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Biomedical subjects

R Müller

Publications and source records attributed to R Müller.

At least 397 records · Page 22Linked to original sources
PubMed1993

Demonstration of highly specific and sensitive antibodies to a naturally occurring tetrahydroisoquinoline alkaloid, salsolidine.

1. We report for the first time on the production and characterization of antibodies against a naturally occurring tetrahydroisoquinoline, namely salsolidine (6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline). 2. Immunogen synthesis was carried out by coupling the hapten salsolidine to bovine serum albumin (BSA) as carrier protein on the basis of reductive amination. 3. By immunization of rabbits with salsolidine-BSA conjugate antisalsolidine antibodies were produced. 4. At a final dilution of 1:1700 the highest-titre antiserum bound 35% of 0.21 pmol [3H]salsolidine. This antiserum was used to develop a radioimmunoassay for salsolidine. 5. Cross-reactivity studies revealed a high specificity of the antiserum to the hapten. 6. The antibodies had a high affinity to salsolidine (Ka = 1.5 x 10(9) M-1). 7. Standard curves covered a measuring range of 0.5-70 pmol/tube and the detection limit was found to be 0.27 pmol/tube.

Animals↗
PubMed1993

HIV prevalence and risk behaviour in injecting drug users in Berlin.

In injecting drug users (IDU) newly entering drug treatment centres in Berlin, HIV seroprevalence continuously decreased from 1985 through 1992. A recent cross-sectional study with multi-site sampling (n = 472) showed significantly differing HIV prevalences by site of recruitment (treatment centres 6%, storefront units 20%, infectious disease clinic 56%). In multivariate analysis, the borrowing of syringes in prison was the strongest independent predictor of HIV infection. A majority of the IDU have reduced risks of infection. However, current risk behaviour is common. Of all IDU, 48% reported the borrowing of syringes within the previous 6 months, only 13% had consequently used condoms. Current borrowing of syringes was associated with younger age, shorter history of intravenous drug use, negative HIV serostatus, and non-participation in methadone maintenance programmes. Continued preventive efforts against HIV transmission among IDU are needed.

Adult↗
PubMed1993

Treatment of chronic hepatitis B with interferon alpha-2b and interleukin-2.

A total of 37 patients with histologically confirmed chronic viral hepatitis B and presence of HBV-DNA and HBsAg in the serum were treated in a randomized, prospectively controlled multicenter trial either with recombinant IFN alpha-2b alone or a combination of IFN alpha-2b and recombinant IL-2. Twenty-two patients from group A were treated with 3 MU of IFN alpha-2b s.c. thrice weekly for 5 months. Starting at month 2 IL-2 was added: priming doses of 1.5 million CU were given s.c. on the first 2 days of each of the remaining 3 months, followed by maintenance doses of 0.3 million CU daily for 5 days per week. Fifteen patients from group B received 5 MU of IFN alpha-2b s.c. thrice weekly for 5 months. Five patients from group A (24%) and 4 patients from group B (28%) cleared HBV-DNA and HBeAg from the serum, and normalized elevated serum aminotransferase activities. The response rate in both groups did not differ significantly. Since side effects were more pronounced during combination therapy than in IFN alpha-2b monotherapy, it is suggested that treatment with IFN alpha-2b alone is preferable to a regimen of IFN alpha-2b/IL-2 applied according to the above schedule.

Adult↗
PubMed1993

Effect of short-term antihypertensive therapy on left ventricular wall tension. A double-blind comparison of isradipine and nifedipine.

The comparative efficacy of the calcium antagonists isradipine and nifedipine in reducing left ventricular peak systolic wall tension was assessed in 25 patients with essential hypertension (20 men, 5 women; mean age: 49 years). After 2 weeks of treatment with either isradipine (2.5 mg twice daily) or slow-release nifedipine (20 mg twice daily), blood pressure was similarly reduced in both groups of patients whereas the thickness of the interventricular septum and left ventricular free wall did not change. Echocardiographic end-diastolic volume of the left ventricle showed no change whereas end-systolic volume significantly decreased with isradipine, but not with nifedipine retard. This led to a significant reduction in peak systolic wall tension in the isradipine group, but not in the nifedipine group. In conclusion, antihypertensive treatment with isradipine produces a reduction in peak systolic wall tension which is not seen with nifedipine, probably because of its negative inotropic effect.

Cardiac Volume↗
PubMed1993

Increased colony growth in peripheral blood cultures from patients with ALL depends on immunological subtype.

The proliferative capacity of precursor cells in bone marrow and peripheral blood of 19 patients with acute lymphoblastic leukaemia (ALL) at diagnosis was studied and results were compared with the immunophenotype of the leukaemic population. Bone marrow proliferative capacity in these patients was strongly diminished, low or absent, independent of the immunophenotype, compared with control values (p < 0.0002). In contrast, the growth pattern in peripheral blood cultures from the same patients varied widely according to the subtype of ALL: whereas in patients with undifferentiated ALL [TdT+, HLA-DR+, CD19+ or-, CD10-, (n = 4) or CD7+, CD5+, CD1-, CD4- and CD8- (n = 1)] PB had strongly reduced proliferative capacity compared with control (p < 0.05), there was excess growth of normal neutrophil and erythroid colonies in BP cultures from patients with a more mature immunophenotype of either B-[CD10+, (n = 11)] or T [CD1+, CD4+ and/or CD8+, (n = 3)] phenotype. This phenomenon was only seen in patients who had circulating lymphoblasts: If their number was low, growth was so prolific that single colonies could not be identified. In the presence of a high blast count, colony growth was less prolific--probably due to a "dilution" effect--but still higher than normal (p < 0.05). We conclude that, in relatively mature ALL of the B- and the T-cell line, the presence of circulating lymphoblasts is associated with increased PB proliferative capacity.

Adolescent↗
PubMed1993

Low dose alpha interferon treatment in chronic hepatitis B virus infection.

Fifty eight patients with chronic viral hepatitis B (HBV) were randomised in a prospectively controlled trial. Thirty patients were treated with 3 million units (MU) of interferon alfa-2b subcutaneously thrice weekly for four months. Twenty eight controls received no treatment. The follow up period after treatment was six months. Twenty eight treated patients and 27 controls completed the protocol. One woman in the treatment group showed a complete response, and eight other treated patients (32%) showed a partial response. Three patients in the control group (11%) lost hepatitis B e antigen and HBV-DNA spontaneously. This finding is statistically significant (p < 0.05). The elimination of HBV markers from the serum was associated with a return to normal of serum aminotransferase activities. Reactivation of hepatitis was not observed after seroconversion.

Adolescent↗
PubMed1993

Antibody-based immunoadsorption as a therapeutic means.

Polyclonal antibodies against human low-density lipoprotein (LDL), covalently coupled to Sepharose CL-4B, are used to remove LDL from the plasma of familial hypercholesterolemic patients. During a single treatment LDL-cholesterol is lowered by more than 60%, and plasma viscosity is decreased by 10%. The usual treatment frequency is once a week. The possible development of human antisheep antibodies was followed for up to 5 years. The ELISA signal rose slightly above baseline reaching a plateau within the first year. Clinically, there have been no signs of column-related adverse reactions. Due to the versatility of immunoapheresis it is also applicable to deplete IgG by coupling antihuman IgG antibodies. These columns might be indicated for patients with high panel reactivity to enable organ transplantation and for patients with autoimmune disease. In vitro tests with plasma from high-panel-reactive dialysis patients have shown that IgG could be depleted by 95% across all subclasses and that panel reactivity could be reduced from 91 to 25%.

Animals↗
PubMed1993

Human cyclin D1 encodes a labile nuclear protein whose synthesis is directly induced by growth factors and suppressed by cyclic AMP.

We show that the cyclin D1 gene is regulated by a variety of growth factors in human diploid fibroblasts (WI-38). Expression of cyclin D1 mRNA is low in quiescent WI-38 cells and reaches a maximum around 10 hours after serum stimulation, i.e. approximately 8 hours prior to the onset of DNA synthesis. A cyclin D1-specific antiserum raised against a bacterially expressed fusion protein detected a 39 kDa polypeptide in WI-38 cells. In agreement with the RNA expression data, cyclin D1 protein synthesis is also serum-inducible, reaching a maximum around 9 hours post-stimulation. The results obtained by pulse-chase experiments, cell fractionation and immunostaining techniques strongly suggest that cyclin D1 is a labile protein (t1/2 approximately 38 min), which is located in the nucleus. Cyclin D1 is directly induced by growth factors, i.e. in the presence of cycloheximide, and its expression does not significantly fluctuate during the cell cycle in synchronized cells. Cyclin D1 therefore fundamentally differs from "classical" cyclins, such as the mitotic cyclin B, whose expression is clearly cell cycle-dependent. Cyclin D1 may rather establish a direct link between growth control mechanisms and the cell cycle. Interestingly, cyclin D1 expression is stimulated by the protein kinase C activator TPA, but suppressed by dibutyryl-cAMP and the adenylate cyclase inducer forskolin, pointing to multiple regulatory pathways controlling cyclin D1 expression.

Base Sequence↗
PubMed1993

Inhibition of transcription blocks cell cycle progression of NIH3T3 fibroblasts specifically in G1.

We have analysed the role of RNA polymerase II-dependent transcription in cell cycle progression. Time-lapse video recording and cytogenetic analysis were used to determine the sensitivity of NIH3T3 cells to the RNA polymerase II inhibitor alpha-amanitin at different stages of the cell cycle. Our results show that alpha-amanitin blocks cells specifically in G1, irrespective of the concentration within the range of 3 to 30 micrograms/ml. This indicates that transcription in G1 is required to overcome a restriction point located in this phase of the cell cycle. In agreement with this conclusion is the requirement for an uninhibited protein synthesis during G1 progression. In addition, the insensitivity of S-phase cells to RNA polymerase II inhibition suggests that the transcription of genes thought to be normally induced during S/G2 is not required for the completion of an ongoing cell cycle. S/G2 progression was however clearly dependent on protein synthesis. This suggests that cells exposed to alpha-amanitin are able to complete their cell cycle because sufficiently high levels of mRNA are present in S/G2 due to basal level transcription, or are left from preceding cell cycles. It is therefore unlikely that transcriptional regulation in S or G2 plays a crucial role in the control of cell cycle progression in NIH3T3 cells.

3T3 Cells↗
PubMed1993

Deregulation of cyclins D1 and E and suppression of cdk2 and cdk4 in senescent human fibroblasts.

The state of cellular senescence is characterised by an irreversible arrest in the G1 phase of the cell cycle. It has previously been shown that three cell cycle genes, cyclin A, cyclin B and cdc2, are not expressed in senescent human fibroblasts. All three gene products have functions after S-phase entry, so that their suppression cannot explain the irreversible G1 arrest. Here, we report that the abundance of transcripts from two other cell cycle genes, cdk2 and cdk4, thought to act during G1-->S progression, is significantly diminished in senescent cells of the diploid human fibroblast line WI-38. Surprisingly, two other cyclins, D1 and E, behave in a completely different way, in that their expression is elevated in senescent cells, especially under conditions of serum starvation. Both the synthesis and the steady-state level of cyclin D1 protein were also found to be markedly higher in senescent cells (3- to 6-fold). Cyclins D1 and E are thus the first genes shown to be overexpressed or deregulated in senescent cells. It is tempting to speculate that this deregulation may be due to the absence, in senescent cells, of a regulatory loop that would normally control their expression. This is supported by our finding that cyclin E-associated kinase activity in senescent cells is reduced approx. 14-fold. Our data also suggest that the deregulated expression of cyclin D1 and E is not sufficient to drive senescent cells into DNA replication.

Base Sequence↗
PubMed1993

Site-directed mutagenesis of the 2-haloalkanoic acid dehalogenase I gene from Pseudomonas sp. strain CBS3 and its effect on catalytic activity.

Two 2-haloalkanoic acid dehalogenases from Pseudomonas sp. strain CBS3 catalyse hydrolytic dehalogenation of chloroacetate and 2-chloropropionate. We used site-directed mutagenesis to introduce specific changes in the dehalogenase I encoding gene (dehCI). Substitution of Asp-10 by Ala-10 resulted in complete loss of dehalogenating activity although expression of the 2-haloacid dehalogenase I was not affected in the mutant as shown by western blot analysis, and although comparison of the mutated enzyme with the wild type enzyme indicated that extensive rearrangements in the three-dimensional structure of the enzyme had not occurred. From these data we suggest that Asp-10 of 2-haloacid dehalogenases I from Pseudomonas sp. strain CBS3 may be the nucleophilic residue in the active-site of this enzyme essential for halide release.

Amino Acid Sequence↗
PubMed1993

Suppression of the growth factor-mediated induction of c-fos and down-modulation of AP-1-binding activity are not required for cellular senescence.

It has been suggested that the impaired response of the c-fos gene to serum growth factors and the concomitant loss of AP-1 activity may be a crucial step in the process of cellular senescence. In the present study, we provide evidence arguing against such a conclusion. Data obtained in five independent experiments showed that both c-fos RNA and protein expression were similar in 'young' and in senescent serum-stimulated WI-38 cells, suggesting that the previously reported suppression of c-fos induction is not an obligatory event in the process of cellular senescence. Likewise, expression of fra-1, c-jun and junB continued to be high in serum-stimulated senescent cells, while induction of fosB was reduced approximately fivefold. Among all genes tested fosB thus seems to be the most suitable marker for the detection of senescent cells. Stimulated senescent cells showed only a approximately twofold reduction of AP-1-binding activity, and senescent cells continuously exposed to serum exhibited normal AP-1-binding activity. These observations support the conclusion that a down-modulation of AP-1 is not crucial for human fibroblasts to enter the senescent state.

Cell Line↗
PubMed1993

[Alopecia areata and diffuse hypotrichosis associated with Ullrich-Turner syndrome. Presentation of 4 patients].

Gonosomal aberrations such as Turner's syndrome are frequently associated with autoimmune diseases or with serological markers for autoimmune diseases. An autoimmune origin has been suggested for alopecia areata. The simultaneous occurrence of alopecia areata and Turner's syndrome has not formerly been reported. We present here four female patients with Turner's syndrome, who also developed typical alopecia areata. In three of these cases alopecia areata first appeared during adolescence, whilst the fourth patient showed an early manifestation at the age of 10. Two of the patients had alopecia areata of the ophiasis type, while the condition was localized in one and diffuse in the fourth. In addition, two of the patients had diffuse hypotrichosis of the scalp and reduced sweat gland activity, with no other signs of ectodermal dysplasia. The third patient had not develop body hair after her childhood, except for some sparse thin hair in the axilla and in the genital area. The coincidence of alopecia areata and Turner's syndrome may indicate some genetic relationship between the two entities.

Adult↗
PubMed1993

Supply and demand factors in occupational health; determinants of self-reported compliance with the work place related requirements of the German Work Safety Law.

The study evaluates the extend to which West German company doctors reported that they carried out the workplace related activities as required by the German Work Security Law 'ASiG'. Postal questionnaires were completed by 502 of West German company doctors. About one third of those who responded, reported that they carried out the requirements of the German Work Safety Law with regard to workplace-related prevention. Multivariate analysis was applied to discover the factors that influenced compliance. We conclude that investment in supply-side factors (doctors' qualifications, experiences and recourses) are not enough to bring about compliance. More important are the demand-side regulations which directly address the health and safety culture of the companies.

Germany↗
PubMed1993

[Hemodynamic effect of molsidomine in coronary patients with heart failure with clinically manifest nitrate tolerance].

Objective of the present study was to investigate the hemodynamic response to molsidomine in nitrate tolerance state. In 13 out of 16 patients (5 women, 11 men, 62 [53/71] years [median, 25%/75%-percentiles]) with chronic heart failure (NYHA stage II-III; median angiographic ejection fraction (EF) 55%) and coronary artery disease (stenosis of at least 75%) the development of tolerance under the continuous infusion of high doses of nitroglycerin (10 mg/h) was observed. Tolerance was defined as a benefit loss of at least 50% of the initial nitroglycerin effect with respect to the pulmonary capillary wedge pressure. Compared to the state of tolerance to nitroglycerin the infusion of 10 mg molsidomine over 15 minutes resulted in significant changes of the median values (25%/75%-percentiles) of mean right atrial pressure from 16 (12/21) to 9 (5/12) mmHg (p < 0.01), mean pulmonary artery pressure from 37 (30/40) to 24 (20/30) mmHg (p < 0.001), mean pulmonary capillary wedge pressure from 22 (18/25) to 15 (10/22) mmHg (p < 0.01) and cardiac output from 4.1 (3.5/4.7) to 5.2 (4.2/5.6) l/min (p < 0.01). This action of molsidomine corresponded to a complete overcoming (> 100%) of the benefit loss observed during the development of nitrate tolerance with respect to all above-mentioned hemodynamic parameters. Under parallel maintainance of nitroglycerin infusion (10 mg/h) these hemodynamic effects of molsidomine, i.e. at least 90% of the peak effect, lasted for 147 (130/182) minutes (median, 25%/75%-percentiles). Baseline values, i.e. a loss of at least 75% of the molsidomine effect, were only reached after 363 (319/412) minutes (median, 25%/75%-percentiles).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗