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Biomedical subjects

Y Manuel

Publications and source records attributed to Y Manuel.

At least 19 recordsLinked to original sources

Detection of Monoclonality in South African T-Cell Lymphoma Cases Using PCR Analysis of T-Cell Receptor-gamma Gene Rearrangements.

Background: The polymerase chain reaction (PCR) has become a useful method to determine monoclonality in T-cell lymphomas. The authors investigated a number of T-cell lymphoma cases to determine (1) the monoclonality detection rate in South African T-cell lymphoma cases and (2) whether variation in detection of monoclonality exists in T-cell lymphoma subtypes. Methods and Results: Thirty T-cell lymphoma cases, including pleomorphic peripheral T-cell lymphomas, precursor T-lymphoblastic lymphomas, large-cell anaplastic lymphomas, and one cutaneous lymphoma, were assessed. DNA was purified from paraffin-embedded tissue and amplified with consensus oligonucleotide primers directed at the rearranged T-cell receptor-gamma genes. Monoclonality was found in 73% of cases, similar to previous reports. Pleomorphic peripheral T-cell lymphomas (89%) were detected most successfully; lymphoblastic (73%) and large-cell anaplastic lymphomas (58%) had lower detection efficiencies. Conclusions: Some T-cell lymphoma subtypes are less successfully detected; additional primer sets should be used to improve detection.

Journal Article↗

Environmental urban lead exposure and blood lead levels in children of Mexico City.

Lead contamination is now a leading public health problem in Mexico. However, there are few data on the lead content of various environmental sources, and little is known about the contribution of these sources to the total lead exposure in the population of children residing in Mexico City. We conducted a cross-sectional study in a random sample of 200 children younger than 5 years of age who lived in one of two areas of Mexico City. Environmental samples of floor, window, and street dust, paint, soil, water, and glazed ceramics were obtained from the participants' households, as well as blood samples and dirt from the hands of the children. Blood lead levels ranged from 1 to 31 micrograms/dl with a mean of 9.9 micrograms/dl (SD 5.8 micrograms/dl). Forty-four percent of the children 18 months of age or older had blood lead levels exceeding 10 micrograms/dl. The lead content of environmental samples was low, except in glazed ceramic. The major predictors of blood lead levels were the lead content of the glazed ceramics used to prepare children's food, exposure to airborne lead due to vehicular emission, and the lead content of the dirt from the children's hands. We conclude that the major sources of lead exposure in Mexico City could be controlled by adequate public health programs to reinforce the use of unleaded gasoline and to encourage production and use of unleaded cookware instead of lead-glazed ceramics.

Adult↗

Modulation of stress proteins by Cd2+ in a human T cell line.

We previously showed in a human T cell line (CEM-C12 cells) that Cd2+ induced gene expression of stress proteins, metallothionein-IIA and heat shock protein 70 in a time- and dose-dependent manner. In the present study, CEM-C12 cells were pretreated for 24 h with 1 microM Cd2+ and then challenged with toxic concentrations of this metal. We found that maximal expression of the metallothionein-IIA and heat shock protein 70 genes was increased and this maximal level occurred at higher Cd2+ toxic concentrations. Actinomycin D chase experiments indicated that Cd2+ pretreatment did not modify metallothionein-IIA mRNA stability. The modulatory effect of Cd2+ pretreatment was dose-dependent from 100 pM to 1 microM. Such pretreatment also enhanced resistance to Cd2+ toxicity. Finally, verapamil, a calcium/potassium channel blocker displaced the dose-response curve for Cd2+ toxicity as well as metallothionein-IIA and heat shock protein 70 gene expression to higher Cd2+ concentrations.

Blotting, Northern↗

Cadmium induces apoptosis in a human T cell line.

Cadmium, a potent toxic metal, poses a serious environmental threat but the mechanisms of its toxicity remain unclear. In the present study, we investigated the nature of cadmium-induced cell death in the human T cell line CEM-C12. Cadmium was time- and dose-dependently toxic for CEM-C12 cells, cell death being preceded by chromatin condensation and DNA fragmentation. Quantification of the latter indicated an increase above 4 microM cadmium, with maximal fragmentation at 8 to 10 microM. By contrast, when CEM-C12 cells were exposed to higher cadmium concentrations (50 microM), cell death increased without concomitant chromatin condensation or DNA fragmentation. Thus, cadmium at low and high concentration kills CEM-C12 cells by apoptosis and necrosis, respectively. Addition of cycloheximide reduced the apoptotic effect of cadmium, suggesting that cadmium-induced apoptosis is an process depending on protein synthesis. Verapamil, a calcium/potassium channel blocker, markedly increased the viability of CEM-C12 cells treated by low cadmium concentrations and prevented DNA fragmentation. The apoptotic effect of cadmium suggests a possible mechanism for lymphocyte damage occurring after in vivo exposure to cadmium.

Apoptosis↗

[Development of molecular biomarkers for the detection of nonbiocompatible substances in the environment].

Many difficult issues confront toxicologists. For instance, animal studies have proved to be difficult for the assessment of human toxicity especially to measure directly the impact of low doses of toxic compounds. Recently, novel molecular approaches to cellular mechanisms involved in the response of "toxic stress" has broaden the field of toxicology. Indeed, the development of biological markers capable of detecting exposure to toxicants before a full-blown toxic response is an important current focus of environmental research. Cells from various organisms respond rapidly to toxic stress by altering their metabolic rates, cell growth or gene transcription controlling basic functions. Examples included are oxidative stress conveyed by peroxisomes, stress proteins implicated in protein folding and in detoxification and/or resistance. A number of potential practical applications of the stress response and stress proteins can be envisioned. Stress gene expression may be considered as a potential "biomonitor" to assess whether cells or organisms are experiencing metabolic stress within their environment. Such biological indicators should provide an early, sensitive, readily and measurable response for monitoring the actions of pollutants. In addition, the development of molecular and cellular probes may lead to new classification schemes for toxic compounds based upon various cellular and molecular responses rather than on toxicant structure.

Biomarkers↗

Cystatin C levels in sera of patients with human immunodeficiency virus infection. A new avidin-biotin ELISA assay for its measurement.

A solid-phase enzyme-linked immunosorbent assay (ELISA) for determining human serum cystatin C is described. In 50 normal samples, cystatin C concentration was 1247 +/- 224 micrograms/L (mean +/- SD) which is in agreement with previously reported levels. Serum levels of cystatin C and beta 2-microglobulin (beta 2-M) were investigated in a time-course study during the development of human immunodeficiency virus (HIV) infection. We found a persistent and uniform increase in the beta 2-M concentration (2762 +/- 1239 micrograms/L). In contrast to beta 2-M, on the basis of cystatin C levels, we found two distinct populations, one of which demonstrated an increased concentration (1620 +/- 618 micrograms/L). Interestingly a second group (21% of patients) exhibited an initial significant decrease in cystatin C concentration with a mean value of 377 (range 55-850) micrograms/L, followed by an increase. The biphasic pattern of cystatin C serum, a major cysteine proteinase inhibitor, during the course of HIV infection suggests a possible role for these proteinases (or proteinase inhibitors) in the development of this syndrome.

Adolescent↗

Metallothionein and tissue damage.

Metallothioneins (MTs) are a class of small cysteine-rich heavy metal binding proteins produced in response to a variety of stresses, inflammation, and as components of the acute-phase response. Although the exact role of MT in this phase is not known, a number of reports have shown that expression of hepatic MT is markedly increased in response to bacterial infection, an effect mediated by lipopolysaccharides. More recently, it has been suggested that MT may play a major role in the prevention of tissue damage. Thus MT has been shown to be an efficient free radical scavenger. Indirect activation of macrophages and neutrophils during the acute phase of inflammation result in a massive release of various species of oxygen metabolites which may be indirectly responsible for the initiation of apoptosis. In addition, expression of MT also increases cell resistance to radiation damage. Together, these results suggest that MT could be part of a generalized protective system in mammalian cells.

Animals↗

Cisplatin nephrotoxicity in cadmium-pretreated rats. Enzymatic, functional and morphological studies.

Treatment of rats with cisplatin or with cisplatin after chronic pre-exposure to cadmium induced a decrease in kidney cytochrome P-450 and glutathione levels, and in glutathione peroxidase and reductase activities. Furthermore, cadmium and cisplatin enhanced lipid peroxidation, oxidized glutathione and N-glucuronyl transferase activity. Glutathione S-transferase (substrate: 1-chloro-2,4-dinitrobenzene) was increased and decreased by cadmium and cisplatin respectively. On morphological observation, cadmium nephrotoxicity was characterized by tubular proximal damage with mitochondrial and lysosomal changes and a widespread vesiculation of tubular cells. A marked focal tubular necrosis associated with cyst formation was observed in cisplatin nephrotoxicity. On the basis of the measured biochemical, functional and histological parameters, it is concluded that cadmium pretreatment did not potentiate the nephrotoxic effect of cisplatin.

Animals↗

Renal kallikrein excretion as a distal nephrotoxicity marker during cadmium exposure in rats.

Cadmium exposure is known to induce hypertension, but development of hypertension is not universal in exposed animals. However, the cellular uptake of cadmium could also exert renal cytotoxic effects which have been, until now, essentially only studied at the proximal tubule level. Kallikrein is an enzyme synthetized in renal cortex and excreted in the urine in the distal tubule. Therefore, to evaluate the distal renal effect of cadmium, we studied the daily urinary kallikrein excretion (UKE) in conscious unrestrained female Brown Norway rats during long-term chronic exposure to 2 dosages of cadmium given subcutaneously 3 times a week, a low dose (LD): 0.25 mg/kg and a high dose (HD): 1 mg/kg. Neither dose of cadmium was able to induce significant hypertension in the treated animals. HD administration for 24 weeks resulted in a decreased UKE associated with an increase in plasma renin activity and sodium and potassium excretions. LD administration had no significant effect on UKE. Twenty weeks after stopping cadmium administration, a persistent reduction in UKE was still observed; furthermore, the group which had been previously administered a LD of cadmium, now also exhibited a reduced UKE. During this re-examination period in both groups, the UKE reductions were associated with normal systolic blood pressure, glycosuria, natriuresis. Our data show that cadmium administration can influence UKE, plasma renin activity, plasma aldosterone concentration and electrolyte excretion without inducing any variation of blood pressure. This may reflect a nephrotoxic, non-hypertensive effect. Since this effect persisted after stopping cadmium administration, it may indicate a prolonged irreversible nephrotoxic effect at the distal nephron level. Thus, UKE may be a useful non-invasive index to evaluate distal nephrotoxicity.

Aldosterone↗

Urinary output modulation of alanine aminopeptidase, gamma-glutamyl transpeptidase and N-acetyl-beta-D-glucosaminidase by castration and testosterone in male normal rat.

The urinary excretion of alanine aminopeptidase (AAP), gamma-glutamyl transpeptidase (gamma-GT) and of N-acetyl-beta-D-glucosaminidase (NAG) was studies in normal and castrated rats receiving either testosterone for 5 post-operative weeks or no hormone. In castrated rats the urinary output of AAP and gamma-GT was significantly lower than in sham control or in castrated rats receiving testosterone. In addition, an excess of exogenously given testosterone had no effect on enzymuria of normal rats. The urinary excretion of NAG was influenced neither by castration nor by testosterone. These results suggest that endogenous testosterone is responsible for a permanent positive control on the urinary excretion of AAP and gamma-GT.

Acetylglucosaminidase↗

Immunofluorescence characterization of light chains in human nephropathies.

Renal tissue from 185 patients with various nephropathies were studied by immunofluorescence, in order to look for the frequency and potential predominance of kappa or lambda light chain glomerular deposits. Four normal renal biopsies were used as controls. An overall study shows that light chains were present in glomeruli in 136 out of 185 cases; kappa light chain deposits were more frequent than lambda light chain deposits (73.5% and 64.3% respectively). An analytical study shows that this was not observed in all nephropathies studied. In mesangial IgA nephropathy, lambda light chain deposits were seen in 81% of cases (29 out of 37) and kappa light chain deposits were observed in 78% (30 out of 37 cases). In lupus nephritis, lambda light chain deposits were present in 13 out of 14 cases (92.8%) whereas kappa light chain deposits were demonstrated in 12 cases (85.7%). In other nephropathies such as membranous, endocapillary proliferative and amyloid nephritis, kappa was the predominant light chain observed in glomeruli or was present in the same number of cases as lambda light chain (mesangiocapillary glomerulonephritis). These findings show that in certain nephritides, for example IgA nephropathy and lupus nephritis, IgA and IgG deposits are mainly composed of lambda light chain in contrast with the normal kappa: lambda ratio in human serum of 2:1.

Basement Membrane↗

Unsuitable value of abdominal fat tissue aspirate examination for the diagnosis of amyloidosis in long-term hemodialysis patients.

Abdominal fat tissue aspiration was used in 22 long-term hemodialysis patients (5-17 years). Fourteen of these patients had carpal tunnel syndrome and amyloid deposits of beta 2-microglobulin in the synovium. One patient had a spontaneous rupture of the spleen with amyloid deposits in spleen vessels. Seven other patients presented carpal tunnel syndrome and/or articular pains, and radiological lytic lesions in bone, strongly suggesting an amyloid origin. As a control group, in 22 patients with biopsy-proven amyloidosis, abdominal fat tissue aspirates were performed and were studied under the same conditions: by light microscopy these tissues were stained with Congo red and examined with a polarizing microscope; these specimens were also studied by electron microscopy. In all hemodialyzed patients, no amyloid deposit was present in fat tissue with Congo red staining and by electron microscopy. On the contrary, amyloid was observed in 17 of 22 cases in other types of amyloidosis. It seems that this method which has been proved to be simple and sensitive for the diagnosis of systemic amyloidosis is not a good marker for the presence of amyloid in long-term hemodialysis patients.

Abdominal Muscles↗

Short lasting increase in urinary specific kallikrein activity during long term administration of furosemide.

Furosemide was administered for seven days to normal rats. Urinary kallikrein excretion showed a biphasic response during the seven consecutive days of study. During the initial three days only the kininogenase activity showed a significant increase without any variation in the excretion of the immunoreactive kallikrein. The specific urinary kininogenase activity was therefore enhanced. After three days of furosemide administration, both the urinary kininogenase activity and urinary immunoreactive kallikrein were augmented. The urinary specific kininogenase activity was that time no more different when compared to the basal value. Considering the delay time of three days, this second part of the response could be a mineralocorticoid mediated effect. In this respect, kidney level of immunoreactive and kininogenase activity of kallikrein are also increased after seven days of furosemide administration. However the short lasting increase in urinary specific kininogenase activity observed during the initial three days is due to a change in the ratio active versus inactive kallikrein without any variation of total kallikrein. It is possible that this immediate response results of a direct effect of furosemide acting either on the preferential excretion of the active form or on the activation of the prokallikrein in the urine.

Animals↗

Compared effects of a low and a high sodium diet on the renal and urinary concentration and activity of kallikrein in normal rats.

Different sodium intakes may affect or alter the urinary excretion of renal kallikrein. We have compared the renal and the urinary effects of sodium depletion and sodium loading with 1% NaCl on total kallikrein, using a direct radio-immunoassay against immunoreactive kallikrein and on active kallikrein assessed by a kininogenase assay with a kinin radio-immunoassay. Sodium depletion resulted in an increase in renal and urinary excretion of both the immunoreactive kallikrein and the kininogenase activity. Sodium loading resulted in a slight but significant decrease in renal tissue immunoreactive kallikrein content without any change in the kininogenase activity, while the urinary excretion of the kininogenase activity was greatly increased and the urinary immunoreactive kallikrein remained steady. This sodium depletion induces consistent effects at the renal and urinary level, resulting probably from a stimulation of biosynthesis. However, during sodium loading, renal and urinary measurements of kallikrein are dissociated. Furthermore, kininogenase activity and immunoreactive kallikrein are not correlated in either of the two studied compartments. Thus sodium loading seems to induce independent effects at the renal and urinary levels, possibly resulting from different mechanisms.

Aldosterone↗

Isolation and characterization of rat kidney alanine aminopeptidase.

Rat alanine aminopeptidase was purified from kidney by isolation of the brush border membrane with CaCl2 followed by differential centrifugation and tryptic proteolysis. It is a glycoprotein with a molecular weight of approximately 210,000 daltons comprising two 110,000-dalton subunits and has an amino acid composition similar to that of the human enzyme. Two zinc atoms are covalently bound to each protein subunit.

Amino Acids↗