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Biomedical subjects

M Ionescu

Publications and source records attributed to M Ionescu.

At least 19 recordsLinked to original sources

Cartilage and bone metabolism in rheumatoid arthritis. Differences between rapid and slow progression of disease identified by serum markers of cartilage metabolism.

Serum concentrations of specific cartilage and bone molecules reflecting tissue turnover were measured in two well-defined patient groups with early rheumatoid arthritis with distinctly different disease outcome to see if early differences in their levels are prognostic of the rate of joint destruction. Compared with a matched normal population, increased concentrations of cartilage oligomeric matrix protein (COMP) were found in all patients who developed rapid hip joint destruction. In contrast, levels of a putative marker of cartilage aggrecan synthesis, the chondroitin sulfate epitope 846, were increased only in patients with slow joint destruction. Levels of bone sialoprotein (BSP) were increased in both groups, as were levels of the C-propeptide of type II procollagen (CPII), a marker of collagen II synthesis. The increased concentrations of the 846 epitope in patients with slow joint destruction suggest increased aggrecan synthesis. The low levels of the 846 epitope in patients with rapid joint destruction, concomitant with elevated levels of CPII, suggest a selective increase in collagen synthesis. The elevated BSP levels indicate an increased bone turnover in both groups. Thus elevated serum levels of COMP may indicate an unfavorable prognosis for rapid joint destruction, whereas elevated 846 epitope indicates a more favorable prognosis.

Adult

Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for pathogenesis.

The metabolism of the cartilage proteoglycan aggrecan was studied in patients with osteoarthritis (OA, n = 83), rheumatoid arthritis (RA, n = 127), and in controls (n = 117) using monoclonal antibody-based radioimmunoassays for glycosaminoglycans in the serum and synovial fluid (SF) to detect epitope 846 on chondroitin sulfate (probably only on recently synthesized molecules) and a keratan sulfate (KS) epitope AN9PI, present on intact and degraded molecules. Epitope 846 levels were always elevated in SF over serum (mean 38-fold in OA and 8.6-fold in RA) being highest in OA patients with the longest disease duration and greatest loss of cartilage, and lowest in RA joints with high leucocyte counts. Serum levels were more often elevated in RA (56%) than in OA (19%) and probably reflect increased aggrecan synthesis in diseased joints. KS levels were higher in SF than in serum in 69% of patients (up to 2.3-fold); levels were inversely (OA) and directly (RA) related to SF leucocyte counts. Serum KS was reduced in both diseases and in RA was inversely related to both systemic and joint inflammation markers. SF 846 levels were inversely related to SF KS in both diseases. These epitopes may provide a measure of the balance between cartilage synthesis and degradation in these diseases.

Adult

[Hearing loss of workers in mining--a 6-year longitudinal study].

Hearing threshold level (HTL) in miners, was determined after six years interval characterized by the same noise exposure. An attempt was made to establish the prognosis regarding the hearing losses extent and the time interval involved in the occurrence of these modifications in the subjects applying the HTL values. 132 workers (miners and miner apprentices) underwent audiometrical examinations, after 6 years interval in the same testing conditions. To evaluate the vibrations possible effects on the HTL, the results registered in a group of workers exposed solely to noise (n = 33)-identical continuous equivalent level/week-were compared to those found in miners. According to age range and the duration of noise exposure, the yearly mean rate for both the low (500-2000 Hz) and high frequencies (2-8 kHz), were calculated based on the hearing threshold differences. The miners, simultaneously exposed to noise and vibration presented yearly decreased HTL values (up to 2000 Hz), as against the subjects exposed solely to noise. The prognosis indicates that in a miner with a duration of exposure above 21 years and/or a mean age of 38, one may expect a loss of the HTL exceeding 30 dB at 4 kHz.

Adult

The risk of thromboembolism and hemorrhage following mitral valve replacement. A comparative analysis between the porcine xenograft valve and Ionescu-Shiley bovine pericardial valve.

To ascertain the risk of thromboembolism and anticoagulant-related hemorrhage following mitral valve replacement with bioprostheses, an 8 year retrospective study between two groups of patients was analyzed. Group I included 206 patients undergoing mitral valve replacement with porcine xenograft valves. They were placed on a regimen of long-term oral anticoagulation (greater than 8 weeks, mean 6 months). Follow-up was 524.3 patient-years, mean 30.5 months. There were 24 thromboembolic events (4.6% per patient-year), four of which were fatal. Actuarially, 80.7% +/- 4.3% are free of thromboembolism at 8 years. There were 12 instances of major bleeding episodes, for a linearized incidence of 2.5% per patient-year; two were fatal. Group II included 322 patients undergoing mitral valve replacement with a bovine pericardial valve. They were placed on a program of short-term anticoagulation (6 weeks only). Follow-up was 1,106 patient-years, mean 46.4 months. There were four thromboembolic episodes (none fatal), an incidence of 0.36% per patient-year. Seven bleeding episodes occurred, 0.63% per patient-year; none was fatal. The difference between the groups reached statistical significance (p less than 0.001). The low risk of thromboembolism with the bovine pericardial valve appears to be due to its superior hydraulic characteristics. Use of this valve allows mitral valve replacement without long-term oral anticoagulation and the associated risk of anticoagulant-related hemorrhage.

Adolescent

Comparison of human and rat liver microsomes by spin label and biochemical analyses.

Detailed lipid analyses of human and rat liver microsomes revealed interesting differences. It was found that human liver microsomes contain twice as much lipid as those from the rat. This increased lipid content is not associated with an increase in content of a particular lipid class; human liver microsomes contain higher amounts of each of the lipid classes. Human and rat liver microsomes differ especially in the essential fatty acid composition of total lipids and phospholipids: human liver microsomes contain more linoleic acid and less arachidonic acid than those of the rat. Such a pattern of distribution of fatty acids is similar to that previously reported for human liver mitochondria and has not been reported for other species. Although the previously reported for human liver mitochondria and has not been reported for other species. Although the unsaturation of lipids is lower in human than in rat liver microsomes, spin label studies revealed a higher fluidity in human membranes. It is suggested that this might arise from a lesser immobilization of lipids by proteins in human liver subcellular membranes.

Animals

Water exchange through erythrocyte membranes: nuclear magnetic resonance studies on the effects of inhibitors and of chemical modifications of human membranes.

The changes in water diffusion across human erythrocyte membranes following exposure to various inhibitors and proteolytic enzymes have been studied on isolated erythrocytes suspended in isotonic buffered solutions. An important issue was to investigate whether the sulfhydryl reacting reagents that have been applied in osmotic experiments showed similar effects on diffusional permeability. It was found that mercurials, including mersalyl, were the only sulfhydryl reacting reagents that were efficient inhibitors. Under optimal conditions a similar degree of inhibition (around 45%) was found with all mercury-containing sulfhydryl reagents. Other reagents, including the sulfhydryl reagent DTNB, phloretin, or H2DIDS, the specific inhibitor of the anion transport system in erythrocyte membrane, did not appear to inhibit significantly the diffusional permeability. No changes in water diffusion were noticed after exposure to erythrocytes to trypsin and chymotrypsin. A new kind of experiments was that in which the effects of exposure of erythrocytes to two or more agents were studied. It was found that none of the chemical manipulations of membranes that did not affect water diffusion hampered the inhibitory action of mercurials. These findings show that the SH groups involved in water diffusion across erythrocyte membrane do not react with any of the other SH reagents aside from mercurials and that the molecular mechanism of water transport is not affected by chymotryptic cleavage of band 3 protein into the 60 and 35 kD fragments. The NMR method appears as a useful tool for studying changes in water diffusion in erythrocyte membranes following various chemical manipulations of the membranes with the aim of locating the water channel.

Adult

Influence of age and sex on hearing threshold levels in workers exposed to different intensity levels of occupational noise.

The influence of age, sex and duration of exposure on hearing threshold level (HTL) was assessed in male and female workers exposed to occupational noise. The noise intensities were of 83 and 98 dB (A) continuous equivalent level. Large differences were noted between males and females exposed to 98 dB (A) as well as between males exposed to 98 and 83 dB (A). We concluded that exposure to 98 dB (A) accelerates the evolution of hearing loss, this trend being more pronounced in males. The 83-dB (A) intensity apparently induces a hearing loss above the values due to socioacusis. To evaluate the noxious effect of noise, the HTLs obtained in the group exposed to 98 and 83-dB (A) were compared to those of the non-exposed group of Royster and Thomas. The highest difference was found in males exposed to 98 dB (A).

Adult

Effect of chlorpromazine on proteins in human erythrocyte membranes as inferred from spin labeling and biochemical analyses.

ESR spectra of erythrocyte membranes labeled with a maleimide spin label (MSL) show two types of label environment: a weakly immobilized component and a strongly immobilized component. Chlorpromazine (CPZ) markedly altered the spectra: at pH 8.0, 3 mM CPZ reduced the amplitude of the spectrum by 40%, and the weakly immobilized component was almost completely removed. In order to clarify the mechanisms of these spectral changes the protein release from erythrocyte membranes induced by CPZ has been followed. CPZ had a weak solubilizing effect on erythrocyte membranes: less than 1% of the membrane protein was released, mainly Band 6. By comparison with the protein release induced by low-salt treatment it was found that the "detergent-like" property of CPZ cannot explain the alterations in the ESR spectra. The nature of the spectral changes induced by CPZ was different from that of changes induced by lowering the pH to 4.5; correlated with other data this shows that changes in organization or conformation of membrane protein cannot explain the CPZ-induced alterations in the ESR spectra. These spectral changes appeared to be due to the reduction by CPZ of the nitroxide free radical. This was documented by the marked reduction of spin concentration of the labeled ghosts in the presence of CPZ resulting in a decrease in amplitude of the ESR spectrum of MSL-labeled erythrocyte ghosts induced by CPZ. The reduction by CPZ of the nitroxide free radical was compared with that induced by ascorbate. It was found that CPZ preferentially reduces the mobile component of the ESR spectrum of MSL-labeled ghosts. The action of CPZ in reducing free radicals may have consequences for patients receiving long-term treatment with phenothiazine derivatives.

Blood Proteins