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Biomedical subjects

M Schmid

Publications and source records attributed to M Schmid.

At least 289 records · Page 16Linked to original sources
PubMed1995

[Adrenal incidentaloma].

Asymptomatic adrenal tumors are discovered more and more frequently with improving quality of diagnostic imaging. Treatment of these tumors, described as incidentalomas is controversial and depends on the one hand on the size of the tumor and on the other hand on morphological appearance in diagnostic imaging. In the literature a tumor size over 3 cm is in general regarded as an indication for operation, based on findings of Copeland et al. where the size of the tumor was correlated with malignancy. In the Department of Surgery in Mannheim 28 operations on adrenal incidentalomas have been performed between 1973-1993. In three patients a carcinoma was found. Four of the removed tumors each of them benign had a diameter smaller than three centimeters. An operation seems to be justified under certain conditions, even in small tumors, because potentially malignant tumors can undergo early and radical surgery. A general recommendation for treatment of the above mentioned tumors, depending only on size and morphology in diagnostic imaging, seems to be difficult. The decision for surgical therapy needs to be evaluated individually for every patient.

Adrenal Gland Neoplasms↗
PubMed1995

Sex chromosome loss and aging: in situ hybridization studies on human interphase nuclei.

A total of 1,000 lymphocyte interphase nuclei per proband from 90 females and 138 males age 1 wk to 93 years were analyzed by in situ hybridization for loss of the X and Y chromosomes, respectively. Both sex chromosomes showed an age-dependent loss. In males, Y hypoploidy was very low up to age 15 years (0.05%) but continuously increased to a frequency of 1.34% in men age 76-80 years. In females, the baseline level for X chromosome loss is much higher than that seen for the Y chromosome in males. Even prepubertal females show a rate of X chromosome loss, on the order of 1.5%-2.5%, rising to approximately 4.5%-5% in women older than 75 years. Dividing the female probands into three biological age groups on the basis of sex hormone function (< 13 years, 13-51 years, and > 51 years), a significant correlation of X chromosome loss versus age could clearly be demonstrated in women beyond age 51 years. Females age 51-91 years showed monosomy X at a rate from 3.2% to 5.1%. In contrast to sex chromosomal loss, the frequency of autosomal monosomies does not change during the course of aging: Chromosome 1 and chromosome 17 monosomic cells were found with a constant incidence of 1.2% and 1%, respectively. These data also indicate that autosome loss in interphase nuclei is not a function of chromosome size.

Adolescent↗
PubMed1995

[Expression of CD44 isoforms in normal human liver and also in regenerative and neoplastic liver changes].

CD44 is a transmembrane glycoprotein of which a large number of isoforms exist. There is evidence, mostly from experimental systems, that isoforms of CD44 generated by alternative splicing of ten variant exons are involved in tumor invasion and metastasis formation. We have evaluated the expression of CD44 standard (CD44s) and variant exons (CD44v) encoded gene products in formalin-fixed and paraffin-embedded human liver specimens, using an immunohistochemical protocol with microwave-based antigen-retrieval and signal amplification. Tissue sections from normal, regenerative and neoplastic liver were studied. Our results indicate that: 1. in normal liver, both, hepatocytes and bile duct epithelia lacked detectable CD44s and CD44v containing isoforms; 2. most cirrhotic liver specimens were unreactive. Some regenerative nodules showed a focal weak positivity for CD44v5 and v9. Most proliferating bile ductules were weakly stained for CD44v9 and some of them also for v5 and v6; 3. most hepatocellular carcinomas displayed a heterogeneous staining of varying intensity for CD44v5, v6, v9 and CD44s. In a few tumors a weak staining for CD44v3 and v4 was also present. Furthermore, there was a tendency to an increased staining intensity of CD44 isoforms with decreasing differentiation; 4. cholangiocarcinomas showed a high expression of CD44s, v3, v5, v6 and v9 containing isoforms. We conclude that neoplastic transformation of hepatocytes and bile duct epithelia is associated with qualitative and quantitative changes in the expression of some CD44 variant exons encoded products. The clinical implications of these findings remain to be determined in a large series of patients.

Adenoma↗
PubMed1994

Synthesis and characterization of 3H-labelled tetrahydrobiopterin.

We synthesized [3'-3H]-5,6,7,8-tetrahydrobiopterin from [8,5'-3H]guanosine 5'-triphosphate ([8,5'-3H]GTP) using GTP cyclohydrolase (EC 3.5.4.16), 6-pyruvoyltetrahydropterin synthase and sepiapterin reductase (EC 1.1.1.153). After purification by cation-exchange h.p.l.c. a solution of radiochemically pure (> 95%) [3'-3H]-5,6,7,8-tetrahydrobiopterin with a specific activity of 9.2 Ci/mmol was obtained. The product proved well suited for studying the binding of tetrahydrobiopterin to nitric-oxide synthase.

Amino Acid Oxidoreductases↗
PubMed1994

The pteridine binding site of brain nitric oxide synthase. Tetrahydrobiopterin binding kinetics, specificity, and allosteric interaction with the substrate domain.

Nitric oxide (NO) synthases contain FAD, FMN, heme, and (6R)-5,6,7,8-tetrahydro-L-biopterin as prosthetic groups. We have characterized the pteridine-binding site of purified brain NO synthase, using 3H-labeled (6R)-5,6,7,8-tetrahydro-L-biopterin as radioligand. Association of [3H]tetrahydrobiopterin followed second-order kinetics (kon = 1.3 x 10(6) M-1 min-1), the dissociation reaction was reversible and first-order (koff = 3.2 x 10(-1) min-1), yielding a kinetic KD of 0.25 microM. Binding of the radioligand was competitively antagonized by several pteridine derivatives with the following order of potency (KI): 7,8-dihydro-L-biopterin (2.2 microM), (6S)-5,6,7,8-tetrahydro-L-biopterin (19 microM), (6R,S)-6-methyl-5,6,7,8-tetrahydropterin (240 microM), and 6,7-dimethyl-5,6,7,8-tetrahydropterin (> 1 mM). The affinity of NO synthase for tetrahydrobiopterin was increased 6-fold in the presence of 0.1 mM L-arginine (KD = 37 nM), and, conversely, tetrahydrobiopterin enhanced the affinity of the enzyme for 3H-labeled NG-nitro-L-arginine about 2-fold. 7-Nitroindazole, which presumably binds to the heme group of NO synthase, competitively inhibited binding of [3H]tetrahydrobiopterin and [3H]NG-nitro-L-arginine with similar Ki values (0.1 microM). Functional as well as binding studies revealed that 7-nitroindazole was competitive with both L-arginine and tetrahydrobiopterin. Our data indicate that brain NO synthase exhibits a highly specific binding site for (6R)-5,6,7,8-tetrahydro-L-biopterin, which allosterically interacts with the substrate domain and may be located proximal to the prosthetic heme group of NO synthase.

Allosteric Regulation↗
PubMed1994

[Scurvy after a suicide attempt by starvation].

A 29-year-old man was admitted to hospital, unconscious and with extensive bleedings in skin and muscles. For many weeks he had been practically starving himself with suicidal intent. Physical examination revealed signs of anaemia and gingivitis with hypertrophy of the tooth borders and bleeding gums, as well as bright blood on rectal examination. There were extensive ecchymoses and petechiae, especially in the legs. Some of the body hair was corkscrew-curly. Haemoglobin level was 7.2 g/dl, mean corpuscular volume 93 fl, reticulocyte count 29/1000. The Rumpel-Leede test was abnormal (60 petechiae/4 cm2), as were the vitamin C level (0.026 mg/dl whole blood) and the ascorbic acid tolerance test. As these findings indicated scurvy, vitamin C was administered, 1 g daily intravenously for 5 days, followed by 500 mg daily by mouth. Remarkable improvement was apparent as early as 72 hours after onset of treatment. The endogenous depression, the underlying cause of the suicide attempt, was treated with clomipramine. When the patient was discharged after 13 days his physical and mental state was much improved.

Adult↗
PubMed1994

Early identification and isolation of inpatients at high risk for tuberculosis.

BACKGROUND: Although it has been recommended that all patients suspected of having tuberculosis be placed in isolation, the feasibility of this recommendation has not been investigated. METHODS: Forty-three patients with pulmonary tuberculosis were compared with 43 control subjects. The control subjects had submitted expectorated sputum, and were culture negative. Variables included chest roentgenogram results, and risk factors used by the Centers for Disease Control and Prevention (Atlanta, Ga) to identify patients at increased risk for tuberculosis. RESULTS: Potential control subjects outnumbered patients by 92:1. Although a positive tuberculin skin test, foreign birth, and weight loss were more common in the patients, 86% of the control subjects had at least one risk factor for tuberculosis. Chest roentgenograms consistent with tuberculosis (cavities or apical or nodular infiltrates) were found in 86% of the patients, but in only 16% of the control subjects (odds ratio, 31.7; 95% confidence interval, 8.6 to 127.7). The positive and negative predictive values of a consistent chest roentgenogram were 6% and 99.8%, respectively. The sensitivity of testing a single sputum specimen was 81%, yet almost half of the control subjects had only one specimen submitted. Of the inpatient cases, 58% were not identified on admission with a median delay of 13 days before isolation. CONCLUSIONS: Isolating all the patients at the time sputum is submitted for testing is not practical and would have resulted in a 92-fold overuse of isolation rooms. The chest roentgenogram was of great value in identifying patients who did not require isolation and was the best available means of identifying inpatients at high risk for active pulmonary tuberculosis.

Adult↗
PubMed1994

Chlorpromazine-induced vanishing bile duct syndrome leading to biliary cirrhosis.

We describe a 33-yr-old pregnant woman in whom a primary biliary cirrhosis-like syndrome developed after 2 wk of chlorpromazine therapy. The clinical course was characterized by severe jaundice lasting 22 mo, intense pruritus, fever, steatorrhea, high alkaline phosphatase levels and hypercholesterolemia. Jaundice resolved with initiation of ursodeoxycholic acid therapy, but subclinical cholestasis and low-level inflammatory activity persisted and ultimately evolved into biliary cirrhosis. The pathological substrate of this severe and prolonged cholestatic reaction was found to be the vanishing bile duct syndrome with a marked transient pseudoxanthomatosis.

Adult↗
PubMed1994

Exclusion of specific human chromosomes into micronuclei by 5-azacytidine treatment of lymphocyte cultures.

Lymphocyte cultures of a male proband were treated with 5-azacytidine. This cytidine analogue induces distinct undercondensation in the heterochromatic regions of chromosomes 1, 9, 15, 16, and Y and increases the frequency of micronuclei formation. In order to analyze the chromosomal content of these micronuclei, in situ hybridizations with biotinylated probes specific for chromosomes 1, 9, 15, 16, and Y were performed. Probes for chromosomes 11, 17, and X were used as controls. Each of 5000 hybridized cell nuclei was scored for associated micronuclei, and signal distribution was documented. In preparations hybridized with probes detecting the 5-azacytidine-sensitive chromosomes a significant fraction of micronuclei showed hybridizations. In contrast, micronuclei in preparations probed for chromosomes 11, 17, and X lacked hybridization signals. The results suggest that in 5-azacytidine-treated cultures the 5-azacytidine-sensitive chromosomes are preferentially excluded into the micronuclei.

Azacitidine↗
PubMed1994

IRES-controlled protein synthesis and genome replication of poliovirus.

Initiation of translation of the single-stranded genomic RNAs of picornaviruses such as poliovirus (PV) and encephalomyocarditis virus (EMCV) is cap-independent and controlled by a long segment within the 5' non-translated region (5'NTR), termed internal ribosomal entry site (IRES). Cellular RNA-binding proteins have been identified that are involved in IRES function in trans. One of these proteins (p57) has been found to be identical to the polypyrimidine tract binding protein (pPTB), a nuclear protein implicated in various processes involving pre-mRNA. Anti-pPTB antibodies inhibit picornavirus mRNA, but not globin mRNA translation, in vitro. Proof for the 5'-independent initiation of translation in vivo was obtained by inserting the EMCV IRES into the ORF of PV thereby constructing a dicistronic, viable poliovirus with the genotype [PV] 5'NTR-P1-[EMCV] IRES-[PV] P2-P3-3'NTR. Dicistronic polioviruses were also constructed that served as novel expression vectors where a foreign gene has been inserted into the PV genome. Incubation of poliovirus RNA in a HeLa cell-free extract leads to the synthesis and processing of viral proteins, viral RNA replication followed by formation of infectious virions. Cell-free synthesis of PV has nullified the dictum that no virus can multiply in a cell-free medium. The genome replication of poliovirus and the mechanism of recombination in poliovirus replication is still not fully understood. Biochemical evidence has been obtained that the conserved NTP-binding motif in PV protein 2C is essential for RNA replication and virus propagation. Finally by using genetic studies we found that during viral RNA synthesis a poliovirus containing two tandemly arranged VPgs (3A-VPg1-VPg2-3Cpro) led to the removal of the 3C-proximal VPg copy.

Carrier Proteins↗
PubMed1994

Chronic viral hepatitis B and C: an argument against the conventional classification of chronic hepatitis.

The classification of chronic hepatitis distinguishing benign chronic persistent hepatitis from severe chronic active hepatitis was constructed without knowledge of well-defined aetiological factors. Better understanding of the different hepatitis-viruses has shed new light on this subject. Chronic viral hepatitis B and C each show typical histological patterns. The validity of the conventional classification has been evaluated by a comparative study of chronic viral hepatitis B and C. 130 biopsies from 110 patients with chronic hepatitis C (CH-C) proven serologically by antibodies (second generation testing) were compared with 105 biopsies from 73 patients with chronic hepatitis B (CH-B). These were scored semi-quantatively. In CH-C, lymphoid follicles and/or aggregates were found in 88.5%, fatty degeneration in 51%, bile duct lesions in 46.2%, and Mallory body-like material in the hepatocytes in 9.2%. The portal lymphocytic infiltration generally predominated over the necro-inflammatory lesions of the parenchyma. Chronic persistent hepatitis (defined by the presence of portal hepatitis) was present exclusively in CH-C. Chronic lobular hepatitis was found exclusively in CH-B. We conclude that the histological criteria described for CH-C are highly suggestive of the diagnosis, that the artificial subdivision of chronic hepatitis into CPH and CAH is obsolete and that the histological assessment of chronic hepatitis should consist of a grading of inflammatory activity (minimal, mild, moderate, severe) and staging of fibrosis (extent of distortion of architecture). The final diagnosis should be based on the demonstration of the aetiological agent.

Chronic Disease↗
PubMed1994

Amplification of (GACA)n simple repeats in an exceptional 14p+ marker chromosome.

An inherited 14p+ marker chromosome with an unusually large differentially staining region (DSR) on the short arm was examined with a number of banding techniques and by non-radioactive in situ hybridization using various repetitive DNA probes. The increase in the size of this variant chromosome was 40% that of a normal chromosome 14. The extra chromosomal material in the DSR consisted mainly of GC-rich constitutive heterochromatin within which two equally sized clusters of 18S + 28S ribosomal RNA genes were located. In situ hybridization demonstrated that the DNA in the DSR was highly enriched in simple tetrameric (GACA)n sequences, whereas the centromeric alphoid sequences and the (TTAGGG)n telomeric repeats were not amplified. Silver staining of the two nucleolus organizer regions (NORs) within the DSR showed that the telomerically located NOR was always more active than the paracentromerically located NOR. A comparison with other DSRs found in human acrocentric autosomes revealed a gradient of transcriptional activity of adjacent multiple NORs. This gradient decreased in the order of their telomeric-paracentromeric-interstitial position, regardless on which acrocentric chromosome the DSR was located.

Child↗
PubMed1994

Incidence of chromosome 18 disomy in human sperm nuclei as detected by nonisotopic in situ hybridization.

Nonradioactive in situ hybridization with an alpha-satellite DNA probe specific for chromosome 18 was performed on human interphase sperm nuclei to detect the frequency of sperm cells disomic for chromosome 18. A total of 16,127 sperm heads from eight healthy donors, aged 23-57 years, was investigated, and a minimum of 2000 sperm nuclei per proband was analyzed. The disomy rate ranged from 0.25% to 0.5%, with an average of 0.36%. This frequency does not differ significantly from that determined for other chromosomes.

Adult↗
PubMed1994

Aneuploidy and ageing: sex chromosome exclusion into micronuclei.

In lymphocyte cultures, the number of aneuploid cell nuclei increases with proband age mainly because of the loss of sex chromosomes. Since one possible cause of aneuploidy in cell nuclei is chromosomal lag at anaphase, with subsequent chromosome loss via micronucleus formation, we scored 5000 interphase nuclei from ten female and ten male probands for associated micronuclei. Whereas, in young (< 10 years) probands, an average of 0.15% interphase nuclei exhibited micronuclei, the frequency rose to 0.46% in older probands (> 70 years). In situ hybridizations with X-specific and Y-specific DNA probes were carried out, and the signal distribution in ten nuclei with associated micronuclei was documented for each donor. Our results indicate that the exclusion of sex chromosomes into micronuclei doubles during a human life, from 11% in young probands to 20% in old donors.

Aged↗
PubMed1994

Incidence of chromosome 3, 7, 10, 11, 17 and X disomy in mature human sperm nuclei as determined by nonradioactive in situ hybridization.

In situ hybridizations were performed on mature human sperm cells with biotin-labeled alpha-satellite DNA probes specific for chromosomes 3, 7, 10, 11, 17, and X in order to reveal the disomy rate for each of these chromosomes. A total of 76,253 sperm nuclei from seven healthy probands aged 23-57 years were analyzed. An average of 12,000 sperm nuclei (at least 1500 per donor) showing hybridization were scored with each probe. The disomy rate as indicated by two distinct hybridization signals turned out to be similar for all chromosomes, ranging from 0.31% to 0.34%. There were no significant interindividual differences and no age correlation in the frequency of disomic sperm cells between the donors.

Adult↗