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Biomedical subjects

A M Bernard

Publications and source records attributed to A M Bernard.

At least 19 recordsLinked to original sources
PubMed1992

Nephropathies and exposure to perchloroethylene in dry-cleaners.

Even in specific risk groups, the relation between exposure to organic solvents and chronic renal diseases remains controversial. Thus, in a collaborative European study, we assessed the renal effects of occupational exposure to perchloroethylene (PCE) in dry-cleaners compared with matched controls who were simultaneously examined. Single high and low molecular weight proteins, kidney-derived antigens and enzymes, and prostanoids were measured in urine. beta 2-microglobulin, creatinine, laminin fragments, and anti-glomerular basement membrane antibodies were also measured in serum. A canonical function based on 23 such variables correctly classified 93% of individuals as either PCE-exposed or controls; with 13 markers, group membership was identified in 87% of subjects. Increased high molecular weight protein in urine was frequently (17/50 vs 1/50, p less than 0.0001) associated with tubular alterations. Changes were consistent with diffuse abnormalities along the nephron in workers exposed to low levels of PCE (median 15 parts per million). Generalised membrane disturbances might account for the increased release of laminin fragments, fibronectin, and glycosaminoglycans, for high molecular weight proteinuria, and for the increased shedding of epithelial membrane components from tubular cells with different location along the nephron (brush-border antigens and Tamm-Horsfall glycoprotein). These findings of early renal changes indicate that solvent-exposed subjects, especially dry-cleaners, need to be monitored for the possible development of chronic renal diseases.

Adolescent↗
PubMed1992

cDNA cloning for mouse thymocyte-activating molecule. A multifunctional ecto-dipeptidyl peptidase IV (CD26) included in a subgroup of serine proteases.

Thymocyte-activating molecule (THAM) was initially characterized as a developmentally regulated, dimeric cell-surface molecule capable of activating mouse thymocytes and T lymphocytes upon monoclonal antibody (mAb)-mediated cross-linking. We recently obtained structural evidence indicating that this molecule is the mouse homologue of the human T cell-activating ectoenzyme CD26 (dipeptidyl peptidase IV, DPP IV). We describe here the cloning and the characterization of THAM cDNA. Two clones (3.3 and 2.8 kilobases) were isolated. THAM-3.3 cDNA contains an open reading frame of 2,280 nucleotides that encodes a protein of 760 amino acids having a calculated size of 87,500 Da. Complete N-glycosylation at each of the nine potential sites would result in a mature 110,000-Da molecule. Protein sequence comparisons revealed a significant homology (in particular in the COOH-terminal domain) between THAM and the rat or human DPP IV or the yeast dipeptidyl aminopeptidase B molecules (92, 85, and 30% sequence identity, respectively). Structural comparison of serine proteases (i.e. acyl-amino acid hydrolase or prolyl endopeptidase) with the most conserved domain of THAM identified a stretch of 200 amino acids containing a putative catalytic triad arranged in a novel topological order (Ser-624, Asp-702, and His-734) thereby defining a subfamily of nonclassical serine proteases. Expression of THAM during thymus ontogeny was found to be mainly regulated at the transcriptional level as determined by RNase protection assay. To investigate directly some of the functions which have been ascribed to DPP IV, we transfected an ovalbumin/Aq-reactive, THAM- T hybridoma cell line with THAM-3.3 cDNA. The resultant transfectants acquired (i) DPP IV enzymatic activity that precisely paralleled the density of surface-expressed THAM; (ii) an Mr = 115,000 (reduced) and 110,000/128,000 (nonreduced) molecule that could be immunoprecipitated by the THAM-specific mAb H194-112; and (iii) the capacity of being triggered by this mAb to release interleukin-2. These data indicate that a single cDNA species can encode a multifunctional molecule (e.g. activation signal-transducing structure and ectopeptidase), the heterodimeric state of which very likely results from a differential post-translational modification of the same protein core.

Amino Acid Sequence↗
PubMed1992

Renal effects of in utero exposure to mercuric chloride in rats.

The transplacental nephrotoxicity of mercuric chloride has been studied in female Sprague-Dawley rats. Mercuric chloride was injected s.c. to rats at the dose of 1 mg/kg during the last 8 gestational days or the whole pregnancy. Both mothers and newborns developed a transient renal dysfunction resulting in an increased urinary excretion of beta 2-microglobulin and albumin. In mothers and their female offspring, these effects were completely reversible and did not influence the subsequent evolution of the renal function. In the male offspring, however, transitory changes in protein excretion were again observed a few months later, concomitantly with an enhanced accumulation of alpha 2u-globulin in the kidney. The transfer of mercury from maternal to fetal tissues was very small. The kidney concentrations of mercury in newborns were more than 300 times lower than in mothers. The barrier role of the placenta is not sufficient to prevent the occurrence of renal effects in the offspring of rats treated with inorganic mercury during pregnancy.

Alpha-Globulins↗
PubMed1992

Soluble protein constituents of the domestic fowl's eggshell.

1. The protein components of the domestic fowl's eggshell are believed to influence appreciably the mechanical properties of the shell and/or its biomineralisation. The purpose of this study was to compare the protein species composing the eggshell matrix in different parts of the shell structure, by SDS-PAGE and chromatography, utilising eggshell cleaned by different methodologies. 2. Protein species were identified whose absence was associated with the removal of the mammillary knobs. In particular, a prominent 81 kDa protein, as well as 38 and 54 kDa calcium-binding proteins, were concentrated within the mammillary layer, as was a 129 kDa insoluble protein. By contrast, soluble proteins of 54, 33, 22, and 14 kDa were enriched in the palisade layer. 3. Our results demonstrate that the mineralised layers of the fowl's eggshell possess a complex array of distinct proteins. The different proteins which have been detected in the mammillary and palisade layers may be related to the distinct crystallisation patterns of calcium carbonate in these zones of the eggshell.

Animals↗
PubMed1992

Intestinal-type alkaline phosphatase in urine as an indicator of mercury induced effects on the S3 segment of the proximal tubule.

Intestinal-type alkaline phosphatase (IAP) is a specific and sensitive marker for alterations of the S3 segment of the human proximal tubule, the preferred part for several nephrotoxins. We studied IAP and other renal parameters in mercury-exposed workers and their controls. IAP excretion is clearly increased in the exposed workers, compared to other parameters, indicating that the determination of this enzyme can be a useful screening test of renal effects in occupational mercury exposure.

Acetylglucosaminidase↗
PubMed1992

APACHE-L: a new severity of illness adjuster for inpatient medical care.

A principal concern regarding Medicare's diagnosis-related group (DRG)-based prospective payment system is whether hospitals caring for more severely ill patients may be undercompensated for the services they provide. Research on possible inequities in hospital payment has been hampered by the absence of an objective, easily obtained, and valid measure of patients' severity of illness. Because laboratory data are objective and computerized in most of our nation's hospitals, a system utilizing such data, if shown to discriminate between patients of differing expected resource use, could prove most helpful in examining possible inequities in prospective payment system hospital payment. At a major teaching hospital, data were used from length of stay inlier patients in the 10 most frequent medical DRGs in the U.S. to develop and evaluate a severity of illness system called APACHE-L. APACHE-L uses the laboratory component of the original APACHE score. Whereas DRGs explained 20% of the variation in length of stay for the top ten DRGs, APACHE-L explained up to an additional 14% of the variation. For ancillary resource use, DRGs explained 10% of the variance, and APACHE-L explained up to an additional 15%. Diagnosis-related group-specific analyses demonstrated that the amount of resource use variance explained by APACHE-L varied widely depending on the DRG (from R2 = .00 for DRG 410, chemotherapy; to R2 = .38 for DRG 320, kidney and urinary tract infections, age greater than 17 years with complications or comorbidities). The APACHE-L score, which is objective and readily available in our nation's hospitals, shows considerable promise as a severity of illness adjuster for a subset of DRGs.

Age Factors↗
PubMed1991

Evidence that thymocyte-activating molecule is mouse CD26 (dipeptidyl peptidase IV).

We previously described a developmentally regulated, Mr 115,000 (reduced) and 110,000/128,000 (nonreduced) mouse T cell-activating molecule (THAM) also expressed on a variety of epithelial cell surfaces, and associated with neutral exoaminopeptidase activity. In the present study, we show that THAM is the mouse counterpart of the human T cell-activating ectoenzyme CD26 (dipeptidyl peptidase IV, DPP IV) and that highly purified THAM lacks neutral exoaminopeptidase activity. This conclusion is based on the following: 1) the N-terminal segments of the THAM Mr 110,000 and 128,000 components shared the same amino acid sequence with the rat DPP IV. These N-termini comprised a short intracytoplasmic tail of six residues followed by a downstream hydrophobic transmembrane segment. 2) THAM-specific mAb H194-112-Affi-Gel immunoadsorbent was capable of removing DPP IV enzymatic activity from mouse thymoma cell detergent extracts. 3) H194-112 reactivity pattern on developing thymocytes was found to parallel that previously reported for membrane-bound DPP IV enzymatic activity. The extent of THAM N-glycosylation, as measured by N-glycanase treatment of H194-112 immunoprecipitates, was found to be similar to that of human and rat DPP IV (i.e., approximately 20 kDa). Cross-linking experiments indicated that THAM was expressed at the cell surface as a dimer of approximately 220 kDa. Its two subunits were found to be structurally related but not identical as shown by their different Mr under nonreducing conditions and by their slightly distinct peptide profiles after proteolytic cleavage. We conclude from these data that DPP IV, in addition to its extracellular matrix receptor and ectoenzymatic functions, is a T cell-activating structure in both human and mouse species.

Amino Acid Sequence↗
PubMed1991

Urinary excretion of proteins and enzymes in workers exposed to hydrocarbons in a shoe factory.

A cross-sectional study was conducted to determine whether exposure to hydrocarbons in a shoe factory may produce renal effects that can be detected by determination of the urinary excretion of proteins and enzymes. The study population included 59 women who had been exposed to petroleum naphtha and toluene and 24 age-matched control women. The time-weighted average exposure to petroleum naphtha, toluene and ethylacetate was 1,619,81 and 160 mg/m3, respectively. The integrity of the renal structures or functions was assessed by measuring the urinary excretion of total protein, beta 2-microglobulin, retinol-binding protein, albumin, transferrin, lysozyme, lactate dehydrogenase and beta-N-acetylglucosaminidase (NAG). The only parameter that was significantly influenced by hydrocarbon exposure was the urinary activity of beta-N-acetylglucosaminidase. Although the health significance of this renal change, which was not accompanied by changes in the urinary excretion of low- or high-molecular-weight proteins, is unclear, the results of the present study are in agreement with our previous observations suggesting that long-term moderate exposure to solvents does not entail a significant risk for the development of nephrotoxicity.

Acetates↗
PubMed1991

Disturbance of sialic acid metabolism by chronic cadmium exposure and its relation to proteinuria.

In workers exposed to Cd (8 years on the average), we have found a significant decrease of sialic acid in erythrocyte membranes (22.61 +/- 1.84 vs 25.80 +/- 3.01 micrograms/mg of protein in controls, p less than 0.05) and an increase of sialic acid concentration in both urine (276.7 +/- 132.3 vs 174.5 +/- 70.9 micrograms/g of creatinine, p less than 0.05) and plasma (761.8 +/- 83.5 vs 640.4 +/- 70.7 micrograms/ml, p less than 0.01). In rats exposed to Cd (100 ppm in drinking water for 5.5 months), we have observed a reduction of the sialic acid level in erythrocyte membranes (31.4 +/- 1.2 vs 33.4 +/- 1.1 micrograms/mg of protein, p less than 0.01) and glomeruli (12.5 +/- 1.3 vs 13.9 +/- 1.6 micrograms/mg of protein, p less than 0.05). These effects in Cd treated rats were accompanied by a loss of the glomerular barrier selectively as reflected by an increased urinary output of albumin and transferrin. After 10 months of Cd exposure, the albuminuria and transferrinuria were negatively correlated with the sialic acid content of glomerular membranes (r = -0.47 and -0.51, p less than 0.05), which suggests that the depletion of sialic acid is involved in the loss of glomerular barrier function induced by long term Cd exposure. In Cd-treated rats, sialidase activity was enhanced in kidney cortex and in serum but not in glomeruli.

Adult↗
PubMed1991

Assessment of the filtration reserve capacity of the kidney in workers exposed to cadmium.

It has been assessed whether an internal dose of cadmium (Cd), as reflected by a Cd concentration in urine not yet sufficient to induce a significantly increased urinary excretion of various plasma proteins (microproteinuria defined as beta 2-microglobulin in urine greater than 300 micrograms/g creatinine, or retinol-binding protein in urine greater than 300 micrograms/g creatinine, or albumin in urine greater than 15 mg/g creatinine, or a combination of these), may affect the filtration reserve capacity of the kidney. The last was determined by measuring the difference between the baseline creatinine clearance and the maximal creatinine clearance after an acute oral load of protein (400 g of cooked red meat). In total 215 men were examined of whom eventually 87 Cd exposed workers (concentration of Cd in urine greater than 2 micrograms/g creatinine) from zinc/cadmium smelters and 92 control workers (concentration of Cd in urine less than 2 micrograms/g creatinine, absence of microproteinuria, normal fasting serum creatinine) were retained for data analysis performed separately for workers aged less or more than 50 years. Microproteinuria was present in 20 Cd workers, all older than 50. This study confirmed the previous observation that the age related decline of the baseline glomerular filtration rate (GFR) is accelerated in male workers with Cd induced microproteinuria; the same observation was made for the maximal GFR. It was found, however, that a renal Cd burden that had not yet caused microproteinuria did not impair the filtration reserve capacity of the kidney. This study therefore validates the previous estimate of the threshold effect concentration of Cd in urine (10 micrograms/g creatinine) that is intended to prevent the occurrence of microproteinuria in male Cd workers. It should be kept in mind, however, that because of the likely interference of the healthy worker effect, this conclusion may not be directly extrapolated to the general population.

Adult↗
PubMed1991

Regular source of ambulatory care and access to health services.

BACKGROUND: To examine why people lack a regular source of ambulatory care (RSAC) and explore whether this commonly used access measure accurately identifies population subgroups at risk for barriers to continuity care. METHODS: Using data from a 1986 national telephone survey, we performed a content analysis of subjects' verbatim reports as to why they lacked an RSAC (n = 5,748). RESULTS: The 16.4 percent of respondents who lacked an RSAC gave the following reasons: 1) financial problems, 8 percent; 2) local resource inaccessibility, 5 percent; 3) not wanting a regular source of ambulatory care, 61 percent; and 4) transitory loss of their regular source of ambulatory care, 18 percent. However, some sociodemographic subgroups reported substantially more problems with access barriers, and these disparities were often not detected by the global measure, RSAC. The poor were not more likely than the non-poor to lack an RSAC (odds ratio [OR] = 0.8; 95% confidence interval, [0.6, 1.1]), but were much more likely to lack an RSAC for financial reasons (OR = 5.2 [2.6, 10.6]). Similarly, rural respondents were not more likely than urban dwellers to lack an RSAC, but were more likely to lack an RSAC because of local resource inaccessibility (OR = 5.8 [2.8, 11.9]). CONCLUSIONS: We conclude that the global measure, RSAC, is not an accurate indicator of whether population subgroups have access barriers to obtaining a source of continuity care.

Adolescent↗
PubMed1990

An integrated inpatient management model.

The academic health center has emerged as the cornerstone of the American health care system. To assess the vulnerability of the academic medical center to the new competitive forces that exist today, a prototype project has been developed that attempts to address the issue of competition in clinical activity, while at the same time enhancing the academic health center's education and research roles.

Academic Medical Centers↗
PubMed1990

Urinary kallikrein activity in workers exposed to cadmium, lead, or mercury vapour.

A significant reduction of kallikrein activity in urine (assayed by its amidolytic activity) was found in 64 normotensive workers who had been exposed to cadmium for 11 years on average and whose cadmium concentrations in urine ranged from 2.2 to 33.1 micrograms/g creatinine. The mean (geometric) urinary kallikrein activity (in U/g creatinine) amounted to 0.52 (range 0.11-1.90) in the control group (n = 193) against 0.39 (range 0.10-1.03) in the cadmium group, and the prevalence of abnormally low activity levels (less than or equal to 0.20 U/g creatinine) amounted to 17.2% in the cadmium group against 5.2% in the control group. A reduction of aldosterone release (aldosterone in urine) associated with an increased natriuresis was also observed. This might constitute a compensatory mechanism maintaining blood pressure in the normal range. These biological effects of cadmium were not reversible after removal from exposure. This study indicates that cadmium can induce an irreversible toxic effect in the distal nephron. It also suggests that an excessive cadmium body burden alone may not be sufficient to induce hypertension, but in individuals whose blood pressure regulation may be impaired by other factors cadmium could stimulate the development of hypertension. This study also supports the recommendation to prevent hypertensive subjects from being exposed to cadmium. There was no indication that moderate exposure to mercury vapour (n = 53; mercury in urine, range 11-224 micrograms/g creatinine; average duration of exposure: six years) or to inorganic lead (n = 23; lead in blood, range 40-67 micrograms/100 ml; average duration of exposure: eight years) was associated with a reduction of kallikrein production by the kidney.

Adult↗
PubMed1990

Assessment of urinary protein 1 and transferrin as early markers of cadmium nephrotoxicity.

Transferrin and protein 1, a sex linked alpha 2-microprotein, were assayed in urine from 58 workers exposed to cadmium (Cd) in a non-ferrous smelter and from 58 age matched referents. These two new markers of nephrotoxicity were compared with urinary beta 2-microglobulin (beta 2-m), retinol binding protein (RBP), albumin, and beta-N-acetyl-glucosaminidase (NAG). The response of protein 1 to Cd tubulotoxicity was similar to that of beta 2-m, RBP, and NAG. In Cd workers, protein 1 had a correlation with urinary Cd (r = 0.56) similar to beta 2-m (r = 0.48), RBP (r = 0.58), and NAG (r = 0.49). Values of these three low molecular weight proteins and of NAG were increased only in workers with urinary Cd higher than 10 micrograms/g creatinine. Urinary transferrin and albumin were similarly affected by exposure to Cd. Their response, however, was clearly more sensitive than that of low molecular weight proteins. Prevalences of positive values of these two high molecular weight proteins were not only higher but also tended to rise at lower concentrations of Cd in urine or blood. This finding suggests that in some subjects subtle defects in glomerular barrier function may precede the onset of proximal tubular impairment after chronic exposure to Cd. It remains to be assessed whether these subjects are more at risk of developing renal insufficiency.

Acetylglucosaminidase↗
PubMed1990

Estradiol dependence of the specific mammary tissue targeting of polyoma virus oncogenicity in nude mice.

We have previously reported (Berebbi et al., 1988) that in athymic nude mice, Polyoma virus induces mammary adenocarcinomas (MAC) at high frequency and exclusively in females. In the present study we show that in nude mice: (1) Ovariectomy results in a reduced frequency of MAC and a longer latency period of induction. When testosterone is administered to ovariectomized females, tumor induction is drastically reduced. (2) When estradiol is administered continuously to ovariectomized females the incidence and kinetics of MAC induction are the same as in control females. (3) MAC are induced in castrated males administered with estradiol although only osteosarcomas are observed in control males. (4) The tumor cells are found to harbor functional estradiol and progesterone receptors. (5) MAC can be transplanted from females to males, indicating that tumor growth is estradiol independent. (6) Estradiol is required only between day 10 and day 20 following polyoma injection, whereas the first tumors are detected only around day 60. Our results indicate that MAC induction by Polyoma virus in nude mice is estradiol-dependent during a short initiation period and that tumor progression is estradiol-independent in spite of the fact tumor cells carry functional estradiol and progesterone receptors.

Animals↗
PubMed1990

[The association of acute polyradiculoneuritis, transitory diabetes insipidus and pregnancy. Apropos of a case and review of the literature].

This is the first report of the association of transitory diabetes insipidus with acute infective polyneuritis (landry Guillain-Barre Syndrome) occurring in pregnancy. The authors try to establish the inter-relationship between each pathological condition and pregnancy. Polyneuritis in its severe form does not seem to increase the risk of prematurity significantly. The severe forms of more generalised neurological condition as compared with the more limited condition has been noted in the literature but it is not possible to state how pregnancy effects the outcome. Plasma exchange procedures are now possible in pregnant women and the benefits of this treatment have been illustrated in severe forms of polyneuritis. There is difficulty still in selecting what criteria are sufficient to start on a therapy that is not without risk. Finally, the association between transitory diabetes insipidus and pregnancy has been reviewed in the literature and a description is given of the many physiopathological mechanisms associated with it. Diabetes insipidus is rarely found in pregnancy. All authors describe a placental factor with these troubles. The most recent theories suggest that prostaglandins and placental vasopressin are implicated. Treatment is suggested and consists of DDAVP (deamino 8-d-arginine vasopressin), which seems to be the most effective. Close collaboration between the obstetrician, the recovery services and the paediatrician is necessary to get the best results for this very severe pathological condition occurring in pregnancy.

Adult↗