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Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 487 records · Page 27Linked to original sources
PubMed1995

Concentration of purine compounds in the cerebrospinal fluid of infants suffering from sepsis, convulsions and hydrocephalus.

Catabolites of purine nucleotides were measured in the cerebrospinal fluid (CSF) of newborn infants with sepsis, seizures and hydrocephalus using isocratic reversed-phase HPLC. The inosine levels in the CSF of the infants with any of the illnesses were significantly higher when compared with the controls. There was a tendency for hypoxanthine levels to be higher in the group of children with hydrocephalus. No significant differences in the concentrations of xanthine, adenine and uric acid were found. The inosine concentration in the CSF is proposed to be a more sensitive indicator of brain injury than the levels of other CSF purines. The levels of all purine metabolites measured in the CSF showed large individual variations. The ratio between hypoxanthine (as an indicator of ATP breakdown) and uric acid (as a scavenger of oxygen free radicals) concentration is proposed as a new criterion to be used in the evaluation of brain injury.

Adenine↗
PubMed1995

Relative roles of natural killer- and T cell-mediated anti-leukemia effects in chronic myelogenous leukemia patients treated with interferon-alpha.

Potential anti-leukemia effects mediated by T cells or by natural killer (NK) cells were investigated in chronic myelogenous leukemia (CML) patients treated with interferon-alpha. Therapy-associated modulation of T cell and NK reactivity was monitored for one year from initiation in autologous mixed lymphocyte-tumor cell reactions and cytotoxicity directed against autologous CML cells, respectively. During the course of IFN-therapy, NK activity against autologous CML cells increased steadily, whereas T cell reactivity fluctuated randomly. Despite the high level of T cell reactivity to autologous tumor cells in short-term (6 days) culture, 1) they failed to respond to synthetic peptides corresponding to the bcr/abl fusion sequence of the patient, and 2) only one proliferative T cell clone (TCC) was isolated which specifically recognized HLA-DR-matched CML cells. This TCC appeared not to recognize synthetic peptides corresponding to the bcr/abl fusion sequence of the patient; the antigen to which it responds remains unknown. To assess potential immunogenicity of bcr/abl peptides, it was attempted to sensitize T cells from normal donors in vitro. Of 109 cell lines obtained from seven different donors, eleven showed peptide-dependent proliferation. Therefore, although these results show that it is possible to isolate apparently CML-specific T cells from patients, as well as to prime T cells against tumor-specific peptide in vitro, the frequency of such T cell-mediated reactivity appears low and its relevance to anti-leukemic effects questionable. On the other hand, the strong time-dependent enhancement of natural killing of autologous CML blasts during IFN-alpha treatment, a phenomenon not observed for T cell reactivity, suggests that natural immunity may be more important in controlling disease.

Amino Acid Sequence↗
PubMed1995

Effect of neurotropic virus infection on neuronal and inducible nitric oxide synthase activity in rat brain.

To elucidate the potential role of inducible nitric oxide synthase (iNOS) and neuronal constitutive nitric oxide synthase (cNOS) in the pathogenesis of virus-induced encephalopathy, the activities of both NOS isoforms were determined in the brains of rats infected with Borna disease virus (BDV) or rabies virus. iNOS activity strongly increased, whereas neuronal cNOS activity significantly decreased in a time-dependent manner after either BDV or rabies virus infection. Choline acetyltransferase activity in the brain remained unchanged during both virus infections, suggesting that the decrease in cNOS activity does not reflect a generalized neuronal loss. Immunohistochemistry and Northern blot analyses indicate that the decrease in neuronal cNOS activity is due to a decrease in cNOS protein and mRNA synthesis. These results suggest that both an excessive generation of NO by activated macrophages or microglia, as well as a decrease of NO production in neurons may contribute to the neuropathogenesis of neurotropic virus infections.

Animals↗
PubMed1995

Treatment of steroid-resistant graft-versus-host disease after allogeneic bone marrow transplantation with anti-CD3/TCR monoclonal antibodies.

Acute graft-versus host disease (GVHD), one of the major complications of allogeneic bone marrow transplantation (BMT), occurs in 30-50% of all patients transplanted from HLA-identical sibling donors and in 50-80% of all patients transplanted from an unrelated or HLA-mismatched family donor, despite GVHD prophylaxis with methotrexate and cyclosporin. We report our experience with OKT3/BMA031 treatment in 14 patients with severe steroid-resistant GVHD following allogeneic BMT. Three of 5 patients treated in the early post-transplant period with OKT3 remitted and 2 of 3 became long-term survivors. Two patients treated for extensive chronic GVHD showed only minor responses. Five of 7 patients treated with BMA031 showed a partial remission; no complete remission was seen after treatment with this antibody. Shortly after the introduction of OKT3 or BMA031 therapy a rapid decline of the lymphocyte count, especially the CD3+ subset, was observed coinciding with a relative increase of CD56+ lymphocytes and of gamma/delta TCR+ T cells. Increasing numbers of CD3+ lymphocytes preceded recurrence of acute GVHD in three patients. In contrast, persisting CD3-lymphocytopenia was associated with complete clearance of acute GVHD. The incidence of infectious complications following OKT3 or BMA031 therapy was high (42%). Thus, to improve treatment results of severe acute GVHD, prophylactic or pre-emptive strategies are required to reduce the rate of fatal viral and fungal infections.

Acute Disease↗
PubMed1995

[Fibrinogen and leukocyte number in coronary heart disease. Correlation with angiography and clinical degree].

In 302 consecutively patients fibrinogen (Clauss method) and leucocyte count were related to the angiographic and clinical degree of coronary atherosclerosis. Fibrinogen (mg/dl) was statistically higher compared to control (C, 267 +/- 55) in patients with one-vessel disease (1-vd (306 +/- 67), 2-vd (331 +/- 73), and 3-vd (328 +/- 62)). Patients with coronary sclerosis (Scl, luminal irregularities and/or stenosis under 50%) showed a tendency to higher fibrinogen levels (291 +/- 58) as compared to controls. Leucocyte count (10(9)/L) compared to C (6.7 +/- 1.8) was significantly higher in 1-vd (7.6 +/- 2.0) and 2-vd (7.6 +/- 1.9). A subgroup analysis was performed with 100 patients having severe forms of angina pectoris (AP III according to the CCS classification, unstable angina). Hundred-sixteen patients with unstable angina (390 +/- 79), particularly with angina at rest during the last 48 h were characterized by the highest fibrinogen values (423 +/- 89, class III B/C Braunwald). Leucocyte count in patients with stable angina (7.2 +/- 1.4) and angina at rest (9.3 +/- 2.7) was significantly higher as compared to control (6.7 +/- 1.8). Hyperfibrinogenemia and relative leucocytosis correlate with the angiographic and clinical extent of coronary artery disease and may offer evidence of a higher degree of thrombogenesis associated with components of inflammation.

Adult↗
PubMed1995

[Demonstration of two trimethoprim/sulfonamide combinations in bronchoalveolar lavage fluid of horses and determination of blood levels].

Five healthy horses were given a sulfadoxine/trimethoprim combination (Borgal, Hoechst AG) i.v. on day 1. The next ten days the horses got once a day a sulfadimethoxine/trimethoprim combination orally (Trafigal, Hoechst AG). The doses were given as recommended. One horse received no medicaments for control. On each horse six bronchoalveolar lavages were performed. Blood samples were taken to calculate blood levels and elimination half lives. To determine the amount of substances in lavage fluid and plasma the high performance liquid chromatography (HPLC) was used. Regularly low quantities of sulfonamides and trimethoprim were detected in lavage-samples. The mean plasma concentration (n = 4) of sulfadoxine and trimethoprim 30 min after i.v. administration was 71.6 and 1.13 micrograms/g respectively. 24 h after injection the sulfadoxine blood level was 3.0 micrograms/g, while trimethoprim was no longer detectable. The average elimination half lives of sulfadoxine and trimethoprim were 7.94 h and 1.35 h respectively. 8 h after oral application (n = 5) the highest mean sulfadimethoxine blood levels of 53.8 micrograms/g were measured. The elimination half life of sulfadimethoxine was 9.77 h. Two hours after feeding the drug the first blood samples were taken. They already contained the highest mean trimethoprim concentration of 0.32 microgram/g plasma.

Animals↗
PubMed1995

[Effectiveness of oral rifampicin against mycobacteriosis in tropical fish].

In vitro studies have shown that rifampicin is an effective antibiotic for mycobacteria infections. Two species of tropical fish, the Firemouth Cichild Cichlasoma meeki and the Congo Tetra Phenacogrammus interruptus, were used to determine whether oral application of rifampicin might serve as an effective treatment for mycobacteriosis in tropical fish. Fish of the two species were infected with M. marinum under controlled conditions. Six or twelve weeks after infection, treatment was begun with medicated fish food containing rifampicin in combination with tetracyclin. Histological examination of epithelial cell granuloma in the anterior and posterior kidneys, as well as in liver and spleen, showed that antibiotic treatment could somewhat reduce the intensity of, but could not successfully eliminate infection. In addition, after treatment, acid-resistant rods could still be isolated from histological samples and M. marinum could be cultured from organ samples.

Administration, Oral↗
PubMed1994

The mating-type region of Schizosaccharomyces pombe contains an essential gene encoding a protein homologous to human modulators of HIV transactivation.

In Schizosaccharomyces pombe, an intrachromosomal crossover between the mating type (MT) expression locus and one of the silent donor cassettes is lethal due to the loss of the intervening L region. The region contains one essential gene, let1. This gene was cloned and sequenced. The deduced amino acid (aa) sequence of let1 shows extensive homologies with SUG1 from Saccharomyces cerevisiae. Significant homologies were also found with the human HIV transactivation modulators, MSS1 and TBP-1, as well as with subunit 4 of the mammalian 26 S protease. The data indicate that let1 is a member of a recently defined multigene family of ATPases.

Adenosine Triphosphatases↗
PubMed1994

Switching gene swi6, involved in repression of silent mating-type loci in fission yeast, encodes a homologue of chromatin-associated proteins from Drosophila and mammals.

The switching gene swi6 of Schizosaccharomyces pombe is involved in the repression of the silent mating-type loci mat2 and mat3. We have cloned the gene by functional complementation of the switching defect of the swi6-115 mutation. DNA sequence analyses revealed an open reading frame of 984 bp coding for a putative protein of 328 amino acids (aa). The isolation of a swi6 cDNA confirmed this result. Gene replacement showed that swi6 is not essential for viability. The Swi6 protein is very hydrophilic; it contains 41% charged aa. A region of 48 aa is homologous to a sequence motif found in the chromatin-associated proteins, HP1 and Polycomb (Drosophila melanogaster), M31, M32 and M33 (mouse), and the human HSM1 protein. This motif is called chromo domain (chromatin organization modifier). Our results indicate that Swi6 is a structural component of chromatin. Swi6 may have the function to compact mat2 and mat3 into a heterochromatin-like conformation which represses the transcription of these silent cassettes.

Amino Acid Sequence↗
PubMed1994

Highly conserved B-subunit genes of Shiga-like toxin II variants found in Escherichia coli O157 strains.

To determine the degree of heterogeneity among Shiga-like toxin-II (SLT-II)-related toxins present in enterohemorrhagic Escherichia coli O157 strains, slt-IIB-related genes of 15 strains were amplified and sequenced. Of these 15 isolates, six contained only the slt-II-related genes, seven strains harbored slt-II-related genes together with slt-II, and two strains had slt-II-related genes plus slt-I. In strains carrying slt-II-related genes alone or in combination with slt-I, the PCR fragments were directly subjected to Taq cycle sequence analysis. Direct sequencing was not possible with the seven strains possessing both slt-II and slt-II-related genes, since the PCR products contained both genes. In order to allow sequence analysis of these slt-II-related genes, the PCR products were first subjected to restriction enzyme digestion with FokI, which selectively digested slt-IIB. This resulted in an undigested 270-bp fragment consisting of pure slt-II-related genes. Interestingly, comparison of the nucleotide sequences revealed 100% homology of all analyzed 15 slt-IIB-related toxin genes. In addition, the nucleotide sequence of slt-IIB-related toxin genes were identical to slt-IIcB. Our findings indicate that SLT-IIc is a major variant form of SLT-II present in E. coli O157 strains.

Bacterial Toxins↗
PubMed1994

The large-sized plasmids of enterohemorrhagic Escherichia coli O157 strains encode hemolysins which are presumably members of the E. coli alpha-hemolysin family.

Most enterohemorrhagic Escherichia coli O157:H7 strains harbor a large-sized (90 kb) plasmid designated pO157 and show an enterohemolytic phenotype. In this study the hemolytic activity of E. coli O157:H7 strain EDL933 was investigated. Curing of strain EDL933 from pO157 resulted in loss of its hemolytic activity. By transformation with Tn801-tagged pO157 (pSK3), the hemolysin-negative E. coli K-12 strains C600 and DH5 alpha became positive for hemolysin production. By transformation of recombinant plasmids carrying a 11.9 kb BamHI fragment and a 5.3 kb SalI fragment of pSK3 hemolytic activity is revealed when transformed in E. coli C600 or DH5 alpha DNA-hybridization of pO157 and subclones with the alpha-hemolysin specific DNA probe was only found under conditions of low stringency. No hybridization was found with enterohemolysin I (EHly1) and enterohemolysin II (EHly2) probes. Our results indicate that a hitherto not described hemolysin belonging to the alpha-hemolysin family is encoded by the 90 kb plasmid of E. coli O157 strains.

Base Sequence↗
PubMed1994

[Diagnosis and treatment of acute sinusitis by Danish general practitioners].

We studied Danish general practitioners' (GP) weighting of symptoms, clinical findings and use of paraclinical investigations when diagnosing acute sinusitis in adults. Questionnaires were sent to 300 representative GPs. Sixty-seven percent answered the questionnaire. The GPs weighted pain and tenderness on application of pressure over the sinuses as the most important symptom and finding. Only a few used paraclinical investigations. The GPs estimated their own diagnostic certainty as being 70%. Detumescent nose-drops were prescribed in 95% of the cases, and antibiotic treatment was given in 50%, most frequently as V-penicillin.

Acute Disease↗
PubMed1994

Purification and PCR-based cDNA cloning of a plastidial n-6 desaturase.

A plastidial membrane-bound n-6 desaturase from spinach (Spinacia oleracea) was purified from chloroplast envelope membranes by anion exchange, cation exchange and ferredoxin-affinity chromatography. The molecular mass of the protein was estimated by SDS-PAGE to be 40 kDa. The highest specific activity of the desaturase in the final preparation was 196 nmol/min per mg protein with free oleic acid as the substrate. The N-terminal amino acid sequence of the blotted protein was determined and used for the construction of a degenerated and inosine-containing oligonucleotide primer for PCR experiments with cDNA transcribed from leaf mRNA. A 3'-RACE experiment with this primer amplified a single band of 1500 bp that after sequencing showed an open reading frame of 382 amino acids corresponding to a protein of 43 kDa. The 5' end of the cDNA was amplified by a 5'-RACE experiment and isolated as a 500 bp fragment. Sequencing of this DNA revealed an additional 65 amino acids at the N-terminus of the native protein that are attributed to a plastidial leader peptide. With appropriate primers derived from these sequences a full-length clone was amplified by PCR and sequenced. Comparison of the plastidial oleate desaturase with the homologous enzyme from cyanobacteria showed about 50% amino acid homology. Comparison with other desaturases revealed three histidine boxes with the general sequence HXXXH that are highly conserved in all membrane-bound desaturases. These boxes might be involved in metal ion complexation required for reduction of oxygen.

Amino Acid Sequence↗
PubMed1994

Differentiation in virulence patterns of Escherichia coli possessing eae genes.

In this study 98 Escherichia coli strains which belonged to traditional enteropathogenic (EPEC) serotypes and 82 enterohemorrhagic E. coli (EHEC) strains were screened by polymerase chain reaction (PCR) for the presence of E. coli-attaching and -effacing (eae) genes. These strains were also hybridized with the enteropathogenic adherence factor (EAF) probe and examined in the fluorescence actin staining (FAS) test. The results obtained from the individual strains demonstrated that all 26 class I EPEC with localized adherence to HEp-2 cells carried EAF and eae genes. In contrast, of 72 EPEC strains with no or diffuse adherence only 1 strain was EAF positive and 6 strains had eae. Of 82 EHEC strains a total of 75 carried eae sequences. Of considerable interest, 15 of 21 E. coli strains that lost their slt genes during subcultivation were found to be eae positive. As controls a total of 53 enterotoxigenic and enteroinvasive E. coli, and 125 E. coli strains from the normal flora were investigated and all displayed negative results in the eae-PCR. From the 201 strains comprising classical EPEC serotypes, EHEC and E. coli with lost slt genes, a total of 126 displayed a positive FAS test and 122 reacted in the eae-PCR. Only 4 strains were FAS test positive but eae-PCR negative. Our data indicate that E. coli strains possessing the eae genes are heterogenous with respect to their virulence determinants. Loss of virulence plasmids and phage-encoded slt genes either in the host or during storage may contribute to this heterogeneity. The eae-PCR detected all class I EPEC and 91.5% of the EHEC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adhesins, Bacterial↗
PubMed1994

Cytomegalovirus in liver biopsies of marrow transplant recipients: detection methods, clinical, histological and immunohistological features.

In a retrospective analysis liver biopsy specimens obtained from 44 marrow transplant recipients were studied to evaluate the frequency of local presence of human cytomegalovirus (CMV) and graft-versus-host disease (GvHD)-like histological and immunohistological alterations in patients with and without liver dysfunction following bone marrow transplantation (BMT). In 22 of 28 patients with marked liver dysfunction after BMT and histopathological alterations described as typical for acute GvHD CMV could be detected in the liver biopsy specimen. The polymerase chain reaction (PCR) technique revealed the highest sensitivity for CMV detection in liver biopsy samples, but in 20 of 22 PCR-positive specimens CMV infection could be confirmed by at least one additional technique. All the liver biopsies obtained from 16 patients with normal liver function lacking histopathological signs of GvHD were CMV negative. In all 3 patients with CMV-positive liver biopsy started on antiviral therapy liver function improved and no generalized CMV disease occurred. All the 4 patients without local presence of CMV started on severe immunosuppressive therapy showed an improvement of liver dysfunction without occurrence of CMV infection. Local CMV infection of the liver could not be differentiated from hepatic GvHD by clinical and histopathological features, nor by immunohistological analysis of the bile duct epithelium. In contrast, only in liver biopsy with local viral presence could an increase in HLA class II- and ICAM-1 expression be demonstrated on hepatocytes. Thus, especially the high negative predictive value of the PCR technique helps to manage the patient with liver dysfunction after BMT.

Adolescent↗