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Biomedical subjects

M Willems

Publications and source records attributed to M Willems.

10 recordsLinked to original sources

Effects of insulin-like growth factors and growth hormone on the in vitro proliferation of T lymphocytes.

The insulin-like growth factors I and II (IGF-I and IGF-II) promote proliferation and differentiation of many cell types. We report that recombinant IGF-I and IGF-II augment both the lectin- and anti-CD3-induced proliferation of human peripheral blood mononuclear cells (PBMC) at concentrations proportional to their binding affinities. IGF-I and IGF-II also augmented the lectin-induced proliferation of purified T lymphocytes. Effects of IGF-I were found in cultures of T cells vigorously depleted for monocytes and supplemented with saturating concentrations of interleukin-1. The latter results indicate that the effect of IGF-I on the proliferation of T lymphocytes can occur independent of monocytes or monocyte-derived factors.

Carrier Proteins

Expression of type I insulin-like growth factor receptors on human peripheral blood mononuclear cells.

Insulin-like growth factor-I and -II (IGF-I and IGF-II), both of which bind to type I IGF receptors, can modulate certain functions of the immune system. We, therefore, studied the expression of type I IGF receptors on purified subpopulations of peripheral blood mononuclear cells. Using two-color flow cytometry, specific binding of a monoclonal antibody directed against the type I IGF receptor (alpha IR3) was found in every subpopulation. Relatively high numbers of receptors were detected on monocytes, natural killer cells, and CD4+ T-helper cells, an intermediate number of receptors on CD8+ suppressor/cytotoxic T-cells, and a relatively low number of receptors on B-cells. The presence of these receptors was confirmed by specific binding of [125I] IGF-I to purified subpopulations. alpha IR3 inhibited the binding of [125I] IGF-I. The specific binding of [125I]IGF-I to monocytes could be completely inhibited by IGF-II and insulin, but higher doses of these peptides were needed than of IGF-I. Scatchard analysis revealed the presence of 734 +/- 426 receptors/monocyte, with a Kd of 0.23 +/- 0.05 nM. A lower number of receptors (230 +/- 52), but with a higher affinity (Kd = 0.05 +/- 0.02 nM), was found on purified T-cells. The positive effect of IGF-I on natural killer cell cytotoxicity indicates that the type I IGF receptors on this cell type are functional. The possibility that IGF-I mediates hormonal effects on the immune system is discussed.

B-Lymphocytes

Hepatitis C.

Until recently the diagnosis of non-A, non-B hepatitis was made by excluding other detectable viral infections of the liver. Progress in molecular biology made it possible to develop assays which can trace antibodies against the hepatitis C virus. This virus plays a major role in the pathogenesis of transfusion-related and sporadic non-A, non-B hepatitis and possibly of other liver diseases. Although the genome of a few isolates of the hepatitis C virus has already been decoded, the viral particles have not yet been visualized.

Genome, Viral

Surrogate markers are not useful for identification of HCV carriers in chronic hemodialysis patients.

Several diagnostic hepatitis C assays have been developed for the detection of antibodies to different antigens of the virus. This virus is the major cause of non-A, non-B hepatitis. Seventy-nine patients undergoing chronic hemodialysis and/or hemofiltration were tested for the presence of anti-HCV antibodies (anti-C-100-3 antibodies and anti-core antibodies), anti-hepatitis B core antibodies (anti-HBc), and aminotransferases (ALT). Seven patients were positive by one or more of the anti-HCV enzyme linked immunoassays (EIAs), while HCV-RNA was detectable in only four patients. These four patients had at least one, but not necessarily the same, positive anti-HCV EIA. HCV-RNA was not detected in patients who had no antibodies as determined by all six anti-HCV EIAs. All patients with a marker for HCV infection had persistent normal levels of transaminases. Three patients had elevated ALT values without a marker for HCV infection and suffered from hepatitis B virus infection. Anti-HBc was detected in 27/72 patients without any marker and in four patients with a marker of HCV infection. However, HCV-RNA was detectable in only one of these four anti-HBc positive patients. It is concluded that surrogate markers (anti-HBc and serum transaminases) are not useful for identification of HCV carriers in chronic hemodialysis patients.

Biomarkers

Adsorption of creatinine to Fuller's earth.

In search for a secondary reference method for the determination of creatinine, the adsorption of creatinine to seven different commercial batches of Fuller's earth have been investigated. Mineralogical investigation of the batches broadly divided them into two subgroups with quite different cation exchange capacities (CEC): dominant smectitic with and without calcium carbonate and dominant palygorskitic with calcium carbonate. Adsorption experiments using 14C-creatinine show, for all Fuller's earth samples, an incomplete adsorption of creatinine. The amount of creatinine adsorbed depends on pH, temperature, concentration of cations as Ca2+ and Na+, and other conditions. Weakly acidic suspensions of Fuller's earth in the course of time change their ability to adsorb creatinine. Compared to a synthetic strong acidic cation exchanger, Fuller's earth is more selective to creatinine. Because of the sensitivity of the adsorption to the various experimental conditions a determination of creatinine in biological fluids using Fuller's earth is too variable. Therefore, we cannot recommend this procedure as a secondary reference method for the determination of creatinine.

Adsorption

[Results of percutaneous transhepatic drainage of the bile ducts].

From September 1980 to December 1986, 72 percutaneous transhepatic cholangiography drainages (PTCD) were performed in 64 patients (58 palliative in malignant obstructions, 14 temporary). The median duration of drainage was 26.8 days (2-183 days). The median survival time in 37 patients with palliative tumour drainage was 55.3 days (7-473 days). 9/37 patients survived longer than 3 months (max. 15.5 months). Complications occurred in 29.5% (10.3% severe). 3/64 patients (4.7%) died. Patients with palliative transpapillary drainages (23), especially with endoprostheses (14), survived longer, and the complication rate was lower. Therefore, we prefer the endoscopic transpapillary approach. PTCD patients must be selected carefully.

Aged

Estradiol-induced synthesis of vitellogenin. III. The isolation and characterization of vitellogenin messenger RNA from avian liver.

The messenger RNA of the hormone-induced protein vitellogenin was isolated from the liver of estrogen-treated roosters. Starting from total polysomal RNA, the vitellogenin messenger was purified 67-fold by oligo (dT)-cellulose chromatography and sizing on a sucrose gradient. The messenger was translated in vitro into a 170 000 dalton polypeptide chain, having the immunochemical characteristics of vitellogenin. From electrophoretic and immunochemical analysis of the in vitro product of translation at least 63% of the messenger activity of the RNA preparation could be attributed to vitellogenin mRNA. Gel electrophoresis of the most purified fraction revealed residual contamination with the larger ribosomal RNA species. The molecular weight of the messenger RNA molecule, obtained by contour length measurements in the electron microscope, lies between 2.5 - 10(6) and 2.8 - 10(6).

Animals