Biomedical subjects

A Schmidt

Publications and source records attributed to A Schmidt.

At least 343 records · Page 19Linked to original sources

PubMed1995

The widespread human desmocollin Dsc2 and tissue-specific patterns of synthesis of various desmocollin subtypes.

By comparison of the cDNA-derived amino acid sequences and the cell type-specific patterns of synthesis we have identified desmocollin Dsc2 as the most widespread, perhaps ubiquitous desmocollin subtype. Using Northern blot analyses and ribonuclease protection assays we have found an approximately 5.6 kb mRNA encoding Dsc2 in all the diverse human tissues, tumors and cell lines examined that are known to possess desmosomes, i.e. not only epithelial cells but also myocardiac cells and lymph nodes. By contrast, desmocollin subtypes Dsc1 and Dsc3 have been detected only in certain stratified squamous epithelia, with the most conspicuous restriction of Dsc1 to epidermis and--remarkably, but unexplained--lymph nodes, and in certain carcinomas and cell lines derived therefrom. We have also determined that both Dsc2 mRNA splice forms, the one encoding the larger polypeptide a and the one coding for the shorter Dsc2b, occur in all the diverse tissues and cell lines examined. We also show that certain cells such as the epidermal keratinocyte line HaCaT and the vulvar carcinoma-derived line A-431 continually synthesize more than one Dsc subtype. The cell type-specific patterns of synthesis of the various Dsg and Dsc subtypes are discussed in relation to tissue development during embryogenesis and to malignant transformations, and the utilization of reagents for the specific Dsg and Dsc subtypes in tumor diagnosis is proposed.

Amino Acid Sequence↗

PubMed1995

Image-guided access techniques.

For increasing safety in access and guidance of endoscopes and instruments, fast real-time radiologic imaging should be integrated. Open designed Magnetic Resonance Imaging (MRI), Computer Tomography (CT), and Electron Beam Tomography (EBT) scanners permit adequate transparency of the operative field. CT and EBT as hybrid scanners can be combined with fluoroscopy. MRI avoids X-ray exposure and entails the possibility of 3D localisation, while open access and keyhole imaging allows nearly real-time guidance of instruments. EBT has the largest gantry (90 cm) for using long instruments, and the image acquisition requires only 50 msec (34 images/sec at 8 levels). However, computed reconstruction of the data takes about 3 times longer than conventional CT. Until EBT can be accelerated, CT will be the golden standard of guidance-techniques in high risk areas, because the tips of the instruments can be precisely visualised within +/- 0.5 mm (MRI: 3.5 mm). MRI-guidance can be used for low risk access techniques. This safe interactive transparent guidance technique has the potential to reduce complications, and it adds significant advantages to micro-invasive operative procedures such as percutaneous diskectomies, pain and cancer therapy with ethanol, or gene-technology implants in the new field of "surgical tomography".

Diagnostic Imaging↗

PubMed1995

Killing and mutation of Chinese hamster V79 cells exposed to accelerated oxygen and neon ions.

Mutation induction by accelerated heavy ions to 6-thioguanine resistance (HPRT system) in Chinese hamster V79 cells was investigated using oxygen and neon ions with energies between 1.9 and 400 MeV/mu, corresponding to LET values between 18 and 754 keV/microns, respectively. Because of technical limitations most experiments could be performed only once. Inactivation and mutation induction cross sections, sigma i and sigma m, were obtained from the slopes of the exponential survival and the linear mutation induction curves, respectively. Both parameters increased with LET up to about 200 keV/microns, where the curves separated for the two types of ions. Calculated RBEs were higher for mutation induction than for killing for all LET values.

Animals↗

PubMed1995

Chimeric proteins containing the cytoplasmic domains of the mannose 6-phosphate receptors codistribute with the endogenous receptors.

We have constructed and transiently expressed in HeLa cells a series of hybrid proteins in which the cytoplasmic domain or both the transmembrane and the cytoplasmic domains of the mannose 6-phosphate/insulin-like growth factor II receptor were fused to the ectodomain of the hemagglutinin of the influenza virus (HA), a typical plasma membrane protein. In addition, we have expressed a hybrid protein containing the luminal domain of HA fused to the transmembrane and cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor. These hybrids were transported through and sorted from the secretory pathway as shown by acquisition of endo-H resistant oligosaccharides and their ability to recruit the Golgi assembly proteins AP-1 on the Golgi membrane. Like the mannose 6-phosphate receptors (MPRs), these hybrid proteins are also present in small amounts at the cell surface where they are likely to undergo endocytosis as disruption of the endocytosis signals contained in the MPR cytoplasmic domains induces their accumulation at the cell surface. Double immunofluorescence studies indicate that these chimeras codistribute with the endogenous MPRs at steady state. The results suggest that the cytoplasmic domains of the MPRs are sufficient to determine the steady-state distribution of the full-length proteins.

Base Sequence↗

PubMed1995

[Microinvasive, CT-controlled periradicular therapy in treatment of chronic intervertebral disk-induced functional disorders].

The disease of the spinal column is number 2 of common diseases world-wide and leads to high business- and commerce-related losses as well as to high expenses for the health care systems. An effective treatment of this disease is given by the microinvasive. CT controlled periradicular therapy (micro PRT). Under visibility, the tip of a canula is led directly and high precisely in close neighbourhood to the prolaps, then locally NaCl and cristaline cortisone (40 mg Volon A) is instillated. The periradicular distribution and the distribution into the epidural space is documented via contrast medium. A retrospective study with 220 patients and a prospective randomized double blind study with 40 patients (10 mg vs. 40 mg Volon A) were carried out. The average age of the retrospective collective was 53.1 +/- 12.4 years, average treatment period 18.4 weeks, and the mean follow-up 17 months. The mean value of successful treatment of lumbal spine was at 60% (spine 88.5%) with protrusion, with prolaps at 75% (spine 94%), with sequester at 94%, and with stenoses at 69% (spine 60%). With 78.8% of the patients, the percentual result was constantly good at the time of questionnaire as to the end of the treatment. 7.7% still took analgesics, 5.9% were post-operated. 1.8% of the patients made a pension application. The average age of patients within the prospective randomized double-blind-study was 47.2 +/- 11.9 years. At 27.5% of the patients, the start of pain was about more than 5 years ago and goes back to about 23 years (72.5% had pain more than 1 year). The mean value of visits was 4 physicians per patient, and 5 months of follow-up. There is a high significant improvement in results within the group with 40 mg Volon A (p = 0.0351479). The entire improvement, subjectively estimated (visual analogical scale) within this group was at 90%. After end of therapy, 83.3% (n = 30) had stopped the taking of analgesics and the neurologic deficit decreased significantly. Furthermore, significant reduction of prolapses could be observed at 60% of the patients in both study groups (n = 156). The CT scopic micro PRT with 40 mg Volon A leads to a significant improvement of pain and neurologic symptoms caused by chronical disk herniation.

Adult↗

PubMed1995

Reduction of exercise-induced myocardial perfusion defects by isosorbide-5-nitrate: assessment using quantitative Tc-99m-MIBI-SPECT.

BACKGROUND: Although nitrates were introduced more than 100 years ago and have been used for the treatment of angina pectoris, there are still some open questions concerning the mechanism of their action on myocardial ischemia. There are also insufficient data regarding the influence of any anti-ischemic medication on the results of myocardial perfusion scintigraphy. METHODS: To assess the influence of a mononitrate, 30 patients with stable angina pectoris, coronary stenosis > or = 70% and normal left ventricular function were examined using quantitative Tc-99m-MIBI exercise-single photon emission computed tomography (SPECT). On the same day, 5 h after a randomized double-blind dose of 60 mg sustained-release isosorbide-5-nitrate or placebo, SPECT was repeated with identical stress protocol. The results were analyzed using a semi-automatic polar coordinate program that allows definition of areas with significant decreased blood flow expressed as a percentage of standard vessel area. RESULTS: In the vessel areas with the largest perfusion defects, the mean defect size decreased after isosorbide-5-nitrate from 38.2 +/- 31.0% to 29.1 +/- 33.8% (reduction by 24%; P < 0.05) and increased from 35.2 +/- 27.6% to 36.6 +/- 27.4% after placebo (increase by 4%; P = NS). The difference between defect size changes was also significant (P < 0.05). CONCLUSION: Acute administration of sustained-release isosorbide-5-nitrate significantly reduces the size of exercise-induced perfusion defects as assessed using quantitative Tc-99m-MIBI-SPECT.

Adult↗

PubMed1995

Detection of problem drinkers: the Alcohol Use Disorders Identification Test (AUDIT).

This study was conducted to test the predictive validity of a new alcohol screening test, the Alcohol Use Disorders Identification Test (AUDIT), in a general medicine teaching clinic and to assess physician recognition and treatment of alcohol and drug disorders. The research procedures included completion of the AUDIT, a standardized diagnostic alcohol and drug assessment, an exit interview, and a chart review. The random sample comprised 132 recruited subjects. The internal reliability of the AUDIT was .77. The optimal cutoff score for the AUDIT in this sample was 5, with a sensitivity of .61 and specificity of .84. The exit interviews revealed that physicians asked their patients about alcohol use and drug use with 20% (n = 26) and 17% (n = 23) of the sample, respectively. Five of the 28 patients who met DSM-IIIR criteria had a diagnosis recorded in the chart.

Adult↗

PubMed1995

In vitro activity of clotrimazole for Candida strains isolated from recent patient samples.

Minimum inhibitory concentrations (MICs) of clotrimazole (CAS 23593-75-1, Bay 5097, clo) were determined for 142 clinical Candida isolates obtained between 1992 and 1994, including the species Candida albicans (96 strains), Candida glabrata (12 strains), Candida krusei (12 strains), and Candida tropicalis (12 strains). For some of the Candida isolates of all four species, the MICs of amphotericin B and fluconazole were also determined. No MICs of clo of > 4 micrograms/ml were found for all four Candida species, the median of MICs of clo for Candida albicans being 0.03 micrograms/ml with a range from < 0.015 to 4 micrograms/ml. The MICs of clo for Candida albicans were on average 2 log stages below the MICs of fluconazole and 1 log step below the MICs of amphotericin B on the microgram/ml level. Taking account of the present in vitro resistance situation, clo is a highly active antimycotic substance for isolates of all Candida species with human pathogenetic relevance.

Antifungal Agents↗

PubMed1994

A null mutation in the perforin gene impairs cytolytic T lymphocyte- and natural killer cell-mediated cytotoxicity.

Lymphocyte-mediated cytotoxicity has been proposed to consist of the polarized secretion of granule-stored perforin leading to target-cell lysis. Nevertheless, perforin-independent pathways were postulated to explain the cytolytic activity of apparently perforin-free lymphocytes and the DNA degradation found in dying target cells. To evaluate the role of perforin, we used gene targeting in embryonic stem cells to produce mice lacking perforin. Mice homozygous for the disrupted gene have no perforin mRNA. The mice are healthy. Activation and granzyme A secretion of perforin-free cytolytic T cells are unaltered. The killing activity of cytolytic T cells as well as natural killer (NK) cells, however, is impaired but not abolished. Approximately one-third of the killing activity remains when lysis of 3T3 fibroblast targets and the apoptotic cell death of YAC-1 NK targets are analyzed. We conclude that perforin is a crucial effector molecule in T cell- and NK cell-mediated cytolysis. However, alternative perforin-independent lytic mechanisms also exist.

Animals↗

PubMed1994

NER, a new member of the gene family encoding the human steroid hormone nuclear receptor.

NER, a new member of the steroid hormone nuclear receptor (NR)-encoding gene family, was isolated from a human osteosarcoma SAOS/B10 cell line cDNA library. NER codes for a polypeptide of 461 amino acids which contains the conserved sequences of the DNA-binding and ligand-binding domains of typical steroid hormone NR. It has highest homology with the retinoic acid receptors: 55% at the DNA-binding domain and 38-40% at the ligand-binding domain. A single transcript of 2.3 kb was detected in all cells and tissues tested. Although no ligand was identified for NER-I, its wide distribution may indicate that this novel steroid hormone NR may play a basic role in cell function.

Amino Acid Sequence↗

PubMed1994

Molecular basis of dark-eyed albinism in the mouse.

Dark-eyed albino (C44H) is a recessive allele at the mouse albino (c) locus, which encodes tyrosinase (monophenol,L-dopa:oxygen oxidoreductase, EC 1.14.18.1), the key enzyme in melanin synthesis. Similar to type IB oculocutaneous albinism in humans, overall production of pigment is greatly reduced in dark-eyed albino mice and obvious only in the eyes. We have studied the molecular basis of the c44H mutation and show that expression of the tyrosinase gene is not affected. After sequencing tyrosinase cDNA isolated from c44H/c44H homozygotes, we uncovered a single base alteration from wild type leading to a serine-to-isoleucine exchange. The importance of this mutation was demonstrated by generating transgenic mice containing a mutated tyrosinase minigene. This showed that the single base change was sufficient to severely depress pigment production in transgenic mice. We therefore conclude that the point mutation is responsible and sufficient to generate the dark-eyed albino phenotype.

Albinism↗

PubMed1994

Polysialic acid expression in the salamander retina is inducible by thyroxine.

Polysialylation of the neural cell adhesion molecule (NCAM) in the retina of Pleurodeles waltl is up-regulated during metamorphosis. Incubation of larvae in thyroxine permanently induced polysialic acid expression in the retina in a concentration-dependent but age-independent manner within 3 days of incubation (3 x 10(-7) M). Retinoic acid had no effect. This suggests direct hormonal regulation of a post-translational modification of NCAM in the amphibian retina.

Aging↗

PubMed1994

Differential structural requirements of heparin and heparan sulfate proteoglycans that promote binding of basic fibroblast growth factor to its receptor.

Heparan sulfate proteoglycans (HSPG) are obligatory for receptor binding and mitogenic activity of basic fibroblast growth factor (bFGF). The capacity of various species of heparin and heparan sulfate (HS) to promote bFGF receptor binding was investigated using both Chinese hamster ovary mutant cells deficient in cell surface HSPG and a soluble bFGF receptor-alkaline phosphatase fusion protein. Highly sulfated oligosaccharides were more effective than medium and low sulfate fractions of the same size oligosaccharide. O-Sulfation in heparin was found to be critical for its capacity to promote binding of bFGF to its receptors. The highest level of bFGF-receptor binding was achieved in the presence of over-sulfated heparin fragments (% sulfur > 14) regardless of whether the N-position was sulfated or acetylated. Unlike receptor binding of bFGF which requires oligosaccharides containing at least 8-10 sugar units, displacement of heparin- or HS-bound bFGF was obtained by oligosaccharides containing as little as four sugar units and by an N-sulfated, O-desulfated heparin fragment (% sulfur = 5.3). A preparation of total cell surface-derived HS induced bFGF receptor binding. A preliminary survey of several defined and affinity purified species of cell surface HSPG, including syndecan, fibroglycan, and glypican failed to identify natural HSPG that promote high affinity receptor binding of bFGF. A similar lack of activity was observed with species of HS isolated from bovine arterial tissue and characterized for their effect on vascular smooth muscle cell proliferation. Moreover, most of these species of HS inhibited in a dose-dependent manner the restoration of bFGF-receptor binding induced by heparin or by total HSPG. These results suggest the involvement of defined heparin-like oligosaccharide sequences and unique species of cell surface and extracellular matrix HS in the regulation of bFGF receptor binding and biological activity.

Animals↗

PubMed1994

Cloning, structure, cellular localization, and possible function of the tumor suppressor gene lethal(3)malignant blood neoplasm-1 of Drosophila melanogaster.

The tumor suppressor gene, lethal(3)malignant blood neoplasm-1+, of Drosophila melanogaster is required for the differentiation of the phagocytic blood-cell type, the plasmatocyte. In the homozygously mutated state it causes the malignant transformation of these blood cells. We present here the cloning, sequencing, structure, and expression of the l(3)mbn-1+ gene during development. The cloned gene was identified by germ-line transformation, generation of revertants, and the detection of the corresponding mRNA in blood cells and other tissues. Homologies of the G-S-rich C-terminus of the putative MBN83 protein to human cytokeratins K1, K10, and mouse loricrin were found. The structure and possible function of the wild-type l(3)mbn-1+ gene are discussed.

Alleles↗

PubMed1994

Comparative dose-related time-action profiles of glibenclamide and a new non-sulphonylurea drug, AG-EE 623 ZW, during euglycaemic clamp in healthy subjects.

Insulin and glucose responses to glibenclamide were studied in comparison to a novel non-sulphonylurea drug (AG) by means of the euglycaemic clamp technique. Nine fasting male subjects were connected to a Biostator and 1.75, 3.5 or 7.0 mg glibenclamide or 1.0, 2.0 or 4.0 mg AG were given and blood glucose concentrations were clamped at 10% below basal values. Glucose infusion rates were registered over 10 h after administration of the tablet. Maximal glucose infusion rates after glibenclamide were 40% higher compared to AG (1.75 vs 1.0 mg, 3.5 vs 2.0 mg, 7.0 vs 4.0 mg, respectively) and were reached after 3-3.5 h for all doses. After glibenclamide, area under the glucose infusion curves and maximal incremental serum insulin responses were higher by 25-40% and by 30% compared to AG when low, medium and high doses of each drug were tested. However, a linear dose relationship was obtained for both drugs when the glucose infusion rate was plotted against the area under the insulin curve. In fact, both drugs were equipotent on a molecular weight basis. The hypoglycaemic index of both drugs (integrated glucose infusion rate divided by integrated insulin release) expressed per mumol of drug revealed a dose-dependent and parallel inverse curvilinear relation to increasing doses. This methodological approach allowed us to quantify and compare the metabolic effects of oral hypoglycaemic agents under standardised experimental conditions.

Administration, Oral↗

PubMed1994

Combined influence of quartz dust, ozone and NO2 on chemotactic mobility, release of chemotactic factors and other cytokines by macrophages in vitro.

In this study the single as well as combined effects of quartz, ozone and nitrogen dioxide (NO2) on some immunofunctions of bovine alveolar macrophages (BAM) were investigated. After incubation with 10 micrograms/ml of particles the chemotactic response of BAM is increased nonspecifically, whereas after incubation with 100 micrograms/ml of quartz chemotaxis is specifically decreased. In addition, quartz induces tumor necrosis factor alpha (TNF-alpha) and chemokines to be released dependent on the concentration. Ozone by itself is also a very potent inducer of the release of chemokines and TNF-alpha, but in combination with ozone, quartz has not more than an additive effect. NO2 alone suppresses drastically the release of TNF-alpha. The results show that quartz, ozone and NO2 alter some immunofunctions of BAM and that by combining toxic particles such as quartz with these gases, additive but not synergistic effects might be expected.

Animals↗

PubMed1994

Cell type-specific desmosomal plaque proteins of the plakoglobin family: plakophilin 1 (band 6 protein).

Desmosomes represent a special type of the plaque-bearing adhering junctions, characteristic of certain pathways of cell differentiation, which compositionally are not identical in the various kinds of desmosome-forming cells. While all desmosomes contain the cytoplasmic plaque proteins desmoplakin I and plakoglobin, they can vary in their specific complement of desmosomal cadherins and by the presence of additional plaque proteins. We have raised monoclonal antibodies recognizing one such 'accessory' plaque protein, the cytokeratin-binding, basic protein plakophilin 1, originally introduced as 'band 6 protein' or 'polypeptide D6', which is an abundant desmosomal component in certain epithelia. Using such antibodies, we have isolated cDNA clones encoding the bovine and the human protein and determined their complete amino acid sequences. The mRNAs, which on Northern blot tests appear as two bands corresponding to approximately 4 and 2.4 kb (bovine) or 5 and 2.6 kb (human), code for 727 amino acids (calculated mol. wt. 80,180; IEP 9.25) in bovine and 726 amino acids (mol. wt. 80,496; IEP 9.34) in human plakophilin. Sequence analyses have revealed the presence of 9.2 repeated units of the arm-motif sequence, confirming our previous conclusion that this protein is a member of a larger family of proteins including, inter alia, several membrane-associated plaque proteins such as vertebrate plakoglobin and beta-catenin as well as the product of the armadillo gene of Drosophila. The plakophilin antibodies and cDNA probes have also allowed us to examine its synthesis in various tissues and cell cultures. While we confirm the occurrence of the protein in cytoskeletal fractions from various stratified squamous, complex, glandular duct and bladder epithelia, where it can be localized to desmosomes, we have, surprisingly, also identified the protein, although at lower amounts, in cytoskeletal fractions from several cultured cell lines in which the protein has not been consistently localized to desmosomes by immunofluorescence microscopy. Examples include cultured cells derived from certain simple epithelia such as the kidney-derived line MDBK and cultured calf lens cells. We have also found that, in all plakophilin 1-positive cells examined, a pool of diffusible ('soluble') cytoplasmic plakophilin exists, including cell lines such as human mammary carcinoma MCF-7 cells in which this soluble plakophilin seems to be the only detectable form. In addition, we have identified some soluble proteins conspicuously cross-reacting with plakophilin 1. Possible functions of plakophilin and its potential value as a marker for specific states of cell differentiation are discussed, particularly with respect to tumor diagnosis.

Amino Acid Sequence↗

PubMed1994

Systolic ventricular function in acute hypothyroidism: a study using Doppler echocardiography.

The influence of thyroid state on left ventricular systolic function was studied in 11 patients (5 men, 6 women, aged 20-55 years) without cardiac disease, who had undergone total thyroidectomy and radioiodine treatment for thyroid cancer before. Pulsed-wave Doppler echocardiographic measuring of aortic blood flow and two-dimensional/time-motion (2D/M-mode) echocardiography were performed on two occasions once while the patients were mildly hyperthyroid on thyroxine replacement therapy and once when they were hypothyroid. During hypothyroidism left ventricular end-diastolic diameter decreased from 48 +/- 5 mm to 46 +/- 5 mm (p < 0.05). The diameter of the aortic ring, the left ventricular end-systolic diameter, the thickness of the interventricular septum and posterior wall, and fractional shortening did not differ significantly between the two studies. The following parameter of aortic blood flow changed significantly when passing from the hyperthyroid to the hypothyroid state: peak velocity (0.86 +/- 0.15 m/s versus 0.72 +/- 0.15 m/s, p < 0.01); mean velocity (0.49 +/- 0.08 m/s versus 0.44 +/- 0.08 m/s, p < 0.01); time- velocity integral (14.1 +/- 3.0 cm versus 12.3 +/- 3.1 cm, p < 0.05); stroke volume (43.0 +/- 9.7 ml versus 35.2 +/- 8.2 ml, p < 0.05); and preejection period (124 +/- 23 ms versus 147 +/- 21 ms, p < 0.01). Peak acceleration, mean acceleration, acceleration time and left ventricular ejection time did not change when the thyroid state was altered. It is concluded that left ventricular contractile function was not affected by acute hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗