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Biomedical subjects

A Bernard

Publications and source records attributed to A Bernard.

At least 541 records · Page 30Linked to original sources

[Differentiation antigens of malignant leukocytes (2)].

One of the most rewarding applications of anti-leucocyte monoclonal antibodies is their use in the study of leukaemias and haematosarcomas. They are now of daily assistance for the diagnosis and classification of these diseases. The availability of malignant cell phenotypes provides a more accurate definition of nosological entities and opens new prospects of a better adaptation of treatment to each individual patient. Moreover, monoclonal antibodies now make it possible to determine the general characteristics of the phenotype of malignant leucocyte populations. Such an improvement in our understanding of these tumours will undoubtedly result in numerous developments during the forthcoming years.

Antigens, Differentiation, B-Lymphocyte↗

[Human leukocyte differentiation antigens].

Over a small number of years many monoclonal antibodies directed against leucocytes have been produced. Their multiplicity and the various nomenclatures utilized may be disconcerting. As a result of the First International Workshop on Human Leucocyte Differentiation Antigens (Paris, 1982), a very clear correspondence between these different antibodies has been established by regrouping into "differentiation classes", each class corresponding to a given molecular species at leucocyte surface. One of the consequences of this international co-operative study has been the development of a nomenclature system now officially adopted by the World Health Organization. In addition, it is now possible to identify the general characteristics of leucocyte surface molecules, which provides information on their organization and function. The international study is in progress, and the results of the Second Workshop (Boston, 1984) will soon be available.

Antibodies, Monoclonal↗

Turbidimetric latex immunoassay for serum ferritin.

A sensitive immunoassay based on latex particle agglutination (latex immunoassay) has been developed for the determination of serum ferritin. Polystyrene particles (0.8 micron) to which anti-ferritin antibody is adsorbed are incubated with serum for 30 min with shaking or 60 min without shaking. The resulting agglutination is quantified by measuring the decrease of absorbance of the latex suspension at 360 nm. Pretreatment of the serum is required to prevent interference from complement, rheumatoid factor and chylomicrons. The lowest detectable concentration of ferritin in serum is about 5 micrograms/l. Within-runs and between-runs coefficients of variation, based on analysis of samples containing 14-820 micrograms/l ferritin, ranged from 3.6 to 13.8%. A correlation coefficient of 0.95 between latex immunoassay and radioimmunoassay was obtained for the determination of ferritin in 46 sera.

Ferritins↗

Cadmium, analgesics, and the chronic progressive nephrosis in the female Sprague-Dawley rat.

Female Sprague-Dawley rats received phenacetin or aspirin at average daily doses of 135 and 27 mg/kg respectively in the diet and either demineralized water (DMW) or a 100 ppm cadmium (Cd) solution as their drinking water for 12 months. This dose of Cd produced borderline tubular toxicity, as measured by the excretion of IV-injected human beta 2-microglobulin. The kidney accumulation of Cd just reached the critical level of 200 ppm in all groups at the end of the study. The various treatments did not significantly affect growth, creatinine clearance, urine osmolality and the urinary excretion of beta-N-acetyl-D-glucosaminidase and aminoacids. No interaction resulted from the concomitant administration of analgesics and Cd. Both aspirin subgroups (receiving DMW or Cd) showed an attenuation of the age-related decline of the renal function as revealed by a lower urinary excretion of albumin and total protein. The accentuation of the mesangial matrix seen upon aging was also partly inhibited in the aspirin rats.

Acetylglucosaminidase↗

Simultaneous occurrence of a T-cell lymphoma and a chronic myelogenous leukemia with an unusual karyotype.

The simultaneous occurrence of malignant T-cell lymphoma and chronic myelogenous leukemia is reported. The lymph nodes contained E rosette forming cells. Blood and bone marrow cell morphology were consistent with the diagnosis of chronic myelogenous leukemia. Lymph nodes, bone marrow and blood mitosis showed a t(6;8) (6pter----6q27 ::8p12----8pter;6qter----6q27 ::8p12----8qter) translocation. So far a number of recent reports have shown simultaneous B lymphoid and myeloid proliferations in some malignancies, this is apparently the first reported case of simultaneous T lymphoid and myeloid proliferations.

Adolescent↗

Anti-laminin antibodies in Sprague-Dawley and brown Norway rats chronically exposed to cadmium.

Sprague-Dawley and Brown-Norway female rats were chronically exposed to cadmium. The metal was administered either in drinking water at a concentration of 20 or 100 ppm for 13 months or intraperitoneally (i.p.) at the dose of 1 mg/kg, 5 times a week for 4 months. Anti-laminin and anti-type IV procollagen antibodies (laminin and type IV procollagen are components of the glomerular basement membranes) were sequentially assessed by radioimmunoassay in serial serum samples. Anti-type IV procollagen antibodies were never detectable whereas anti-laminin antibodies were transiently found in the serum of Sprague-Dawley rats only. In the i.p. group, the antibodies were detected between week 4 and 8, whereas in the oral treatment group, they were detected between month 6 and 8. At the same time, the concentration of cadmium in kidney cortex averaged about 100 ppm in the 20 ppm cadmium group and about 200 ppm in the 2 other treatment groups. The pathogenic significance of these antibodies in chronic cadmium intoxication of Sprague-Dawley rats remains to be assessed since their occurrence was not associated with concomitant immunoglobulin deposits in the kidneys.

Animals↗

In vitro effects of lead, mercury and cadmium on the enzymic activity of red-blood cell pyrimidine 5'-nucleotidase.

The decrease of pyrimidine 5'-nucleotidase (P5N) in human erythrocytes, detected in persons occupationally exposed to lead (Pb), is not an in vitro artefact resulting from the release of lead during erythrocyte hemolysis but is a true reflection of the enzyme activity in vivo. Like Pb, mercury (Hg) and cadmium (Cd) ions exhibit an important in vitro inhibitory action on the P5N enzymic activity. However, when the metals are preincubated as metallothionein complexes with P5N preparations, their inhibitory power disappears.

5'-Nucleotidase↗

Distal tubular dysfunction in rats chronically exposed to a 'white spirit' solvent.

Inhalation exposure of male Sprague-Dawley rats to an industrial white-spirit solvent composed of a C10-C12 mixture of branched-chain unsubstituted satured aliphatic hydrocarbons at 6500 mg/m3 for over 9 months resulted in decreased urinary concentrating ability, decreased net acid excretion following a mild ammonium chloride load and increased urinary lactate dehydrogenase (LDH) activity, whereas urinary beta-N-acetyl-D-glycosaminidase (NAG) activity remained normal. These observations suggest the existence of distal tubular alteration in the rat kidney.

Acetylglucosaminidase↗

The heterogeneity and functional capacities of human thymocyte subpopulations.

Analysis of human thymocytes with monoclonal antibodies belonging to five distinct clusters of differentiation (CD1, CD3-CD5, CD8) revealed a high degree of phenotypic heterogeneity. Six subpopulations could be defined in the thymic compartment characterized by the presence of CD1 antigens (cortical type); four subpopulations could be defined in the compartment characterized by the lack of CD1 but by the presence of CD5 antigens (medullary type); two subpopulations could be defined in the compartment characterized by the lack of both CD1 and CD5 antigens. Thymic samples could be categorized as either high responder or low responder to phytohemagglutinin alone. The defect of low responders was, to a large extent, attributable to a lack of interleukin 2 availability in the medullary type compartment. Yet, cortical-type subpopulations, both from high and low responders, were able to respond to phytohemagglutinin alone to the same extent. Undesirable cell contamination was excluded by limiting dilution analysis. Moreover, cortical-type cells were found to be able to respond to concanavalin A alone, while medullary-type cells and total populations did not respond to concanavalin A alone. Thus, the human thymus includes a number of cell subpopulations involved in complex functional interactions.

Antibodies, Monoclonal↗

Ethanol from Whey: Continuous Fermentation with a Catabolite Repression-Resistant Saccharomyces cerevisiae Mutant.

An alternative method for the conversion of cheese whey lactose into ethanol has been demonstrated. With the help of continuous-culture technology, a catabolite repression-resistant mutant of Saccharomyces cerevisiae completely fermented equimolar mixtures of glucose and galactose into ethanol. The first step in this process was a computer-controlled fed-batch operation based on the carbon dioxide evolution rate of the culture. In the absence of inhibitory ethanol concentrations, this step allowed us to obtain high biomass concentrations before continuous fermentation. The continuous anaerobic process successfully incorporated a cell-recycle system to optimize the fermentor productivity. Under conditions permitting a low residual sugar concentration (</=1%), maximum productivity (13.6 g liter h) was gained from 15% substrate in the continuous feed at a dilution rate of 0.2 h. Complete fermentation of highly concentrated feed solutions (20%) was also demonstrated, but only with greatly diminished fermentor productivity (5.5 g liter h).

Journal Article↗

Urinary cadmium and lead concentrations and their relation to blood pressure in a population with low exposure.

The 24 hour urinary excretion of cadmium (U-Cd) and lead (U-Pb), and the excretion of beta-2- microglobulins and retinol binding protein concentration in spot urines, were determined in a random 4% sample of the population of a small Belgian town. Blood pressure and body weight were measured on two separate occasions. U-Cd averaged 2.4 nmol/24 h in 46 youths, increased with age, and was significantly higher in 57 adult men as compared with 59 women (9.3 v 7.2 nmol/24 h; p less than 0.01). U-Pb averaged 28 nmol/24 h in youths and similarly increased with age: adult men excreted more lead than women (64 v 40.0 nmol/24 h; p less than 0.001). Among men, manual workers excreted more cadmium (12.6 v 7.5 nmol/24 h; p less than 0.05) but a similar amount of lead (62 v 61 nmol/24 h) compared with office workers. After adjusting for sex and age, U-Cd and U-Pb were not related to body weight and cigarette consumption. In simple regression analysis, U-Cd was positively correlated with both systolic (r = +0.30; p less than 0.05) and diastolic (r = +0.38; p less than 0.01) blood pressure in women. After adjusting for other contributing variables, however, a weak but negative relation became apparent between systolic pressure and U-Cd in women (t = -2.21; p = 0.033) and between diastolic pressure and U-Cd in men (t = -2.04; p = 0.047). In women urinary beta-2-microglobulin was related to diastolic pressure (r-0.44; p<0.01) and after adjusting for age to both systolic (t=2.75; p=0.009) and diastolic (t=-3.07; p=0.004) pressure. In none of the sex-age groups did U-Pb and retinol binding protein contribute to the blood pressure variability.

Adolescent↗

Characterization of cadmium proteinuria in man and rat.

In workers chronically exposed to cadmium and without signs of renal insufficiency, plasma proteins with molecular weight ranging from 11,800 to 450,000 are excreted in greater amount in urine. Increased urinary excretion of low and high molecular weight proteins can occur independently. Because of its greater stability in urine and provided a sensitive immunological technique is used, the determination of retinol-binding protein is a more practical and reliable test of proximal tubular function than beta 2-microglobulin. The evaluation of renal function of workers removed from cadmium exposure indicates that cadmium-induced renal lesions, albeit of slow progression, are not reversible when exposures ceases. In workers chronically exposed to cadmium or removed from cadmium exposure, metallothionein in urine is directly correlated with cadmium in urine but not with cadmium in blood or years of cadmium exposure. The association between cadmium in urine and metallothionein in urine is independent of the status of renal function and the intensity of current exposure to cadmium. Whereas the repeated IP injection of high doses of cadmium to rat gives rise to a mixed or tubular type proteinuria, the prolonged oral administration of cadmium results mainly in the development of a glomerular type proteinuria. The former is usually reversible after cessation of treatment whereas the latter is not. Circulating antiglomerular basement membrane antibodies have been found in man and in rat chronically exposed to cadmium. The pathogenic significance of this finding deserves further investigation.

Adult↗

Acute diquat intoxication. Interest of its repeated determination in urine and the evaluation of renal proximal tubule integrity.

A 33-year old farmer ingested approximately 300 ml of a 20% solution of diquat along with about 80 mg flunitrazepam. The patient presented neurological (coma grade I), digestive (oro-pharyngeal erosions, ileus), hepatic (cytolysis), hematological (thrombopenia) and renal (tubular dysfunction) signs. Plasma creatinine did not exceed 1.22 mg/dl (upper normal value), but retinol binding protein level in urine (a marker of renal tubular dysfunction) reached a value of 337 mg/d (normal values less than 300 micrograms/d). Its level returned to normal value 18 days after the ingestion. Four hours after the poisoning, diquat level in blood amounted to 10.4 mg/l, but its level was below the detection limit (0.2 mg/l) 6 hours later. In urine, however, diquat was detected until day 13. The following therapy was applied: ventilation (FiO2:0.21), gastro-intestinal lavage, hemoperfusion, anti-oxidants and prolonged forced diuresis. The patient made an uneventful recovery. intestinal washout must be applied with caution since an ileus is a classical complication of diquat poisoning. Hemoperfusion was found to be of little value. The interest of prolonged application of forced diuresis is suggested by the detection of diquat in urine for about 2 weeks along with the presence of biological signs of renal tubular dysfunction.

Adult↗

Preferential elimination of NK and CTL functions by anti-D44 monoclonal antibody.

Monoclonal antibodies reactive with T cells at various stages of maturation were used in negative selection experiments to study their effects on NK function in the presence of complement. Anti-D47 and anti-A50, respectively, directed against corticothymocytes and mature peripheral E+ cells were without effect. Anti-D66 reactive with an epitope of the T cell E receptor inhibited up to 60% of NK activity. Anti-D44, which primarily recognizes corticothymocytes and 60 to 80% of the E(+)-PBL was found to abrogate NK activity together with alloreactive CTL reactivity but to leave intact most of the MLR and PHA proliferative responses. Therefore D44 appears as a discrete antigen allowing preferential elimination of NK cells and CTL from PBL.

Antibodies, Monoclonal↗

A novel human leukocyte differentiation antigen: monoclonal antibody anti-D44 defines a 28 Kd molecule present on immature hematologic cells and a subpopulation of mature T cells.

Anti-D44 is a cytotoxic IgG2b monoclonal antibody (MAb), which reacts with two polypeptides of 28 and 30 Kd from human peripheral T cells after western blotting. The antigen is present in low density on bone marrow cells from the myeloid lineage, probably including most CFU-GM; the antigen is present on megakaryocytes but is not detectable on erythroid cells as well as pre-B and B cells. Growth of BFU-E appears to be partially inhibited after treatment with anti-D44 + complement, an effect that should be due to bone marrow T cells rather than to BFU-E destruction. With maturation, the antigen is barely detectable on mature polymorphonuclear neutrophils, and is not detectable on platelets and monocytes. In contrast, cells from the thymic cortex carry a high density of this molecule; medullary thymocytes carry a low density. Large thymocytes ("thymoblasts") distinct from epithelial or interdigitating cells also bear a high density of the antigen. In the periphery, a subpopulation of T cells displays a high density of D44 molecules. D44 antigenic density is not linked to cell growth or to T cell activation. Double labeling and cell sorting experiments have shown that 40% of E rosette-forming cells are D44(+)-CD4+, 10% are CD8(+)-D44+ and 10% are CD4(-)+CD8-, CD2+. In an accompanying report, correlation is shown between expression of the D44 defined molecule on T cell subpopulations and the function they exert. Immunoperoxidase studies of skin, brain, and kidney tissues, facilitated by the fact that the antigen is resistant to inclusion in Epon, which permits staining of semi-thin sections, have not revealed any positive nonhematologic cell.

Animals↗

[2nd malignant tumors in children. Study of 38 cases].

Thirty-eight children, followed in the pediatric Department of Institut Gustave-Roussy, developed second malignant neoplasms. Intervals between the two neoplasms ranged from 1 to 26 years. The second neoplasms were defined as having a different histologic diagnosis than the first ones: osteosarcoma, fibrosarcoma, thyroid carcinoma, leukemia were the most frequent second neoplasms. The potential carcinogenic part of chemotherapy and radiotherapy is emphasized. In addition, some genetic susceptibility may enhance the carcinogenic effects of therapy. Nevertheless the incidence of second malignant neoplasms is low. Its estimation is discussed here.

Adolescent↗