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Biomedical subjects

M Fischbach

Publications and source records attributed to M Fischbach.

At least 91 records · Page 5Linked to original sources
PubMed1991

Aldosterone biosynthesis induced by ACTH and angiotensin II in newborn rat adrenocortical cells transfected by c-EJ-Ha-ras oncogene.

Adrenocortical cells were obtained by fractionated trypsination of newborn rat adrenal glands and transfected with a plasmid containing the EJ/T24-Ha-ras oncogene. Isolation of adhesive cells led to a proliferative cell line with an overexpression of 21 kDa ras protein. These cells incubated with corticosterone or deoxycorticosterone as the precursor produced a high level of 18-hydroxycorticosterone and aldosterone as identified by gas chromatography- mass spectrometry. ACTH and angiotensin II increased the basal production of aldosterone nineteen-fold and six-fold respectively. Under ACTH stimulation the ratio between aldosterone and 18-hydroxycorticosterone production was 1:3. The transformation of corticosterone under angiotensin II stimulation yielded up to 41% of 18-hydroxycorticosterone (4.7 micrograms/mg of cell protein per 24h) and 4.4% of aldosterone (0.5 microgram/mg of cell protein per 24h) in a low potassium concentration medium (6 mmol/l). To our knowledge this is the first report of continuous proliferative adrenocortical cells producing aldosterone.

18-Hydroxycorticosterone↗
PubMed1991

Maintenance of liver function in long term culture of hepatocytes following in vitro or in vivo Ha-rasEJ transfection.

Collagenase isolated rat hepatocytes were transfected with liposome encapsulated pEJ (LE-pEJ), a plasmid carrying the human cellular activated Ha-rasEJ oncogene. A proliferative cell line was cloned from these cells transfected in vitro. It secreted per day 0.87 micrograms albumin and 0.32 microgram transferrin per 10(6) cells, and 11.06 nmol free and conjugated bile acids (BA) per mg protein. Also, it metabolized 2-acetylaminofluorene (2-AAF) into N- and ring-hydroxylated metabolites and 2-aminofluorene at rates of 1.50, 9.73, and 1.98 nmol/mg cell protein/24 hr, respectively. Rats were i.v. injected with both LE-pEJ and LE-p17hGHneo carrying the hGH cDNA gene, and secreted hGH in the plasma which induced the synthesis of anti-hGH antibodies. A cell line was cloned from cultures of primary hepatocytes isolated from the liver of transfected rats. After 2 to 3 months in culture, this cell line secreted per day 18.9 micrograms albumin and 11.0 micrograms transferrin per 10(6) cells, 38.75 nmol total BA per mg cell protein, and up to 31 ng hGH per 10(6) cells without cloning hGH recombinant cells. A 24 hr control culture of primary hepatocytes isolated from non transfected rats secreted 25.5 micrograms albumin and 11.7 micrograms transferrin per 10(6) cells, and produced 21.64 nmol total BA and 2.13 nmol N-OH-2-AAF per mg cell protein. Hence, Ha-rasEJ transfection of either hepatocytes in vitro or liver cells in vivo, initiated cell cycles leading to presumptive proliferating hepatocytes which express liver function.

2-Acetylaminofluorene↗
PubMed1991

Cellular retention, toxicity and carcinogenic potential of seafood arsenic. I. Lack of cytotoxicity and transforming activity of arsenobetaine in the BALB/3T3 cell line.

Cytotoxicity, morphological neoplastic transformation, intracellular retention and metabolic behaviour have been investigated in BALB/3T3 Cl A 31-1-1 cells for arsenobetaine, the main form of arsenic in certain seafoods, in comparison to inorganic sodium arsenite. In order to avoid false results, particular attention was paid to the purity, checking for the presence of any trace amounts of inorganic arsenic as well as methylated contaminants in the chemically synthesized arsenobetaine. Cytotoxicity and morphological transformation assays gave obvious positive results for sodium arsenite at a dose exposure of 10 microM. On the other hand, concentrations of arsenobetaine as high as 500 microM failed to induce either cytotoxic effects or neoplastic transformations. The absence of cytotoxicity and transforming potential of arsenobetaine in comparison to inorganic arsenite can be explained by the different degree of retention and the intracellular behaviour of the two arsenic species. Cellular retention of arsenobetaine was dose dependent for exposure concentrations ranging from 1 to 500 microM with a mechanism resembling a simple diffusion (1.4 and 760 pmol of As/10(6) cells were cell associated for the two concentrations at 24 h respectively). About 95% of the intracellular arsenobetaine was present in the cytosol fraction and the attempt to detect any intracellular degradation of the organoarsenic compound failed. Thus, the low retention efficiency of arsenobetaine, its inability to interact with intracellular components and the absence of biotransformation in the cell could explain the lack of cytotoxicity and transforming potential observed in the BALB/3T3 cells. These findings reinforce the view that in humans exposed to different chemical species of arsenic the contribution to the total health risk, including the carcinogenic potential, of arsenobetaine ingested with marine foodstuffs would be negligible.

Animals↗
PubMed1991

Solute equilibration curves, crossing time for urea and glucose during peritoneal dialysis: a function of age in children.

Glucose is absorbed from the dialysate more rapidly in younger than in older children on CAPD leading to a relatively early loss of ultrafiltration during dwell time. In order to assess peritoneal permeability and in term to prescribe optimal management of CAPD, we tested peritoneal equilibration curves (EC) for urea and glucose, especially the crossing time point of these two ECs. Baseline values were obtained from 8 patients divided in two groups by age at start of CAPD: group I (N = 4) mean age 1 year 6 months, mean body weight 8.25 +/- 3.17 kg, group II (N = 4) mean age 12 years 6 months, mean body weight 33.5 +/- 1.5 kg. The crossing time point is earlier in group I (49 +/- 14 min) than in group II (101 +/- 20 min) (p less than 0.001). Followup of each patient, during a mean time of 20 months in group I and 23 months in group II, establishes that the curves crossing time point for each patient remains stable.

Age Factors↗
PubMed1991

[Double profile dialysis: ultrafiltration and sodium variable description and clinical validation in the child].

Despite significant technical improvements (bicarbonate dialysate, volumetric ultrafiltration control) high intradialytic ultrafiltration is troublesome in children, specially in the proportion of patients presenting a normal or low blood pressure even with overweight. We used, in this group of children (overhydratated without vascular repercution) a modelling of both sodium and ultrafiltration during dialysis, in order to achieve dry body weight without increasing session time despite hypotension risks. The usefulness and practicability of sodium and ultrafiltration modelling together during dialysis in children is analysed in a short time study (for plasma volume changes calculation) and in a long term follow up study over a year (for clinical tolerance). Today, we reserve this form of dialysis only for a single session needed by overhydratation (more than 5% of dry body weight) in order to achieve dry body weight maintaining dialysis session time constant without increasing side effects (hypotension).

Blood↗
PubMed1989

Urinary tract infections with tissue penetration in children: cefotaxime compared with amoxycillin/clavulanate.

In children, the site of urinary tract infection (acute pyelonephritis or cystitis) cannot usually be accurately determined from the clinical presentation. The severity of the urinary tract infection (risk of renal scars) is best correlated with its estimated degree of tissue penetration clinically (fever, general condition) and on laboratory tests (sedimentation rate, C-reactive protein). The duration of parenteral antibiotic therapy, especially in children (taking account of difficult venous access and the cost of hospitalization) needs to be specified beyond the initial period required for sterilization of the urine (usually less than 48 h). We conducted a study in children older than one year to compare the efficacy and tolerance of two treatment regimens for urinary tract infection with tissue penetration: cefotaxime 100 mg/kg/d in four divided iv doses for 14 days (group I) and amoxycillin/clavulanate 100 mg/kg/d in four divided iv doses for seven days with conversion to the oral route at a dosage of 50 mg/kg/d for seven days (group II). The randomised protocol included ten patients in each group, comparable with respect to sex, age and history. Clinical efficacy (time until the patient became afebrile), bacteriological efficacy (sterilization of the urine), and biological efficacy (time to normalization of the indices of the acute inflammatory response) were identical for both groups regardless of the duration of iv antibiotic treatment (seven days for amoxycillin/clavulanate; 14 days for cefotaxime). The only side effect was diarrhoea, which affected three patients and did not require modification of the oral treatment regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Amoxicillin↗
PubMed1989

Beta-2-microglobulin in hemodiafiltered children: long-term efficiency follow-up.

Data of beta 2-microglobulin (beta 2M) levels are not well known in hemodialyzed children. We analyzed 28 children, all maintained on thrice weekly hemodiafiltration (HDF) with highly permeable membrane (mean age 8 years 7 months, mean time on dialysis 32 months). beta 2M is significantly elevated: 34 + 8.5 mg/l without differences for sex but correlated to residual urinary volume. The kinetics of beta 2M removal during HDF with different dialysis membranes (polysulfone, polyacrylonitrile), and with the same membrane (polysulfone) used in diffusive (hemodialysis), in convective (hemofiltration) and in diffusive and convective (HDF) modes reveals that polysulfone membranes in HDF mode allow the greatest beta 2M serum level drop over dialysis session time (-60 +/- 12%). Five children, anuric, mean time on dialysis 75 months (65-94), chronically on thrice weekly (3 x 3 h) HDF with first polyacrylonitrile then polysulfone membranes are investigated regarding beta 2M levels and amyloidosis risks. Despite the high removal rate of beta 2M with these dialytic modes, beta 2M serum levels do not decrease during this five-year study. High beta 2M serum extraction seems to be compensated by high beta 2M cell generation. Further investigation is necessary for the explanation of the presumed high beta 2M generation rate in the HDF with polysulfone membranes before recommendation of safe long-term use of such highly permeable membranes for prevention of amyloidosis risks in dialytic patients.

Adolescent↗
PubMed1988

[Renal transplantation in thrombosis of the inferior vena cava. Implantation of the graft vein in the portal vein].

An 8-year old girl with chronic renal failure underwent allogeneic renal transplantation with implantation of the renal vein of the graft on the portal vein, as the inferior vena cava was obstructed by thrombosis. The possible technical obstacles to renal transplantation are reviewed on that occasion, and solutions are suggested. In the presence of thrombosis of the inferior vena cava it seems necessary to determine its level and to look for a patent venous segment all the way up to the diaphragm. If no such segment is found, then the renal vein can be implanted on the portal vein.

Child↗
PubMed1988

Sequential hypertonic haemodialysis in children.

Sequential hypertonic dialysis (SHD) was studied in two binephrectomized children over a period of 6 weeks. Each dialysis session comprised four periods of 45 min. The concentration of sodium in the dialysate [Na(D)] during the first period was 190 mmol/l and during the second period 140 mmol/l. The sequence was then repeated. The sodium-free water clearance [C(ONa)] was calculated from the measurements of the ultrafiltrate clearance and of the sodium clearance. Despite the short periods of hypertonic dialysis, C(ONa) was positive, suggesting that water was removed from the intracellular compartment as well as from the extracellular fluid. The transfer of fluid from the intracellular space improved circulatory stability during rapid removal of large volumes of fluid by ultrafiltration. SHD was also associated with increased removal of potassium and phosphate. Comparison of clinical parameters before and during SHD showed a tendency towards increased sodium balance and the possibility of raised cardiovascular morbidity. SHD stabilized blood volume during ultrafiltration, encouraging removal of uraemic toxins. SHD with this level of Na(D) is only a study dialysis method.

Child↗
PubMed1988

Alterations of serum high-density lipoproteins and hepatic lipase activity in congenital hypothyroidism.

Fourteen term newborns and infants with congenital hypothyroidism were studied before (T0) and after (T1) 1 month of replacement therapy. From T0 to T1 serum total cholesterol and high-density-lipoprotein cholesterol remained constant and at normal levels whereas low-density-lipoprotein apolipoprotein B and triacyglycerol concentrations increased slightly. The proportion of large-size high-density-lipoprotein subfraction was high at T0 and decreased very significantly at T1. Conversely, postheparin serum hepatic lipase activity was low before treatment and increased after thyroxine therapy. Lipoprotein lipase activity remained low throughout the study. These results suggest that, in contrast to adult hypothyroidism, low-density-lipoprotein catabolism is not altered in congenital hypothyroidism. However, as in adults, a defect of lipolytic enzyme activities is present and can induce an impairment of the elimination of cholesterol via the high-density-lipoprotein route and, potentially, of the catabolism of triglyceride-rich lipoproteins. Beyond the scope of congenital hypothyroidism, one should keep in mind these results when attending infants with transient low thyroid hormone levels and lipid intolerance.

Congenital Hypothyroidism↗
PubMed1988

[Urinary infections in children].

Urinary tract infection is frequent in childhood, usually without major consequences. Its diagnosis is often overestimated and needs precise bacteriological and cytological tests; systematic exploration of the urinary tract must be proposed if these tests are positive. The clinical presentation and the incidence of uropathies is strongly related to age. The therapeutic protocol will depend on germ, age, symptoms and results of morphological examinations.

Anti-Bacterial Agents↗
PubMed1988

[Severe theophylline poisoning in children. Value of hemodialysis with high permeability membrane].

The authors report a massive accidental ingestion of enteric-coated theophylline (Armophilline ) by a young child. A status epilepticus and elevated theophylline serum concentration (167 mg/l) led to use hemodialysis with high dialytic clearance. The elevated clearance was obtained by the use of high permeability membrane, by bicarbonate dialysate and the best quality of vascular access (Hickman catheter).

Child, Preschool↗
PubMed1987

Autosomal recessive and dominant forms of polycystic kidney disease are not allelic.

Linkage analysis has been carried out in 11 kindreds with autosomal recessive polycystic kidney disease (ARPKD) using the genetic marker 3'HVR, closely linked (theta = 0.05) to the gene of the autosomal dominant type. Close linkage (theta less than or equal to 0.20) between the locus of the marker and that of ARPKD can be excluded. These data strongly suggest that the loci for the autosomal recessive and dominant forms of polycystic kidney disease are not allelic.

Alleles↗
PubMed1987

[Anti-HLA immunization following transfusions of leukocyte-poor blood].

We have followed the evolution of leucocyte antibodies in patients receiving multiple blood transfusions of leucocyte-poor blood. The number of leucocytes present in one unit of transfused blood was always less than 1 X 10(8). We observed that such preparations were able to re-stimulate antibodies which had disappeared, but especially they were able to provoke a first immunisation in some patients never immunized in the past. The specificities of these antibodies corresponded to one or several antigens present in the donor of the transfused unit. This study shows that leucocyte immunisation cannot always be avoided in spite of the selection of blood products containing very few white cells.

Adolescent↗