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Biomedical subjects

J Seifert

Publications and source records attributed to J Seifert.

At least 91 records · Page 5Linked to original sources
PubMed1988

Ontogenesis and properties of the convulsant recognition site(s) of the gamma-aminobutyric acid (GABA) receptor complex in chicken embryo.

Ontogenesis of the convulsant (picrotoxinin or t-butylbicyclophosphorothionate (TBPS] site(s) was defined in chicken embryonic brain with the radioligands [35S]TBPS and [3H]t-butylbicycloorthobenzoate [( 3H]TBOB). Binding of the radioligands is detectable from day 6 of incubation. The increase in binding after day 14 of incubation is due to an increase in the number of binding sites. The pharmacological properties of the embryonic recognition site(s) do not undergo significant changes during hatching based on the affinity of embryonic and chick brain membranes for [3H]TBOB; the rate of association and dissociation for TBOB; non-competitive inhibition of [3H]TBOB binding and modulation of 1R, alpha S-cis-cypermethrin interaction with the recognition site(s) by GABA; and inhibition of radioligand binding by endrin, picrotoxinin and TBPS. Early development and in vitro susceptibility of the recognition site to convulsive toxicants makes the embryo a possible target for a variety of drugs and environmental toxicants acting at this site.

Aging↗
PubMed1988

Biosynthesis of pyrimidine nucleotides and level of cytochrome P-450 in rat liver and kidney after clofibrate administration (an in vivo study).

Like other lipid-soluble xenobiotics, clofibrate (ethyl-2-(4-chlorophenoxy)-2-methylpropanoate) increased the level of microsomal cytochrome P-450 in liver and decreased the utilization of 14C-orotic acid for the synthesis of hepatic cytidine nucleotides. This phenomenon was associated with the increased (a) uptake of 14C-cytidine, (b) total content of cytidine components of the acid-soluble extract and (c) utilization of this nucleoside for the synthesis of RNA. No changes were observed in uridine components. Clofibrate also increased the level of cytochrome P-450 in kidney microsomes; the degree of induction was almost the same as in the liver. The variations of renal pyrimidine metabolism after administration of the drug were analogous to those observed in the liver.

Animals↗
PubMed1988

The stimulatory effect of muramyl dipeptide (MDP) on the proliferation processes in parenchymal organs of rats.

The administration of muramyl dipeptide (MDP) in a single dose of 2 mg/kg increased markedly the utilization of 3H-thymidine for the synthesis of DNA thymine in liver, kidney and thymus, while no effect has been observed in spleen. Higher doses of MDP (5 mg and 10 mg) did not further increase the effect, but, on the contrary, in some tissues such as thymus, the effect was abolished. The repeated administration of 1 mg/kg of MDP for 7 days, contrary to single administration, had no effects. The measurement of proliferation activity in the experiment where DNA in the organs has been previously labeled with 3H-thymidine, has shown that the repeated administration of MDP (1 mg/kg) led to a more rapid decay in specific activity of DNA thymine in liver, kidney and thymus, but no effect was seen in spleen. The activities of thymidine kinase in the cytosole fraction of thymus and spleen after a single administration of MDP (1 mg/kg), are influenced in different ways. While in thymus the enzyme activity increased between 16 and 24 h, not being markedly changed in the early intervals, in spleen a significant decrease in phosphorylation of 14C-thymidine can be observed as early as 2 h after administration, and the decrease persists up to 48 h.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Effect of nafenopin and clofibrate on uptake and utilization of labeled thymidine for DNA synthesis in rat liver and kidney.

The mitogenic effect of nafenopin and clofibrate in the liver is paralleled by a decreased utilization of [14C]thymidine for kidney DNA synthesis. Analogous changes in the liver and kidney DNA biosynthesis after nafenopin administration occur if [14C]orotic acid is added as a precursor of DNA pyrimidines. There is a time correlation between the uptake of labeled thymidine and its utilization for DNA synthesis in the liver during the initial stages of the mitogenic effect of the drug. Later on--after administration of a low dose of nafenopin or of repeated doses of clofibrate--the specific activity of DNA thymine does not differ from the values observed with the control group: the total radioactivity of the thymine components of the acid-soluble extract is even increased. The existence of a correlation between decreased utilization of [14C]thymidine for DNA synthesis and the total radioactivity of the thymine components of the acid-soluble extract in kidney can be observed only during the early stages after nafenopin administration. Subsequently, when the depression of the specific activity of kidney DNA thymine still persists, the specific activity of the thymine components of the acid-soluble extract does not differ from control values. The utilization of [14C]thymidine for DNA synthesis in the kidney is decreased after repeated clofibrate administration only 24 h after the last dose of the drug; these values later increase and even exceed control values. The total radioactivity of the thymine components of the kidney acid-soluble extract is unchanged.

Animals↗
PubMed1987

Cooperative Group of Additional Immunoglobulin Therapy in Severe Bacterial Infections: results of a multicenter randomized controlled trial in cases of diffuse fibrinopurulent peritonitis.

A multicenter randomized controlled clinical trial, which was carried out in 10 hospitals in the Federal Republic of Germany between 1979 and 1983, studied the influence of i.v. immunoglobulin G on the mortality in patients with diffuse acute fibrinopurulent peritonitis. Altogether 288 patients were enrolled in the trial. There was no statistically significant difference in the mortality rates within the treated group (46%) vs the control group (41%). The power of the statistical test to detect a decrease of the mortality by 20% was calculated to be 0.93. This result did not change when we eliminated 50 patients not strictly obeying the entrance criteria of the analysis, or when we focused on a subgroup of patients with initial deficiency of immunoglobulin G. Factors influencing mortality were a preceding laparotomy, serum creatinine level above 2 mg/100 ml, and necessity for artificial respiration. These factors, reflecting the surgical situation and the severity of shock, essentially explain the mortality differences observed between the participating hospitals.

Bacterial Infections↗
PubMed1987

Effect of clofibrate on DNA synthesis in rat liver and kidney.

A single dose of clofibrate (400 mg/kg), given to rats, increased the incorporation of (3H)thymidine into liver DNA, in a period of 20-30 h after administration. However, (3H)thymidine incorporation into hepatic DNA of rats treated repeatedly was identical to that of control animals. After the administration of a single dose of clofibrate a small increase in (3H)thymidine incorporation also occurred in kidney DNA; repeated doses, however, resulted in a marked suppression of labeling.

Animals↗
PubMed1987

Absorptive capacity of the transplanted small bowel.

Small bowel transplantation (SBT) has been carried out in man in several cases without success, because immunologic problems were unsolved. In experimental SBT a 'two step' model was developed, which enables long term observation of immunologic phenomena. In this model the graft is in a heterotopic position to the recipient's own small bowel. After 35 days the recipient's own bowel is removed and replaced by the graft, now in orthotopic position and again in contact with luminal chymus. To investigate functional and morphological changes, which result from the procedure, the resorption of glucose and water was measured in syngeneic transplanted rats by an in vivo recirculation system and the mucosa was evaluated three dimensionally. The graft mucosa showed a significant reduction in villus height, crypt length and villus surface and a corresponding decrease in glucose and water absorption during heterotopic position. If the graft came into the orthotopic position, the mucosa did regenerate which was expressed by the significant longer crypts of the graft compared with those of the controls, although the graft's villus height and surface are still smaller. Glucose and water absorption increased and were higher in orthotopic transplanted animals, when absorption was expressed per unit intestinal length. The results indicate that in the 'two step' model of SBT the absorption of water and glucose is influenced to such an extent, that recovery is possible after three weeks, thus enabling orthotopic SBT. This almost complete recovery of the mucosa is further evidence of the regeneratory capacity of the small bowel, which enables clinical small bowel transplantation.

Animals↗
PubMed1987

Direct immunostaining of TSH receptor related autoantibodies in Graves' disease.

Ten thyroid specimens from patients with Graves' disease were investigated immunohistologically with respect to the localisation of thyrotropin (TSH) receptor related autoantibodies. After conventional preparation of formalin-fixed and paraffin-embedded thyroid slices for immunostaining, 3-5 micron tissue sections were incubated with a porcine thyrotropin receptor containing membrane preparation (pTSH-R). The TSH receptor containing membrane fragments bound to the thyroid tissue were revealed with a slightly modified unlabelled PAP technique according to Sternberger, using an antiserum to pTSH-R obtained from immunized rabbits. This technique resulted in a staining of a considerable portion of plasma cells within the lymphoplasmacellular infiltrates of all the Graves thyroids. No staining occurred if for negative control either pTSH-R or its antiserum from rabbit was omitted. In addition, the staining reaction was markedly reduced by pretreatment of pTSH-R with serum from patients with Graves' disease in order to occupy its binding sites for autoantibodies prior to the staining procedure. It is concluded that the staining of the intrathyroidal plasma cells is due to their synthesis of autoantibodies directed against TSH receptor related structures of thyroid epithelia. The results are in keeping with the concept that the thyroid as the target organ itself is the site of autoantibody synthesis in Graves' disease.

Autoantibodies↗
PubMed1987

[Can macromolecules be absorbed and what effect does the immune status have on it?].

It was shown by means of radioactive labelling that adult animals and humans are also able to absorb protein intact in its biological active form from the gastro-intestinal tract. A large part of these macromolecules retains their original biological activity. Depending on size, particles (polls, synthetic particles) can also be absorbed. The energy supply is not influenced by this phenomenon. It is postulated that a rudimentary mechanism present in the lymphatic system of the gastro-intestinal tract is involved. This absorbation mechanism receives information from the immune system about foreign and the body's own substances and about useful and unuseful nutriment. On the basis of investigations, carried out by us, it is speculated that immunological information takes place over the lymphatic tissue of the gastro-intestinal tract and is passed on the lymphatic system.

Animals↗
PubMed1987

[Causes and treatment of seasickness].

Seasickness is usually induced by conflicting sensory cues. However, very little is known about the neural pathways and processes which play a role in the development of nausea. Since the symptoms, for example, pallor, sweating and vomiting are all of parasympathetic origin, the common antiemetic drugs are anticholinergically efficient. More recently, additional drugs and modified forms of application have been introduced to reduce the soporific side effects. It is pointed out that onboard behaviour and even choice of vessel can be of more importance than use of antivertiginous drugs. Besides attention to the individual adaptation to the atypical seagoing environment, simple behaviour patterns such as fixation on the horizon, avoiding of head movements and reduction of conflicting sensory cues can be very effective in reducing symptoms.

Antiemetics↗
PubMed1987

[Effectiveness of various immunoglobulin preparations administered by the intravenous route in peritonitis in the rat model].

Intraabdominal sepsis in rats was induced as a sublethal infection (mortality rate of controls: 60%-80%) and as a lethal infection (mortality rate of controls: 100%). The effectivity of different immunoglobulin (IgG) preparations alone or together with an antibiotic combination therapy (gentamicin + piperacillin) was then tested. In sublethal infection, 5 intravenous administrations of three 7S-IgG preparations and a plasmin-treated preparation at a dosage of 0.5 g/kg b.w. were able to reduce lethality only slightly, whereas a 5S-IgG preparation was able to reduce lethality by 30% significantly. Intraperitoneal administration of two 7S-IgG preparations (s-sulfitolysis, 42 degrees C/ammonium sulfate) and the 5S-IgG preparation reduced lethality to 27%, 37% and 47%, respectively, whereas another 7S-IgG (iodoacetamide/dithiothreitol) and a plasmin-treated preparation failed to reduce lethality significantly. The convincing results obtained with the 5S-IgG preparation are probably due to the fact that Fc-mediated side-effects could be avoided. The better effectivity of intraperitoneal compared to intravenous administration can be explained by much higher concentrations of specific antibodies at the site of infection. In the lethal infection model the mortality of animals treated with antibiotics only was 50%. The additional intravenous administration of 7S-IgG (42 degrees C/ammonium sulfate), a plasmin-treated preparation and a 5S-IgG was unable to reduce mortality any further. These findings are in contrast to several publications which postulate synergism of antibiotics and immunoglobulins.

Animals↗
PubMed1987

[Principles of particle resorption in the gastrointestinal tract].

The uptake of allergens by the epithelium of gastrointestinal tract is not sufficiently investigated. This is true especially for the absorption of small particles like spores and pollen. By means of scanning-electron-microscopy it is possible to locate particles easily and to observe absorption solutions of 0.5 micron and 1 micron latex particles, of 15 microns Urtica pollens and of 35 microns Lycopodium spores and further on by cannulation of the thoracic duct the transport of particles was investigated. After a short time of absorption latex particles were found to be concentrated on M-cells of Peyer's patches (PP) and were found in a close contact to macrophages inside the lymph follicles. There was a constant proportion of M-cells to absorptive-like cells in PP from about 1 to 12. Obviously all particles were also transported by thoracic duct lymph. The results obviously indicate: primary absorption of small particles occurs in M-cells of PP; absorption time is dependent on particle size and transport of particles is achieved by abdominal lymph.

Allergens↗
PubMed1986

Ca2+-dependent ryanodine binding site: soluble preparation from rabbit cardiac sarcoplasmic reticulum.

The Ca2+-dependent ryanodine binding site of rabbit cardiac sarcoplasmic reticulum is solubilized by treatment with 20 mM CHAPS detergent and 1 M NaCl for 30 min at 0 degrees C. Ca2+ added at 5 microM enhances binding, at 0.5 mM increases both the affinity and number of [3H]ryanodine binding sites, while at 10 mM only the number of binding sites is increased. Mg2+ up to 1 mM does not significantly affect [3H]ryanodine binding. Radioligand binding is strongly enhanced by all alkali metal chlorides except LiCl. NaCl increases the rate of association of the ligand and the affinity of the binding site but does not influence the dissociation. NaCl and CaCl2 enhance the thermal stability of the [3H]ryanodine-binding protein. Thiol groups are essential for [3H]ryanodine binding. Ruthenium red and Cd2+ inhibit binding, while theophylline is stimulatory at low (micromolar) Ca2+ concentrations by a mechanism other than phosphodiesterase inhibition. Gel permeation chromatography establishes that the ryanodine binding protein is localized only in the high molecular mass fraction (greater than 669 kDa). Polyacrylamide gel electrophoresis of the proteins following treatment with SDS and 2-mercaptoethanol indicates that more than 90% are of low molecular mass (34-70 kDa) and that two stain blue with Stains-all as expected of Ca2+-binding proteins.

Animals↗