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Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 577 records · Page 32Linked to original sources

The switching gene swi6 affects recombination and gene expression in the mating-type region of Schizosaccharomyces pombe.

The products of 11 switching (swi) genes are required for efficient mating-type (MT) switching in homothallic (h90) strains of Schizosaccharomyces pombe. The MT region of h90 comprises three cassette genes: the expression site mat1:1 and two silent loci, mat2:2 and mat3:3. Besides reducing MT switching, the swi6 mutation leads to deletions in the MT region caused by intrachromosomal cross-overs between two paired cassettes. These deletions only arise if DNA double-strand breaks are present at mat1:1, which initiate MT switching. Furthermore, swi6 allows meiotic recombination in the K region, a region of 16 kb between mat2:2 and mat3:3; in wild-type strains no recombination occurs in K. swi6 also allows the simultaneous expression of two different cassettes in the same haploid cell. Thus swi6 may have an influence on the general chromatin structure in the MT region.

Blotting, Southern↗

Characterization of a novel enzyme, N6-acetyl-L-lysine: 2-oxoglutarate aminotransferase, which catalyses the second step of lysine catabolism in Candida maltosa.

A novel aminotransferase catalyzing the second step of lysine catabolism, the oxidative transamination of the alpha-group of N6-acetyllysine, was identified and characterized in the yeast Candida maltosa. The enzyme was strongly induced in cells grown on L-lysine as sole carbon source. Its activity was specific for both N6-acetyllysine and 2-oxoglutarate. The Km values were 14 mM for the donor, 4 mM for the acceptor and 1.7 microM for pyridoxal-5-phosphate. The enzyme had a maximum activity at pH 8.1 and 32 degrees C. Its molecular mass estimated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis was 55 kDa. Since the native molecular mass determined by gel filtration was 120 kDa, the enzyme is probably a homodimer.

Candida↗

Treatment of fish parasites. 9. Effects of a medicated food containing malachite green on Ichthyophthirius multifiliis Fouquet, 1876 (Hymenostomatida, Ciliophora) in ornamental fish.

For systemic therapy against trophozoites of the skin-inhabiting stage of Ichthyophthirius multifiliis in ornamental fish, the latter were fed medicated food flakes containing malachite green once daily for 1-11 days ad libitum. Naturally or artificially infected cardinal tetras (Paracheirodon axelrodi), blue gouramis (Trichogaster trichopterus), or clown loach (Botia macracantha) were used in the trials. The fish were maintained in aerated 12.5- or 60-1 aquaria at 23 degrees C. Ultrastructural investigations (scanning and transmission electron microscopy) revealed clear deleterious effects of malachite green on the parasitic stages. Following the initial application, the inner membrane of the mitochondria was destroyed. In fish fed for 2 days, aggregation of the mucocysts and polymerization the microtubules within the macronucleus occurred. Finally, the trophozoite's membrane was completely destroyed. In fish fed for 4 days, the medicated food killed all trophozoites of I. multifiliis. Sensitive ornamental fish (e.g., P. axelrodi) showed no adverse effects after they had been fed with only the medicated food flakes for 2 months. Therefore, the oral administration of malachite green using this newly developed medicated food considerably reduces the risk of toxic effects on the fish hosts, which are sometimes caused by malachite green following its application by immersion therapy. The feeding of flakes medicated with malachite green provides and easy-to-handle and highly effective treatment of I. multifiliis in ornamental fish.

Animal Feed↗

Retrospective approach to explain growth retardation and urolithiasis in a child with long-term nutritional acid loading.

An infant with phenylketonuria unintentionally received a highly acidic low phenylalanine diet for 29 months. Temporary growth retardation and urolithiasis were observed, probably as direct effects of chronic acid loading. Caries at the age of 6 years may be a late consequence. This case report shows that chronic dietary acid load may cause serious side effects.

Acid-Base Equilibrium↗

Development of height and weight in children with diabetes mellitus: report on two prospective multicentre studies, one cross-sectional, one longitudinal.

Optimal regimen for insulin therapy should lead to normal longitudinal growth and weight gain in children with diabetes mellitus. However, reports published so far indicate that this goal of paediatric diabetology is currently not achieved in a considerable number of patients. In a cross-sectional sample of 89 children with insulin dependent diabetes mellitus (IDDM) for more than 3 years, we found the relation of height to weight to be significantly different compared to 102 healthy school children of similar age. Using bivariate analysis, body shape in these children with diabetes was shifted towards small and obese (P less than 0.05) compared to control children. We subsequently initiated a longitudinal study and followed children from the onset of diabetes for the following 3 years, recording height, weight and bone age as well as glycosylated haemoglobin and daily insulin requirement. At diagnosis, height SDS was identical in children with IDDM (+0.04 +/- 0.10) compared to control children (-0.07 +/- 0.10; M +/- SE), while weight SDS was -0.26 +/- 0.10 in children with diabetes (controls: + 0.01 +/- 0.01). Bone age was identically retarded in newly diagnosed IDDM children (-0.73 +/- 0.12 SDS) and in our control group of children from the same regional background (-0.50 +/- 0.12; n.s.). In this group of children with diabetes mellitus followed prospectively, height to weight relationship differed from controls after 2 and after 3 years of the disease (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Flow cytometric analysis of uterine sarcoma: ploidy and S-phase rate as prognostic indicators.

Flow cytometry of various gynecological tumors has shown that aneuploid tumors and a high S-phase rate carry a prognosis worse than that of diploid tumors or tumors with a low S-phase. The aim of this study is to investigate the prognostic importance of DNA ploidy and S-phase rate in relation to mitotic count, tumor stage, tumor grade, and histology in 37 patients with uterine sarcoma stages I-IV (FIGO). Flow cytometry was performed on archival paraffin-embedded tumor tissue and the histologic specimens were reviewed by a single pathologist. Nineteen (51%) of the tumors were classified as DNA aneuploid. The S-phase fraction (SPF) was determined in 33 cases. The mean SPF (+/- SD) was 15.0% (+/- 9.5%). The mean SPF was three times higher in aneuploid tumors than in diploid cases. Both the proportion of aneuploid tumors and the mean SPF were significantly higher in later stage tumors, more poorly differentiated tumors, and tumors with a higher mitotic index. No significant differences were seen between histologic types with respect to the two cytometric variables. The 5-year cancer survival rate was only 11% in aneuploid cases compared with 59% in diploid cases (log rank, P = 0.0002). There was a significantly worse prognosis in cases with a higher SPF (P = 0.0009) and in case with a higher mitotic index (P = 0.0016). In the multivariate survival analysis using the Cox proportional hazards model, DNA ploidy showed a significant prognostic value (P = 0.046) even when adjusted for stage, grade, and mitotic index. When adjusted for stage and grade only, SPF showed significant additional prognostic value.

Adult↗

[Histochemical light and electron microscopic investigations on an eosinophilic granuloma].

An eosinophilic granuloma has been investigated by means of histochemical proofs for enzymes and tissue elements and common staining methods. The best method was be found the proof for the enzyme phenol oxidase (EC 1.14.18.1). In this way it is possible to determine eosinophils rapidly and surely and to receive an overview on the frequency and distribution of these cells. The histiocytic-like cells was identified electron microscopical as Langerhans' cells. This cells are in narrow contact to many eosinophilic granulocytes. Their granula have manifold changes in their structure. The granula are possibly able to produce new structures of the cell. The eosinophilic granuloma correspond to a cell mediating immunological defence reaction approximate to the type of a delayed hypersensitivity.

Acid Phosphatase↗

Mdr1/P-glycoprotein, topoisomerase, and glutathione-S-transferase pi gene expression in primary and relapsed state adult and childhood leukaemias.

In a variety of adult and childhood leukaemia cell samples collected at different states of the disease, we analysed in a series of sequentially performed slot-blot or Northern-blot hybridisation experiments the expression of genes possibly involved in multiple drug resistance (MDR) (mdr1/P-glycoprotein, DNA topoisomerase II, glutathione-S-transferase pi), and the expression of the DNA topoisomerase I and histone 3.1 genes. Occasionally, P-glycoprotein gene expression was additionally examined by indirect immunocytofluorescence using the monoclonal antibody C219. No significant difference in mdr1/P-glycoprotein mRNA levels between primary and relapsed state acute lymphocytic leukaemias (ALL) was seen on average. Second or third relapses, however, showed a distinct tendency to an elevated expression of this multidrug transporter gene (up to 10-fold) in part well beyond the value seen in the moderately cross-resistant T-lymphoblastoid CCRF-CEM subline CCRF VCR 100. Increased mdr1/P-glycoprotein mRNA levels were also found in relapsed state acute myelogenous leukaemias (AML), and in chronic lymphocytic leukaemias (CLL) treated with chlorambucil and/or prednisone for several years. Topoisomerase I and topoisomerase II mRNA levels were found to be very variable. Whereas in all but one case of CLL topoisomerase II mRNA was not detected by slot-blot hybridizations, strong topoisomerase I and topoisomerase II gene expression levels, frequently exceeding the levels monitored in the CCRF-CEM cell line, were seen in many cell samples of acute leukaemia. If topoisomerase II mRNA was undetectable, expression of topoisomerase I was clearly visible throughout. These observations might be valuable considering the possible treatment with specific topoisomerase I or topoisomerase II inhibitors. Significant positive correlations were found (i) for topoisomerase I and histone 3.1 gene expression levels in general (P less than 0.001), and (ii) in the CLL samples additionally for the expression levels of the mdr1 gene, and the histone 3.1, topoisomerase I, and glutathione-S-transferase pi genes, respectively.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Anesthesia and acute hepatic porphyrias].

Acute hepatic porphyrias are inherited disorders of heme biosynthesis. A characteristic feature of acute porphyrias is the occurrence of acute attacks which are often precipitated by drugs. Many of the commonly used anaesthetic agents may trigger such a potentially lethal attack. Thus, only safe agents should be administered to predisposed patients. Recommendations given are based on results from animal experiments and on a series of anecdotal reports. Regional anaesthesia is presented as anaesthetic technique of choice. General anaesthesia should be based on a fentanyl-nitrous oxide regimen, with propofol as induction agent. In the case of an acute attack, treatment consists of glucose and haematin administration.

Anesthetics↗

[Suture fixation of a Swan Ganz catheter to the left brachiocephalic vein during re-thoracotomy].

This case report describes the intraoperative fixation of a Swan-Ganz catheter at the left brachiocephalic vein by a suture during rethoracotomy in a cardiac surgical patient. In case of a rethoracotomy by median sternotomy the right-sided veins should be preferred for the insertion of a Swan-Ganz-catheter. Furthermore the free mobility of the catheter should be controlled before closure of the thorax.

Brachiocephalic Veins↗

Nosocomial sinusitis in ventilated patients. Nasotracheal versus orotracheal intubation.

A total of 68 postoperative patients whose lungs were ventilated for more than 4 days were studied prospectively during a one-year study period to investigate the effect of the mode of intubation on the paranasal sinuses. After an initial X ray of the skull showing no pathological findings, patients were assigned randomly to one of the study groups; the lungs of patients in group A were ventilated via an orotracheal tube (n = 32), and patients in group B via a nasotracheal tube (n = 36). X ray examinations of the sinuses were performed at regular intervals. Diagnosis of sinusitis was confirmed by transantral needle puncture and culture of fluids obtained. Antibiotic regimens were altered according to laboratory testing. Two patients in group A developed signs of sinusitis in comparison to 15 patients in group B (p less than 0.01). However, there were significantly more airway complications in the orotracheal group, particularly during the period of weaning from ventilation. We conclude that orotracheal intubation should be preferred as the routine route of intubation.

Aged↗

Molecular cloning and characterization of two lincomycin-resistance genes, lmrA and lmrB, from Streptomyces lincolnensis 78-11.

Two different lincomycin-resistance determinants (lmrA and lmrB) from Streptomyces lincolnensis 78-11 were cloned in Streptomyces lividans 66 TK23. The gene lmrA was localized on a 2.16 kb fragment, the determined nucleotide sequence of which encoded a single open reading frame 1446 bp long. Analysis of the deduced amino acid sequence suggested the presence of 12 membrane-spanning domains and showed significant similarities to the methylenomycin-resistance protein (Mmr) from Streptomyces coelicolor, the QacA protein from Staphylococcus aureus, and several tetracycline-resistance proteins from both Gram-positive and Gram-negative bacteria, as well as to some sugar-transport proteins from Escherichia coli. The lmrB gene was actively expressed from a 2.7 kb fragment. An open reading frame of 837 bp could be localized which encoded a protein that was significantly similar to 23S rRNA adenine(2058)-N-methyltransferases conferring macrolide-lincosamide-streptogramin resistance. LmrB also had putative rRNA methyltransferase activity since lincomycin resistance of ribosomes was induced in lmrB-containing strains. Surprisingly, both enzymes, LmrA and LmrB, had a substrate specificity restricted to lincomycin and did not cause resistance to other lincosamides such as celesticetin and clindamycin, or to macrolides.

Amino Acid Sequence↗

Two different allelic mutations in the lecithin-cholesterol acyltransferase gene associated with the fish eye syndrome. Lecithin-cholesterol acyltransferase (Thr123----Ile) and lecithin-cholesterol acyltransferase (Thr347----Met).

We have elucidated the genetic defect in a 66-yr-old patient with fish eye syndrome (FES) presenting with severe corneal opacities and hypoalphalipoproteinemia. The patient's plasma concentration of high density lipoprotein (HDL) cholesterol was reduced at 7.7 mg/dl (35.1-65.3 mg/dl in controls) and the HDL cholesteryl ester content was 31% (60-80% in controls); however, total plasma cholesteryl esters were similar to normal (60% of total cholesterol vs. a mean of 66% in controls). The patient's plasma cholesterol esterification rate was slightly reduced at 51 nmol/ml per h (control subjects: 61-106 nmol/ml per h), whereas lecithin-cholesterol acyltransferase (LCAT) activity, assayed using a HDL-like exogenous proteoliposome substrate, was virtually absent (0.9 nmol/ml per h vs. 25.1-27.9 nmol/ml per h in control subjects). DNA sequence analysis of the proband's LCAT gene revealed two separate C to T transitions resulting in the substitution of Thr123 with Ile and Thr347 with Met. The mutation at codon 347 created a new restriction site for the enzyme Nla III. Analysis of the patient's polymerase chain reaction-amplified DNA containing the region of the Thr347 mutation by digestion with Nla III confirmed that the proband is a compound heterozygote for both defects. The patient's daughter, who is asymptomatic despite a 50% reduction of LCAT activity, is heterozygous for the Thr123----Ile mutation. Our data indicate that the regions adjacent to Thr123 and Thr347 of LCAT may play an important role in HDL cholesterol esterification, suggesting that these regions may contain a portion of the LCAT binding domain(s) for HDL.

Aged↗

Demonstration of cytomegalovirus (CMV) DNA and anti-CMV response in the synovial membrane and serum of patients with rheumatoid arthritis.

One hundred forty-seven synovial membranes were investigated for the presence of human cytomegalovirus (CMV). In 11 of 83 synovial membranes of patients with rheumatoid arthritis (RA), but only in 2 of 64 synovial membranes from patients with other joint disorders, CMV-DNA could be detected by the polymerase chain reaction (PCR) technique (p less than 0.05). In contrast, the percentage of seropositive patients was not significantly different between the 2 groups of patients and no blood sample from any patient tested revealed the presence of CMV by PCR. Only in patients with RA and CMV positive synovial membranes was the titer of CMV specific antibodies in the synovia higher than in the serum. Thus, the local presence of CMV in the synovial membrane and associated local antiviral responses might participate in the pathogenesis of synovitis in a minority of patients with RA.

Antibodies, Viral↗

[Surfactant administration in acute respiratory failure].

We report the case of a 21-year-old man who developed adult respiratory distress syndrome (ARDS) after severe lung contusion due to a car accident. At the scene of the accident the patient was awake and oriented, but there were signs of hypoxaemia (SaO2 by pulse oximetry: 86%). The trachea was intubated in the emergency room and, after diagnosis of multiple rib fractures on the right side (the patient nos. 4-11) and emergency treatment, was extubated 16 h later. During spontaneous breathing there was no improvement of pulmonary function, and the patient was transferred to the intensive care unit 5 days later and reintubated because of acute respiratory failure. He then developed the signs of severe ARDS. No improvement occurred during conventional ventilatory treatment including inversed-ratio ventilation, high-frequency ventilation, and ventilation via a double-lumen tube. On day 15 a bovine surfactant preparation (38 mg/kg body wt.) was instilled into both lungs. Initially there was deterioration of the pulmonary function, probably due to crusts in the bronchial mucous membrane. After aspiration of the crusts at bronchoscopy, there was progressive respiratory improvement. The inspired oxygen concentration and PEEP level could be reduced, and the ventilatory ratio normalised within 14 days. This therapeutic intervention improved pulmonary function and probably led to the successful outcome after 36 days of ventilatory support.

Accidents, Traffic↗

Intracellular cytosine arabinoside accumulation and cytosine arabinoside triphosphate formation in leukemic blast cells is inhibited by etoposide and teniposide.

Cytosine arabinoside (ara-C) is one of the most active compounds in the treatment of acute leukemias. In the majority of current protocols ara-C is combined with other cytotoxic agents in an attempt to increase antileukemic activity. The present study investigated the impact of etoposide, teniposide, amsacrine, mitoxantrone, anthracyclines, and asparaginase on the cellular accumulation of ara-C and its intracellular metabolism in order to provide a better rationale for combination therapy. Intracellular accumulation and phosphorylation of ara-C were determined in peripheral blast cells from twenty patients with acute leukemias after exposure to 1 and 10 mumol/l ara-C alone and after preincubation with 1 and 10 micrograms/ml etoposide, 10 and 100 micrograms/ml teniposide, 10 mumol/l amsacrine, 500 ng/ml mitoxantrone (or daunorubicin or doxorubicin) or 10 mumol/l asparaginase. Ara-C accumulation at 10 mumol/l was decreased by 1 microgram/ml etoposide (67 +/- 18% of control), 10 micrograms/ml etoposide (30 +/- 22%), 10 micrograms/ml teniposide (12 +/- 23%), 100 micrograms/ml teniposide (10 +/- 18%), and amsacrine (51 +/- 21%). Intracellular ara-CTP formation was determined at an extracellular concentration of 10 mumol/l and preincubation with these drugs. The intracellular formation of ara-CTP was decreased by 1 microgram/ml etoposide (77 +/- 15% of control), 10 micrograms/ml etoposide (32 +/- 22%), 10 micrograms/ml teniposide (10 +/- 9%), 100 micrograms/ml teniposide (0 +/- 0%), but not by amsacrine. These data indicate that prior exposure to etoposide and teniposide influence ara-C metabolism and possibly cytotoxicity, and thus should not immediately precede ara-C administration in clinical trials.

Acute Disease↗