Biomedical subjects

M Munch

Publications and source records attributed to M Munch.

25 records · Page 2Linked to original sources

PubMed1995

B-lymphoblastoid cell lines from multiple sclerosis patients and a healthy control producing a putative new human retrovirus and Epstein-Barr virus.

On several occasions we have observed retrovirus-like particles (RVLPs) by transmission electron microscopy (EM) of cultured T cells from a patient with MS. Later we established spontaneously formed B-lymphoblastoid cell lines (LCLs) from a patient with an MS-like disease and from another patient with MS who had a reactivated Epstein-Barr virus (EBV) infection. Both LCLs were found by EM to produce RVLP and EBV particles. Reverse transcriptase (RT) assays were positive in purified viral material from both LCLs. To substantiate these findings we initiated an intensified culturing procedure and were able to establish LCLs from 5 out of 21 consecutive MS patients and 1 out of 13 consecutive healthy controls. All LCLs were found to produce both RVLP and EBV particles by EM. Whether the putative new retrovirus(es) and EBV have any causal relationship to MS is still not known, but the findings support this possibility.

Adult↗

PubMed1994

Casual blood pressure in a general Danish population. Relation to age, sex, weight, height, diabetes, serum lipids and consumption of coffee, tobacco and alcohol.

A population survey was conducted on 3608 randomly selected Danes aged 30, 40, 50 and 60 years respectively. Of these, 3400 were not in medical treatment for arterial hypertension. The following parameters were investigated: sex, age, serum lipid levels (total cholesterol, HDL cholesterol, triglycerides), presence of diabetes mellitus, height, body mass index (BMI), and average daily consumption of coffee, tobacco and alcohol. Analysis with multiple linear regression showed that all variables with the exception of triglycerides, HDL cholesterol and height were significantly associated with systolic blood pressure. Likewise all factors except diabetes, triglycerides and height were significantly associated with diastolic blood pressure. Further analysis in which the effect of each parameter was corrected for by the effects of the remaining variables, demonstrated that apart from age and sex only BMI and high alcohol consumption were positively associated with differences in blood pressure greater than a few mmHg. However, the variation in both systolic and diastolic blood pressures was only partly accounted for by the parameters studied--in the covariates analysis R2 for systolic blood pressure was 0.28 and R2 for diastolic blood pressure was 0.30. In conclusion, this investigation demonstrated that blood pressure is relatively independent of other factors important in the development of cardiovascular disease. Of the above-mentioned factors with some influence on blood pressure only age, BMI and high alcohol consumption have potential clinical importance.

Adult↗

PubMed1993

Interconversions between active, inert and substrate forms of denatured/refolded type-1 plasminogen activator inhibitor.

The latent form of type-1 plasminogen activator inhibitor (PAI-1) acquires inhibitory activity by denaturation followed by refolding. We show here that the reactions of denatured/refolded PAI-1 with plasminogen activators are affected by low concentrations of SDS, which may remain after using SDS for denaturation. Without SDS, the active fraction of denatured/refolded PAI-1 comprised around 60%. Increasing SDS concentrations led to conversions to an inert form without inhibitory activity; then to a substrate form, that is being cleaved proteolytically in the reactive centre by the activators without complex formation, and finally to a second inert form. The first two conversions were associated with changes of the reactivity with monoclonal antibodies and of the thermal stability, respectively. Our results define clearly different interconvertible forms of denatured/refolded PAI-1, distinguish these from the latent and the reactive-centre-cleaved forms, and provide conditions for reproducibly producing reactive-centre-cleaved PAI-1 and PAI-1/activator complexes.

Animals↗

PubMed1992

Purified alpha 2-macroglobulin receptor/LDL receptor-related protein binds urokinase.plasminogen activator inhibitor type-1 complex. Evidence that the alpha 2-macroglobulin receptor mediates cellular degradation of urokinase receptor-bound complexes.

Complexes between 125I-labeled urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) bound to purified alpha 2-macroglobulin (alpha 2M) receptor (alpha 2MR)/low density lipoprotein receptor-related protein (LRP). No binding was observed when using uPA. The magnitude of uPA.PAI-1 binding was comparable with that of the alpha 2MR-associated protein (alpha 2MRAP). Binding of uPA.PAI-1 was blocked by natural and recombinant alpha 2MRAP, and about 80% inhibited by complexes between tissue-type plasminogen activator (tPA) and PAI-1, and by a monoclonal anti-PAI-1 antibody. In human monocytes, uPA.PAI-1, like uPA and its amino-terminal fragment, bound to the urokinase receptor (uPAR). Degradation of uPAR-bound 125I-uPA.PAI-1 was 3-4-fold enhanced as compared with uncomplexed uPAR-bound uPA. The inhibitor-enhanced uPA degradation was blocked by r alpha 2MRAP and inhibited by polyclonal anti-alpha 2MR/LRP antibodies. This is taken as evidence for mediation of internalization and degradation of uPAR-bound uPA.PAI-1 by alpha 2MR/LRP.

Amino Acid Sequence↗

PubMed1991

Type-1 inhibitor of plasminogen activators. Distinction between latent, activated and reactive centre-cleaved forms with thermal stability and monoclonal antibodies.

Type-1 inhibitor of plasminogen activators (PAI-1) occurs in purified preparations in a latent form that can be activated with denaturants; in vivo, latency is prevented by binding to vitronectin. We have compared latent, denaturant-activated and reactive centre-cleaved human PAI-1 with respect to thermal stability and affinity to monoclonal antibodies. By both criteria, latent and cleaved PAI-1 are very similar or indistinguishable, and clearly different from active PAI-1. Our findings suggest that the conformations of latent and reactive centre-cleaved PAI-1 are similar and resemble the so-called relaxed (R) serpin conformation, while that of active PAI-1 is different and resembles the stressed (S) serpin conformation.

Antibodies, Monoclonal↗

PubMed1991

[Should athletic injuries be treated with non-steroidal anti-rheumatic agents (NSAID)? Tenoxicam, piroxicam and placebo in the treatment of acute stress-induced injuries].

A total of 212 patients with acute sports injuries were allotted at random to treatment with 20 mg tenoxicam daily, 20 piroxicam daily or a placebo for ten days. The injuries could be subdivided into six groups: Tendinitis, periostitis, sprains, tendovaginitis, epicondylitis and muscular ruptures. Treatment was well tolerated and analysis of the total material showed a slight but significantly better effect in the group treated with the active drugs. More detailed analysis revealed that this increased effect was produced by a definitely better therapeutic result in the group of patients with tendinitis treated with non-steroid anti-inflammatory drugs (NSAID) while, in the other types of injury, no definite effect could be observed. On the basis of these observations, the authors conclude that acute tendinitis may be treated with NSAID (tenoxicam) while the question is not yet solved where other acute stress-induced injuries are concerned.

Acute Disease↗

PubMed1990

[Treatment of severe primary hypercholesterolemia with lovastatin (Mevacor). A new therapeutic principle].

An open clinical trial comprising 59 outpatients with severe hypercholesterolemia (including 35 patients with familial hypercholesterolaemia) and considerable predisposition to ischaemic cardiac disease revealed a dosage-related pronounced effect of lovastatin on serum cholesterol and subfractions of this. After dietary regulation for a period of four months, a decrease in serum cholesterol of 11.7% was observed and after further treatment for six months with lovastatin with an average dose of 59 mg per 24 hours, the serum cholesterol decreased with a total of 45% of original value. Low density lipoprotein (LDL)-cholesterol decreased 44% and high density lipoprotein (HDL)-cholesterol increased by over 21%. Serum triglyceride fell by 20%. The serum-cholesterol/HDL-cholesterol ratio was reduced from 8.8 to 4.9. Only slight and transient subjective side-effects were observed and none of the patients dropped out of the trial for this reason. One patient with recognized ischaemic heart disease died from myocardial infarction. A tendency towards increasing liver parameters and creatin kinase was observed in the group as a whole but was not significant.

Adult↗