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Biomedical subjects

M Michael

Publications and source records attributed to M Michael.

At least 91 records · Page 5Linked to original sources
PubMed1994

A fast method for obtaining highly pure recombinant herpes simplex virus type 1 thymidine kinase.

Recombinant Herpes Simplex Virus Type 1 thymidine kinase (TK) was isolated in a fast and gentle two-step procedure from Escherichia coli as a thrombin cleavable fusion protein. The TK was expressed as an inducible glutathione S-acetyl transferase fusion protein and purified in a first step by glutathione affinity chromatography. Proteolytic cleavage of the column bound TK with thrombin led to a truncated enzyme, resulting from two new and hitherto unknown cleavage sites, determined by N-terminal sequencing. In a second step, the TK was further purified from the cleavage products by ATP affinity chromatography, yielding homogeneously pure TK as shown by SDS-PAGE and mass spectrometry. Both the fusion protein and the purified enzyme show enzymatic activity with the same Km value of 0.2 microM for the natural substrate thymidine. Determination of the native molecular weight indicated that the pure enzyme and the fusion protein are biologically active as homodimers. Therefore the recombinant enzyme has the same biochemical characteristics as the viral TK, expressed in infected cells.

Amino Acid Sequence↗
PubMed1994

Pharmacodynamics of opioids: recent developments.

The pharmacodynamic phase of a drug describes its interaction with its biological receptor and the creation or prevention of a signal that subsequently leads to the phenomenon, the biological response. Molecular definition of the ligands interaction with its target proteins might be the appropriate approach for understanding the action of opioid and opioid-like drugs. Characterization of the ligand as well as of the receptor protein is essential for this rational approach. This review shows some aspects how far research has come. We are now at the beginning of understanding what perfect peptidomimetics like morphine are actually mimicking, an understanding, that has led to new efficient molecular tools for the pharmacology of opioids.

Amino Acid Sequence↗
PubMed1994

Measuring, managing, and improving quality in the end-stage renal disease treatment setting: committee statement.

The Institute of Medicine (IOM) committee that organized the conference reported in this issue of the journal on assessing quality of care and quality of life, wishes to emphasize that it regards the task of measuring quality as one that can be approached systematically, albeit with caution. Outcomes of end-stage renal disease (ESRD) care by dialysis and transplantation (and variations of outcomes among treatment units) and related processes of care need to be measured in ways useful to clinicians. In addition to clinical measures of outcome, the committee also favored giving greater attention to functional outcomes and health-related quality of life. The interest in maintaining and improving quality in the treatment setting reflects an underlying need to encourage its systematic assessment on a sustained basis, with appropriate weight devoted to practical issues.

Humans↗
PubMed1994

Assessment of visual contrast sensitivity in hyperbaric oxygen.

Hyperbaric oxygen therapy is used in ophthalmology in ischemic pathologies of the anterior and posterior segments. Our experiment was done on a healthy group of volunteers aged between 10 and 50 yr. We examined the subject's vision before and after acute HBO exposure (60 min at 2.5 atm abs with pure oxygen) to verify whether vasoconstriction induced by hyperoxemia can influence eyesight. We measured the psychophysical determination of the threshold contrast according to Maione-Maffei's zebra test. The results demonstrated that contrast sensitivity is significantly improved for almost all the studied frequencies in normal subjects after acute HBO exposure. We hypothesize that the visual system has a reserve which is activated by an improvement of retinal oxygenation.

Adolescent↗
PubMed1993

Modelling by homology of the HSV1-TK sequence embedded structural alignment.

Modelling by homology is an approach to the rational design of new drugs based on the construction of ligand protein interaction complexes. Because in most cases the 3D-structure of the target protein is not known from biophysical data, this approach yields a theoretical procedure which establishes at least parts of the protein by comparison with isofunctional proteins, assuming that much of the structural information is embedded in the amino acid sequence. This approach should be of considerable importance for proteins with divergent primary structures but with a high degree of isofunctionality, the latter demanding a similar active site folding pattern. This study is a pattern recognition approach based on additive secondary structure prediction and surface probabilities from residue variabilities. The comparison of the additive properties yields a sequence alignment of the viral thymidine kinases with the adenylate kinases having a closely related functionality. X-ray structures of adenylate kinases can then be used as templates to derive a 3D-structure prediction of the thymidine kinase active site.

Adenylate Kinase↗
PubMed1992

[Chronic hepatitis treated with alpha-interferon].

The newest results on the interferon treatment of chronic viral hepatitis on the ground of controlled trials are reported. In chronic type B hepatitis about 35 percent of patients, while in chronic type C hepatitis 80 percent of patients showed good response, though in the latter disease relapse is frequent following the stop of interferon treatment. In hepatitis Delta infection further therapeutic studies are warranted. The duration of the interferon treatment in chronic viral hepatitis is still an unsolved question.

Chronic Disease↗
PubMed1992

Lipopolysaccharide priming potentiates calcium ionophore stimulated human placental prostaglandin E2 release in vitro.

In this study, the effect of bacterial endotoxin (lipopolysaccharide; LPS) and of LPS priming on the in vitro release of PGE2 from human placental explants was investigated. Both LPS and the calcium ionophore A23187 significantly stimulated PGE2 release (P less than 0.05). Simultaneous exposure of placental explants to both LPS and A23187 revealed no additive or synergistic stimulation of PGE2 release. LPS priming of placental tissue significantly increased A23187-stimulated PGE2 release when compared to non-LPS-primed tissues. The addition of exogenous arachidonic acid (the substrate for PGE2 synthesis) also significantly (P less than 0.05) stimulated PGE2 release. There was, however, no significant further stimulation of PGE2 release following LPS priming in arachidonic acid treated explants. These data suggest that LPS not only increases basal PGE2 release in human placentae, but also potentiates agonist-stimulated PGE2 release, possibly by increasing tissue capacity for endogenous arachidonic acid liberation.

Calcimycin↗
PubMed1991

High mortality among patients with the leukemoid reaction and alcoholic hepatitis.

We describe a patient with severe alcoholic hepatitis, markedly elevated white blood cell count, and high fever. After review of the English literature, we discovered reports of other cases similar to our case. The striking feature in all of these cases was a high short-term mortality rate, despite predictions of a favorable outcome. We therefore believe these patients represent a subgroup of patients with alcoholic hepatitis and that the leukemoid reaction is a poor prognostic sign in this disease.

Adult↗
PubMed1991

Regulation of the human immune response to ragweed pollen by immunotherapy. A controlled trial comparing the effect of immunosuppressive peptic fragments of short ragweed with standard treatment.

A new allergenic preparation consisting of peptic fragments of short ragweed has been tested for its clinical effectiveness. Such enzymatically derived fragments have been shown in prior murine studies to retain the T epitopes of the original allergen but to have a severe reduction in the number of B epitopes. Three groups of ragweed hayfever patients were placed on pre-seasonal immunotherapy. One group received a conventional ragweed preparation that had been enriched for antigen E (Amb a I), designated as Pool 2. The second group was given fragments of Pool 2 (fSRW) prepared by peptic digestion and the third group was injected with histamine as a placebo. Groups treated with the fSRW and Pool 2 had significantly reduced symptom-medication scores compared with the placebo-treatment group. However, fSRW-treated patients fared significantly better than Pool 2 patients (P less than 0.02). fSRW injections caused a significant rise in preseasonal specific IgG, antibodies as well as suppression of the seasonal anamnestic specific IgE increase. Similar, but not quite as marked changes occurred with Pool 2 treatment. fSRW was well tolerated and non-toxic. Thus, allergen modification by enzymatic degradation, as demonstrated here, appears to be a promising new approach for allergen immunotherapy.

Adult↗
PubMed1990

Screening for genetic disorders: therapeutic abortion and IVF.

This paper examines a proposal to make use of IVF techniques to provide an alternative to therapeutic abortion of fetuses with genetic abnormalities. We begin by describing the proposed procedure, and then show that, considered in itself, it is morally on a par with therapeutic abortion. However, once the wider practical implications are brought into view, the proposed new procedure loses its initial appeal. The pros and cons are not sufficiently clear-cut entirely to rule out the IVF procedure, so the paper concludes by indicating some further complications which may follow, should the procedure come to be adopted.

Abortion, Therapeutic↗