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Biomedical subjects

I Moldovan

Publications and source records attributed to I Moldovan.

At least 19 recordsLinked to original sources
PubMed2004

Interaction of human immunoglobulin G with CD16 on natural killer cells: ligand clearance, FcgammaRIIIA turnover and effects of metalloproteinases on FcgammaRIIIA-mediated binding, signal transduction and killing.

Human natural killer (NK) cells express low-affinity Fc immunoglobulin G (IgG) receptor (FcgammaRIIIA/CD16). The binding of monomeric IgG (mIgG) and F(ab')(2) fragments of 3G8 anti-CD16 monoclonal antibody (mAb) to FcgammaRIIIA was investigated by flow cytometry. Over 90% of NK cells bound endogenous IgG, and during incubation at 37 degrees C, the FcgammaRIIIA occupancy decreased slowly. Approximately 90% of NK cells bind mIgG or F(ab')(2) fragments of 3G8 anti-CD16 mAb. The calculated half-time (T(1/2)) of in vitro mIgG dissociation from FcgammaRIIIA was 130 min. By cross-linking the mIgG ligand with F(ab')(2) fragments of anti-human IgG antibody, the T(1/2) decreases to 85 min. In kinetics study, it has been shown that (125)I-mIgG bound to FcgammaRIIIA is slowly released in the culture supernatant, maybe eluted at acid pH, or partially internalized and degraded. The binding of IgG to FcgammaRIIIA was increased by 53.8% on cells cultured in the presence of RU36156, a matrix metalloproteinase (MMP) inhibitor. Furthermore, an increase in phosphorylation of Lyn tyrosine kinase, after cross-linking of mIgG-FcgammaRIIIA complex, was observed on NK cells treated with RU36156. When the FcgammaRIIIA was occupied by mIgG, the capacity of NK cells to kill K562 target cells was decreased by RU36156, because the MMP inhibitor protects CD16 from proteolysis. Our data demonstrate that binding of mIgG to human NK cells is followed by ligand dissociation and/or internalization, enzymatic degradation and exocytosis. The RU36156 MMP inhibitor protects FcgammaRIIIA from cleavage, augments NK-cell activation and may interfere in their killing capacity.

Cytotoxicity Tests, Immunologic↗
PubMed1999

Regulation of production of soluble Fc gamma receptors type III in normal and pathological conditions.

CD16 (Fc gamma R type III), a low affinity IgG Fc receptor, is found in two forms, a transmembrane Fc gamma RIIIa expressed by NK cells and monocytes and a phosphatidylinositol-linked Fc gamma RIIIb present on neutrophils. Exposure of neutrophils to inflammatory signals induces a rapid loss of CD16 expression and release of a soluble form of CD16 (sCD16). Soluble CD16 circulates in plasma, levels being reduced in sera from patients with multiple myeloma. In the present manuscript the authors summarize work that aimed to better understand: (i) the role of proteinases in sCD16 production and CD16 membrane shedding; and (ii) the regulation of sCD16 levels in multiple myeloma patients and the possible biological consequences of its decrease in this disease. Soluble CD16 was purified from human serum. Its N-terminal sequencing demonstrated that it originates from neutrophil CD16 and its C-terminal sequencing showed that the cleavage site was between Val 196 and Ser 197, close to the membrane anchor. Analysis of the effect of protease inhibitors revealed that the cleavage leading to sCD16 production by PMA-activated neutrophils was metalloproteinase-dependent. In addition, membrane and sCD16 were sensitive to serine proteinases released by azurophil granules or added under purified form. The reduction of sCD16 levels that occurs in patients with multiple myeloma was associated with a slight decrease in circulating neutrophils, but not with a significant defect in sCD16 production by neutrophils, as detected in vitro. Moreover, addition of a recombinant sCD16 to plasmocytoma lines did not significantly modify their proliferation and Ig secretion.

Amino Acid Sequence↗
PubMed1999

Evaluation of apoptosis of tumor and of apparently normal cells in human renal carcinoma.

Apoptosis of tumor cells and of apparently normal renal cells (ANRC) isolated from the same kidney in 42 untreated patients with renal carcinomas (RC) was evaluated. Thirty five of the investigated tumors were of Grawitz type in different grades of differentiation. The intensity of the apoptotic process was routinely assessed by propidium iodide staining and flow-cytometry analysis. Similar results were obtained in the same cases by using TUNEL assay, by staining with annexin V and by DNA electrophoresis. In 85% of Grawitz carcinomas the proportion of apoptotic tumor cells was quite high, with mean% +/- SD of 57.7+/-27.3, whereas in transitional cell carcinoma of the bladder (TCC), the mean percentage of cells in apoptosis was of 22.3+/-13.9. Unexpectedly, in ANRC displaying normal morphology and normal DNA content (diploidy), the mean% +/- SD of apoptotic cells were found to exceed that of apoptotic tumor cells, 79.2+/-21.6. The percentages of cells expressing Fas receptor and/or Fas ligand varied between large ranges in both tumor and ANRC, thus suggesting that other mechanisms are also involved in the activation of apoptosis. Immunohistochemical studies showed that the intensity of apoptosis correlated well with high p-53 and low bcl-2 expression. The intensity of apoptosis was generally not correlated with the cell proliferation index (S phase fraction), suggesting that in RC apoptosis can be activated in any stage of the cell cycle. Further investigations are necessary to understand the peculiar behaviour of tumor cells as well as of ANRC in renal carcinomas as compared to other types of malignancies.

Apoptosis↗
PubMed1998

Identification of the cleavage site involved in production of plasma soluble Fc gamma receptor type III (CD16).

CD16 (FcgammaR type III) is a low-affinity IgG Fc receptor (R) that exists in two isoforms, a transmembrane FcgammaRIIIa expressed by NK cells and monocytes, and a phosphatidylinositol-linked FcgammaRIIIb expressed by neutrophils. A soluble form of CD16 (sCD16) circulates in plasma. The cleavage site and the nature of the enzyme(s) involved in production of sCD16 were investigated. Soluble CD16 was purified to apparent homogeneity from human serum by eight steps, including anion exchange and immunoaffinity chromatography. Serum sCD16 was sequenced at both ends, as well as a recombinant form of sCD16 used as control. N-terminal sequencing demonstrated that serum sCD16 originates from neutrophil FcgammaRIIIb and C-terminal sequencing suggested that the cleavage site is between Val 196 and Ser 197, close to the membrane anchor. Addition of a hydroxamate-based inhibitor of Zn2+ metalloproteinases (RU36156) led to a dramatic decrease of sCD16 production by phorbol 12-myristate 13-acetate-activated neutrophils, whereas inhibitors of serine proteinases had no significant effect, showing the metalloproteinase dependence of this cleavage process.

Amino Acid Sequence↗
PubMed1976

[Etiopathogenesis of varicocele and therapeutic conclusions].

The many pathogenic theories for varicocele, mostly hypothetic, have shown the uncertainty of the cause of the disease including the use of the word "essential". Anatomical, phlebomanometric and phlebographic studies determined the main cause of varicocele, the short course of the aorto-mesenteric artery which, by stricture of the left renal vein in the standing position, produces reno-spermatic venous reflux producing varicose dilatation of the left spermatic plexus and, thus, varicocele. In addition to this main cause, the vascular background with a qualitative deficiency of the connective tissue and prolonged standing during work, are the main factors which favour the onset of varicocele. An active, early therapeutic attitude and high ligature of the left spermatic vein give the best results.

Humans↗
PubMedDate not supplied

[Control of the metabolic state of diabetic patients by determining the concentration of serum glycosylated proteins (the fructosamine test)].

The method for determining glycosylate serum proteins is based on the ketoamines property (fructosamine) of reducing nitro-tetrazoline blue, in alkaline medium, to a coloured, photometric product. The technique is simple, rapid, reproducible and cheap. The method was used for investigation of 52 diabetics and 17 normal subjects. The normal values were between 1.50-2.70 mmol/l, uncertain between 2.70-3.00 mmol/l, and certainly pathological above 3.00 mmol/l. The level of serum fructosamines shows the glycemia variations for an average period of about two weeks, before determination. It is one of the valuable parameters for detecting and following the patients with diabetes mellitus, and has also a prognostic value in the evolution of the disease.

Adolescent↗
PubMedDate not supplied

Fibronectin and phagocytosis in acute and chronic infections.

Serum fibronectin (Fn) level and phagocytosis function were investigated during acute and chronic infections. Serum Fn concentration was significantly decreased in septic patients (mean +/- ES, 80 +/- 12 micrograms/ml, p less than 0.001) and was increased in chronic bronchitis patients (575 +/- 18 micrograms/ml, p less than 0.001) as compared to the controls. The phagocytosis index was decreased in septicaemia and not significantly changed in chronic bronchitis. Phagocytosis dysfunction was associated to a low serum Fn level in acute infections. Phagocytosis was stimulated in vitro, by purified Fn. Serum Fn concentration reflects the reticuloendothelial function and could be a marker of infection together with other parameters.

Acute Disease↗
PubMedDate not supplied

[Right varicocele].

The authors present two cases of varicoceles on the right side, and demonstrate that, excepting cases when it is symptomatic, this localisation is due to visceral or vascular malformation, especially involving the flowing of the right spermatic vein. The authors have demonstrated by urographic, phlebographic and arteriographic techniques the presence of vascular and renal anomalies that had led to the development of varicoceles on the right side. The presence of this type of varicoceles in the author's statistics is of 1/3270 (0,6%).

Adult↗