrary, one of the r-selection. Diverse and varying sociocultural and demographic conditions prevailing in modern world would revive either of these phylogenetic programs of reproductive strategies, leading as the case may be, to adaptive or pathological reproductive or helping behaviours.

Ontogeny of active avoidance in the rat: learning and memory. Ontogenetic development of active avoidance learning, extinction and retention was studied in rats. The learning of a 1-way active avoidance was most rapid between Weeks 4 and 6, although some slight gender-related differences were evident. No such unambiguous development was detected in forced extinction. The 24-hr retention of avoidance peaked at the age of 4 weeks whereas 1-month retention was best in animals trained at the age of 8 weeks. The retrieval of memory trace also had best values at these ages. Retention of forced extinction was found to peak in 6-week animals. The existence of developmental "critical periods" must be considered cautiously as various functions have different time courses depending upon the chosen parameters in assessment.

Coronary artery bypass operation in dialysis patients. To analyze the short- and long-term morbidity and mortality among maintenance dialysis patients who have undergone coronary artery bypass operations, we identified 25 such patients at the Mayo Clinic and three recently published large single-center studies that provided sufficient detail for meaningful comparison. Two independent observers reviewed the new information with regard to pertinent historical, clinical, and laboratory data. The perioperative mortality was 20%. Among the perioperative survivors, 1- and 2-year survival rates were 95% and 77%, respectively. The 3-year actuarial survival was 70%. Uniformly, the symptoms diminished, and the need for antianginal medication was decreased. In the three other large published series, the perioperative mortality ranged from 3 to 20%, and coronary artery bypass performed earlier after the onset of the symptoms seemed to result in a lower perioperative mortality. We conclude that elective coronary artery bypass in dialysis patients is associated with acceptable short-term morbidity and mortality and effective relief of symptoms. Surgically treated patients may have a survival advantage. Thus, we advocate aggressive early investigation and surgical treatment of these patients.

Incorporation of chimeric gag protein into retroviral particles. The product of the Rous sarcoma virus (RSV) gag gene, Pr76gag, is a polyprotein precursor which is cleaved by the viral protease to yield the major structural proteins of the virion during particle assembly in avian host cells. We have recently shown that myristylated forms of the RSV Gag protein can induce particle formation with very high efficiency when expressed in mammalian cells (J. W. Wills, R. C. Craven, and J. A. Achacoso, J. Virol. 63:4331-4343, 1989). We made use of this mammalian system to examine the abilities of foreign antigens to be incorporated into particles when fused directly to the myristylated Gag protein. Our initial experiments showed that removal of various portions of the viral protease located at the carboxy terminus of the RSV Gag protein did not disrupt particle formation. We therefore chose this region for coupling of iso-1-cytochrome c from Saccharomyces cerevisiae to Gag. This was accomplished by constructing an in-frame fusion of the CYC1 and gag coding sequences at a common restriction endonuclease site. Expression of the chimeric gene resulted in synthesis of the Gag-cytochrome fusion protein and its release into the cell culture medium. The chimeric particles were readily purified by simple centrifugation, and transmission electron microscopy of cells that produced them revealed a morphology similar to that of immature type C retrovirions.

Immunophenotyping of 515 cases of acute lymphoblastic leukemia in China. Using cell surface markers and a panel of monoclonal antibodies, 515 cases of acute lymphoblastic leukemia (ALL) were immunophenotyped. T cell type ALL (T-ALL), non-T cell type ALL (Non-T-ALL) including common ALL (C-ALL), Null-ALL and B cell type ALL (B-ALL) were found. These major subtypes of ALL were further divided according to their phenotypes in detail. It was noticed that the phenotypes of these subtypes of ALL reflected basically the phenotypes of normal T or B cells at various differentiation stages or certain population of lymphocytes. The diagnosis of cell lineage was more precise when based on immunophenotyping than morphological description. The combination of morphological and immunological classification can improve the diagnosis of acute leukemias. In addition, it was observed that the immunophenotyping was relevant to clinicopathologic features, responses to therapy and prognosis of ALL patients. The incidences of major subtypes of ALL, the age distribution of ALL subsets and male sex bias with T-ALL in Chinese are discussed.

Detection of clinically significant prostate cancer by transrectal ultrasound-guided systematic biopsies. Systematic biopsies are a useful, sensitive means to detect carcinoma of the prostate. However, multiple biopsies pose a risk for detecting clinically insignificant prostate cancer, that is those cancers less than 0.5 cc in volume, which occur in approximately 32% of all white men more than 50 years old. Systematic biopsies were positive for cancer in 442 of 816 patients and 60 (14%) demonstrated only a minute focus of cancer (3 mm. or less) in 1 of the 6 biopsy specimens. In 27 patients with these minute foci who underwent radical prostatectomy a wide range of cancer volumes was observed; 30% of these 27 cancers were less than 0.5 cc (15% less than 0.2 cc) and may not have required therapy. Thus, the overall risk of detecting an insignificant cancer is 4.0% with systematic biopsies. Performance of confirmatory biopsies in patients with a minute focus (3 mm. or less) of cancer on initial systematic biopsies resulted in cancers less than 0.5 cc being removed in only 1 of 10 radical prostatectomies (10%, none was less than 0.2 cc). Thus, with the addition of confirmatory biopsies the risk of detecting insignificant cancer is 1.4%. Conservative management is recommended for patients without significant cancer on repeat biopsies in whom initial biopsies have revealed only a minute focus of cancer in 1 of the biopsy cores. We believe that concern is also warranted for patients who have 3 mm. or less of cancer demonstrated by several nonsystematic biopsies directed at a suspicious hypoechoic lesion in whom the digital rectal examination is normal.

Ventricular function before and after direct revascularization surgery. A proposal for an index of vascularization to correlate angiographic and ventriculographic findings. In order to determine the effect of direct bypass surgery on the total coronary arterial supply to the heart, a numerical construct was devised to incorporate the development of new obstructive lesions and the presence of patent or nonpatent grafts. This construct, termed a vascularization index (VI), was used to evaluate left ventricular function and anginal symptoms after coronary artery bypass surgery in 56 patients. Patients with an increase in local or total arterial blood supply (positive delts VI) often had similar directional changes in segmental wall motion and ventricular ejection fraction. Patients with a decrease in local or total arterial blood supply (negative delta VI), due to either nonpatent grafts or progression of atherosclerotic disease, also usually had similar directional changes in segmental wall motion and ventricular ejection fraction. (Although nearly all patients reported a decrease in anginal symptoms after surgery, delta VI could not identify degree of improvement.) Use of an integrated approach in describing pre and postoperative myocardial blood supply appears to be the most reliable method of explaining changes in left ventricular function.

[The possibility of elaborating conditioned reflexes on the basis of emotional reactions evoked by electrical stimulation of limbic structures]. In experiments on cats with chronically implanted electrodes a conditioned stimulus (200 c/s tone) was paired with electrical stimulation of limbic structures, which produces pronounced emotional behaviour: defensive, aggressive, alimentary or drinking reactions. It has been shown that conditioned reactions are not elaborated on the basis of electrical stimulation, which activates alimentary, drinking or aggressive behaviour. Neither is a conditioned reflex formed to the combination of sound and stimulation of the brain structures, which inhibits alimentary behaviour. A distinct conditioned fear reaction sets in as a result of combination of sound and electrical stimulation of brain structures, which evoke defensive behaviour. The data obtained are analyzed in the light of the significance of natural requirements of the organism for the elaboration of conditioned reflexes.

Acidic amino acids evoke a smaller [Ca2+]i rise in GABAergic than non-GABAergic hippocampal neurons. Changes in intracellular calcium concentration ([Ca2+]i) in response to topical application of the glutamate agonists N-methyl-D-aspartate (NMDA), or amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were measured in cultured rat hippocampal neurons loaded with Fluo-3 and visualized in a confocal laser scanning microscope. These neurons were subsequently stained for the presence of the enzyme marker for gamma-amino butyric acid (GABA), glutamate decarboxylase (GAD). GAD-positive, putative interneurons were less responsive to NMDA and AMPA than GAD-negative neurons. The time course of the rise and decay of [Ca2+]i was similar in the two groups of neurons. Also, there was no clear difference in the shape and size of these two neuron groups indicating that the difference between them is not due to diffusion distances. These data indicate that interneurons are probably more able to handle a calcium load than other neurons, a difference that may underly their resistance to treatments which cause degeneration of other neurons in the hippocampus.

[The interaction of growth hormone secretion and gonadal function in adolescents with delayed physical development]. The studies conducted in adolescents with physical underdevelopment allowed a conclusion on reduced anabolic processes particularly growth process at the expense of both STH and sex steroids: T and E2. Studies of sex steroid and gonadotrophic hormone concentrations in blood serum revealed dysfunction of the hypothalamo-hypophyseal-gonadal system in this group of patients. Evaluation of androgen receptor level in protein cytosol fraction from the pubic skin of undersized youths with delayed sexual development demonstrated its significant reduction against the control group that may be explained by incomplete ability for androgen receptor synthesis due to relatively low T-level and its biologically active free fraction and low sensitivity of target tissues to androgens as a result of dissociation between functional activity of STH and T.

Studies on immune tolerance to heat-aggregated human IgG in rabbits: its relevance to the production of rheumatoid factors. Rabbits neonatally tolerized with native monomeric human IgG and subsequently immunized with heat-aggregated human IgG emulsified in Freund's complete adjuvant, at a time when B cells but not T cells should have spontaneously recovered from tolerization, resulted in the production of an antibody resembling human rheumatoid factors directed against a single antigenic determinant in the Fc region of the IgG molecule. Rabbits immunized in an identical fashion after adult tolerization treatments failed to respond during the period corresponding to B-cell tolerance, but subsequently produced antibody or similar specificity to that produced by neonatally tolerized animals. These results indicate that no completely new antigenic determinants are created on heat aggregation of IgG, but there appears to be some potentiation of immunodominance of an already existing determinant. A possible mechanism for the production of rheumatoid factors in rheumatoid arthritis is suggested.

Coronary arteriography: indications and pitfalls. Selective coronary arteriography has become an unusually useful technique in evaluating patients with known or suspected ischemic heart disease. The contribution of F. Mason Sones in developing the technique and in emphasizing that properly performed studies in experienced hands can be done at an acceptable risk cannot be overemphasized. Although the study can give information only on the anatomical aspects of the disease, it has remarkably broadened ouo understanding of the whole spectrum of coronary arteriosclerosis and ischemic heart disease. This is related to the fact that the method has provided the opportunity to study an extraordinarily large number of patients representing virtually every clinical subset of the disease. The importance of nonanatomical factors, better prognostic information about the disease, and more complete understanding of the hemodynamic ocrrelates and mechanisms of drug action have resulted from investigative studies using coronary arteriographic methods. Because ischemic heart disease is such a complex and variable entity, it is important to stress that coronary arteriography and left ventricular angiography can provide only anatomical information, and that the method has significant but ordinarily recognizable limitations. Some of these limitations are technical and are not important considerations in experienced hands in well-run laboratories. Other problems are inherent in the anatomical complexity of the disease and the coronary circulation. Hence, appropriate emphasis on the details of the patient's history, including risk factors and age, as well as other selected clinical laboratory studiies, such as exercise electrocardiography, are important in assessing the patient's total problem. Because of these factors, the greatest value of coronary arteriography is realized when it is performed as part of a thoughtful, detailed--and highly individualized--evaluation of the patient.

Electrocardiographic and antiarrhythmic effects of intravenous amiodarone: results of a prospective, placebo-controlled study. The antiarrhythmic efficacy of intravenously administered amiodarone was examined in a prospective, randomized, placebo-controlled study that involved 77 patients after coronary artery bypass surgery. Amiodarone was given after surgery in a loading bolus of 300 mg for 2 hours followed by 1200 mg every 24 hours for 2 days and 900 mg every 24 hours for the next 2 days. Amiodarone suppressed both supraventricular and ventricular arrhythmias within 12 hours after the start of therapy. Particularly, the incidence of atrial fibrillation (5% vs 21% in the control group; p less than 0.05) and of nonsustained ventricular tachycardia (3% vs 16%; p less than 0.05) was reduced by amiodarone. Heart rate was slowed (p less than 0.001) and repolarization--as judged by JTc interval--was prolonged compared with the control group (p less than 0.01). In two patients, amiodarone infusion was stopped because of excessive QTc prolongation. No detrimental hemodynamic effects of the drug were observed. Thus the intravenous administration of amiodarone appears to be suitable for patients in whom rapid suppression of symptomatic supraventricular and ventricular arrhythmias is warranted in the presence of left ventricular dysfunction.

[A ruptured aneurysm in the hypoplastic proximal anterior cerebral artery (A1 portion); case report]. A case of ruptured aneurysm in the hypoplastic proximal anterior cerebral artery (A1 portion) is reported. This 25-years old man complained of the sudden onset of severe headache and vomiting on January 11, 1989. He was referred to our hospital on the same day, and CT scan revealed subarachnoid hemorrhage. Cerebral angiography on the next day revealed an aneurysm in the hypoplastic A1 portion of the right anterior cerebral artery, and no branch was present at the site of the aneurysmal neck. He was operated on using the right pterional approach. The A1 portion was trapped and the aneurysm was removed successfully. The histology of the aneurysm was that of the usual type of the saccular aneurysm. The post-operative course was uneventful. He was discharged with no neurological deficit two months after the operation. As far as we know, there has been no report on a ruptured aneurysm in the hypoplastic A1 portion. We also reviewed the 55 aneurysms in the A1 portion that have been reported in the literature.

[A simple method of testing the sensitivity to antineoplastic agents on human tumors in vivo]. BRO human melanoma cells, encapsulated in fibrinogen clots and implanted under the subrenal capsule of immunosuppressed mice, serve as a model for evaluating the effects of chemotherapeutic agents on human tumors in vivo. Histological examination of 8-day tumors in mice which had received 4.5 Gy prior to implantation, showed that the cells were largely viable. Radiation at this dose exerted no significant additional toxicity for mice given therapeutic doses of anticancer drugs. Effects of anticancer agents on tumor growth correlated well with other methods for evaluating the effects of chemotherapy on BRO cells in vivo.

Biosynthesis of yeast mannan. Isolation of Kluyveromyces lactis mannan mutants and a study of the incorporation of N-acetyl-D-glucosamine into the polysaccharide side chains. One side chain in the cell wall mannan of the yeast Kluyveromyces lactis has the structure (see article). (Raschke, W. C., and Ballou, C. E. (1972) Biochemistry 11, 3807). This (Man)4GNAc unit (the N-acetyl-D-glucosamine derivative of mannotetroase) and the (Man)4 side chain, aMan(1 yields 3)aMan(1 yields 2)aMan(1 yields 2)Man, are the principle immunochemical determinants on the cell surface. Two classes of mutants were obtained which lack the N-acetyl-D-glucosamine-containing determinant. The mannan of one class, designated mmnl, lacks both the (Man)4GNAc and (Man)4 side chains. Apparently, it has a defective alpha-1 yields 3-mannosyltransferase and the (Man)4 unit must be formed to serve as the acceptor before the alpha-1 yields 2-N-acetyl-glucosamine transferase can act. The other mutant class, mnn2, lacks only the (Man)4GNAc determinant and must be defective in adding N-acetylglucosamine to the mannotetrasose side chains. Two members of this class were obtained, one which still showed a wild type N-acetylglucosamine transferase activity in cell-free extracts and the other lacking it. They are allelic or tightly linked, and were designated mnn2-1 mnn2-2. Protoplast particles from the wild type cells catalyzed a Mn2+-dependent transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to the mannotetraose side chain of endogenous acceptors. Exogenous mannotetraose also served as an acceptor in a Mn2+-dependent reaction and yielded (Man)4GNAc. Related oligosaccharides with terminal alpha (1 yields 3)mannosyl units were also good acceptors. The product from the reaction with alphaMan(1 yields 3)Man had the N-acetylglucosamine attached to the mannose unit at the reducing end, which supports the conclusion that the cell-free glycosyltransferase activity is identical with that involved in mannan synthesis. The reaction was inhibited by uridine diphosphate. Protoplast particles from the mmnl mutants showed wild type N-acetylglucosamine transferase activity with exogenous acceptor, but they had no endogenous activity because the endogenous mannan lacked acceptor side chains. Particles from the mnn2-1 mutant failed to catalyze N-acetylglucosamine transfer. In contrast, particles from the mnn2-2 mutant were indistinguishable from wild type cells in their transferase activity. Some event accompanying cell breakage and assay of the mnn2-2 mutant allowed expression of a latent alpha-1 yields 2-N-acetylglucosamine transferase with kinetic properties similar to those of the wild type enzyme.

Preparation of sera for typing of adenovirus infections by immunofluorescence. The conditions for preparation of adenovirus antisera with group, subgroup and type-specific reactivity to be used in the immunofluorescence technique have been evaluated. Group-specific antibodies were prepared by passing an antiserum against virions or hexons of one serotype through an immunosorbent column containing soluble viral components of an adenovirus type belonging to a different subgroup. The group-specific antibodies were recovered from the solid phase by elution at pH 2.8. Reagents specific for subgroup I and II were obtained by passing anti-dodecon sera through an immunosorbent column containing soluble viral components from heterologous subgroups. In this case antibodies not attaching to the absorbent were recovered. Sera against fibers of subgroup III members could be used as subgroupspecific sera without absorption. Type-specific antibodies were prepared by removal of antibodies of other specificities by passing anti-virion or anti-hexon sera through immunosorbent columns containing soluble viral components of an adenovirus type belonging to the same subgroup. Reagents specific for seven adenovirus types representing Rosen's three subgroups were prepared according to the outlined procedures.

Paradoxical blood flow responses in the diabetic neuropathic foot: an assessment of the contribution of vascular denervation and microangiopathy. Blood flow is abnormal in the diabetic neuropathic foot, and this may be of importance in the pathogenesis of complications. Arteriovenous shunting is increased, and blood flow through these channels may paradoxically decrease in response to local heating. Peak skin blood flow is also reduced in these patients. It is not known whether these blood flow abnormalities may reflect diabetic microangiopathy, or whether they simply reflect vascular denervation. The skin blood flow response to a local thermal stimulus was studied in four non-diabetic patients with a unilateral traumatic neuropathy and foot ulceration. All showed a decrease in skin blood flow (to 68% of basal) at the great toe during local heating in the neuropathic limb, in contrast to the normal limb, in which blood flow increased to 180% of basal. Peak skin blood flow was also greatly reduced in the neuropathic limb, being only 29% of the normal limb. Neuropathy alone can be responsible for abnormal skin blood flow responses in the neuropathic foot.

Immunohistochemical localization of matrix proteins in the femoral joint cartilage of growing commercial pigs. The immunocytochemical localization of several matrix macromolecules, including collagen type II and proteoglycans, in the distal femoral articular-epiphyseal cartilage complex of 15 commercial pigs between the age of 6 and 18 weeks was studied. Early osteochondrotic lesions, i.e., chondronecrosis in the resting region of the growth cartilage, as well as extensions of necrotic cartilage into the subchondral bone, were present in all animals, except those 6 weeks old. A battery of antibodies were used for identification of macromolecules in the matrix at different stages of the disease. Chondrocyte involvement in the process could be studied by identifying the sequence of alterations in matrix macromolecules as the lesion developed. The immunostaining for aggrecan (large aggregating proteoglycans), cartilage oligomeric matrix protein, fibronectin, collagen type II, fibromodulin, and biglycan was more prominent in the areas of chondronecrosis, extending into the subchondral bone, than in the normal resting region. This altered pattern of matrix macromolecules resembled that of the matrix of the proliferative chondrocytes and suggests that the chondrocyte maturation had stopped in the proliferative zone. The matrix in the areas of chondronecrosis in the resting region resembled that in the normal resting region. Thus the chondronecrosis appears to have preceded alterations of the matrix composition. The antibody reactivity pattern was, however, altered in the matrix of the clustered chondrocytes in areas of chondronecrosis. Staining in these regions suggested a more prominent appearance of fibronectin and collagen type II than in the normal matrix of the resting region. These changes are suggestive of attempt to repair.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of T-cell-mediated immunity against MethA fibrosarcoma by intratumoral injections of a bacillus Calmette-Guérin nucleic acid fraction. MY-1, which consists of DNA and RNA extracted and purified from bacillus Calmette-Guérin (BCG), has been shown to have strong antitumor activity against various experimental tumors. To examine the role of T cells in the antitumor mechanism of MY-1, the effect of MY-1 injection on the development of tumor-specific immunity against MethA fibrosarcoma was investigated. MY-1 injections inhibited tumor growth less effectively in T-cell-deficient nude mice than in normal BALB/c mice. MethA tumor growth was suppressed after inoculation with L3T4-positive lymphocytes from tumor-bearing mice treated with MY-1. MethA-specific delayed-type hypersensitivity was also detected in tumor-bearing mice treated with MY-1. Immunohistochemical analyses showed that many L3T4-positive and a few Lyt2-positive cells infiltrated the regressing tumors. These results indicate that intratumoral MY-1 injections induce a MethA-specific, L3T4-positive cell-mediated, delayed-type hypersensitivity, which is necessary for the tumor regression.

Avian nephritis virus infection of chicks: virology, pathology, and serology. Avian nephritis virus (ANV), G-4260 strain, was inoculated orally into 1-day-old specific-pathogen-free chicks of the line 15I for virological, pathological, and serological study of the ANV infection of chicks. The virus titer and incidence of appearance of fluorescent antigens in the kidneys were highest at 4 days postinoculation (PI) and decreased gradually. The degeneration of proximal tubules was the principal pathological change in kidneys of chicks at 4 days PI, and interstitial nephritis was the principal pathological change in kidneys of chicks from 6 to 14 days PI. Moreover, gouty nodules were apparent in the kidneys of more than half of the chicks at 10 days PI. The plasma urate value of infected chicks was clearly higher than that of control chicks, reaching a maximum at 10 days PI, then gradually decreasing. The serum antibody was detected from 4 days PI and increased gradually. The chicks affected with visceral urate deposits or urate deposits in the digitated joints showed high plasma urate values (more than 100 mg/dl).

kfrA gene of broad host range plasmid RK2 encodes a novel DNA-binding protein. The korABF operon of broad host range IncP plasmid RK2 encodes proteins that coordinate expression of many other operons and that aid plasmid stability by providing at least part of a partitioning apparatus. The kfrA gene lies downstream from this operon and its transcription is repressed by all except one of the proteins encoded by this operon (KorA, KorFI, KorFII and KorB). We report here that transcription from the kfrA promoter is autoregulated by the kfrA gene product. We have purified KfrA, which is an acidic polypeptide of 308 amino acid residues, and show that it is a site-specific DNA-binding protein whose operator overlaps the primary kfrA promoter. Deletion analysis suggests that this activity is critically dependent on the N-terminal section of KfrA, which appears to contain an alpha-helix-beta-turn-alpha-helix motif. Circular dichroism confirmed the structural prediction that KfrA is almost entirely alpha-helical. The position of predicted turns suggests that, while amino acid residues 1 to 80 may form a globular domain of four or five helices, residues 80 to 280 of KfrA may adopt an extended coiled-coil domain containing a heptad repeat segment, which is probably responsible for formation of the multimers detected by crosslinking. The possibility that this unusual structure serves a second function, for example in providing a bridge to host structures required for plasmid partitioning, is discussed.

In vitro metabolism and biological activity of all-trans-retinoic acid and its metabolites in hamster trachea. The in vitro metabolism of all-trans-[11,12-3h]retinoic acid to several more polar compounds has been demonstrated in a hamster tracheal organ culture system. The production of these metabolites is dependent on the presence of tissue. The physiological significance of these compounds is shown by the cochromatography of several of the in vitro formed metabolites synthesized from [carboxy-14C]retinoic acid with metabolites isolated from the intestine and urine of hamsters previously injected with 0.1 to 1.5 microgram of [3H]retinoic acid. One of the metabolites shows about one-tenth the biological activity of all-trans-retinoic acid when tested in a hamster tracheal organ culture assay. This biologically active metabolite is converted by the hamster trachea in vitro to a biologically inactive metabolite.

Hemangiosarcoma of the spleen: report of a case and review of previously reported cases. Splenic hamangiosarcomas are rare tumors, usually discovered at autopsy. In a few instances the diagnosis was made premortem, at the time of splenectomy for spontaneous rupture. The tumors usually present with abdominal pain, left upper guadrant mass and tenderness, and occasionally with a microangiopathic type of anemia. The histogenesis of the tumor is in dispute. Some authors feel that they are degenerations of hemangiomas. Others feel that they arise de novo in the spleen. There is not proven association of thorotrast administration or vinyl chloride exposure to the development of hemangiosarcomas in the spleen. The prognosis of the tumor is uniformly poor and most of the patients surviving laparotomy have followed a uniformly fatal clinical course. In a few cases treated with chemotherapy there has been no evidence of clinical benefit. The case report in this article presented with essentially all the features enumerated above.

Studies on in vivo priming of the TNP-reactive cytotoxic effector cell system. I. Comparison of the effects of intravenous inoculation with TNP-conjugated cells on the development of contact sensitivity and cell-mediated lympholysis. A comparison was made of the effects of i.v. inoculation of trinitrophenyl-(TNP) conjugated syngeneic cells on the subsequent in vitro generation of TNP-reactive effector cell activity and on the in vivo development of TNP-contact sensitivity. The administration of syngeneic TNP-conjugated spleen cells before 2,4,6-trinitro-1-chlorobenzene (TNCB) painting abolished the capability of animals to develop TNP-contact sensitivity. In contrast, the same treatment resulted in an appreciable augmentation in the generation of TNP-reactive cytotoxic effector cell activity as measured by subsequent in vitro sensitization with TNP-conjugated cells. The possible mechanisms by which enhanced TNP-reactive cytotoxic effector cell activity was elicited under conditions identical to those that induced unresponsiveness for TNP-contact sensitivity are discussed.

Endocrine control of the immunosuppressive activity of the submandibular gland. Extracts of the submandibular gland (SMG) of rats contain fractions that stimulate the in vitro proliferation of Con A-treated lymphocytes. One of the stimulatory fractions was also shown to induce in vivo immunosuppression in rats and mice in several experimental models. Since many other biologically active factors of the SMG had been found to be hormone dependent, we investigated the effects on the immunosuppressive factor of hypophysectomy (Hx) and of hormonal reconstitution in male Fischer rats. Hx induced a marked atrophy of the SMG together with an almost complete disappearance of both the in vitro lymphocyte-stimulating activity and the in vivo immunosuppressive activity, the latter assayed with the contact sensitivity reaction in mice. The treatment of the Hx rats with pituitary hormones demonstrated that prolactin (PRL), thyroid stimulating hormone (TSH), and luteinizing hormone (LH) induced a significant reconstitution of these biological activities, growth hormone led to the recovery of the lymphocyte-stimulating activity but not of the immunosuppressive activity, while follicle-stimulating hormone, and adrenocorticotropic hormone did not induce any recovery of these biological activities. In view of the positive results obtained with TSH and LH further experiments were done to compare the effects of thyroid and sex hormones with those of PRL. The results demonstrated that testosterone and thyroid hormones induced significant recovery of the lymphocyte-stimulating and the immunosuppressive activity. The combination of these two hormones with PRL produced the most effective results. On the other hand, estrogens and progesterone had no significant effects. These results confirm the effectiveness of androgens and thyroid hormones in stimulating the production of biologically active factors by the SMG. Moreover, they demonstrate that PRL, a hormone not previously considered to increase the activity of the SMG, stimulates the production of immunoregulatory factors in Hx animals.

Role of calcium in different layers of vascular smooth muscle in norepinephrine contraction. The role of calcium present in adventitial and media-intimal layers of rabbit aorta in the fast (F-) and the slow (S-) components of norepinephrine (10(-5) M) contraction was evaluated in this study. An increased sensitivity and decreased maximum tension to response to norepinephrine was observed in adventitia-free aorta as compared to whole aorta. Incubation in calcium-free Ringer solution with or without EDTA decreased the F-component of norepinephrine contraction of the adventitia-free aorta, whereas the F-component of the whole aorta was not affected. The S-component of both preparations was abolished in calcium-free Ringer solution. Norepinephrine increased calcium uptake into whole and adventitia-free aortic strips. An increase in calcium uptake induced by norepinephrine during the F-component of norepinephrine contraction was also observed. 45Ca efflux studies revealed the presence of an exchangeable calcium fraction in the adventitial layer. These data suggest that F-component of norepinephrine contraction is partially dependent on the extracellular calcium distributed in the adventitial layer of rabbit aorta.

Reassociation with beta 2-microglobulin is necessary for Db class I major histocompatibility complex binding of an exogenous influenza peptide. A synthetic peptide corresponding to residues 365-380 of the influenza nucleoprotein (NP365-380) has been previously shown to associate with class I major histocompatibility complex-encoded molecules and to stimulate cytotoxic T lymphocytes [Townsend, A. R. M., Rothbard, J., Gotch, F. M., Bahadur, G., Wraith, D. & McMichael, A. J. (1986) Cell 44, 959-968]. We find that intact Db class I heterodimers on the cell surface are unreceptive to binding this antigen. However, NP365-380 readily associates with Db molecules on the plasma membrane in the presence of exogenous beta 2-microglobulin. In addition, there is a second pathway through which this peptide associates with class I molecules that requires energy and de novo protein synthesis. These findings have implications for maintaining the immunological identity of cells and for the use of peptides as vaccines for priming cytolytic T-cell immunity.

Double-blind evaluation of intradiscal chymopapain for herniated lumbar discs. Early results. The authors report 66 patients with signs, symptoms, and a myelographic abnormality of herniated lumbar disc, who were not responsive to conservative treatment. The discs were injected at random with either chymopapain or a placebo. Neither patient nor surgeon knew which agent was used until after the results had been tabulated. Unless early laminectomy was necessary for intractable pain, all patients were followed for 2 months or more. There was no statistically significant difference in incidence or quality of improvement between the two groups: chymopapain was successful in 58% while placebo was successful in 49% (p = 0.15). Early results from this study indicate that most, if not all, of the putative effectiveness of chemonucleolysis probably derives from a placebo effect.

Characterization of 6-hexadecanoylamino-4-methylumbelliferyl-beta-D- galactopyranoside as fluorogenic substrate of galactocerebrosidase for the diagnosis of Krabbe disease. 6-Hexadecanoylamino-4-methylumbelliferyl-beta-D-galactopyranoside (HMGal) has been shown to be a specific fluorogenic substrate of galactocerebrosidase and to facilitate the simple enzymatic diagnosis of Krabbe disease in human patients and in twitcher mice. HMGal hydrolysis at pH 4.5 is optimally stimulated by sodium taurocholate (0.25%) and oleic acid (0.05%) with a Km of 0.150, 0.04 and 0.03 mM, respectively for control mouse kidney, human fibroblasts and leukocytes. In control samples, the specific activity (nmol/mg prot./h) for HMGal is higher than for the natural substrate, galactocerebroside, and is severely deficient in the twitcher mouse and in patients with Krabbe disease. Comparative investigation of galactocerebrosidase activity in fibroblasts, leukocytes and brain with radioactive and fluorogenic substrates reveals a good agreement between the results of the two methods. Galactocerebroside (Gal-Cer) is a competitive inhibitor of HMGal hydrolysis in mouse kidney homogenates while GM1-ganglioside has no inhibitory effect in the same assay system. The sensitivity and specificity of this fluorogenic substrate for galactocerebrosidase provides a simple and rapid method for the diagnosis of Krabbe disease, and for the purification of this enzyme from normal tissues.

Immune responses to fractionated cytomegalovirus (CMV) antigens after HIV infection. Loss of cellular and humoral reactivity to antigens recognized by HIV-, CMV+ individuals. In order to delineate the molecular pathogenesis of the increased susceptibility to CMV disease in HIV infection, the patterns of antigen responsiveness in HIV-infected and non-infected individuals were investigated. CMV was fractionated by SDS-PAGE and electroblotted onto nitrocellulose. Lymphoproliferative responses of healthy HIV-, CMV+ individuals and HIV+, CMV+ asymptomatic patients to a whole CMV antigen preparation and to 20 fractions of nitrocellulose-bound CMV were then compared. Three fractions of approximate molecular weight of 130-165, 65-75, and 55-65 kD appeared to contain the major T cell stimulating antigens for HIV-, CMV+ individuals. A statistically significant depression of responses to fractions containing antigens in the ranges of 130-165 kD and 55-65 kD but not to whole CMV was seen in HIV+ individuals compared with controls. In healthy controls, the sum of the proliferative responses as measured by 3H-thymidine uptake to these three major fractions was approximately equal to the response to a whole CMV antigen preparation, whereas it was less than half of this response in five out of six HIV+ subjects. When antibody activities to CMV antigens were analysed by immunoblotting of sera from the two subject groups and also sera of ARC and AIDS patients, a selective loss of reactivity was revealed in 10 out of 19 HIV+ subjects to a band of 26-28 kD whereas all 15 HIV-, CMV+ controls recognized this band. Serum IgG and IgM values were both significantly higher in HIV+ individuals than in controls. These findings suggest that specific lesions in the repertoire of immune responsiveness to CMV antigens occur in HIV+ individuals.

[Value and limitations of determination of total serum CPK in patients with complicated myocardial infarct. Case statistics for 1974-1977]. The Authors, starting from a casuistic formed over four years at the "Servizio di Anestesia e Rianimazione dell'Ospedale Fatebenefrateli di Milano" where there is no coronaric unit and that gathers patients with complicated myocardial infarction, considered the developing of the enzyme CPK in the various clinical phases of these patients. On the basis of these data, we confirm with other Authors have already observed: that is, the value of the total serum CPK isn't a prognostic index fit in the evaluation of the clinical developing of the person with myocardial infarction, especially if complicated.

Two new combinations of estrogen and progestogen for prevention of postmenopausal bone loss: long-term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding. Bone mass, calcium and lipid metabolism, climacteric symptoms, bleeding, blood pressure, and weight changes were studied in 62 healthy postmenopausal women at 3-month intervals throughout 2 years of treatment with continuous estradiol valerate (2 mg) plus cyproterone acetate (1 mg), sequential estradiol valerate (2 mg) plus levonorgestrel (75 micrograms), or placebo. During the 2 years of the study, bone mineral content of the distal and ultradistal regions of the forearm (measured by single-photon absorptiometry) remained unchanged in the hormone groups, whereas bone mineral content at these sites decreased by 5 and 6%, respectively, in the placebo group. Bone mineral density in the spine (measured by dual-photon absorptiometry and dual-energy x-ray absorptiometry) increased by 3-4% in the hormone groups and decreased by 2% in the placebo group. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium/creatinine) decreased significantly to premenopausal levels in the hormone groups, but remained unchanged in the placebo group. Serum concentrations of total and low-density lipoprotein cholesterol were significantly reduced by 5-10% (P less than .05-.01) in the estradiol + cyproterone acetate group and by 10-15% (P less than .001) in the estradiol valerate + levonorgestrel group. There were no significant changes in high-density lipoprotein cholesterol in the hormone groups. Virtually no changes were observed in the placebo group. Climacteric symptoms and hot flushes were significantly reduced in both hormone groups compared with the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of diarrhoea, tail length and sex on the incidence of breech strike in modified mulesed Merino sheep. Merino sheep were treated with purgative to induce scouring and the effects of tail length and sex on the incidence and origin of breech strike were examined. In sheep treated with the modified Mules operation, those with tails docked very short were strongly predisposed to tail strike, and to a lesser extent, crutch strike. Tails docked level with, or just below, the tip of the vulva in ewes, and at the equivalent length in wethers, were struck far less frequently. Within each tail length group, wethers tended to be more susceptible than ewes. L. cuprina was the principal species of fly involved in strikes, although the presence of L. sericata and C. augur was conspicuous.

[Recurrent peripheral nerve palsies and concomitant chronic neuropathy. Neuromusclar electrophysiologic study and neuropathologic examination: apropos of 5 cases]. The authors report 5 personal cases (3 in the same family) of patients suffering from recurrent peripheral nerve palsies usually induced by pressure and review the relevant literature. There is evidence in such cases of a mild, chronic, diffuse, subclinical neuropathy which can be recognized by electrophysiological examination. Examination of peripheral nerve biopsy material in such cases shows evidence of both axonal and Schwann cell abnormalities with evidence of neurogenic atrophy of skeletal muscles. This chronic subclinical neuropathy which is often familial can be distinguished from other chronic primary neuropathies with or without myelin sheath proliferation and hypertrophy.

Antitumor activity of a derivative of mitomycin, 7-N-[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]mitomycin C (KW-2149), against murine and human tumors and a mitomycin C-resistant tumor in vitro and in vivo. The antitumor activity of a mitomycin derivative, 7-N-[2[[2-(gamma-glutamylamino)ethyl]dithio]ethyl]mitomycin C (KW-2149), was evaluated in murine and human tumor models, including a mitomycin C (MMC)-resistant tumor in vitro and in vivo. KW-2149 showed a profound effect against i.p. inoculated P388 leukemia on both a single and an intermittent administration schedule. Against s.c. implanted colon adenocarcinoma 38 (colon 38). KW-2149 was as effective as MMC in ILS% and in tumor growth inhibition on a single-administration schedule. Both compounds were similarly effective when an intermittent schedule was used. KW-2149 showed activity against human tumor xenografts and was effective in two of four non-small-cell lung carcinomas but was not effective against three gastric adenocarcinomas on the single-administration regimen. The activity of KW-2149 against gastric adenocarcinoma was inferior to that of MMC on a single-administration schedule. However, the antitumor activity of KW-2149 was higher on an intermittent schedule than on a single-administration regimen. The antitumor activity of KW-2149 against human tumor xenografts was similar to that of MMC on an intermittent schedule, and the former drug was effective against both gastric adenocarcinomas and both non-small-cell lung carcinomas. KW-2149 was more effective than MMC against a subline of P388 leukemia that is resistant to MMC in vitro as well as in vivo.

Intracerebral oxytocin is important for the onset of maternal behavior in inexperienced ewes delivered under peridural anesthesia. Measurement of cerebrospinal concentrations of oxytocin (OT) in intact and peridural-anesthetized ewes showed that central release of OT during parturition is inhibited by this anesthesia. Also, observations of maternal behavior and attraction to amniotic fluid (AF) in inexperienced peridural-anesthetized parturient ewes after intracerebroventricular injections of either OT (2 x 10 micrograms) or saline showed that OT infusions increased the proportion of maternal females (2/17 vs. 10/20; p = .01) and attraction to AF. This study confirms that in sheep vaginocervical stimulation activates the oxytocinergic system, which induces the onset of maternal behavior, and that this action is not limited to maternally experienced females.

Effects of triiodothyronine, triiodothyroacetic acid, iopanoic acid and iodide on the thyrotropin-releasing hormone-induced thyrotropin release from superfused rat pituitary fragments. The effects of triiodothyronine, triiodothyroacetic acid, iopanoic acid and potassium iodide were investigated on basal and stimulated thyrotropin release in an in vitro experimental model. Rat pituitary fragments were superfused by Medium-199 with or without T3 (10(-7) mol/l), triiodothyroacetic acid (10(-8)-10(-6) mol/l), iopanoic acid (10(-7)-10(-5) mol/l) or potassium iodide (10(-7)-10(-4) mol/l). This was followed by a 6-min pulse of thyrotropin-releasing hormone (10(-8) mol/l). TSH was measured in 3-min fractions. The TRH-induced TSH release from the pituitary fragments was inhibited by T3 (10(-7) mol/l), by triiodothyroacetic acid (10(-7)-10(-6) mol/l), and by high concentrations of iodide (10(-4) or 10(-5) mol/l). Iopanoic acid had no significant effect at the concentrations tested. It is assumed that in vitro, and at similar concentrations, the inhibitory effect of triiodothyroacetic acid on the TRH-induced TSH secretion is comparable to that of T3, whereas iopanoic acid may have no direct detectable effect. In contrast, a direct inhibitory effect of inorganic iodide, at least in pharmacological concentrations in vivo, cannot be excluded.

[Lipids and total bile acids in the blood of patients with inflammatory bowel diseases]. We evaluated the total plasma bile acids, total lipids, total cholesterol, total triglicerides, LDL-cholesterol, HDL-cholesterol, phospholipids and lipoproteins (APOA-A and APO-B) in 25 patients with inflammatory bowel disease: 20 with ulcerative colitis (UC) and 5 with Crohn's disease. In comparison to 17 healthy volunteers, the total plasma bile acids were decreased in all patients. The serum level of total cholesterol, LDL-Ch, HDL-ch and APO-A was significantly lower in patients with Crohn's disease and ulcerative colitis (p less than 0.01) than in normal controls; total triglycerides and APO-B were decreased only in the group with Crohn's disease (p less than 0.05). Thus, decreased values of total plasma bile acids malabsorption, and they suggest a more important romalabsortion, and they suggest a more important role of the colon in the preservation of bile acids.

Cerebral tissue pulmonary embolization due to head trauma: a case report with immunohistochemical confirmation. Pulmonary embolization of cerebral tissue as the result of severe head trauma is an uncommon, if not rare, phenomenon, and few cases have been reported in the literature. The authors discuss the case of a 51-year-old male who died six days after suffering extensive head trauma in a motor vehicle collision. At autopsy, white-gray emboli were found in several subsegmental pulmonary arteries. The results of histologic examination with the hematoxylineosin stain gave the impression that the emboli were necrotic cerebral tissue; however, routine special stains for neural tissue produced inconclusive results. Immunohistochemical staining of the emboli with monoclonal mouse anti-human neurofilament protein (Dako Corp., Carpinteria, California) confirmed the cerebral nature of the emboli. To the authors' knowledge, this is the first reported case of pulmonary embolization of cerebral tissue confirmed by immunohistochemistry.

Characterization of Ia antigens in mouse serum. Sera obtained from normal B10.BR mice were shown to inhibit selectively a specific anti-Ia alloantiserum. Partial purification of the Ia antigenic activity was accomplished by isolation of the high density lipoproteins from these sera by fractional precipitation with sodium phosphotungstate and MgCL2. Both H-2.23 and Iak antigens present in this high density lipoprotein fraction were completely adsorbed by rabbit anit-rat beta2-microglobulin immunoadsorbents, whereas specific anti-H-2.23 immunoadsorbents removed only the H-2 activity. These data deomnstrate that Ia antigens, like H-2 antigens in the sera of B10.BR mice are associated with high density lipoproteins and further suggest that both H-2 and Ia antigens are associated with a beta2-microglobulin-like molecule.

Effect of a macrolide (spiramycin) on the pharmacokinetics of L-dopa and carbidopa in healthy volunteers. In one well-equilibrated parkinsonian patient treated with combined L-dopa and carbidopa (Sinemet), we have observed changes in treatment efficacy while receiving spiramycin (Rovamycine) for an intercurrent respiratory infection. A preliminary study of the pharmacokinetics of L-dopa and its main metabolites 3-O-methyldopa (3-OMD) and dihydroxyphenylacetic acid (dopac) in two parkinsonian patients treated with Sinemet has revealed a marked decrease in the AUC0-360 of these two metabolites after a 3-day course of Rovamycine. In order to confirm this interaction, we have studied the modifications of the pharmacokinetics of L-dopa, 3-OMD, dopac, and carbidopa in eight male healthy volunteers after a single dose of Sinemet 250 (L-dopa, 250 mg and carbidopa, 25 mg) before and after a 3-day course of Rovamycine. Our study confirms this interaction. After spiramycin, we observed a marked reduction in AUC0-360 for L-dopa (p less than 0.001), 3-OMD (p less than 0.001), and carbidopa (p less than 0.001), and an increase in AUC0-360 for dopac (p less than 0.01). The L-dopa elimination half-life was increased (p less than 0.012); differences in peak plasma concentrations did not attain statistical significance. We think that these modifications in L-dopa pharmacokinetics after spiramycin are due to nonabsorption of carbidopa secondary to modified gastrointestinal motility.

Deficiencies in sex-regulated expression and levels of two hepatic sterol carrier proteins in a murine model of Niemann-Pick type C disease. Hepatic sterol carrier protein-2 (SCP2) and sterol carrier protein-X (SCPx) levels in normal and in mutant Niemann-Pick Type C mice were determined by immunoblotting with antiserum against rat SCP2. A 14-kDa protein (SCP2) was detected in the cytosol fraction and a 58-kDa protein (SCPx) was found in both cytosolic and organellar fractions. Expression of hepatic SCPx protein was developmentally regulated in a sex-specific pattern. The amounts of organelle-associated SCPx increased 4-fold during sexual development of normal males but decreased dramatically during development of normal females. Levels of hepatic SCP2 increased much less dramatically during sexual maturation of normal males and females. Adult Niemann-Pick Type C mice were deficient in both hepatic SCPx and SCP2. The deficit in SCPx in affected males reflected a failure to increase hepatic SCPx levels during sexual maturation. In affected males SCPx remained at levels found in immature mice. Affected male and female mice were also unable to maintain levels of hepatic SCP2. The level of SCP2 was near normal in affected immature males and subnormal in affected immature females. During sexual maturation hepatic SCP2 declined in affected animals.

Bioavailability of vitamin B-6 in pregnant rats. The cause for reduced plasma pyridoxal phosphate (PLP) concentration during pregnancy is not well understood. In this study, nonpregnant (control) and pregnant rats were gavaged with [3H]pyridoxine for assessment of the intestinal absorption, tissue distribution, metabolic utilization and urinary excretion of the vitamin. In addition, plasma PLP and pyridoxal levels and erythrocyte aspartate aminotransferase (EAST) activity were measured. There was 50% lower plasma PLP concentration and 50% greater EAST activity in the pregnant rats and no difference in the stimulation of EAST with exogenous PLP. There was no difference in the intestinal absorption, hepatic uptake and retention or urinary excretion of the radioisotope. Less than 3% of the oral dose was detected in fetal/uterine tissue of the pregnant rats. Results of this study indicate that reduced plasma PLP concentration during pregnancy is not a result of diminished total vitamin B-6 body pools or fetal sequestration of vitamin B-6. Low plasma PLP during pregnancy may be a result of altered distribution of PLP between the plasma and erythrocytes.

The value of arterial, venous and arteriovenous levels of lipid metabolism parameters in healthy individuals and patients with peripheral arterial occlusive disease (PAOD). For a group of 28 patients with PAOD (mean age, SD 63.7 +/- 10.2 years) and 16 healthy subjects (61.7 +/- 11.9 years) we examined several lipid analytes in femoral arterial and venous blood. Compared with healthy controls, PAOD patients showed significantly lower HDL cholesterol levels (p less than 0.01) and significantly higher levels of triglycerides (p less than 0.01). In addition, a significant negative A-V difference in triglycerides (p less than 0.05) and a significant inverse association between arterial HDL cholesterol and A-V difference in triglycerides (r = -0.48; p less than 0.01) were present. Predominantly the last two unexpected findings are discussed in this study.

Epidermal cell kinetics of the pig: a review. Age-related changes in cell kinetic parameters for the epidermis of pigs have been shown to be small, indicating that young pigs may be used for experimental studies. It was not possible to draw any firm conclusions about any strain-related differences in the cell kinetics of the epidermis of the pig. Lower LI values have been quoted for the miniature pig and the Yorkshire pig than for the Large White pig. However, these differences may be related to variations in experimental technique. The cell kinetic data for the Yorkshire pig are not consistent. Very high values for the mitotic index suggested a high rate of cell turnover, whilst data from single pulse labelling and grain count halving studies indicate a relatively low rate of cell turnover. The results from continuous labelling studies on the epidermis of the Yorkshire pig suggest that the basal cell turnover time (TT) is a factor of two or more shorter (136 h) than the estimates obtained using other methods. In the Large White pig estimates of TT were similar using a variety of techniques and were comparable with the TT estimate for the Yorkshire pig obtained using the continuous labelling method. There is some degree of inconsistency in the literature with regard to possible diurnal variations in the cell kinetic parameters for the epidermis. In the study of Archambeau & Bennet (1984) distinct diurnal variations were found in the LI, although the reliability of this finding is questionable due to the small number of animals used. Later studies by Morris et al. (1987) have suggested that diurnal variations are negligible in the epidermis of the pig. The majority of labelled cells (80%) in pig epidermis are located in the basal layer, although a significant proportion (20%) occurs suprabasally, in the cell layer immediately above the basal layer. Therefore, the epidermis can be regarded as having a bilayered proliferative cell compartment. The results from studies on irradiated pig skin (Morris & Hopewell, 1986, 1988, 1989) are not consistent with the presence of a homogeneous proliferative compartment in the epidermis, and are best explained by the occurrence of an heterogeneous proliferative compartment consisting of a stem cell subpopulation and a much larger population of transit proliferative cells.

Mammalian protein serine/threonine phosphatase 2C: cDNA cloning and comparative analysis of amino acid sequences. Complementary DNA encoding rat protein phosphatase 2C alpha was obtained from a liver library and used to isolate the homologous cDNAs from rabbit liver and human teratocarcinoma libraries. The amino acid sequences of the three enzymes deduced from the cDNA (382 amino acids) were extremely similar (greater than 99% identity), the maximum number of differences (between rat and human) being four. Amino acid sequences of peptides corresponding to 238 residues (61%) of the protein phosphatase 2C beta isoform from rabbit skeletal muscle were determined and showed 12 differences from the recently published sequence of the rat liver enzyme deduced from the cDNA (95% identity).

Benzothiazole hydroxy ureas as inhibitors of 5-lipoxygenase: use of the hydroxyurea moiety as a replacement for hydroxamic acid. A novel series of N-[(2-benzothiazolylthio)alkyl]-N'-hydroxyurea derivatives (9-25) was synthesized and evaluated for biological activity as inhibitors of 5-lipoxygenase both in vivo (mouse zymosan peritonitis assay) and in vitro (Ca2+ ionophore-stimulated human peripheral blood leukocyte model). The compounds of this series were based on the corresponding hydroxamic acid derivatives (1, 3, 4, and 5) which were moderately active in vitro but inactive in vivo. A number of compounds in the hydroxyurea series exhibited oral activity for 5-lipoxygenase inhibition. Results of studies relating structure to in vivo and in vitro 5-lipoxygenase activity are reported.

Role of the clotting system in cell-mediated hypersensitivity. II. Kinetics of fibrinogen/fibrin accumulation and vascular permeability changes in tuberculin and cutaneous basophil hypersensitivity reactions. Radioactive tracers and immunofluorescence were employed to detect and quantitate fibrinogen/fibrin deposition in two types of cell-mediated hypersensitivity reactions in the guinea pig. Classic delayed hypersensitivity (DH) reactions to Old Tuberculin and to the azobenzenearsonate hapten were characterized by a progressive increase in the fibrinogen (125-I-HF) content which exceeded that of the albumin tracer (131-I-HSA) and paralleled the development of induration and erythema. Accumulation of 125-I-HF could be related both to increased vascular permeability to 125-I-HF and, more specifically, to retarded efflux of extra vascular 125-I-HF from tuberculin reaction sites. Warfarin inhibited 125-I-HF accumulation and the formation of urea-insoluble 125-I-HF (cross-linked fibrin) as well as induration in tuberculin reactions. Immunofluorescence studies revealed the site of Fib deposition to be extravascular, among the connective tissue fibers of the dermis, similar to that in DH reactions in man. In contrast, little 125-I-HF accumulated in cell-mediated reactions rich in basophils--cutaneous basophil hypersensitivity (CBH) reactions to keyhole limpet hemocyanin, ovalbumin, and dinitrochlorobenzene--due in part to less vascular leakage of macromolecules and to decreased formation of urea-insoluble fibrin. By immunofluorescence Fib deposits were found in CBH reactions in a pattern similar to that in DH reactions, but the intensity of staining was appreciably less. Thus, fibrin accumulation further distinguishes DH from CBH reactions and is very likely responsible for the induration characteristic of DH reactions.

Extramacular disciform lesions simulating uveal tumors. The purpose of this study is to identify clinical, ultrasonographic, and fluorescein angiographic features of extramacular disciform lesions that allow differentiation from uveal tumors. This was a retrospective study of 19 patients referred to our ocular oncology unit with a possible malignancy who had a diagnosis of an extramacular disciform lesion made after complete evaluation. The level of accuracy for each diagnostic technique alone was as follows: clinical (79%), ultrasonography (83%), and angiography (83%). Fluorescein angiography had limited utility because of severe media opacities in seven cases. No tumor developed an intraocular malignancy during the follow-up period. A combination of the above, noninvasive techniques can be used to correctly diagnose extramacular disciform lesions.

Changes in the microvillus cytoskeleton during rhabdom formation in the retina of the crayfish Procambarus clarkii. Changes in the microvillus cytoskeleton during the formation of the light-receptive rhabdom in the crayfish retina were examined at four structurally distinct stages. The cytoskeleton of microvilli in early rhabdoms is composed of a regularly packed bundle of 12-25 actin filaments. The polarity of S1 decorated filaments indicates that the plus end of the actin filaments is located at the microvillus tip. The hexagonal packing of filaments within the bundle, their spacing, and the presence of cross-striations along the bundle in longitudinal sections indicate the filaments are held together by cross-linking proteins. Electron microscopic observations and data from three-dimensional reconstructions of individual microvilli indicate that the filaments arise from a concentration of dense material at the tip of the microvillus and extend into the cytoplasm as a rootlet. Over the four developmental stages examined there is an increase in the number of microvilli forming the rhabdomeres and a 50% decrease in the mean cross-sectional area of individual microvilli. During this same period the number of actin filaments forming the microvillus cytoskeleton also decreases. Following this decline, microvilli of late stage rhabdoms, which are structurally similar to adults, contain only two to four filaments. These changes are discussed in relation to the three phases of growth described for stereocilia and brush border microvilli.

Immunofluorescence study of the hypothalamo-infundibular LRH tract and serum gonadotropin levels in the female squirrel monkey during the estrous cycle. The study of LRH reactive neurons of the medial basal hypothalamic group was made with rabbit antisera to unconjugated synthetic LRH, in normally cycling female squirrel monkeys. The specifically immunoreactive material present along the hypothalamo-infundibular LRH tract shows significant modifications that are particularly distinct in the lateral, posterior and anterior labia of median eminence, with a maximum concentration during the early and middle follicular phases, a sudden fall to a minimum concentration during the late follicular and ovulatory phases and with a progressive increase during the luteal and early follicular phases. Serum FSH and LH levels show a progressive decrease from the luteal phase to the late follicular phase, with differential modifications suggesting that a double regulation might take place in cycling squirrel monkeys. A parallel is suggested between the specifically reactive material along the hypothalamo-infundibular tract, serum gonadotropin levels and variations in the medial basal hypothalamic and infundibular LRH concentrations during the estrous cycle in the squirrel monkey.

Dihydrodipicolinate reductases from Bacillus cereus and Bacillus megaterium. Dyhydrodipicolinate reductases were purified 100-fold from crude extracts of B. cereus and B. megaterium and their properties were compared with those of the reductase from B. subtilis. The molecular weights of the reductases of B. cereus and B. megaterium were fount to be 155,000 and 150,000, respectively. These reductases were shown to be free of flavin, unlike the B. subtilis enzyme, which contains flavin. Both NADPH and NADH acted as coenzymes for these two reductases. NADPH being three or four times more effective than NADH. The Km values for NADPH and dihydrodipicolinate were 8 micrometer and 62 micrometer, respectively, with B. cereus reductase, and 13 micrometer and 59 micrometer with B. megaterium reductase. The pH optima of the enzymes from B. cereus and B. megaterium were pH 7.4 and 7.2, respectively. The reductases were inhibited by dipicolinate noncompetitively with respect to dihydrodipicolinate and the Ki values were 85 micrometer and 140 micrometer, respectively. Lysine and diaminopimelate were not inhibitory. The properties of the reductases from B. cereus and B. megaterium were similar, but they differed considerably from those of the B. subtilis enzyme. However, all three Bacillus reductases were markedly inhibited by dipicolinate, unlike the enzyme from E. coli.

Mechanisms of reflex cardiac arrest in tetraplegic patients. Four patients with physiologically complete high cervical spinal-cord lesions, sustained within the previous 6 weeks, were observed. All needed intermittent positive-pressure ventilation. In the stage of spinal shock, stimuli to the trachea induced bradycardia, and in two patients cardiac arrest resulted. The bradycardia occurred when the patients were hypoxic, and seemed to be due to a vaso-vagal reflex. Normally this reflex is opposed by sympathetic activity, and during hypoxia by increased pulmonary (inflation) vagal reflex activity due to increased breathing. In these patients, however, compensatory sympathetic activity was prevented by the cervical cord lesion, and increased pulmonary vagal reflex activity by the fact that the breathing was artificial and therefore did not increase with hypoxia. Treatment in emergency includes the administration of atropine. Adequate oxygenation and, if this cannot be achieved, maintenance atropin should prevent the bradycardia and cardiac arrest associated with stimulation of the trachea in artificially ventilated tetraplegic patients.

[The forensic medical evaluation of the results of determining diatomaceous plankton in the diagnosis of drowning]. Evaluation of demonstrative value of method based on diatom plankton determination as a diagnostical sign of death due to drowning was performed. Plankton was detected in the viscera in 37% of cases (as a whole 376 bodies of people who drowned in fresh water were examined). Plankton was detected in aspiration type of drowning and its mixed variant. In spastic and reflector types of drowning plankton wasn't detected. According to author's opinion this method is an objective diagnostical test to determine the cause of death of people when their bodies are found in water.

Crystal structure of the unique parvalbumin component from muscle of the leopard shark (Triakis semifasciata). The first X-ray study of an alpha-parvalbumin. The three-dimensional structure of parvalbumin from leopard shark (Triakis semifasciata) with 109 amino acid residues (alpha-series) is described at 1.54 A resolution. Crystals were grown at 20 degrees C from 2.9 M-potassium/sodium phosphate solutions at pH 5.6. The space group is P3(1)21 and unit cell dimensions are a = b = 32.12 A and c = 149.0 A. The structure has been solved by the molecular replacement method using pike 4.10 parvalbumin as a model. The final structure refinement resulted in an R-factor of 17.3% for 11,363 independent reflections at 1.54 A resolution. The shark parvalbumin shows the main features of all parvalbumins: the folding of the chain including six alpha-helices, the salt bridge between Arg75 and Glu81, and the hydrophobic core. Compared to the structure of beta-parvalbumins from pike and carp, one main difference is observed: the chain is one residue longer and this additional residue, which extends the F helix, is involved through its C-terminal carboxylate group in a network of electrostatic contacts with two basic residues, His31 in the B helix and Lys36 in the BC segment. Furthermore, hydrogen bonds exist between the side-chains of Gln108 (F helix) and Tyr26 (B helix). There is therefore a "locking" of the tertiary structure through contacts between two sequentially distant regions in the protein and this is likely to contribute to making the stability of an alpha-parvalbumin higher in comparison to that of a beta-parvalbumin. The lengthening of the C-terminal F helix by one residue appears to be a major feature of alpha-parvalbumins in general, owing to the homologies of the amino acid sequences. Besides the lengthening of the C-terminal helix, the classification of the leopard shark parvalbumin in the alpha-series rests upon the observation of Lys13, Leu32, Glu61 and Val66. As this is the first crystal structure description of a parvalbumin from the alpha-phylogenetic lineage, it was hoped that it would clearly determine the presence or absence of a third cation binding site in parvalbumins belonging to the alpha-lineage. In beta-pike pI 4.10 parvalbumin, Asp61 participates as a direct ligand of a third site, the satellite of the CD site. In shark parvalbumin, as in nearly all alpha-parvalbumins, one finds Glu at position 61. Unfortunately, the conformation of the polar head of Glu61 cannot be inferred from the X-ray data.(ABSTRACT TRUNCATED AT 400 WORDS)

Smoking cessation program: baseline carbon monoxide and serum thiocyanate levels as predictors of outcome. One hundred and sixty-two smokers who participated in an aggressive smoking cessation program underwent analysis of expired air carbon monoxide (CO) and serum thiocyanate (SCN) at entry and one year later. Persons who failed to quit smoking had higher baseline CO and SCN and smoked more cigarettes per day than did those who succeeded in quitting. The use of CO, SCN, number of cigarettes smoked, age, and blood pressure at baseline permitted accurate classification of over 70 per cent of the subjects into groups which would succeed and fail in their effort to quit smoking. Persons who failed to quit reduced the reported number of cigaretts smoked per day by one-third, but there was no corresponding reduction in CO and SCN, suggesting that self-reporting of a reduction in the number of cigarettes smoked may not lead to a corresponding decline in exposure.

Human lymphocytes lack substance P receptors. Substance P (SP), a neuropeptide found in high concentrations in the gut, is reported to have many potent immunomodulatory actions. This study evaluated some effects of SP on human peripheral blood lymphocytes (PBL) and jejunal intraepithelial lymphocytes (IEL) and the expression of SP receptors on these and other lymphocytes types. In contrast to previous studies, SP (10(-8) or 10(-12) M) did not affect the proliferation (spontaneous or mitogen-induced) nor spontaneous cytotoxicity by PBL or IEL. To determine whether this unresponsiveness was due to an absence of SP receptors, the SP binding potential of these and other human lymphocyte types was determined by Scatchard analysis of radioligand binding. The IM-9 B lymphoblastoid cell line, used as a positive control, demonstrated 4838 +/- 603 or 3131 +/- 832 receptors per cell, with a Kd of 0.21 +/- 0.01 or 0.18 +/- 0.09 nM, using [3H]SP or 125I-SP, respectively. No receptors were found on PBL, polymorphonuclear leukocytes, splenocytes, IEL, or jejunal lamina propria lymphocytes using either radioligand. These findings dispute the presence of large numbers of SP receptors on lymphocytes in peripheral blood, spleen, or intestinal mucosa, and argue against any major effect of SP on T cell proliferation or spontaneous cytotoxicity.

Comparative studies of the cross-linked regions of elastin from bovine ligamentum nuchae and bovine, porcine and human aorta. 1. The preparative Edman degradation of desmosine-containing peptides permitted the isolation of peptides C-terminal to the desmosine cross-links in bovine, porcine and human aortic elastin as well as bovine ligamentum nuchae elastin. This identifies the lysines in the tropoelastin which give rise to the desmosine cross-links. 2. The sequences from bovine aortic elastin were identical with those obtained from bovine ligamentum nuchae elastin but differed from those obtained from the other species. The most striking difference involves the occurrence of phenylalanine in bovine elastin and tyrosine in porcine and human elastin C-terminal to the desmosine cross-links. 3. The sequences of the C-terminal peptides were found to fall into two distinct classes, one starting with hydrophobic residues, the other starting with alanine. It is proposed that thehydrophobic residue prevents the enzymic oxidative deamination of the adjacent lysine e-amino group and this then contributes the nitrogen to the pyridinium ring of the cross-links.

[Characteristics of the palate and palatine folds in twins]. In a sample of 95 pairs of twins (36 mz and 59 dz) the traits were analysed which define the shape of the palate, the intensity, direction and ramification of the plicae palati, the intensity and location of the raphae palati mediana and the shape and size of the papila incisiva. The impressions of the palates were made with optosil and these models were photographed. The photographs were analysed. The results indicate a significant genetic determination of the shape of the palate and the papilla incisiva and of the direction of the plicae palati. The analysed traits give the greatest values to the Hc index of inheritance.

Growth inhibition of Plasmodium falciparum involving carbon centered iron-chelate radical (L., X-)-Fe(III) based on pyridoxal-betaine. A novel type of antimalarials active against chloroquine-resistant parasites. Malaria parasites have been shown to be more susceptible to oxidative stress than their host erythrocytes. In the present work, a chloroquine resistant malaria parasite, Plasmodium falciparum (FCR-3) was found to be susceptible in vitro to a pyridoxal based iron chelator--(1-[N-ethoxycarbonylmethylpyridoxlidenium]-2-[2'-pyridyl ] hydrazine bromide--(code named L2-9). 2h exposure to 20 microM L2-9 was sufficient to irreversibly inhibit parasite growth. Desferrioxamine blocked the drug effect, indicating the requirement for iron. Oxygen however, was not essential. Spectrophotometric analysis showed that under anoxic conditions, L2-9-Fe(II) chelate undergoes an intramolecular redox reaction which presumably involves a one electron transfer and is expected to result in the formation of free radical. Spin trapping coupled to electron spin resonance (ESR) studies of L2-9-iron chelate showed that L2-9-Fe(II) produced free radicals both in the presence and absence of cells, while L2-9-Fe(III) produced free radicals only in the presence of actively metabolising cells.

Stimulation of renal sodium reabsorption by angiotensin II. Various parameters of renal function were studied before, during, and after the infusion of physiological increments of angiotensin II directly into one renal artery of anesthetized dogs. During water diuresis and during antidiuresis induced with exogenous antidiuretic hormone (ADH), angiotensin II consistently reduced UNaV, UKV, and CPAH, and increased the filtration fraction in the infused kidney. Urinary osmolality was increased only in the presence of ADH, while during water diuresis angiotensin II had no apparent effect on urinary osmolality or flow rate. During saline diuresis, a mean increment of angiotensin II concentration of 14 pg/ml was sufficient to significantly reduce UNaV and urinary flow rate. Changes in CCr, CPAH, and filtration fraction did not correlate with changes in sodium excretion, and intracortical distribution of blood flow remained unaltered. These data support the hypothesis that normal circulating levels of angiogensin II play a direct renal role in the control of sodium, potassium, and water homeostasis, and that angiotensin II exerts a direct, stimulatory effect on tubular sodium reabsorption independent of changes in GFR, RPF, filtration fraction, or intracortical distribution of blood flow.

Aqueous humor pilocarpine and timolol levels after instillation of the single drug or in combination. Aqueous humor levels of pilocarpine and timolol in rabbits after administration of either 2% pilocarpine or 0.5% timolol in single-drug solutions were compared with the concentrations found after instillation of a fixed combination of 0.5% timolol and 2% pilocarpine drops. Time intervals considered were 15 min, 30 min, 1 hr, 4 hr, and 8 hr after application. Drug concentrations were analyzed in individual aqueous samples by high-performance liquid chromatography. No statistically significant differences in either pilocarpine or timolol concentrations in aqueous humor were found at any time tested between the single-drug preparations and the combination.

Effect of nitrogen sources on oxidoreductive enzymes and ethanol production during D-xylose fermentation by Candida shehatae. The effect on D-xylose utilization and the corresponding xylitol and ethanol production by Candida shehatae (ATCC 22984) were examined with different nitrogen sources. These included organic (urea, asparagine, and peptone) and inorganic (ammonium chloride, ammonium nitrate, ammonium sulphate, and potassium nitrate) sources. Candida shehatae did not grow on potassium nitrate. Improved ethanol production (Y(p/s), yield coefficient (grams product/grams substrate), 0.34) was observed when organic nitrogen sources were used. Correspondingly, the xylitol production was also higher with organic sources. Ammonium sulphate showed the highest ethanol:xylitol ratio (11.0) among all the nitrogen sources tested. The ratio of NADH- to NADPH-linked D-xylose reductase (EC 1.1.1.21) appeared to be rate limiting during ethanologenesis of D-xylose. The levels of xylitol dehydrogenase (EC 1.1.1.9) were also elevated in the presence of organic nitrogen sources. These results may be useful in the optimization of alcohol production by C. shehatae during continuous fermentation of D-xylose.

Resistance of female Fischer-344 rats to the hepatonecrogenic and hepatocarcinogenic actions of a choline-devoid diet. A series of experiments was performed to investigate the response of female Fischer-344 rats to a choline-devoid (CD) diet. In contrast to findings previously made in male Fischer-344 rats, hepatocellular carcinomas did not develop in females chronically fed the diet. Their liver actually showed only minimal histopathological changes. For these reasons, the steatogenic and hepatonecrogenic actions of a CD diet were compared in male and female Fischer-344 rats. Young adult females were found to be largely resistant to both. The results were taken as further evidence of the primary and essential role played by an enhanced cell turnover in the pathogenesis of the carcinomas induced in male Fischer-344 rats by this non-chemical, nutritional model of hepatocarcinogenesis. A high incidence of preneoplastic and benign lesions developed in breast, pancreas or stomach of females chronically fed the CD diet. However, a similar spectrum and high incidence of lesions was observed in control rats fed a choline-supplemented diet. These findings were attributed to an enhanced occurrence of spontaneous lesions, most likely due to the high fat content (15%) of the two diets used.

Reassessment of lead exposure in New Jersey using GIS technology. In order to prevent children's exposure to lead, a variety of sources must be controlled. The New Jersey Department of Environmental Protection and Energy (NJDEPE) is using its Geographic Information System to identify areas within Newark, East Orange, and Irvington, New Jersey, where there may be greater environmental exposure to lead. Sensitive populations are identified through the U.S. Bureau of the Census information. Blood screening data provided by the New Jersey Department of Health (NJDOH) provide reported patterns of elevated blood lead in the study area. Comparisons of these spatial patterns will assist the NJDEPE in its soil sampling activities and lead exposure research, will provide information for public education, and will provide valuable information on sections of the study area where further screening and public education may be needed.

Correlates of self-care among the independent elderly: self-concept affects well-being. There was a significant positive correlation between self-care and self-concept, suggesting that psychosocial interventions that enhance an older person's self-concept may be expected to improve self-care and, conversely, that participation in self-care activities may be expected to strengthen self-concept. Although functional health status was not significantly correlated with self-care, it was related to self-concept, suggesting either that functional health has a role in maintaining self-concept among older persons or that self-concept positively contributes to functional health status. Self-concept and self-care can be enhanced in older persons by communicating respect and demonstrating caring behaviors, reinforcing health-promoting behaviors, encouraging activities of daily living that contribute to independence, and by avoiding a focus on self-care deficits.

Gonadotropin-releasing hormone (GnRH) agonists and GnRH antagonists do not alter endogenous GnRH secretion in short-term castrated rams. The administration of GnRH agonists and antagonists suppresses pituitary LH secretion. However little is known about their effects on endogenous GnRH secretion. To determine if GnRH analogs act on GnRH secretion through a short or ultrashort loop feedback mechanism, experiments were performed to analyze GnRH secretion in hypophyseal portal blood of conscious short-term castrated rams under both agonist or antagonist treatment. In Study 1, six rams were castrated and surgically prepared for portal blood collection on day -7. Portal and peripheral blood were collected simultaneously every 10 min for 14-15 h on day 0. Five hours after the beginning of the portal blood collection, animals were injected im with 5 mg potent GnRH antagonist (Nal-Glu). In Study 2, six rams were treated daily from day -11 to day 0 with the GnRH agonist D-Trp6 GnRH (0.5 mg im). Castration and surgical preparation for portal blood collection were performed on day -7. On day 0 portal and peripheral blood were collected simultaneously every 10 min for 10-11 h. In both studies, to determine whether an increase in GnRH concentration in hypophyseal portal blood can overcome the inhibitory effect of the GnRH analogs, between 5 and 5.5 h after the injection of the analogs, endogenous GnRH secretion was stimulated by Naloxone administration (3 x 100 mg, iv, at 30-min intervals) followed by a bolus of exogenous GnRH (2 x 10 micrograms, iv at 30-min intervals). In Study 1, Nal-Glu administration led to a rapid cessation of pulsatile LH secretion for the duration of blood collection while GnRH pulse frequency and amplitude were not affected. GnRH and LH pulse frequency before and after Nal-Glu administration were, 6.2 +/- 0.6 vs. 5.7 +/- 0.8 (NS) and 5.3 +/- 0.3 vs. 0.3 +/- 0.2 pulses/6 h (P less than 0.001) respectively. In Study 2, peripheral LH secretion was completely suppressed while GnRH secretion (portal blood) remained pulsatile. GnRH pulses frequency and pulse amplitude were 4.3 +/- 0.3 pulses/6 h and 43.0 +/- 4.7 pg/ml, respectively. In both experiments, neither stimulation of endogenous GnRH secretion by naloxone nor administration of exogenous GnRH allowed reinitiation of LH secretion. However, additional studies in two animals of each treatment group (study-III) showed that this was clearly a dose related effect in antagonist treated but not in agonist-treated animals since higher doses of exogenous GnRH (i.e. 100 micrograms or 1000 micrograms) can increase significantly LH levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of potassium ethylxanthogenate on the acetaminophen hepatotoxicity in mice. The effects of potassium ethylxanthogenate (PEX), acetaminophen (AAP) and their combination on the activity of serum transaminases, liver glutathione level and the activity of some drug metabolizing enzyme systems in male albino mice are studied. PEX (80 mg/kg p. o.), applied one hour before AAP (737.5 mg/kg p. o.) or simultaneously with it, prevents the AAP-induced rise in transaminases. PEX reduces significantly the AAP-induced depletion of the liver glutathione. Eighteen hours after the administration of a hepatotoxic dose of AAP, there is a statistically significant decrease of the activity of aniline hydroxylase, ethylmorphine demethylase, uridine diphosphoglucuronyl transferase, glutathione-S-transferase, NADPH-cytochrome-c-reductase, the P-450 content and a 5-fold increase of TBA-reactive products. PEX, introduced one hour before AAP or simultaneously with it, prevents these changes. The basic mechanism through which PEX reduces the liver toxicity of AAP is assumed to be the decrease in the amount of toxic metabolite formed.

[Traumatic injuries and diseases of the diaphragm]. The article analyses experience in diagnosing the pathological condition and treating 125 patients with acute injury to the diaphragm (61 patients) and chronic traumatic diaphragmatic hernias (64 patients). The authors indicate the therapeutic and diagnostic means in this pathological emergency due to the acute trauma of the chest and abdomen or incarceration of the abdomen. The diagnostic errors and their consequences are analysed. Operation was conducted on 104 patients. In ruptures of the diaphragm in the zone of the esophageal hiatus the cardia was drawn downwards and fastened under the diaphragm; in cases of fractures of the bony framework of the chest with the formation of fragments, panel fixation of the costal fragments and the sternum was carried out by the authors' methods. The results of the surgical interventions are shown (18 patients--17.4% died) with emphasis on the character of the disorders and the lapse of time from the development of the emergency to the application of therapeutic aid.