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Biomedical subjects

J L Bernheim

Publications and source records attributed to J L Bernheim.

At least 19 recordsLinked to original sources
PubMed1993

Effect of timing of antihypertensive therapy on glomerular injury: comparison between captopril and diltiazem.

Recent studies have suggested that the progression of experimental chronic renal disease may be prevented by early use of antihypertensive drugs. It is unclear, however, whether such therapies may also affect established and progressive renal disease. In the present study we compared the effects of captopril (CEI) and diltiazem (CCB), started either at week 10 or at week 24 on the evolution of adriamycin nephropathy (AN). Rats were studied at weeks 7, 16, 24, 32, and 38 of the disease. None of the treatments influenced the development of nephrotic range proteinuria. The use of CCB from week 10 was even associated with increased proteinuria. The moderate hypertension of ADR rats was reduced to the same degree with both drugs. Inulin clearance (GFR) was significantly reduced in all ADR rats. However, in ADR rats treated with CEI from week 10 and in those treated with CCB from week 24, the GFR was relatively higher. Glomerular injury, evaluated by semiquantitative methods, was not ameliorated by CEI treatment. Earlier CCB treatment (week 10) worsened glomerular lesions, whilst CCB treatment initiated at week 24 reduced significantly the degree of mesangial expansion and focal glomerular sclerosis. We conclude that, in addition to their common antihypertensive action, the specific effect of drug therapy seems to be crucially time dependent.

Animals↗
PubMed1988

The role of fluorinated pyrimidine analogues in the induction of the in vitro expression of the fragile X chromosome.

The modes of action of 5-fluoro-2'-deoxyuridine (FdUrd) and 5-fluoro-2'-deoxycytidine (FdCyd) were studied in PHA-stimulated lymphocytes from normal volunteer donors and a fragile X patient. In both cell types, FdUrd and FdCyd inhibited cell proliferation at concentrations of 3 x 10(-8) M. Thymidylate synthetase was identified as the decisive target for the action of both FdUrd and FdCyd, as judged from the following observations: First, addition of thymidine to the culture medium was able to counteract both FdUrd and FdCyd toxicities, whereas addition of dCyd had no observable effect. Second, inhibition of the in situ thymidylate synthetase activity measured as an increase in the level of [3H]-dThd incorporation coincided with the inhibition of cell proliferation. Third, the inhibition of the thymidylate synthetase-dependent incorporation of [3H]-dUrd into newly synthesized DNA coincided with the inhibition of cell proliferation. The effects of FdUrd and FdCyd on the in vitro expression of fragile site Xq27 of fragile X chromosomes was shown to be based on the depletion of the intracellular pool of thymidine-5'-monophosphate (dTMP), as judged from the following observations: First, both the FdUrd- and FdCyd-dependent induction of site Xq27 coincided with the antiproliferative effects of the respective fluoropyrimidines. Second, addition of thymidine (dThd) to the culture medium both prevented the expression of site Xq27 and neutralized the cytotoxicity of FdUrd and of FdCyd. On the basis of these findings, we provide further evidence for the concept that the fragile X site is located in an AT-rich region.

Base Composition↗
PubMed1986

[Evaluation of the quality of life during treatment].

Biomedical advances to further the quality of life (QL) of cancer patients must nowadays be complemented by psycho-social evaluation and intervention. The challenge is to quantify the qualitative and to objectivate the subjective. To evaluate QL during treatment of individual patients, open interviews are unsurpassed. However, to measure QL of patient groups, questionnaires are necessary. Some examples from the QL literature illustrate the main drawbacks of questionnaires: lack of sensitivity, specificity, and iterative applicability. To circumvent these problems, it is suggested to add a global self-assessment of QL to questionnaires. Such an instrument, Anamnestic Comparative Self-Assessment is briefly described.

Humans↗
PubMed1985

Reversible renal failure due to psychogenic urinary retention.

A case of advanced, reversible renal failure due to psychogenic urinary retention occurring in a 17 year old female, is reported. The diagnosis of psychogenic urinary retention was made on the basis of existent florid psychopathology and the concomitant exclusion of an organic cause. Family psychodynamics are discussed. Psychosocial intervention led to a resumption of normal micturition, the disappearance of the urinary retention with resultant improvement of renal function.

Acute Kidney Injury↗
PubMed1984

5-fluorouracil and 5-fluoro-2'-deoxyuridine follow different metabolic pathways in the induction of cell lethality in L1210 leukaemia.

The mode of action of 5-fluorouracil (FUra) and 5-fluoro-2'-deoxyuridine (FdUrd) on L1210 leukaemia has been studied. It is shown that FUra and FdUrd follow different routes of metabolism and have different targets with respect to their cytotoxic activity. FUra is converted to 5-fluorouridine-5'triphosphate ( FUTP ), which is incorporated into nascent RNA. FdUrd is converted to 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), which inhibits the de novo synthesis of 2'-deoxythymidine-5'-monophosphate (dTMP). Conversion of FUra to FdUMP does occur, but this phenomenon does not contribute to the final cytotoxic effect. No conversion of FdUrd to FUra has been detected.

Animals↗
PubMed1984

In vitro assessment of cytotoxic agents in murine cancers: comparison between antiproliferative and antimetabolic assays.

Different methods were compared for the in vitro evaluation of the therapeutic effects of the antineoplastic agents doxorubicin, cisplatin, fluorouracil, and vinblastine sulfate in a model system of murine tumor cell lines consisting of L1210 leukemia, P815 mast cell leukemia, and B16 melanoma. Excellent correlations were found with the in vivo effects with the use of a soft agar clonogenic assay, irrespective of the method of growth assessment (i.e., visual colony counting or incorporation of tritiated thymidine in proliferating colonies). Drug effects on the proliferation of tumor cell lines in liquid medium frequently led to an overestimation or underestimation of the actual in vivo effects. Direct incorporation of the radiolabeled precursors thymidine, uridine, and leucine after pretreatment with drugs always led to the prediction of resistance and was therefore considered unreliable.

Animals↗
PubMed1983

Rate of DNA synthesis in exponentially growing cell lines in the presence and absence of antimetabolites.

Experimental tumor cell lines were used to show that in the presence of 5-fluorodeoxyuridine (FdUrd), the rate of DNA synthesis remains unaltered as long as a saturating concentration of thymidine is present. This unimpeded rate of DNA synthesis in combination with FdUrd-blocked de novo thymidylate synthesis makes it possible to accurately measure the total rate of increase of DNA using tritiated thymidine of known specific activity. The observed amount of incorporated tritiated thymidine is in excellent agreement with the calculated theoretical maximal incorporation in cultures with exponentially increasing DNA and cell number.

Antimetabolites↗
PubMed1983

Parathyroid hormone secretion and responsiveness to parathyroid hormone in primary hypomagnesemia.

Parathyroid function was studied in two infant sisters with primary hypomagnesemia while they were both hypomagnesemic and hypocalcemic. In one of the infants, plasma immunoreactive parathyroid hormone (iPTH) was elevated, the calcemic response to exogenous parathyroid hormone (PTH) was absent, and the phosphaturic response was normal. Restoration of serum magnesium with i.v. magnesium corrected the hypocalcemia, with no further rise of plasma iPTH. In the other infant, plasma iPTH was undetectable, and exogenous PTH produced both phosphaturic and calcemic responses. Normalization of serum magnesium with i.v. magnesium resulted in a prompt release of endogenous PTH and correction of the hypocalcemia. These findings suggest that, in the first patient, hypocalcemia was associated with lack of response of the bone to both endogenous and exogenous PTH, while in the second patient, hypocalcemia was associated with inhibition of PTH release and a normal calcemic response to exogenous PTH. The factors that determine whether magnesium deficiency will result in inhibition of PTH release, in a lack of response of the bone to endogenous and exogenous PTH, or both, remain to be clarified.

Female↗
PubMed1980

Minimal-change nephropathy and malignant thymoma.

A 56-year-old man had fever, precordial pain, and a mediastinal mass. The mass disappeared two months later and the patient remained asymptomatic for 2 1/2 years. At that time a full-blown nephrotic syndrome developed, with minimal-change glomerulopathy. The chest x-ray film showed the reappearance of a giant mediastinal mass. On biopsy of the mass, malignant thymoma was diagnosed. Association between minimal-change disease and Hodgkin's disease is well known, while the association with malignant thymoma has not been previously reported. The relationship between malignant thymoma and minimal-change disease is discussed, and a possible pathogenic mechanism involving cell-mediated immunity is proposed.

Humans↗
PubMed1979

[Leiomyoma of the small bowel with hypercalcaemia: presence of a substance with parathormone activity (author's transl)].

A leiomyoma of the small bowel produced laboratory features of hyperparathyroidism which disappeared promptly after tumour resection. Hypercalcaemia, hypophosphatemia, hyperchloremia, elevated chloride/phosphorus ratio, increased urinary cyclic AMP, and blood levels of immunoreactive parathormone were present. Electron microscopy showed dense round granules in the tumour cells.

Aged↗