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Biomedical subjects

S Schmidt

Publications and source records attributed to S Schmidt.

At least 343 records · Page 19Linked to original sources

Biodegradation and transformation of 4,4'- and 2,4-dihalodiphenyl ethers by Sphingomonas sp. strain SS33.

The bacterium Sphingomonas sp. strain SS33, obtained from parent diphenyl ether-mineralizing strain SS3 (S. Schmidt, R.-M. Wittich, D. Erdmann, H. Wilkes, W. Francke, and P. Fortnagel, Appl. Environ. Microbiol. 58:2744-2750, 1992) after several weeks of adaptation on 4,4'-difluorodiphenyl ether as the new target compound, also utilized 4,4'-dichlorodiphenyl ether for growth. Intermediary halocatechols were also mineralized via the ortho pathway by type I enzymes. 4,4'-Dibromodiphenyl ether was not used as a carbon source although transformation by resting cells yielded mononuclear haloaromatic compounds, such as 4-bromophenol and 4-bromocatechol. The same was true for the conversion of 2,4-dichlorodiphenyl ether, which yielded the respective (halo-) phenols and (halo-) catechols.

Bacteria↗

Intracerebral hematoma related to thrombolysis for myocardial infarction.

The incidence of intracerebral hematomas after myocardial infarction increases after thrombolysis. As noted in the case described, clots formed after the administration of thrombolytic agents may remain liquid, and this blood can be drained by a catheter. However, in this case, the patient continued to bleed locally. This problem requires the development of methods to stop such ongoing local bleeding. It may be prevented in the future by improved thrombolytic drugs.

Aged↗

Effect of syngeneic islet antigen administration on complement-dependent antibody-mediated cytotoxicity to islet cells and diabetes onset in diabetes-prone BB/OK rats.

Diabetes-prone BB/OK rats aged 30 to 35 days were subjected to three sequential intrasplenic injections of unfractionated homogenate prepared from Langerhans' islets of newborn syngeneic BB/OK rats. Syngeneic islet antigen administration resulted in increased complement-dependent antibody-mediated cytotoxicity (C'AMC) to rat pancreatic islet cells in serum, compared to buffer-treated control animals as detected by 51Cr-release assay. However, the increase of anti-islet-cell cytotoxicity neither impaired glucose tolerance nor affected the incidence of diabetes and the age at manifestation. In contrast to BB/OK rats developing diabetes, animals remaining long-term normoglycaemic did not show an enhancement of cytotoxicity to islet cells within twelve days after the first islet antigen injection as revealed retrospectively. In conclusion, humoral mediated anti-islet-cell cytotoxicity is not decisively involved in pancreatic beta-cell destruction and promotion of diabetes development in BB/OK rats, but animals becoming diabetic seem to be characterized by a stronger immunological reactivity upon syngeneic islet antigen challenge as indicated by an increase of anti-islet C'AMC compared to long-term normoglycaemic rats.

Animals↗

Humoral-mediated cytotoxicity to rat pancreatic exocrine cells in serum of diabetes-prone BB/OK rats--predictive value for diabetes onset.

Diabetes-prone BB/OK rats were checked in a follow-up study between 40 and 200 days of age for the appearance of humoral-mediated cytotoxicity to rat pancreatic exocrine cells in serum by 51Cr-release assay. BB/OK rats maintaining normoglycaemia were characterized by a pronounced decrease of anti-exocrine cell cytotoxicity in serum at 75 and 105 days of age compared to the initial value at day 40. In contrast, in animals developing diabetes cytotoxicity was found more frequently and the level of cytotoxicity did not likewise decrease during the period up to diabetes onset. With respect to the prediction of diabetes in individual BB/OK rats the retrospective analysis revealed that 81.0% of those animals displaying cytotoxicity at 75 days of age subsequently developed diabetes. If sera from BB/OK rats were identified as non-cytotoxic at day 75 and also at 105 days of age normoglycaemia persisted in 83.3% of these animals. Thus, screening of young diabetes-prone BB/OK rats for the presence of humoral-mediated cytotoxicity to pancreatic exocrine cells in serum seems to facilitate the identification of potential diabetic or long-term normoglycaemic animals in the BB/OK rat population.

Animals↗

[Use of the Glasgow Coma Scale in pediatric craniocerebral trauma].

Over five years the applicability of a modified Glasgow Coma Scale was analysed in 38 children (mean age 7.2 +/- 3.8 years) with head and associated injuries (47.4%). The score was estimated after the accident and in the course of intensive therapy. At the beginning of the treatment on the intensive care unit, the cases were staged according to the severity of the head injuries (Glasgow Coma Scale: 4-8, 9-12 and 13-19 points). At the stage evaluated as between 4 and 8 points, 50% of the patients died and the survivors were ventilated (11.7 +/- 10.7 days) and intensively treated (45.7 +/- 31.5 days). All patients had had neurological damage. Additional injuries worsened the prognosis in the acute phase. 42.9% of the patients received intracranial pressure monitoring. In the patients between 9 and 12 points, the time of ventilation (3.7 +/- 2.9 days) and of intensive therapy (19.5 +/- 13.3 days) decreased. Over 13 points, all patients had a shorter duration of treatment (10.8 +/- 8.8 days) and a quick and good recovery. The Glasgow Coma Scale has the advantage of an examination with a quantitative analysis and resulting effective diagnostic and therapeutic measures. Even the inexperienced physician can use the Glasgow Coma Scale with success at the site of the accident.

Adolescent↗

[Heparin-associated thrombocytopenia as a problem in heparin therapy].

The clinical picture of HAT (heparin-associated thrombocytopenia) is being described in reference to a typical case report. If not recognized in time, HAT may lead to serious thrombo-embolic complications, which may eventually lead to death. Considering the wide applications of routine heparin in therapy and prophylaxis, HAT deservers more clinical attention. Routine monitoring of platelet counts during heparin treatment is crucial and essential.

Aged↗

Metabolism of 3-methyldiphenyl ether by Sphingomonas sp. SS31.

The bacterium Sphingomonas sp. SS31, which was obtained from the diphenyl ether-degrading strain Sphingomonas sp. SS3 by an adaptation process, utilized 3-methyldiphenyl ether for growth in addition to diphenyl ether. The initial enzymatic attack onto this compound proceeded by a regioselective, but non-specific dioxygenation at the carbon carrying the ether bridge and the adjacent carbon of the unsubstituted as well as the methyl-substituted aromatic nucleus. Upon spontaneous decomposition, the resulting unstable hemiacetal structure yielded 3-methylphenol and catechol, or phenol, 3-methylcatechol, and 4-methylcatechol, respectively. Phenol and 3-methylphenol were oxidized to the corresponding catechols which, after subsequent ortho-cleavage, were channeled into the oxoadipate pathway.

Adaptation, Physiological↗

Reversal of multidrug resistance by two novel indole derivatives.

Two new fused indoles were found to overcome multidrug resistance in P388/Adr cells in vitro. These agents potentiated the cytotoxicity of the antitumor drugs Adriamycin, vinblastine, and vincristine in multidrug-resistant cells with no effect on drug-sensitive parent P388 cells. They significantly increased the ATP-dependent accumulation of [3H]-vinblastine and inhibited efflux of the labeled drug from resistant cells. These compounds also inhibited photoaffinity labeling of P-glycoprotein by [3H]azidopine in P388/Adr cells and membranes isolated from these cells. In addition, the calcium antagonist activity of these compounds was very weak compared with that of verapamil. These data suggest that the compounds reported here may specifically overcome multidrug resistance without the serious hypotensive effects associated with calcium antagonists and that this activity may be independent of their ability to block calcium transport.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Photodynamic laser therapy with antibody-bound dyes. A new procedure in therapy of gynecologic malignancies].

In the present paper, a new therapeutic concept of photodynamic laser therapy using antibody-linked dyes for the treatment of gynecological malignancies is described. So far, HPD (hematoporphyrin derivative) has been employed in this area, but is associated with toxic systemic reactions. We see a solution to this problem in the linking of a systemically non-toxic dye--known to induce photodynamic reactions while not itself being selectively accumulated within tumor cells--to an antibody directed against a selective tumor-associated antigen. The results of our study demonstrate the efficacy of this therapeutic concept as exemplified by the selective destruction of dye-labeled ovarian carcinoma cells by laser light of a defined wavelength (675 nm). The potential of this form of photodynamic therapy extends far beyond its use in ovarian carcinoma.

Antibodies, Monoclonal↗

Chemical synthesis of 2'-deoxyoligonucleotides containing 5-fluoro-2'-deoxycytidine.

2'-Deoxyoligonucleotides with 5-fluorocytosine residues incorporated at specific positions of the nucleotide sequence are tools of great potential in the study of the catalytic mechanism by which DNA cytosine methyltransferases methylate the 5-position of DNA cytosine residues in specific sequence contexts. Chemical synthesis of such oligonucleotides is described. Two alternative approaches have been developed, one of which proceeds via a fully protected phosphoramidite of 5-fluoro-4-methylmercapto-2'-deoxyuridine 2, the other via a fully protected phosphoramidite of 5-fluoro-2'-deoxycytidine 3. Either building block can be used in automated oligonucleotide synthesis applying standard elongation cycles and deprotection procedures exclusively. The methylmercapto function of 2 is replaced by an amino group in the final ammonia treatment used for cleavage from support and base deprotection.

Base Sequence↗

The use of oligonucleotide probes containing 2'-deoxy-2'-fluoronucleosides for regiospecific cleavage of RNA by RNase H from Escherichia coli.

Protected 2'-deoxy-2'-fluorouridine and 2'-deoxy-2'-fluorocytidine suitable for incorporation into oligonucleotides via the phosphoramidite approach have been prepared. Five modified and two unmodified oligonucleotides have been synthesized to investigate the regiospecific cleavage of a 5S RNA from Escherichia coli by RNase H. In order to show whether the modified oligonucleotides are able to hybridize with the RNA the physico-chemical properties (melting curves, CD spectra) of analogous DNA/oligodeoxyribonucleotide duplexes have been examined. The modified oligonucleotides are shown to form stable duplexes with a DNA-matrix which exist in an A-like form. Two of the modified probes containing four 2'-deoxy-2'-fluorocytidines or two 2'-deoxy-2'-fluorouridines direct the splitting by RNase H of only one phosphodiester bond of the RNA.

Base Sequence↗

The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1.

To identify the principal neutralization determinant (PND) of simian immunodeficiency virus (SIV), antisera were generated using recombinant gp110 [the SIV analog of the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein, gp120], gp140, several large recombinant and proteolytic envelope fragments, and synthetic peptides of the SIVmac251 isolate. When purified under conditions that retain its native structure, gp110 bound CD4 and elicited antisera that neutralized SIVmac251 with high titer. Native gp110 also completely inhibited neutralizing antibody in sera from SIVmac251-infected macaques. In contrast, denatured gp110 and gp140, large envelope fragments, and synthetic peptides (including peptides analogous to the HIV-1 PND) elicited very low or undetectable neutralizing antibody titers and did not inhibit neutralizing antibody in infected macaque sera. Enzymatically deglycosylated gp110 efficiently absorbed neutralizing antibodies from macaque sera, showing that neutralizing antibodies primarily bind the protein backbone. A 45-kDa protease digest product, mapping to the carboxyl-terminal third of gp110, also completely absorbed neutralizing antibodies from infected macaque sera. These results show that the PND(s) of this SIV isolate depends on the native conformation and that linear peptides corresponding to the V3 loop of SIV envelope, in contrast to that of HIV-1, do not elicit neutralizing antibody. This may affect the usefulness of SIVmac for evaluating HIV-1 envelope vaccine approaches that rely on eliciting neutralizing antibody.

Antigens, Viral↗

Evidence against linkage of schizophrenia to chromosome 5q11-q13 markers in systematically ascertained families.

Ten pedigrees systematically ascertained in Germany were tested for linkage to chromosome 5q11-q13. In order to replicate the previous report by Sherrington et al (1988), families with a bipolar family member were omitted from the lod score calculations, all diagnoses were based upon Research Diagnostic Criteria, and four different models of the affection status were calculated, including the model for which Sherrington et al calculated the highest lod scores. None of the families investigated showed a positive lod score. Using multipoint linkage analyses, we were able to exclude the region for which a positive linkage has been reported.

Chromosomes, Human, Pair 5↗

Mutations in the cdc10 start gene of Schizosaccharomyces pombe implicate the region of homology between cdc10 and SWI6 as important for p85cdc10 function.

The cdc10 gene of the fission yeast Schizosaccharomyces pombe is required for traverse of start and commitment to the mitotic cell division cycle rather than other fates. The product of the gene, p85cdc10, is a component of a factor that is thought to be involved in regulating the transcription of genes that are required for DNA synthesis. In order to define regions of the p85cdc10 protein that are important for its function a fine structure genetic map of the cdc10 gene was derived and the sequences of 13 cdc10ts mutants determined. The 13 mutants tested define eight alleles. Eleven of the mutants are located in the region that contains the two copies of the cdc10/SWI6 repeat motif, implicating it as important for p85cdc10 function.

Amino Acid Sequence↗

Phase I trial of a 72-h continuous-infusion schedule of fazarabine.

Fazarabine (Ara-AC), a structural analog derived from the antitumor nucleoside cytosine arabanoside (Ara-C) and 5-azacytidine (5-AC), was studied in a phase I clinical trial. Doses ranging from 0.2 to 2.0 mg m-2 h-1 were given intravenously over 72 h every 28 days. The maximum tolerated dose (MDT) was 2.00 mg m-2 h-1. The dose-limiting toxicity was myelosuppression, with granulocytopenia being quantitatively more important than thrombocytopenia or anemia. Nonhematologic toxicity was minimal. Associated with the solvent dimethylsulfoxide (DMSO) was a bitter taste and a garlic-like odor.

Adult↗

Expression of insulin-like growth factor II (IGF-II) and IGF-II, IGF-I and insulin receptors mRNAs in isolated non-parenchymal rat liver cells.

The insulin-like growth factor II (IGF-II) is involved in embryonic growth. Modifications of its expression might play a role in the development of primary liver cancer in humans and woodchucks. In the liver, little information is available on the cell types involved in its synthesis. We have investigated the expression of IGF-II as well as IGF-II, IGF-I and insulin receptor mRNAs in non parenchymal liver cell preparations in rats of various ages. The results indicate that Kupffer cells, endothelial cells and fat-storing cells express both IGF-II and the three different receptor mRNAs. Furthermore, a switch from a fetal to an adult IGF-II mRNA profile was obtained in the different cell preparations. Therefore, our results indicate that regulation of IGF-II gene expression can be analyzed through these isolated liver cell preparations. These results might also be important in investigating the potential role of IGF-II in liver carcinogenesis.

Animals↗