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Biomedical subjects

M Kayser

Publications and source records attributed to M Kayser.

At least 55 records · Page 3Linked to original sources

Subchronic toxicity studies of 3-methyl-1-butanol and 2-methyl-1-propanol in rats.

1. 90-day subchronic toxicity studies with 3-methyl-1-butanol (MEB) and 2-methyl-1-propanol (MEP) were performed on rats to evaluate the toxicological profile of the compounds under conditions of drinking water studies, to identify the potential target organs, and to determine no-observable-adverse-effect-levels (NOAELs) respective of the substances. The test substances were administered to groups of 10 male and 10 female Wistar rats in drinking water at concentrations of 0, 1000 p.p.m. (about 80 mg/kg/d), 4000 p.p.m. (about 340 mg/kg/d) and 16,000 p.p.m. (about 1250 and 1450 mg/kg/d of MEB and MEP respectively). 2. 16,000 p.p.m. was found to be the maximal concentration for both alcohols applicable to rats in drinking water. Higher concentrations had an influence on palatability and could thus not be tested in drinking water studies. 3. At 16,000 p.p.m. MEB a marginal increase in the red blood cell count as well as a slight decrease in the mean corpuscular volume and the mean corpuscular hemoglobin content was observed in males only. These changes are considered to be treatment-related, although the toxicological significance of these findings is unclear. No other substance-related effects were found on body weight (b.w.), mortality, various parameters of clinical chemistry, organ weights, gross pathology and histopathology. 4000 p.p.m. MEB did not cause any substance-induced changes. Therefore, the NOAEL of MEB was defined as 4000 p.p.m. for male and 16,000 p.p.m. for female rats under conditions of oral application via drinking water. 4. MEP concentrations up to and including 16,000 p.p.m. did not induce any signs of toxicity and were therefore defined as the NOAEL respective of this substance for rats under conditions of drinking water application.

Animals↗

Genetic relationships of Asians and Northern Europeans, revealed by Y-chromosomal DNA analysis.

We have identified a new T-->C transition on the human Y chromosome. C-allele chromosomes have been found only in a subset of the populations from Asia and northern Europe and reach their highest frequencies in Yakut, Buryats, and Finns. Examination of the microsatellite haplotypes of the C-allele chromosomes suggests that the mutation occurred recently in Asia. The Y chromosome thus provides both information about population relationships in Asia and evidence for a substantial paternal genetic contribution of Asians to northern European populations such as the Finns.

Animals↗

Analysis of molecular variance (AMOVA) of Y-chromosome-specific microsatellites in two closely related human populations.

The analysis of seven Y-chromosome-specific microsatellite loci revealed a high level of polymorphism in two closely related human populations (Dutch, n = 89, and German, n = 70). Four of these loci were found to generate at least 77 different haplotypes, only 15 of which were shared by the two populations. These results demonstrate that highly informative PCR-based DNA typing of the Y chromosome is now feasible. Assuming a stepwise mutation model, a network comprising all minimum spanning evolutionary trees connecting the haplotypes was constructed. Analysis of molecular variance based upon this network indicated that the within-population heterogeneity with respect to haplotype descent was significantly smaller than the between-population heterogeneity, suggesting that males were more closely related to males from their own population as opposed to males from the other population. These findings suggest that Y-chromosomal microsatellites might be very useful not only for forensic purposes but also in association studies of multifactorial traits, allowing the characterization of the level of genetic distinctiveness of supposedly inbred or isolated populations and discrimination even between closely related populations.

Analysis of Variance↗

Increased microsatellite variability in Macaca mulatta compared to humans due to a large scale deletion/insertion event during primate evolution.

Human (GATA)n microsatellites D12S66 and D12S67 could be successfully amplified by polymerase chain reaction (PCR) in various species of apes and monkeys. In 86 unrelated animals of the most intensively studied species Macaca mulatta we demonstrated five alleles at "D12D66" differing in size in increments of 4 bp (159-175 bp), whereas 17 alleles were observed at locus "D12S67". The alleles of the latter locus are distributed in two separate groups with no alleles of intermediate size. Six alleles were found between 108-128 bp and 11 alleles between 181-249 bp. Mendelian inheritance of the codominant allele was proven by family studies. Sequencing of the "D12S67" locus revealed that the shorter alleles are characterized by a single perfect (GATA)n stretch whereas the longer alleles consist of two blocks of (GATA)n repeats separated by an intervening sequence of 9 bp. The composite structure of the longer alleles closely resembles that of the 12 human D12S67 alleles (229-273 bp). The enormous species variation in the fragment size range, with the smallest allele found in Macaca mulatta (108 bp) and the largest (364 bp) in Gorilla gorilla gorilla strongly indicates that D12s67 has been subjected to recurrent mutations over the course of primate evolution including a large deletion and/or insertion event.

Alleles↗

Establishment of enzyme-linked immunosorbent assay using purified recombinant 83-kilodalton antigen of Borrelia burgdorferi sensu stricto and Borrelia afzelii for serodiagnosis of Lyme disease.

The 83-kDa antigen of Borrelia burgdorferi was expressed as a recombinant protein in Escherichia coli and purified for use in an enzyme-linked immunosorbent assay (p83-ELISA). Antibodies to the 83-kDa antigen of both the immunoglobulin G (IgG) and IgM isotypes could be detected in all stages of Lyme disease. Sensitivity varied, depending on the clinical stage of illness. In early stages, as defined for 118 patients with erythema migrans, it was found to be 20% (24 of 118 patients: 7 with IgM, 16 with IgG, and 1 with IgM and IgG). Of the patients with late-stage Lyme arthritis and acrodermatitis chronica atrophicans, 94% (16 of 17:2 with IgM and IgG and 14 with IgG) and 86% (36 of 42:2 with IgG and IgM and 34 with IgG) revealed positive results in the p83-ELISA, respectively. p83 displays sequence heterogeneity according to the genomospecies, but when the reactions of serum specimens from acrodermatitis chronica atrophicans patients and arthritis patients with p83 derived from representative strains of B. burgdorferi sensu stricto and Borrelia afzelii in ELISAs were compared, no differences in specificity and sensitivity were seen. When 82 serum specimens from healthy controls were tested, none had IgG and only 3 (4%) had IgM antibodies, indicating a high specificity. Positive reactions with antibodies against Treponema pallidum (1 of 37 patients; IgG) and Epstein-Barr virus (1 of 44 patients; IgM) and with autoantibodies of various specificities (1 of 53 patients; IgG) were seen with < 3% of the serum samples te11111111111111111111 high speficicity for B. burgdorferi.2+ 13% for IgM antibodies, the IgM p83-ELISA provided little diagnostic information for Lyme disease, whereas the IgG p83-ELISA appears to be a suita ;e test for serodiagnosis of advanced-stage Lyme disease.

Antibodies, Bacterial↗

Collagenase and gelatinase production by calcifying growth plate chondrocytes.

The regulation of cartilage resorption is important both in cartilage pathophysiology and angiogenesis. Previous work has identified a link between calcification and activation of collagenolysis. The aim here was to test whether production of collagenase itself is also calcification-dependent, using a high-density growth plate chondrocyte culture model of calcification. Ultrastructural studies indicated that calcification occurred around large hypertrophic cells. There was no indication of phagocytosis of crystals even by cells lying next to mineral aggregates, although remodeling of the organic matrix by cell processes was evident. Release of collagenase activity increased dramatically between 24 and 48 h postcalcification, from low or undetectable basal levels. In contrast, gelatinase production was not calcification-dependent. Collagenase was released almost entirely in the latent form, being a consequence of increased protein synthesis rather than activation of existing enzyme. This linkage of calcification with latent collagenase production represents part of a coordinated remodeling of both collagenous and mineral components of the matrix which may also extend, in vivo, to the control of microvascular invasion and resorption.

Animals↗

[Concept of functional therapy exemplified by fresh closed humeral fracture].

The method of functional treatment of closed humerus fractures has gained an established position of success. A good outcome has proved to depend not only on correct indication, but it also depends decisively on physiotherapeutic exercises. The challenge to the physiotherapist has grown, and a standardised concept is now required. The authors' own approach is described in some detail. Excellent success was obtained from 80 in 82 cases, with average periods of treatment being shortened by something between two and four weeks.

Braces↗

Eighteen-year anamnesis of osteoid osteoma--a diagnostic problem?

The 18-year history of osteoid osteoma in a woman aged 43 is presented. The typical physical and radiographic findings are described. Total removal of the tumor resulted in prompt and permanent relief of symptoms. Diagnosis, histopathology, differential diagnosis, treatment, and prognosis of the tumor are discussed.

Adult↗

[Post-traumatic pain syndromes of the shoulder joint--differentiation and treatment].

The main symptom of posttraumatic trouble in the shoulder-joint is the painful immobility. We had to differentiate between genuine shoulder pain originating in shoulder alternation and shoulder pain in consequence of other diseases. Significant causes of posttraumatic shoulder pain are the impingement syndrome with tendon alteration or lesion or, due to fractures, the instable shoulder joint as well as shoulder rigidity. An exact diagnosis and, in consequence an exact treatment can only be accomplished basing on accurate history and specific clinical examination.

Humans↗

[The infected elbow joint fracture].

Post-traumatic infection of the elbow joint is a serious complication, because the bone structure and the thin soft tissue cover make all actions directed at reconstruction and at calming the infection difficult. A good overall prognosis for later function depends decisively on early diagnosis, stability of the fragments and the earliest possible initiation of functional therapy. If this cannot be achieved, the infection must first be treated by transfixation techniques and the joint function restored subsequently. In late cases with chronic inflammation and destruction, nothing but resection arthroplasty or arthrodesis is still possible.

Fracture Fixation, Internal↗

[Results of the surgical treatment of distal femoral fractures].

In a follow-up of 97 operated distal femoral fractures good and satisfactory results were found in 64% of the cases. 22% unsatisfactory and 14% poor findings attribute mainly to the comminuted supracondylar fracture types. More than half of the patients were multiple injured. In 83% of the cases the internal fixation was obtained by the use of the condyle buttress plate.

Adult↗

Human antibody response to immunization with 17D yellow fever and inactivated TBE vaccine.

The antibody response against flaviviruses tick-borne encephalitis (TBE), Kyasanur Forest disease (KFD), Murray Valley encephalitis (MVE), West Nile fever (WNF), Japanese B encephalitis (JE), dengue 2 (DEN-2), and yellow fever (YF) was studied in humans after administration of an inactivated TBE virus vaccine. Individuals were either prevaccinated with 17D yellow fever (experimental group) or without any previous exposure to flaviviruses (control group). The appearance of serum titres of homologous and heterologous haemagglutination inhibition (HI) antibodies, heterotypic DEN-2 neutralizing antibodies, and TBE enzyme-linked immunosorbent assay (ELISA) antibodies were examined. Individuals prevaccinated with the 17D yellow fever developed an antibody pattern that contrasted with that of the control group. This pattern was characterized as follows: (1) Predominantly anti-TBE IgG antibodies appeared earlier and in higher titres than in the control group, (2) heterologous HI antibodies cross-reacting with the WN flavivirus subgroup preceded the appearance of homologous HI antibodies, (3) a broad spectrum HI response was observed against all flaviviruses tested, and (4) low titre heterotypic DEN-2 neutralizing antibodies were formed in about half of the cases. These observations are discussed in the context of cross-reactivity, cross-protection and virus infection enhancement.

Antibodies, Viral↗

Cardiovascular effects of the calcium-agonistic dihydropyridine BAY K 8644 in conscious dogs.

The hemodynamic effects of the dihydropyridine-derivative BAY K 8644 (methyl-1,4-dihydro-2, 6-dimethyl-3-nitro-4-(2-trifluoro-methylphenyl)-pyridine-5-carboxylate), a chemical analogue of Nifedipine, were evaluated in 9 conscious, chronically instrumented dogs. Compared to Nifedipine, BAY K 8644 displays an opposite pharmacological profile. Dose-dependent hemodynamic effects are observed at doses of 4 micrograms/kg i.v. and above. With 32 micrograms/kg i.v. BAY K 8644 increases total peripheral vascular resistance by 100%. It causes a rise of both, systolic and diastolic, blood pressure up to 196/138 mm Hg at spontaneous sinus rhythm and up to 216/162 mm Hg when keeping heart rate constant at 150 beats/minute. Spontaneous heart rate reflexly drops to 52 beats/minute. Cardiac contractility as indicated by LV(dP/dt)max markedly increases from 2800 to 5600 mm Hg/s at spontaneous sinus rhythm and from 2900 to 6100 mm Hg/s while pacing at 150 beats/minute. These effects are apparently neither affected by alpha-adrenergic blockade with Phenoxybenzamine (5 mg/kg i.v.) nor by beta-blockade with Propranolol (0.5 mg/kg i.v.) but can be reserved by equivalent doses of Nifedipine. In conclusion, the Calcium-agonistic dihydropyridine BAY K 8644 due to its novel mechanism of action could be the precursor of a new class of positive inotropic or antihypotensive drugs.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗