Biomedical subjects
Publications and source records attributed to H Werner.
The presence of immunoreactive vasoactive intestinal peptide (VIP) in human milk has been demonstrated by high performance liquid chromatography and a specific radioimmunoassay. Immunoreactive VIP-like peptide co-eluted with the synthetic marker on a reversed phase C18 column. The levels of the neuropeptide ranged between 67 and 161 pg VIP/ml milk.
The presence of immunoreactive and biologically active somatostatin in sheep and human milk has been demonstrated. Milk somatostatin exhibits similar chromatographic behavior to that of synthetic somatostatin-14 on both reversed-phase C18 and cation-exchange high-performance liquid chromatography columns. Milk, in contrast to plasma, contains only somatostatin-14-like material. Milk somatostatin was capable of inhibiting the basal and the prostaglandin-induced release of growth hormone from anterior pituitary cell cultures in a pattern similar to synthetic somatostatin-14. The concentrations of the peptide, as determined by radioimmunoassay, were found to be 113 pg/ml in human milk and 150 +/- 4.8 pg/ml (mean +/- range) in sheep milk. These values are severalfold higher than the corresponding concentration of the peptide in the plasma of these species. These findings are analogous to our previous observations concerning two other hypothalamic hormones, luliberin and thyroliberin [Baram, T., Koch, Y., Hazum, E. and Fridkin, M. (1977) Science (Wash. DC) 198, 300-302]. The high concentration of somatostatin and other neuropeptides in milk implies either an active concentrating mechanism in the mammary gland or an additional extrahypothalamic source for the synthesis and release of these peptides.
Serial blood samples were collected from the unfed spiny dogfish shark (Squalus acanthias) by use of a cannula chronically implanted in the dorsal aorta. Plasma glucose, alanine, lactate, and beta-hydroxybutyrate levels were estimated by standard enzymatic procedures. The metabolite levels were estimated immediately after the surgery, for an additional 3 to 5 postoperative days before experimental use, and for 7 to 9 days after a single infusion of mammalian insulin (50, 100, and 250 IU/kg body wt) or the control solution. Plasma glucose, alanine, and lactate levels declined for 1 or 2 days after the surgery, but beta-hydroxybutyrate levels were essentially unchanged. Plasma glucose levels remained relatively stable for the remainder of the pretreatment period, and in the control animals during the subsequent treatment period. In contrast, plasma alanine and beta-hydroxybutyrate levels increased during both the pretreatment period and the treatment period in the control animals. Plasma lactate levels increased in the control animals after Day 3 of the treatment period. Insulin infusions resulted in severe, prolonged depressions of plasma glucose and alanine levels. Plasma lactate levels also fell after insulin infusion, but the depressed levels were interrupted by precipitous, large increases, followed by sharp declines, that were evident for one to three sampling periods and whose onset varied between Days 3 and 5 in individual animals. The levels increased again in some animals between Days 6 and 9. Plasma beta-hydroxybutyrate levels were comparatively resistant to insulin. After an early decline, plasma beta-hydroxybutyrate rose to levels that were near the control levels by Days 2 through 4, but fell to near the initial levels by Day 5 and thereafter. The results suggest that the spiny dogfish, a species that consumes reliable and abundant amounts of protein and lipid, but little carbohydrate, and that may feed as seldom as every 2 weeks, uses ketone bodies (beta-hydroxybutyrate and presumably acetoacetate) as primary fuels. Glucose is apparently synthesized by gluconeogenesis, alanine and lactate are probable substrates, and ketone bodies are the likely sources of energy. The evidence supports the hypothesis that glucose is synthesized to maintain muscle glycogen reserves that are used for anaerobic glycolysis when the animal is engaged in predation, escape, or other circumstances that dictate vigorous swimming. If other tissues and organs require glucose as a fuel source, the amounts must be exceptionally small.
It was found that serotonin can induce the secretion of a chemotactic activity for polymorphonuclear granulocytes and the secretion of charge-changing in in lymphocyte cultures derived from guinea pigs and mice. The serotonin antagonists methysergide, pizotiphen, cyproheptadine and ketanserin inhibited the secretion of the serotonin-elicited factors, whereas the histamine-type 2 antagonist metiamide had no inhibitory effect. Moreover, the production of Concanavalin A-induced lymphokines (migration inhibition factor for macrophages, chemotactic factor for polymorphonuclear granulocytes and for thymocytes, charge-changing lymphokines) was suppressed in the presence of serotonin in the lymphocyte cultures. The fractionation of the supernatants derived from the serotonin-stimulated lymphocytes revealed that serotonin produced an activity with a molecular weight of 40 kDa in the presence of which the Con A-elicited response was completely inhibited. These findings support the regulatory role of serotonin with respect to immune reactions.
Significant resistance against influenza virus and Mycobacterium tuberculosis infections was induced when trehalose dimycolate from M. tuberculosis or M. bovis but not M. avium was combined with muramyl dipeptide. Trehalose dimycolate from M. tuberculosis, in contrast to that from M. avium, could confer resistance against Toxoplasma gondii infections.
The influence of the cytoskeleton active drugs Cytochalasin B and Colchicine on the 3H-thymidine and 14C-uridine incorporation of Con A stimulated lymphocytes of mice was studied. Both drugs had no influence on the entry of the Con A incubated lymphocytes into the G1-phase but inhibited significantly the entry into the S-phase of the cell cycle. Cytochalasin B and Colchicine differ in their effect on the release of charge changing lymphokines. Colchicine did not influence this release in contrast to Cytochalasin B. The results show that both Cytochalasin B and Colchicine suppress cellular processes which are necessary for going beyond the commitment point. A possible importance of the microfilaments for the release of lymphokines and of the microtubuli for the expression of lymphokine receptors is discussed.
Clinically supposed cases of echinococcosis can be strongly confirmed by application of serodiagnostic techniques. In certain cases false-negative reactions have to be taken into account. This has been observed in 4 out of 51 parasitologically confirmed cases. One patient had a hyalin cyst, a case in which supposingly no antigen diffused into the host's system. In two cases the cysts were calcified, in one patient only no explanation could be given.
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Nonspecific vaginitis is a very common clinical syndrome. In patients with nonspecific vaginitis the normal, lactobacillus-dominated microbial flora is replaced by Gardnerella vaginalis and certain anaerobes, preferably bacteroides spp. The mechanisms by which anaerobes or Gardnerella vaginalis or a combination of these organisms produce the disease condition are still unknown. Treatment with ampicillin and certain other drugs is often effective, but metronidazole appears to be the most effective antimicrobial for this condition. The optimal dose and duration of metronidazole therapy require further study.
Studies were carried out to determine the fate of virulent Toxoplasma gondii challenge in immune animals. Toxoplasma strains isolated from human, swine, rabbit and cat hosts were used for the primary immunization of mice. Brains were removed at various intervals after the challenge and subinoculated into normal mice. Prior immunization with one of the nine toxoplasma strains enabled the mice either to eliminate or harbour the challenge organisms without loss of virulence. The outcome of challenge infection was dependent on the parasite strain used for the immunization and the time interval between challenge and subinoculation. Mice immunized with strain KSU isolated from a cat eliminated repeatedly administered challenge from 80% of animals. Strain S 162 isolated from a swine eliminated similar challenge from only 20% of animals. The results indicate that the extent of protection against virulent T. gondii can vary widely and is related to the immunogenicity of the original immunizing strain.
The zymosan-triggered chemiluminescence response of peritoneal exudate cells from mice infected with relatively virulent or avirulent Toxoplasma gondii strains was examined at various intervals after infection. Toxoplasma infections increased the background chemiluminescence compared with controls, but higher values were attained earlier in virulent than avirulent infection. A phase of transient unresponsiveness to zymosan was observed with both types of toxoplasma strains. Chemiluminescence continued to decline even after the addition of zymosan on day 3 of infection with the virulent strain but only on day 10 with the avirulent strain. Generation of chemiluminescence was enhanced in mice which had been infected with either strain for 1 month.
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Explore the source record for details and available documents.
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Beads of calf serum proteins (CSB) with antigen-antibody complexes or antigen by activation with glutaraldehyde were used as immunoadsorbents for the fractionation of mouse lymphocytes. T-lymphocytes could be separated by this method with high purity. The precursors of antibody-forming cells were completely eliminated from spleen and bone marrow cell suspensions. The unspecific binding of lymphocytes to CBS or Sepharose was similar and not selective for T or B lymphocytes.
The in vitro inhibitory activity of tinidazole, metronidazole, ornidazole, cefoxitin and moxalactam was determined against 150 isolates of clinically important anaerobes including Bacteroides fragilis, Bacteroides bivius and Clostridium perfringens by means of agar dilution tests. The members of 18 gramnegative and 14 grampositive species were inhibited by tinidazole at less than or equal to 0,01-8 micrograms/ml thus being without exception susceptible to the drug. A similar in vitro activity was recorded for metronidazole and ornidazole. Though cefoxitin and moxalactam generally had a good in vitro activity against most anaerobic species, single strains of Bacteroides thetaiotaomicron, B. distasonis, Clostridium difficile and Eubacterium rectale were resistant to these drugs. With regard to its in vitro activity, tinidazole seems to be a promising substance for the therapy of anaerobic infections.
Virtually all anaerobic infections arise endogenously. Underlying conditions often associated with anaerobic infections are diabetes mellitus, corticosteroid therapy, leukopenia, immunosuppression, vascular disease, tissue anoxia and aerobic infection. Various enzymes and other materials produced by the anaerobes act as virulence factors. There is an impressive incidence of anaerobic bacteria in infections involving the lung and pleural space, in liver abscesses, biliary tract infections, skin and soft-tissue infections and bacteremia. Location of infection, previous therapy with aminoglycoside antibiotics and other clues suggest that a given patient may have an anaerobic infection. Whenever possible, a specimen should be obtained by needle and syringe to avoid normal flora. Specimens must be transported to the laboratory under anaerobic conditions. Therapy involves the use of antimicrobials, preferably drugs with a high activity against beta-lactamase-producing Bacteroides spp.