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Biomedical subjects

A Bernard

Publications and source records attributed to A Bernard.

At least 325 records · Page 18Linked to original sources

Diet fatty acid composition, age and rat jejunal microvillus enzyme activities.

1. Lactase, sucrase, maltase, trehalase and alkaline phosphatase activities of rat proximal jejunum were measured in 3, 6, 9, 12, 18 and 24-month-old rats fed with diets differing in their fatty acid composition. 2. A drop of 47-53% of the specific enzyme activity was observed with disaccharidases against a decrease of 71% for alkaline phosphatase in the 24-month-old rats compared to the 3-month-old rats. 3. Changes in dietary fatty acid composition, either in the saturated or monounsaturated ratio, or in the polyunsaturated fatty acid composition, did not significantly interfere with this aging effect.

Aging↗

Monitoring of early nephrotoxic effects of industrial chemicals.

Long-term exposure to certain industrial chemicals (e.g. heavy metals, some halogenated hydrocarbons) may cause progressive degenerative changes in the kidney, possibly leading to renal insufficiency. The screening tests most widely used to assess the integrity of the kidney (i.e. serum creatinine or BUN and the quantitative or semi-quantitative measurement of total proteinuria) lack sensitivity; they do not permit the detection of renal disturbances at a stage when removal from exposure may prevent progression of the disease process and are not suitable to determine the no-effect levels of potentially nephrotoxic chemicals. During the last decades new markers have been proposed for the early detection of structural and/or functional changes at various sites of the renal parenchyma. Some tests mainly attempt to assess the integrity of the glomerulus (e.g. high Mr proteinuria such as transferrinuria and albuminuria; increased excretion of some components of the glomerular basement membrane or the mesangium matrix, increased plasma concentration of low Mr proteins such as beta 2-microglobulin and free retinol binding protein), the proximal tubule (e.g. urinary excretion of several low Mr plasma proteins, tubular enzymes and antigens), the loop of Henle and distal tubule (e.g. excretion of various prostanoids). Currently, the majority of these tests are of limited value at the individual level because their health significance, even when they are persistently abnormal, has not yet been sufficiently studied. In workers exposed to Cd, however, it has been shown that a persistent low Mr proteinuria is predictive of an exacerbation of the age-related decline of the GFR; this biological change should be considered as an adverse effect. Currently, the principal application of these tests lies in the framework of epidemiologic studies designed to assess permissible exposure levels to nephrotoxic pollutants. The study of dose-effects/response relationships based on a large battery of renal markers has allowed the better determination of the internal dose of Cd, which is not associated with significant renal risk.

Animals↗

Administration modalities and intestinal lymph absorption of arachidonic acid in rats.

We investigated the effects of the proportion of arachidonic acid on lymph lipoprotein synthesis in rats, when infused in the presence of lipids with varying degrees of saturation. A single dose of 90 mumol of lipid was administered intraduodenally and intestinal lymph was collected. Emulsion lipid constituents were 90 mumol of [14C]arachidonic acid alone, or either 30 mumol of [14C]arachidonic acid or 5 mumol of [14C]arachidonic acid and 25 mumol of linoleic acid, with 30 mumol of a free fatty acid and 30 mumol of a monoglyceride (the more saturated: oleic acid + monopalmitin; the more unsaturated: linoleic acid + monoolein). Radioactive lymph recovery of [14C]arachidonic acid infused alone reached 32.6 +/- 1.3% of the radioactivity administered and the presence of another fatty acid and a monoglyceride increased it from 38.7 +/- 2.6 to 51.9 +/- 1.1%. For 30 mumol of arachidonic acid, integration into lymph phospholipids was higher when arachidonic acid was infused with oleic acid and monopalmitin than with linoleic acid and monoolein (7.3 +/- 2.7 and 2.8 +/- 0.2% at the absorption peaks, respectively), and it was 4.8 +/- 0.5% when arachidonic acid was infused alone. For 5 mumol of arachidonic acid, the degree of unsaturation of the added lipid did not modify phospholipid incorporation, which was maintained at 6.9 to 7.2%. The proportion and size of chylomicrons increased with the degree of lipid emulsion unsaturation. Percentages of [14C]phospholipids and of chylomicrons were highly correlated. The proportion of arachidonic acid and degree of lipid emulsion unsaturation affected lymphatic arachidonic acid absorption modalities.

Animals↗

Fertilization and embryonic development of human oocytes after cooling.

Injury to living cells resulting from rapid cooling to temperatures at or near 0 degrees C has long been recognized, and the phenomenon, which is termed 'cold shock', has been known to occur in some mammalian gametes. Although human embryos have been successfully stored at low temperatures, cryopreservation of the human oocyte is proving to be more difficult. Whether or not this lack of success is a direct result of cellular injury brought about by 'cold shock' is the purpose of the current investigation. Human oocytes were cooled, in the absence of cryoprotectants, at two different cooling rates (-3 degrees C/min and -1000+ degrees C/min) to a temperature of 0 degrees C and rewarmed prior to insemination. In both cases fertilization after cooling was similar to the rates achieved in a routine in-vitro fertilization and embryo transfer procedure. After cooling at -3 degrees C/min, the rate of fertilization was 19/22 (86%) and after cooling at -1000+ degrees C/min, 9/9 (100%), with non-cooled control rates of 62/87 (71%) and 35/50 (70%) respectively. Fertilized oocytes from both groups were successfully cultured for a further 24 h before termination of the experiment.

Cryopreservation↗

The distribution of the CDW52 molecule on blood cells and characterization of its involvement in T cell activation.

The O97 mouse mAb was used to define, together with the CAMPATH-1 mAb series, the CDw52 in the course of the Fourth International Workshop on Human Leucocyte Differentiation Antigens. O97 and CAMPATH-1M produce full competitive inhibition and react with an epitope dependent on O-linked sugar residues. The two mAb, however, display significant differences in reactivity with leukocyte populations--in fact the reactivity of O97, which also exerts a powerful cytotoxic effect with human C', is similar to mAb from the CAM-PATH-1 series having the broadest one. Noteworthy, O97 spares PBL, NK, and LAK precursors, permitting an easy purification of these cells; O97 is able to kill long-term colony-forming cells in bone marrow culture and characteristically reacts, in contrast to CAMPATH-1M, with erythrocytes. Western blotting has revealed a strikingly different molecular size on red cells, since CDw52 mAb revealed a broad band ranging from 6-16 kDa, instead of the 21-28 kDa revealed from leukocyte extracts. In agreement with immunofluorescence data, O97 revealed abundant material from red cells in Western blotting, while reactivity of CAMPATH-1M was very faint. Overall, these results show that distinct molecular forms of the CDw52 molecules are present on different blood cells. We have also characterized an activation signal that can be delivered to T cells via the CDw52 molecule by CAMPATH-1M but not by O97. This is an accessory signal that can complement a primary activation signal delivered via the CD2 pathway but not via the CD3-TcR pathway. This is similar to the effects obtained with the CD45R (2H4) mAb, 2H4 and CAMPATH-1M mAb having additive effects on T cell activation via CD2.

Antibodies, Monoclonal↗

Construction of vaccinia virus recombinants expressing several measles virus proteins and analysis of their efficacy in vaccination of mice.

Measles virus genes encoding the haemagglutinin (HA), fusion protein (F) or nucleoprotein (NP) have been inserted into the vaccinia virus genome either alone or in various combinations. In each case the measles virus genes were expressed from the 7.5K promoter and were incorporated into the thymidine kinase (tk) or K1L loci of the Copenhagen strain of vaccinia virus. Cells infected by the recombinants synthesized measles virus proteins indistinguishable from those induced in measles virus-infected cells. However, in some instances the level of expression in cells infected by recombinants expressing more than one measles virus gene was reduced when compared to those encoding a single gene. The sera from mice immunized with recombinants containing either HA, HA.F, HA.NP or HA.F.NP had similar levels of measles virus neutralizing antibodies which remained constant throughout a 7 month period. Analysis of these sera by immunoprecipitation of radiolabelled measles virus confirmed the presence of specific antibody to each of the antigens where appropriate. The introduction of the measles virus genes into the K1L and the tk sites despite attenuating the virus for mice by 10-fold and 1000-fold respectively did not affect the vaccination efficiency, i.e. ability to induce measles virus antibody and protect mice. Vaccination of BALB/c (H2d) mice with HA and F, but not NP, recombinants completely protected the animals against a lethal measles virus challenge. In contrast, although the HA recombinant protected CBA (H2k) mice, the F recombinant did so poorly. However, by immunizing CBA mice with a recombinant expressing both F and NP, protection was increased to more than 75%. Our findings demonstrate the ability of three measles virus antigens expressed from the vaccinia virus genome alone or in combination to contribute to protective immunity against measles virus infection of mice. They also suggest that the association of measles virus antigens in a single recombinant DNA vaccine could be beneficial to overcome host-related restriction of the immune response to particular antigens.

Animals↗

Comparison of nephrotoxicities of different polyoxyethyleneglycol formulations of amphotericin B in rats.

The aim of the present study was to assess whether amphotericin B (AmB)-Myrj 59, AmB-polyoxyethyleneglycol 24 cholesterol (PC), and AmB-Synperonic A50 (SA50) were less nephrotoxic than AmB-deoxycholate (DC). Rats were treated with the different AmB formulations (10 mg/kg of body weight) intraperitoneally or with the surfactants alone. A group of control rats receiving the vehicle was also examined. After 6 days of daily intraperitoneal injections of AmB-DC, decreased body weight and glomerular filtration rate as well as increased degree of diuresis, uremia, microalbuminuria, and N-acetyl-beta-D-glucosaminidase excretion in urine were noted. Urinary excretion of potassium and sodium was also decreased in AmB-DC-treated rats. Most of these effects were more pronounced with AmB-PC and AmB-SA50. In contrast, AmB-Myrj 59 was less nephrotoxic than AmB-DC. Indeed, after 6 days of treatment with AmB-Myrj 59, the natriuria, kaliuria, albuminuria, and glomerular filtration rates were unchanged compared with those of controls. Moreover, the body weight loss and uremia increase of the rats treated by AmB-Myrj 59 were less than those of the rats treated with the commercial preparation. Among the surfactants, only PC was toxic for the rats. The intrinsic toxicity of PC and the higher systemic exposure to AmB could contribute to increased toxicities of AmB-PC and AmB-SA50, respectively. AmB-Myrj 59 was less nephrotoxic than AmB-DC at equivalent areas under the plasma concentration-time curves. These preliminary results suggest that this formulation could be a good alternative to the commercial product.

Amphotericin B↗

Charge-dependent renal uptake of beta 2-microglobulin in conscious rats.

The influence of molecular charge on the tubular reabsorption of proteins was studied in conscious rats injected intravenously with beta 2-microglobulins of different isoelectric points (pI). Native human beta 2-microglobulin (pI 5.8), two anionized (pI 4.85 and 5.55) and three cationized derivatives (pI 7.2, 8.35 and 8.7) were used. The six forms of beta 2-microglobulin had a molecular radius between 15.7 and 15.9 A. The renal uptake was estimated by measuring the amount excreted in urine with a sensitive immunoassay. The ability of rat kidney to reabsorb beta 2-microglobulin was clearly related to the net charge of the protein. Increasing the pI of the protein significantly reduced the urinary excretion, whereas lowering it had the opposite effect. Anionization was particularly effective in reducing the beta 2-microglobulin uptake, since a decrease of the pI of one unit enhanced the urinary output by two orders of magnitude. This charge-dependency persisted when the tubular reabsorption of proteins was partly inhibited by lysozyme. By contrast, it was practically abolished by lysine, probably because the inhibitory effect of this amino acid on protein tubular reabsorption is not competitive. The administration of ammonium chloride in rats produced an immediate and transient elevation of rat beta 2-microglobulinuria. This phenomenon, which was partly inhibited by the subsequent administration of sodium bicarbonate, presumably results from a competition between the NH4+ ion and beta 2-microglobulin for tubular binding sites. These data support the hypothesis that proteins bind to the luminal membrane of tubular cells mainly via positively charged amino groups.

Acidosis↗

Selective increase in the urinary excretion of protein 1 (Clara cell protein) and other low molecular weight proteins during normal pregnancy.

The effect of normal pregnancy on the tubular transport of proteins has been studied by measuring four low molecular weight (Mr) proteins in the urine of pregnant women: protein 1 (a recently discovered urinary protein identical to Clara cell protein), beta 2-microglobulin, retinol-binding protein and alpha 1-microglobulin. The urinary excretion of albumin and beta-N-acetylglucosaminidase was also determined. One hundred and fourteen women with uncomplicated pregnancy were examined: 22 in the first trimester, 42 in the second and 50 in the third trimester. They were compared to 40 age-matched non-pregnant women. The urinary excretion of the four low Mr proteins was significantly increased during the second and third trimester of pregnancy. During the last trimester, the mean relative increases in the urinary excretion of these proteins ranged from 2.8 to 15.6 and prevalences of elevated values from 25 to 46%. This rise in low Mr urinary protein excretion was particularly important in some pregnant women, representing (e.g. for protein 1) more than a 100-fold increase above normal. The urinary excretion of beta-N-acetyl-D-glucosaminidase was also increased during pregnancy but the albuminuria remained stable. These changes in low Mr urinary proteins were reversible after delivery and most likely resulted from a transient decrease in the reabsorptive capacity of the proximal tubule associated with an increase of the filtered load. However, some women excreted high amounts of protein 1 which could not be accounted for by a decreased tubular reabsorption and which might originate from a secretion by the urogenital tract.

Acetylglucosaminidase↗

Lack of renal changes in stainless steel welders exposed to chromium and nickel.

Biochemical markers of kidney damage were examined in 52 male stainless steel welders (manual metal arc welding) exposed to chromium and nickel. No difference was found in the mean urinary excretion of total proteins, albumin, protein 1, transferrin, retinol-binding protein, lactate dehydrogenase, lysozyme, or beta-N-acetylglucosaminidase in a comparison with matched referents. Beta 2-microglobulin was slightly increased in those welders with a urinary chromium concentration of greater than 64.5 nmol.mmol-1 creatinine. The prevalences of abnormal values did not differ from those observed in the reference group. No correlation was found between the concentrations of chromium or nickel in urine and that of proteins or enzymes. No consistent or clinically significant renal impairment was revealed among the stainless steel welders exposed to a chromium air concentration slightly above the current threshold limit value of the American Conference of Governmental Industrial Hygienists for water-soluble hexavalent chromium compounds (50 micrograms.m-3).

Acute Kidney Injury↗

[Cystic tumor of the mediastinum of digestive origin. Apropos of a new case. Diagnostic and pathogenic hypotheses].

An incidental discovery of a posterior and inferior mediastinal cyst-like opacity allowed us to diagnose a pulmonary sequestration in a 45-year old woman. The operative findings showed an hour-glass tumor of the inferior mediastinum with an abdominal prolongation attached by a stalk onto the top of the stomach. These findings made us change our diagnosis in favour of an abdomino-thoracic gastric duplication. This new hypothesis was not confirmed by the results of the pathological report which revealed two kinds of tissue; intestinal in the abdomen and broncho-pulmonary in the chest. Two diagnoses where then proposed: complex hamartoma or mediastinal bronchogenic cyst. The pathogenic interpretation in such cases is still very controversial. English authors are prone to classify them as broncho-pulmonary foregut malformations. Macroscopic and microscopic data of the specimen led us to consider our case-report to be a foregut malformation.

Angiography↗

Cadmium and health: the Belgian experience.

Studies in the 1970s on chronic cadmium poisoning in man in Belgium showed that the earliest effect was renal dysfunction with proteinuria. Subsequent studies were focused on the characterization of cadmium proteinuria, the diagnosis and prognosis of cadmium nephropathy and the assessment of the concentrations in urine and renal cortex leading to its occurrence. Chronic exposure to cadmium in industry gives rise to a proteinuria which may be tubular, glomerular or mixed in character. This proteinuria may be accompanied or preceded by a variety of other renal effects. In active male workers, three main groups of thresholds for urinary cadmium have been identified for the induction of these effects with corresponding thresholds in the renal cortex. However, these estimates probably cannot be extrapolated to the general population exposed to cadmium mainly by the oral route. The results of a large-scale cross-sectional study (Cadmibel) suggest that subclinical changes in tubular function may occur in the general population above a threshold of urinary cadmium as low as 2 micrograms/24h.

Belgium↗

Effects of cadmium exposure on the cardiovascular system and on calcium metabolism: results of a cross-sectional population study.

This paper summarizes the findings of the Cadmibel Study, a cross-sectional population study of the health effects of cadmium, but only with respect to the cardiovascular system and calcium metabolism. The study disproved the hypothesis that exposure to cadmium would lead to an increase in blood pressure and in the prevalence of hypertension and other cardiovascular diseases. On the other hand, there was a positive relationship between urinary cadmium (Cd-U) and both serum alkaline phosphatase activity and urinary excretion of calcium. The regression coefficients obtained after adjustment for significant co-variates indicated that, when Cd-U increased two-fold, serum alkaline phosphatase and urinary calcium rose by 4% and 0.25 mmol/24 h, respectively. These findings suggest that calcium metabolism is gradually affected as cadmium accumulates in the body. The morbidity associated with the latter phenomenon is still unknown, and requires further investigation, preferably in a longitudinal prospective population study, in which the incidence of morbid events would be monitored in relation to the cadmium body burden.

Adult↗

Assessment of the causality of the cadmium--protein relationships in the urine of the general population with reference to the Cadmibel study.

The assessment of acceptable exposure levels to cadmium in the work or general environment frequently relies on the analysis of the relationships between urinary cadmium (an indicator of the body burden) and proteins used as markers of nephrotoxicity. A possibility which cannot be excluded a priori is that the relationships between cadmium and proteins in urine might sometimes result from renal dysfunction unrelated to cadmium toxicity. To test this hypothesis, we have measured cadmium in the urine of 114 pregnant women of whom about 20% had developed a reversible tubular proteinuria. Cadmium excretion was correlated significantly with age but not with duration of pregnancy nor with low molecular weight urinary proteins. This indicates that tubular dysfunction unrelated to cadmium exposure does not necessarily increase cadmium excretion. Hence, these data support the conclusion of the recent Cadmibel Study on the renal tubular effects of cadmium on the general population of Belgium.

Acetylglucosaminidase↗

[Preoperative evaluation of respiratory function in thoracic surgery. Do reliable predictive criteria exist in that type of surgery?].

A cautions analysis of the respiratory preoperative study may decrease morbidity and mortality after pulmonary surgery. To search for predictive criteria of respiratory complications following this kind of surgery, 454 patients have been studied retrospectively. Morbidity was defined as the need for postoperative ventilation. Preoperative criteria were divided in clinical (age, obesity, history of pulmonary disease, dyspnea, score of Karnofsky), laboratory (blood gases, spirometry) and surgical (kind of procedure). Three criteria were significant for morbidity (15 ventilated patients) and mortality (27 deaths): age (> 65 years), obesity, hypocapnia (pCO2 < 4.1 kPa-31 mmHg). Analysed spirometric values were no significant.

Age Factors↗

Adrenocortical carcinoma in surgically treated patients: a retrospective study on 156 cases by the French Association of Endocrine Surgery.

BACKGROUND: Because of the rarity of adrenocortical carcinoma, survival rates and prognosis for patients who have undergone operation are not well known. The purpose of the French Association of Endocrine Surgery was to evaluate these factors in all patients treated during a 12-year period by its members. METHODS: One hundred fifty-six patients (95 women, 61 men) with a mean age of 47 years were included. Functional symptoms were found in 52% of patients, and hormonal studies revealed secreting tumors in 62% of cases. Ninety-four percent of the patients underwent resection of the adrenal tumor, and 20% of them had extensive resection because of invasive cancers. Complete resection was achieved in 127 patients (81%) and incomplete resection in 29 patients. Mean tumor weight was 714 gm (range, 12 to 4750 gm), and the mean diameter was 12 cm (range, 3 to 30 cm). The results of the tumor staging were stage I, eight patients (5%); stage II (local disease), 75 patients (48%); stage III (locoregional disease), 39 patients (25%); and stage IV (metastases), 34 patients (22%). RESULTS: The 5-year actuarial survival rates were 34% overall, 42% in curative group, 53% in local cancer group, 24% in regional disease group, and 27% in the reoperated group. One-year actuarial survival rate of the palliative group was 9% (median survival, 6 months). Multivariate analysis showed that better prognosis occurred in patients younger than 35 years of age (p = 0.01) and in patients with androgen-secreting tumors, precursor-secreting tumors, or nonsecreting tumors (p = 0.003). Mitotane improved the survival rate only in patients with metastases who received it after operation (vs non-mitotane-treated patients [p < 0.05]). CONCLUSIONS: In this study age, extent of disease, aspect of the surgical resection, and type of hormonal secretion influenced survival.

Adrenal Cortex Neoplasms↗

[Postoperative morbidity and mortality of infectious complications of colonic diverticulosis: multifactorial study].

The objective of this study was to determine parameters influencing the mortality due to postoperative adverse events, by taking into account surgical techniques and many other perioperative parameters. From 1967 to 1989, 83 patients were operated for pericolic abscess (level 1, n = 22), pelvic abscess (level 2, n = 38) purulent peritonitis (level 3, n = 16) and fecal peritonitis (level 4, n = 7). Surgical techniques were: first colostomy with drainage (n = 21), first resection without immediate anastomosis (n = 34), and first resection with immediate anastomosis (n = 28). The overall complications were 51% (n = 42) with a mortality of 28% (n = 23). During univariate analysis, variables linked to postoperative complications were neurologic events (p < 0.0001), cirrhosis (p = 0.01), current treatment by steroids (p = 0.007), infectious level (p = 0.002), first colostomy (p = 0.005) and first resection with anastomosis (p = 0.007). Postoperative mortality was linked with neurologic events (p < 0.0001), age (p = 0.005), infectious level (p = 0.04), first colostomy (p = 0.005), and first resection with anastomosis (p = 0.0012). Logistic regression determined 3 independent variables influencing complications: neurologic events (p < 0.0001), first colostomy (p = 0.01), and infectious level (p = 0.002). The mortality determined by multivariate analysis was dependent on 3 variables: neurologic events (p < 0.0001) first colostomy (p = 0.007) and age (p = 0.01). The adjusted relative risk was 17 for neurologic events and 6 for first colostomy.

Abscess↗