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Biomedical subjects

M Schmid

Publications and source records attributed to M Schmid.

At least 415 records · Page 23Linked to original sources
PubMed1990

Immunocytogenetics. VI. A nonhistone antigen is cell type-specially associated with constitutive heterochromatin and reveals condensation centers in metaphase chromosomes.

We report a nonhistone antigen to be cell type-specifically associated with constitutive heterochromatin. Human autoantibodies were used to analyze by indirect immunofluorescence the pattern of association of the antigenic protein with the heterochromatin of murine chromosomes, as well as those of other representative vertebrate species. The evolutionary stability of its cell type-specific distribution pattern suggests that this nonhistone antigen plays an important role in the structure and/or function of constitutive heterochromatin. In mitotic chromosomes, the antigen was localized to discrete granules scattered throughout the entire chromatin. These structural elements may function as condensation centers, with each granule representing an aggregation of anchoring complexes for the chromatin loops.

Animals↗
PubMed1990

Human autoantibodies to spermatogenic antigens and Sertoli cells.

Immunofluorescence staining using human autoantibodies is a simple and reliable method for investigation of meiotic and post-meiotic cells. Patients suffering from autoimmune diseases often produce circulating autoantibodies to antigens of germ cells and Sertoli cells. Four hundred human autoimmune sera were screened by indirect immunofluorescence on mouse seminiferous tubule cells. Autoantibodies of several specificities were found: one group reacted with organelles of meiotic prophase spermatocytes or spermatozoa. Included in this group were autoantibodies to synaptonemal complexes, sex vesicle, acrosome, and sperm tail. A second group of autoantibodies was found to stain different spermatogenic cell types uniformly, such as round spermatids or Sertoli cells.

Animals↗
PubMed1990

Famotidine. Pharmacokinetic properties and suppression of acid secretion in paediatric patients following cardiac surgery.

The pharmacokinetic and pharmacodynamic properties of the H2-receptor antagonist famotidine have been well described in adult subjects. However, similar data for children are not available. Therefore, this study looked at the disposition of the drug (given to prevent aspiration following cardiac surgery) in 10 paediatric patients with normal kidney function (age range 2 to 7 years, bodyweight 14 to 25 kg) after a single intravenous dose of famotidine 0.3 mg/kg. Plasma concentrations of the drug and gastric pH values were both monitored for 20 hours by high performance liquid chromatography and aspiration of gastric juice, respectively. Plasma famotidine concentrations declined with an elimination half-life of 3.3 +/- 1.8 h (mean +/- SD) and the drug was effective in elevating the gastric pH above 3.5 for about 9 hours in 6 patients. The variable volume of distribution and total plasma clearance of famotidine averaged 1.4 +/- 1.0 L/kg and 0.3 +/- 0.17 L/h/kg, respectively. In 4 patients unchanged famotidine could also be measured in a 12-hour urine fraction. The amount excreted (21 to 79%) correlated with clearance (r = 0.97). All these data are comparable to those obtained in healthy adults, indicating that paediatric patients receiving intensive medical treatment after cardiac surgery can handle famotidine in a way very similar to healthy adult subjects. A dosage of 0.3 mg/kg every 8 hours appears to be advisable.

Cardiac Surgical Procedures↗
PubMed1990

Natriuresis-pressure relationship in polycystic kidney disease.

We studied, under outpatient conditions, nine patients with autosomal dominant polycystic kidney disease who were hypertensive on their usual diet, and nine normotensive healthy probands. The subjects were examined in random order on the 7th day after equilibration on a low-sodium diet (20 mmol/day) and again on the 7th day after equilibration on the same diet but with added sodium to yield a final intake of 200 mmol/day (or vice versa). Blood pressure was monitored non-invasively for 2 h at 4-min intervals using an automatic system. In healthy probands, mean arterial pressure (MAP) was similar on the low- and the high-sodium diets (92.7 versus 91.9 mmHg). In hypertensive patients, a significant (P less than 0.02) increase in mean MAP (107.2 versus 111.2 mmHg) and in systolic blood pressure (140.6 versus 148.7 mmHg) was observed irrespective of whether the glomerular filtration rate (GFR) was normal or reduced. The natriuresis pressure curve showed an upward shift (resetting) and a positive slope (sodium sensitivity). Patients with a reduced GFR as shown by inulin clearance differed from probands and patients with a normal GFR, by showing greater proportional changes in GFR and body weight. In hypertensive patients, atrial natriuretic factor (ANF) levels were higher at baseline and showed an exaggerated response to sodium loading. Changes in angiotensin II (Ang II) or in Ang II binding sites on platelets were similar in patients and controls and changed appropriately with the sodium intake. These data show a resetting of the natriuresis-blood pressure relationship and an increased blood pressure sensitivity to sodium in hypertensive patients with adult, dominant, polycystic kidney disease.

Adult↗
PubMed1990

[Chemical and thermal compatibility of all-ceramic systems].

The chemical and thermal compatibility of the all-ceramic systems Vitadur-N, Hi-Ceram and In-Ceram as well as the combinations of Dicor with Vitadur-N, Dicor with NBK 1000 and Dicor with Vivodent, respectively, were investigated by means of electronmicroscopy and microprobe measurements at the interface of each compound, and thermomechanical analyses of the components were performed. The results show good contact at the interface of all combinations investigated. No evidence was found for diffusion at the interface except in the In-Ceram system, were a migration of K+ from Vitadur-N dentine into the glassy phase of In-Ceram occurs. The thermomechanical analyses showed a good thermal compatibility of all compounds investigated.

Biocompatible Materials↗
PubMed1990

Combination therapy of 4'-O-tetrahydropyranyl-doxorubicin, 5-fluorouracil, and high-dose folinic acid in patients with advanced breast cancer: a phase I-II study (preliminary results).

Previous clinical studies have suggested that 4'-O-tetrahydropyranyl-doxorubicin (THP) as well as 5-fluorouracil/high-dose folinic acid (5-FU/HDFA) are active and well-tolerated drugs in breast cancer treatment. This phase I-II study was designed to determine the maximum tolerated dose (MTD) of THP in combination with 5-FU/HDFA as a weekly schedule and to examine the activity and safety of this drug regimen in patients with advanced breast cancer. 5-FU and HDFA were set at doses of 350 mg/qm i.v. and 500 mg/qm i.v., respectively, whereas the THP dose has been escalated in increments of 5 mg/qm i.v. beginning at a dose level of 10 mg/qm until reaching of MTD in at least four patients in one dose level. For determination of MTD the first six cycles of each patient have been taken into account. Up to July 1990, 21 patients previously not treated with chemotherapy for metastatic breast cancer were entered into the study; the latest patient entered at 35 mg/qm THP dose level. A total of 270 cycles have been administered so far. Anemia and leukopenia was limited to ECOG grades I and II. Other toxicities were mild or moderate. No acute or subacute cardiotoxicity has been observed. Up to July 1990, MTD had not been reached. In the second part of the study, at least another 14 patients have to be entered in a dose level one below the MTD to evaluate the activity and safety of this regimen in a phase II trial.

Adult↗
PubMed1990

Determination of Y chromosome aneuploidy in human sperm nuclei by nonradioactive in situ hybridization.

Sperm nuclei from eight normal, healthy donors were hybridized in situ with the biotin-labeled Y-specific pHY2.1 DNA probe to evaluate the X:Y ratio, the location of the Y chromosome, and the frequency of Y aneuploidy in human sperm. The streptavidine-horseradish-peroxidase and DAB detection system used permitted the unequivocal identification of sperm heads with zero, one, or two hybridization signals and proved superior to either quinacrine staining or radioactive in situ hybridization. The low incidence of 0.27% of sperm nuclei with two Y chromosomes that was found is similar to the frequency of XYY males among newborns. The average proportions of X- and Y-bearing sperm nuclei were 50.3% and 49.4%, respectively, corresponding to the expected 1:1 ratio. The Y heterochromatin was located in the central part of the nucleus in 58% of the Y-carrying sperm cells.

Aneuploidy↗
PubMed1989

Antagonism of glycerol trinitrate activity by an inhibitor of glutathione S-transferase.

The in vitro spasmolytic activity of glycerol trinitrate was measured on the KCl-contraction of aorta strips from the rabbit. In the presence of sulphobromophthalein, a known inhibitor of glutathione S-transferase, the dose-activity curve for the nitrate was displaced to the right. Much smaller displacements were obtained with the control spasmolytic substances--papaverine and S-nitroso-N-acetylpenicillamine. It was confirmed that sulphobromophthalein inhibits glutathione S-transferase activity in aorta homogenates. Aorta extracts did not detectably catalyze the reaction between glutathione and sulphobromophthalein and the glutathione level was not decreased by treating the intact aorta with sulphobromophthalein. It is concluded that sulphobromophthalein acts as a specific antagonist of the spasmolytic activity of glycerol trinitrate, probably as a result of its inhibition of glutathione S-transferase. It thus seems probable that glutathione and glutathione S-transferase are involved in the pharmacological activation of the organic nitrates.

Animals↗
PubMed1989

Increased frequencies of sister chromatid exchanges at common fragile sites (1)(q42) and (19)(q13).

Human lymphocyte cultures were treated with 5-azadeoxycytidine for the induction of the common fragile sites at 1q42 and 19q13 and with 5-bromodeoxyuridine for differential sister chromatid staining. A remarkably high frequency of sister chromatid exchanges was observed directly at the gaps of both fragile sites. In addition, the rate of sister chromatid exchanges occurring at the region corresponding to 1q42 without a concurrent visible gap was also increased. This confirms previous data on increased intrachromosomal recombination in common and rare fragile sites of various categories.

Azacitidine↗
PubMed1989

5-Azadeoxycytidine induced undercondensation in the giant X chromosomes of Microtus agrestis.

Fibroblasts of female Microtus agrestis were treated with 5-azadeoxycytidine (5-aza-dCyd) at a final concentration of 10(-5) M during the last 2 h of culture. This cytidine analogue induces distinct undercondensation of the constitutive heterochromatin in the giant X chromosomes. The undercondensed heterochromatic thread exhibits longitudinal segmentation reminiscent of a chromomere pattern. In the late-replicating X chromosome, 5-aza-dCyd also inhibits condensation of the genetically inactivated euchromatin (facultative heterochromatin). The described effects of 5-aza-dCyd on the X chromosome structure appear to be incorporation independent.

Animals↗
PubMed1989

Digoxigenated oligonucleotide probes specific for simple repeats in DNA fingerprinting and hybridization in situ.

A fast, reproducible and non-hazardous technique for non-isotopic DNA fingerprinting is presented. The method is based on digoxigenated oligonucleotides, which are specific for simple repetitive DNA sequences. The use of digoxigenin/anti-digoxigenin detection avoids many drawbacks inherent in e.g. the biotin/streptavidin system which often causes a poor signal-to-background ratio. Synthesis and purification of digoxigenated oligonucleotides and their use in filter hybridization are described in detail. Hybridization patterns obtained with four different radioactively labeled oligonucleotides have been compared with those of the respective digoxigenated probes. When slightly less stringent hybridization conditions are applied for digoxigenated oligonucleotides than for those labeled with 32P, the signal intensities are satisfying but additional minor bands occur as a result of the reduced stringency. With one explainable exception, these bands increase the information content of the fingerprint. In addition, hybridization of the digoxigenated (CAC)5 probe has been performed in situ with human metaphase chromosomes. The hybridization patterns in many mitoses resemble R-bands.

DNA↗
PubMed1989

Centromeric association of a microchromosome. A new category of non-random arrangement of metaphase chromosomes.

A supernumerary microchromosome measuring 0.5-1 microns found in over half of the metaphases of a CREST scleroderma patient and his daughter has been characterized by various cytogenetic techniques. The microchromosome consisted of constitutive heterochromatin and contained nuclear antigens reacting with specific anti-kinetochore antibodies. The most remarkable property of the microchromosome was its non-random position: it was closely associated with the centromere of any of the normal chromosomes in the majority of the metaphases. Furthermore, an inordinately high rate of Y chromosome aneuploidy was found in the CREST scleroderma patient. The origin and structure of the microchromosome, its possible connection with the CREST variant of scleroderma, and the phenomenon of centromeric association are discussed.

Aged↗
PubMed1989

Centromeric association and non-random distribution of centromeres in human tumour cells.

Centromere arrangement in interphase and metaphase cells of two human tumour cell lines was analysed using anti-kinetochore antibodies as immunofluorescent probes. In GLC1 interphase nuclei, kinetochores were non-randomly positioned around the nucleolus and close to the nuclear membrane. During S and early G2 phase, necklace-like strands of kinetochores were formed in the centre of the nucleus. The duplication of sister kinetochores during the G2 phase was not synchronized. At late G2 phase, a relatively random topological distribution of centromeres was observed with short linear arrays of sister kinetochores. Carefully spread metaphase plates of MDA-MB231 cells generally exhibited a linear alignment of centromeres and large centromeric clusters. In completely pulverized MDA-MB231 cells, centromeres showed a strong tendency to associate with each other.

Breast Neoplasms↗
PubMed1989

The Y chromosome of the mouse is decondensed in Sertoli cells.

The condensation of the Y chromosome in mouse cells was studied with two repetitive DNA probes, pY353/B and M34. Both DNA probes are specific to the Y chromosome and hybridize in situ along the whole chromosome. Due to the high resolution of the in situ hybridization technique with non-radioactive labeled DNA probes it was possible to observe the degree of condensation of the Y chromosome in the interphase cell nuclei of various somatic tissues and on testes preparations. The Sertoli cells were the only cell type in which the Y chromosome was always observed to be in a highly decondensed state. The decondensation of the Y chromosome in the Sertoli cells supports the view that the genetic activity of the Y chromosome is cell autonomous and opens the way to its molecular analysis.

Animals↗
PubMed1989

Effects of the benzodiazepine receptor antagonist flumazenil in hepatic encephalopathy in humans.

If increased gamma-aminobutyric acid (GABA)-mediated neurotransmission contributes to the mediation of hepatic encephalopathy, it may be possible to induce ameliorations of the syndrome by pharmacologically antagonizing a component of the GABA/benzodiazepine receptor complex. To test this possibility we administered the benzodiazepine receptor antagonist flumazenil by intravenous injection to 14 patients with hepatic encephalopathy complicating cirrhosis. Flumazenil administration induced variable and transient, but distinct, improvements of the mental status in 71% of the patients. The degree of encephalopathy improved from stage IV to stage II in 4 patients and from stage IV to stage III in 2 patients. The mental status of all patients with less advanced encephalopathy (3 with stage III, 1 with stage II) also improved, but these responses were clinically less impressive. The arousal effect occurred within minutes after the injection and lasted for 1 to 2 h. Furthermore, it was associated with a significant increase of the mean electroencephalographic frequency from 4.2 to 5.2 cycle/s. Of the 8 patients who were ultimately discharged from the hospital, 7 had responded to flumazenil. No patient who died within 48 h of receiving flumazenil had shown any arousal effect. These findings strongly favor a prominent pathogenetic role of increased GABAergic tone in hepatic encephalopathy in humans and suggest that a positive response to flumazenil might be of prognostic value in predicting short-term survival in encephalopathic patients with liver disease.

Adult↗
PubMed1989

Clonotypic chromosomal aberrations in long-term lines of myelin-specific rat T lymphocytes.

A panel of 16 long-term rat T lymphocyte lines and clones were screened for cytogenetical abnormalities using chromosomal banding techniques. All T lines were CD4+, recognizing the relevant antigen in the molecular context of major histocompatibility complex (MHC) class II determinants. With one exception (an ovalbumin-specific line), all lines were specific for myelin proteins, and apart of one BS rat-derived T line and its clones, all lines were selected from the Lewis strain of rat. After in vitro culture of more than 1 year, all lines and clones exhibited subtle but definite chromosomal aberrations, which included deletions, enlargement, translocations and formation of isochromosomes. All lines were near diploid, structural chromosomal changes being more frequent than numerical abnormalities. Each T line investigated had an individual pattern of chromosomal changes. In our analysis, 16 of the 22 different chromosomes had changes in at least one line. Chromosome 9 and the X chromosome appeared to have an enhanced susceptibility of alterations. In two cases, chromosomal markers could be traced through different stages of in vitro culture of the T lines.

Animals↗
PubMed1989

Immunocytogenetics. II. Human autoantibodies to synaptonemal complexes.

Synaptonemal complex (SC) autoantibodies are spontaneously produced by patients with various autoimmune diseases. Immunofluorescence staining of pachytene cells localized the antigen to the central element or transverse filaments of the SC but not to the lateral elements. Specific antibody labeling was confined to the SC at synapsis. Cytochemical tests showed that the SC autoantigen is a basic protein possibly bound to DNA. An unusual characteristic of the SC autoantigen is its species specificity. Patients were found whose sera selectively labeled the SCs of other humans, mice, or newts. The combining of anti SC and anti-kinetochore antibodies provides a new immunocytochemical method for the analysis of SC karyotypes. The optimum conditions for preparation of pachytene cells for visualization by indirect immunofluorescence were determined. The nature and functions of the SC antigen, as well as possible applications of SC-specific autoantibodies in cytogenetics and cell biology, are discussed.

Animals↗