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Biomedical subjects

K Schenck

Publications and source records attributed to K Schenck.

At least 55 records · Page 3Linked to original sources
PubMed1990

Synthesis and biochemical evaluation of tritium-labeled 1-methyl-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1H-indazole-3-carboxa mide, a useful radioligand for 5HT3 receptors.

The advent of potent, highly selective 5HT3 receptor antagonists has stimulated considerable interest in 5HT3 receptor mediated physiology and pharmacology. To permit detailed biochemical studies regarding interaction of the indazole class of serotonin (5HT) antagonists with 5HT3 receptors in multiple tissues, we synthesized 1-methyl-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1H-indazole- 3-carboxamide (LY278584, compound 9) in high specific activity, tritium-labeled form. This radioligand was selected as a synthetic target because of its potency as a 5HT3-receptor antagonist, its selectivity for this receptor viz a viz other 5HT-receptor subtypes, and the ability to readily incorporate three tritia via the indazole N-CH3 substituent. Alkylation of N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1H-indazole-3-carboxamide (8) with sodium hydride and tritium-labeled iodomethane, followed by HPLC purification, resulted in [3H]-9 with a radiochemical purity of 99% and a specific activity of 80.5 Ci/mmol. This radioligand bound with high affinity to a single class of saturable recognition sites in membranes isolated from cerebral cortex of rat brain. The Kd was 0.69 nM and the Bmax was 16.9 fmol/mg of protein. The specific binding was excellent, and accounted for 83-93% of total binding at concentrations of 2 nM or less. The potencies of known 5HT3-receptor antagonists as inhibitors of [3H]-9 binding correlated well with their pharmacological receptor affinities as antagonists of 5HT-induced decreases in heart rate and contraction of guinea pig ileum, suggesting the central recognition site for this radioligand may be extremely similar to or identical with peripheral 5HT3 receptors.

Animals↗
PubMed1989

Effect of LY53857, a selective 5HT2 receptor antagonist, on 5HT-induced increases in cutaneous vascular permeability in rats.

Both serotonin and histamine increased cutaneous vascular permeability in rats; however, serotonin was approximately 100-fold more potent than histamine. LY53857 (0.1 and 1.0 mg/kg, i.p.), a selective 5HT2 receptor antagonist, blocked serotonin- but not histamine-induced increases in cutaneous vascular permeability. the alpha 1 receptor antagonist, prazosin, did not significantly affect increases in vascular permeability produced by serotonin. These data extend previous studies with LY53857 by further documenting its selectivity as a 5HT2 receptor antagonist. In addition, these results with a selective 5HT2 receptor antagonist provide evidence that 5HT2 receptor activation may be the predominant mechanism associated with vascular permeability changes induced by serotonin.

Animals↗
PubMed1989

MHC class II invariant chains in antigen processing and presentation.

Most protein antigens cannot elicit a T-cell response unless they are processed to peptides, which are then presented to T lymphocytes by surface MHC class II molecules. Recent evidence supports an essential role of the invariant chain associated with class II MHC polypeptides in antigen processing.

Antigens↗
PubMed1989

Serum levels of antibodies against Actinobacillus actinomycetemcomitans in various forms of human periodontitis.

Serum levels of IgG, IgA, and IgM antibodies against extracts from Bacteroides gingivalis PER8, Actinobacillus actinomycetemcomitans Y4, and Bacteroides fragilis NCTC 9343 were determined in three categories of periodontitis patients by means of enzyme-linked immunosorbent assay. The test groups comprised 10 patients with juvenile periodontitis (JP), 18 young patients with severe periodontitis (YP), and 31 patients with adult periodontitis (AP). Nine subjects with healthy periodontium (HP) served as a reference group. Increased frequencies of patients with significantly elevated IgG and IgA antibody values against B. gingivalis and A. actinomycetemcomitans were found in the three periodontitis groups as compared with the HP group. The AP group, however, showed lower IgM values than the other groups. The results support the contention that A. actinomycetemcomitans may play a contributory role in adult periodontitis and that B. gingivalis is a suspected periopathogenic bacterium in juvenile periodontitis. The clinical YP classification was not supported by the present serologic findings.

Actinobacillus↗
PubMed1988

Production and characterization of monoclonal antibodies recognizing head activator in precursor form and immunocytochemical localization of head activator precursor and head activator peptide in the neural cell line NH15-CA2 and in hydra.

A synthetic gene for the hydra neuropeptide head activator (HA) was used to produce large amounts of an HA bacterial fusion protein. From this protein an HA-containing fragment was cleaved out, attached in high copy number to carrier proteins, and used as an immunogen to produce monoclonal antibodies able to recognize head activator in precursor form. Using such antibodies and others with different specificities for HA epitopes in combination with different fixation procedures, we detected HA immunoreactivity in three locations in the HA-rich neural cell line NH15-CA2. A precursor-like HA immunoreactivity was present in the cytoplasm of cells and detected, independent of fixation procedure, by monoclonal antibodies characterized as HA-precursor-specific. With antibodies specific for the HA peptide, two immunoreactivities could be distinguished, one within cells and one at the outer cell membrane. HA was detected within differentiated cells with long processes when crosslinkers such as carbodiimide or glutaraldehyde were applied together with agents like methanol. HA peptide bound to target cells was restricted to small round cells with an undifferentiated morphology, especially to those in the process of cell division. In hydra HA precursor immunoreactivity was localized in interstitial cells and in developing nerve cells. HA peptide immunoreactivity was present in nerve cells, but was more concentrated on and in target cells such as interstitial cells and epithelial cells. In tissue sections immunoreactive cells were especially abundant in regions of high HA content such as hypostome, subhypostomal region, and the future head region of developing buds.

Animals↗
PubMed1987

Antibodies against lipopolysaccharide from Bacteroides gingivalis before and after periodontal treatment.

Specific serum antibody activities of the IgG, IgA and IgM isotypes against lipopolysaccharide (LPS) prepared from Bacteroides gingivalis were measured by an enzyme-linked immunosorbent assay (ELISA) in a group of 12 periodontally healthy subjects and a group of 26 patients with periodontitis. The latter group received periodontal therapy, completed within about 1 yr. A serum sample was obtained from each participant at the first periodontal examination; a second sample was taken about 2 yr later. The mean antibody levels calculated for the healthy group did not change significantly between the first and second examination. The correlation coefficients computed between the two sets of measurements were 0.93, 0.90 and 0.96 for IgG, IgM and IgA respectively (P less than 0.05). Periodontal treatment significantly improved the clinical status of the patients and was followed by a statistically significant mean reduction in specific antibody levels to the LPS preparation (IgG: 15%, IgA: 30% and IgM: 15%).

Adult↗
PubMed1987

IgG subclass distribution of serum antibodies against lipopolysaccharide from Bacteroides gingivalis in periodontal health and disease.

Serum IgG1, IgG2, IgG3 and IgG4 antibody levels directed against lipopolysaccharide (LPS) from Bacteroides gingivalis were measured in the sera from systemically healthy subjects with and without periodontitis. An enzyme-linked immunosorbent assay was used that included coating of microtiter plates with LPS, and subsequent incubation with patient sera followed by mouse monoclonal subclass-specific antibodies, biotinylated sheep anti-mouse IgG and alkaline phosphatase conjugated to streptavidin. Anti-LPS IgG antibodies were dominated by IgG2, and moderate amounts only of IgG1, IgG3 and IgG4 were found. The periodontitis patients had significantly higher anti-LPS IgG1, IgG2 and IgG3 levels when compared to the subjects with healthy periodontium (p less than 0.05, Mann-Whitney test).

Antibodies, Bacterial↗
PubMed1986

Effect of nitrendipine, diltiazem, trifluoperazine and pimozide on serotonin2 (5-HT2) receptor activation in the rat uterus and jugular vein.

The present study explored the calcium source used in serotonin (5-HT)-induced contractions mediated by 5-HT2 receptor activation in the rat uterus and jugular vein in vitro. In the rat uterus, the calcium channel antagonists, nitrendipine and diltiazem, and the neuroleptic agents, trifluoperazine (TFP) and pimozide, antagonized potently and noncompetitively 5-HT-induced contractions. These data are compatible with the contention that 5-HT-induced contractions in uterine smooth muscle require extracellular sources of calcium. In contrast, neither diltiazem nor nitrendipine inhibited the contractile response to 5-HT in the rat jugular vein although 5-HT-induced contractions in the jugular vein required the presence of extracellular calcium. This difference in sensitivity to calcium channel antagonists between the uterus and jugular vein was not related to differences in the receptor occupancy-response curves for 5-HT as these were similar in the rat uterus and jugular vein. Furthermore, in the jugular vein, neither diltiazem nor nitrendipine were markedly effective in blocking contractions produced by potassium chloride, an agent that activates voltage-dependent calcium channels, suggesting that this tissue lacks calcium channels susceptible to blockade by conventional calcium channel antagonists. Although responses to 5-HT in the jugular vein were only affected marginally by calcium channel antagonists, TFP and pimozide produced concentration-dependent rightward parallel shifts of 5-HT-induced contractions in the jugular vein. Furthermore, both TFP and pimozide showed high affinity at 5-HT2 binding sites in rat brain cortical membranes and the apparent dissociation constant at 5-HT2 receptors in the jugular vein was 38 and 31 nM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Enzyme-linked immunosorbent assay for human IgG, IgA, and IgM antibodies to antigens from anaerobic cultures of seven oral bacteria.

Monocultures of 7 oral bacteria were grown anaerobically, and antigens were partially purified from the supernatant fluids by gel filtration. Isoelectric focussing showed that the antigen fractions contained PAS-positive material and proteins focussing between pH 3.5 and pH 5.5. Specific activity against the 7 antigen fractions was observed for IgG, IgA, and IgM in serum from patients with periodontal disease by means of enzyme-linked immunosorbent assay (ELISA). Conditions for antigen coating in ELISA were studied, and large variations with regard to optimal concentration were found among the 7 fractions. The ELISA readings were virtually unaffected by increasing the pH of the coating buffer from 5 to 9. Addition of sheep serum to the incubation buffer was disadvantageous as the serum showed moderate antibody activity to the 7 antigen fractions, and human serum apparently contained IgM antibodies to sheep IgG. Addition of 0.5% BSA improved the reproducibility of ELISA considerably, although the sensitivity was somewhat decreased.

Anaerobiosis↗
PubMed1979

[Childhood and prepuberal schizophrenia ].

The author gives a short review of modern aspects concerning schizophrenia in childhood. Very early forms of the preschool age are excluded for nosological reasons. Age-specific phenomenology, differential diagnosis, course and prognosis as well as the outcome of the disease are discussed.

Adolescent↗
PubMed1979

Coronary artery spasm--a case with fatal outcome.

The case of a 45-year-old man with nocturnal angina and angiographically verified spontaneous spasm of the left anterior descending and left circumflex coronary arteries is described. The patient died suddenly one month after investigation, despite treatment with a beta-blocker and nitroglycerin. Other forms of pharmacological treatment should be tried in such patients.

Angina Pectoris↗
PubMed1978

[On the diagnostic efficiency of the body-coordination-test for children (KTK) (author's transl)].

The diagnostic efficiency of KTK was examined by evaluation of catamneses of children who mostly during their first year of life underwent neurosurgical treatment for subdural effusions. In addition, the influence of intelligence, side of hemispheric lesion, equivocal neurological signs and physical impairment, body height and weight as well as foot preference on the performance of motor tasks was examined. The results suggest sufficient practical advantages of KTK for the detection of brain damage in children.

Body Height↗