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M Herrmann

Publications and source records attributed to M Herrmann.

At least 163 records · Page 9Linked to original sources

PCR and reverse dot hybridization for the detection of endogenous retroviral transcripts.

Two degenerated oligonucleotide primers, known to amplify a fragment of the pol gene in all retroviruses tested so far have been used to amplify pol related sequences from human genomic DNA. Cloning and sequencing these fragments confirm a retroviral relationship for most of them and define 96 groups on the basis of their internal similarity. 96 pol fragments were probed with PCR amplified cDNA in reverse dot hybridization to investigate pol related transcripts. PCR amplified genomic DNA served as a control for contamination of genomic DNA in the RNA preparations. Isopycnic centrifugation in cesium trifluoroacetate yielded RNA with the lowest possible amounts of contaminating DNA. This technique is a powerful and a well-controlled tool for the detection of endogenous retroviral transcripts and may be helpful for investigating the involvement of endogenous retroviruses in various diseases.

Amino Acid Sequence↗

Preliminary experience with the Toronto SPV stentless porcine bioprosthesis for aortic valve replacement.

From November 1992 to March 1993 fourteen patients received the Toronto SPV stentless porcine xenograft as aortic valve replacement. Median age was 56 years (range 32-70 years). 7 patients were male and 7 female. Implanted valve sizes ranged from 23 mm to 29 mm, the majority of patients received valves with 27 and 29 mm tissue diameter. A learning process was evident by aortic crossclamp time decreasing with experience. No valve-related mortality or morbidity occurred. Postoperatively echocardiography showed near normal valve performance in most patients. The longevity of the valve, however, still has to be established. Meanwhile we continue the implant of stentless bioprostheses as aortic valve substitutes in selected patients.

Adult↗

Single-dose pharmacokinetics of oral fleroxacin in bacteremic patients.

Fleroxacin is a new broad-spectrum quinolone which can be given by the oral route. The present study was designed to assess the influence of bacteremia on the pharmacokinetics of a single oral dose of fleroxacin. Thirteen patients with proven bacteremia (one or more pairs of positive blood cultures, no hypotension) were given a single 400-mg fleroxacin dose orally on two occasions while also receiving standard antibiotic therapy. The first dose was administered 12 to 36 h after the last positive blood culture was drawn (day 1), and a second dose was administered 7 days later (day 7 +/- 2) to compare the pharmacokinetics between the acute and the convalescent phases of the disease. Following each administration of fleroxacin, serial plasma samples were collected for up to 72 h and were analyzed for unchanged drug by a reversed phase high-pressure liquid chromatography technique. There were no significant changes in the following pharmacokinetic parameters (mean standard deviation) the maximum concentration of drug in serum (6.4 +/- 1.5 versus 6.7 +/- 1.9 mg/liter), the minimum concentration of drug in serum, defined as the concentration of drug in serum at 24 h postdose (3.0 +/- 1.7 versus 2.5 +/- 1.2 mg/liter), the time to the maximum concentration of drug in serum (2.3 +/- 1.4 versus 2.0 +/- 1.2 h), and the elimination half-life (19.7 +/- 8.0 versus 17.9 +/- 6.9 h). Fleroxacin clearances were compared for each individual patient. A positive correlation (R2 = 0.787) was found between the values measured on day 1 and day 7. Oral clearance of fleroxacin (CL = CL/F, where F is bioavailability was slightly, but not significantly, reduced during the bacteremic phase (oral clearance, 43.8+/- 23.5 versus 48.5 +/- 17.5 ml/min.). When compared with previous results obtained in healthy young subjects, longer times to the maximum concentration of drug in serum and elimination half-lives and higher areas under the curve were observed. This could be due to the bacteremic state, the old age of the patients (mean, 66 years), and the low renal clearance (mean calculated creatinine clearance, 71.1 ml/min). A single oral dose of 400 mg of fleroxacin provides sufficient levels in serum to cover susceptible microorganisms for at least 24 h in bacteremic patients. Renal function appeared to be the key element that had to be taken into consideration to adapt fleroxacin dosage profiles in our patient population. Bacteremia itself appeared to amplify that phenomenon, but to a much lesser extent than renal function did.

Administration, Oral↗

Regulation of susceptibility and cell surface receptor for the B-lymphotropic papovavirus by N glycosylation.

The host range of the B-lymphotropic papovavirus (LPV) in cultured human cells is limited to a few B-lymphoma-derived cell lines. The constitutively expressed cell surface receptor for the virus is a major determinant restricting the LPV host range (G. Haun, O. T. Keppler, C. T. Bock, M. Herrmann, H. Zentgraf, and M. Pawlita, J. Virol. 67:7482-7492, 1993). Here we show that human B-lymphoma cells with low-level susceptibility are rendered highly susceptible to LPV infection by pretreatment with the N glycosylation inhibitor tunicamycin but remain nonsusceptible to infection by the related polyomavirus simian virus 40. Among the selective N glycosylation processing inhibitors, deoxymannojirimycin, but not deoxynojirimycin, swainsonine, or castanospermine, could mimic the effect of tunicamycin. Tunicamycin treatment also induced a drastic enhancement of the cells' LPV-binding capacity, indicating that the induction of LPV susceptibility might be mediated by an increase in the number of functional cell surface receptors and/or by increased receptor affinity. Sialidase sensitivity of the tunicamycin-induced LPV receptor showed that oligosaccharides carrying terminal sialic acids are necessary for binding and are likely to be O linked. The constitutive LPV receptor is also sialic acid dependent, which points to a possible identity with the sialic acid-dependent tunicamycin-induced LPV receptor. We conclude that removal or modification of certain N-linked oligosaccharides in human B-lymphoma cells can enhance expression or functional activity of the sialylated LPV receptor.

B-Lymphocytes↗

A neural model of the dynamic activation of memory.

We study an Attractor Neural Network that stores natural concepts, organized in semantic classes. The concepts are represented by distributed patterns over a space of attributes, and are related by both semantic and episodic associations. While semantic relations are expressed through an hierarchical coding over the attribute space, episodic links are realized via specific synaptic projections. Due to dynamic thresholds expressing neuronal fatigue, the network's behavior is characterized by convergence toward the concept patterns on a short time scale, and by transitions between the various patterns on a longer time scale. In its baseline, undamaged state, the network manifests semantic, episodic, and random transitions, and demonstrates the phenomenon of priming. Modeling possible pathological changes, we have found that increasing the 'noise' level or the rate of neuronal fatigue decreases the frequency of semantic transitions. When neurons characterized by large synaptic connectivity are deleted, semantic transitions decay before the episodic ones, in accordance with the findings in patients with Alzheimer's disease.

Alzheimer Disease↗

Group A beta-haemolytic streptococcus septicaemia: the toxic strep syndrome. Report of our cases developing septic shock and multiple organ failure.

During the last two decades, severe group A beta-haemolytic streptococcal infections have been defined as the "toxic strep syndrome", and have been reported not only in immunocompromised or elderly people, but also occasionally in previously healthy patients. We describe 4 patients presenting with the toxic strep syndrome, requiring surgery and intensive care, and briefly review the related literature. Fatigue, localized pain and other nonspecific symptoms were associated with the onset of the disease, followed by septic shock with multiple organ failure. Early diagnosis and surgical intervention, if necessary, are mandatory. Subsequently, appropriate supportive treatment of vital organ dysfunction and penicillin as the antibiotic of choice represent the cornerstones of the management of this syndrome.

Adult↗

Adhesion of Staphylococcus aureus to surface-bound platelets: role of fibrinogen/fibrin and platelet integrins.

Platelets adhering to artificial or biologic surfaces have been implicated in the pathogenesis of catheter infections or endocarditis; however, the ligands involved in Staphylococcus aureus interaction with adherent platelets remain incompletely understood. Radiolabeled S. aureus Cowan I were incubated with purified platelets adherent to polymethylmethacrylate (PMMA) coverslips and washed, and adhesion was determined. Platelets promoted adhesion of S. aureus approximately 30-fold compared with adhesion to albumin-PMMA. In the presence of both plasma (1% vol/vol) and platelets, adhesion was extensively promoted, with 30% (of inoculated) S. aureus adherent (150-fold increase). Platelet pretreatment with anti-GPIIb/IIIa monoclonal antibodies or inhibitors of platelet activation decreased plasma-enhanced adhesion, suggesting a role of platelet activation in S. aureus adhesion. Plasma-enhanced adhesion was sensitive to thrombin antagonists, proteinase inhibitors, heparin, or antifibrinogen antibodies, indicating that fibrinogen/fibrin is necessary for bridging between adherent platelets and S. aureus. In conclusion, S. aureus adhesion to immobilized platelets may play a role in the pathogenesis of invasive bloodstream infections or endocarditis.

Bacterial Adhesion↗

A soluble form of the human transferrin receptor is released by activated lymphocytes in vitro.

Soluble transferrin receptors (sTfR) were detected in culture supernatants of activated human peripheral blood mononuclear cells (PBMC) using a sandwich ELISA technique with two non-cross-reacting TfR MoAbs. Mitogenic stimulation of lymphoid cells induced both up-regulation of TfR surface density and release of sTfR to the medium. Peak levels of sTfR in culture supernatants occurred at day 4 after activation, 1 day later than maximum expression of TfR in the plasma membrane. Production of sTfR was independent of proliferation, as demonstrated by measuring sTfR release by PBMC, which had been irradiated with a dose of 20 Gy before activation. In addition to these in vitro experiments, we tested the sera of 85 patients with systemic lupus erythematosus (SLE), an autoimmune disease accompanied by in vivo activation of lymphocytes, for their sTfR levels. No correlation of these data was detectable to serum concentrations of the soluble alpha-chain of the IL-2 receptor, an unequivocal marker of lymphocyte activation. However, they correlated negatively to the haemoglobin content of the patients' erythrocytes, indicating that erythroid progenitors are the predominant source of sTfR in SLE patients' sera.

Antibodies, Monoclonal↗

Molecular characterization of the enniatin synthetase gene encoding a multifunctional enzyme catalysing N-methyldepsipeptide formation in Fusarium scirpi.

The gene encoding the multifunctional enzyme enniatin synthetase from Fusarium scirpi (esyn1) was isolated and characterized by transcriptional mapping and expression studies in Escherichia coli. This is the first example of a gene encoding an N-methyl peptide synthetase. The nucleotide sequence revealed an open reading frame of 9393 bp encoding a protein of 3131 amino acids (M(r) 346,900). Two domains designated EA and EB within the protein were identified which share similarity to each other and to microbial peptide synthetase domains. In contrast to the N-terminal domain EA, the carboxyl terminal domain EB is interrupted by a 434-amino-acid portion which shows local similarity to a motif apparently conserved within adenine and cytosine RNA and DNA methyltransferases and therefore seems to harbour the N-methyl-transferase function of the multienzyme.

Amino Acid Sequence↗

The cell surface receptor is a major determinant restricting the host range of the B-lymphotropic papovavirus.

The B-lymphotropic papovavirus (LPV) productively infects only a subset of human B-lymphoma-derived cell lines while transfection of the viral genome yields infectious viral particles in a much wider variety of human hematopoietic cell lines. We have analyzed the contribution of a putative LPV receptor on the cell surface of B-cell lines in restricting the virus host range. In order to establish a quantitative virus binding assay for LPV, infectious virus particles were highly purified by metrizamide equilibrium density centrifugation and used as immunogens to raise seven mouse monoclonal antibodies specific for LPV VP1. Virus particle binding was quantitated in an indirect, nonradioactive assay with an LPV VP1-specific enzyme-linked immunosorbent assay. Binding of LPV particles to permissive human B-lymphoma cell line BJA-B occurred within minutes. Kinetics and capacity of binding were similar at 4 and 37 degrees C. A BJA-B cell was estimated to bind approximately 600 virus particles at conditions under which 50% of the administered virus was bound. The sialidase and trypsin sensitivities of the cellular virus binding moiety show that sialylated and proteinaceous components are necessary components of the LPV receptor on BJA-B cells. Despite a high binding capacity of BJA-B cells for simian virus 40, LPV binding was not significantly affected by a 20-fold excess of simian virus 40 particles, indicating that these related polyomaviruses do not bind to the same receptor on BJA-B cells. Reduction of LPV binding to sialidase-pretreated BJA-B cells was accompanied by a similar reduction of infection, indicating that virus binding may be a limiting factor in the LPV replicative cycle. The two highly LPV-permissive human B-lymphoma cell lines BJA-B and Namalwa displayed high virus binding whereas low and nonpermissive hematopoietic cell lines showed reduced or undetectable virus binding. We conclude that the inability of LPV particles to productively infect the nonpermissive human hematopoietic cell lines analyzed is probably due to the absence or insufficient expression of a functional cell surface receptor.

Antibodies, Monoclonal↗

Depression in acute and chronic aphasia: symptoms, pathoanatomical-clinical correlations and functional implications.

Depressive alterations were investigated in 21 acute and 21 chronic aphasic patients with single left sided strokes. The assessment of depression was based on a psychometrically evaluated German version of the Cornell Scale for Depression (CDS) and the Research Diagnostic Criteria (RDC). No significant difference was found concerning depression sum-scores between the two aphasic groups. The acute group, however, exhibited significantly higher ratings in items related to physical signs of depression and disturbances of cyclic functions. Patients corresponding to the RDC-syndrome of major depression were only found in the acute group. Neither age, sex nor degree of hemiparesis discriminated the patients on the severity of depressive symptoms. In the acute patient group, nonfluency of aphasia was the only parameter that could be identified which had an effect on the mood symptom scores. A CT scan analysis in the acute patient group showed an association between the severity of depression and anterior lesions. A significant correlation was found between CDS sum-scores and the proximity of the anterior border of the lesion to the frontal pole of the hemisphere whereas the volume of lesions seemed to have no effect on depressive alterations in acute aphasic patients. Superimposition of the lesions of the aphasic patients with major depressive disorders showed a common subcortical lesion area involving putaminal and external pallidal structures.

Acute Disease↗

Autoimmune diseases in humans, e.g. autoimmune rheumatic diseases.

In spite of increasing evidence that viruses and especially retroviruses could act as etiologic factors in autoimmune and especially autoimmune rheumatic diseases, clear-cut evidence for an involvement of these agents is still missing. Findings, which, for example, indirectly support the hypothesis that retroviruses might play a part, are the demonstration of antibodies to the gp24 in SLE and Sjögren's patients as well as the description of retroviral antigens in the inflamed synovium of rheumatoid arthritis patients. Furthermore, evidence comes from animal models that viruses, such as the Visna or Caprine arthritis encephalitis virus, induced chronic inflammatory diseases in sheep and goats. More recently, a mouse model for rheumatoid arthritis and Sjögren's syndrome was reported in mice transgenic for HTLV-1tax. It is hoped that, especially from the experimental animal models, the possible role of retroviruses as etiological factors in autoimmune rheumatic diseases can be clarified.

Animals↗

[Cutaneous malignant melanoma in New Caledonia (South Pacific) 1973-1991. A study of 97 cases].

The Cancer Registries have been operational in the South Pacific since 1958 (Papua New Guinea), Fiji (1965) and New Caledonia (1977) and complete cancer incidence rates are available, based on histologic data. We studied 97 melanomas, histologically confirmed, which were diagnosed in New Caledonia from 1973 to 1991. New Caledonia is located in the same latitude as Queensland in Australia, known for having the highest incidence of melanoma in the world. Standardised incidence rates (world population) were 9.82 and 7.65/100,000/year for European males and females, compared to 1.65 and 1.05 for Melanesian and Polynesian males and females. The European population is exposed and Melanesians/Polynesians are relatively protected as are black Americans or Africans. The mixed populations are protected, but no study is available as to the exact proportion of mixed people (20%?) in the entire population. For Europeans, among males, the main areas in which melanomas occur are the trunk (45%) the arm (13%) and the leg (13%). Among females, the main areas are the leg (27%), the trunk (20%) and the head (18%). Screening for melanoma has been more effective in the last 6 years, a period in which we diagnosed half the total cases and generally at earlier stages. Prognosis was poor for this period (1973-1991): the five year survival rates were 64% +/- 8%, not as good as in Europe or Australia, but these lesions were diagnosed between 1973 and 1985 and were generally more invasive. A better prognosis will probably be observed in a few years, and another evaluation of melanoma screening should be made in the future as well the study of precursors and early lesions.

Adult↗

[Biomonitoring for the evaluation of a mercury burden from amalgam fillings. Mercury determination in urine before and after oral doses of 2,3-dimercapto-1-propanesulfonic acid (DMPS) and in hair].

The statistically significant correlation between mercury urine concentrations of 67 male volunteers aged 16 to 72 years (mean: 1.20 micrograms/l, range 0.1-5.0; 1.57 micrograms/24 h, range 0.1-7.8) and their amalgam filling index (r = 0.653; p < or = 0.0001) indicates that amalgam fillings burden the organism with mercury. Oral gavage of 300 mg DMPS (Dimaval) elevated mercury elimination in the urine by a factor of 9.2. The correlation between mercury elimination in the 24 h urine with and without DMPS is statistically highly significant (r = 0.89, p < or = 0.0001). This means that the information yield from mercury determination in urine is usually not improved by DMPS. For toxicological evaluation of mercury excretion in urine we propose to employ 1/20 of the BAT-level for inorganic mercury (200 micrograms/l). This approach is frequently used in setting MIK levels based on MAK levels. We refer to the resulting standard as BUT level (Biologischer Umweltstofftoleranzwert). The BUT level for inorganic mercury in urine is thus 10 micrograms/l. The mean determined in the cohort under investigation was ca. 10 times lower than the proposed threshold value. Therefore the present findings do not suggest a risk to health due to mercury in the volunteers examined here. Hair analysis of the same volunteers did not correlate with inorganic mercury burden from amalgam fillings. However, a weak correlation was found between hair mercury levels and fish consumption. Since fish are mainly a source of organic mercury, hair analysis may be useful for biological monitoring of this form of mercury.

Administration, Oral↗