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Biomedical subjects

C Bauer

Publications and source records attributed to C Bauer.

At least 253 records · Page 14Linked to original sources

Regulation of erythropoietin production is related to proximal tubular function.

Regulation of renal erythropoietin (EPO) production is based on an intrarenal oxygen sensor. Whereas the sensitivity of this oxygen sensor to variations in renal oxygen supply is well established, the influence of changes in renal oxygen consumption has not yet been elucidated. Diuretic drugs, which inhibit active sodium reabsorption, reduce tubular oxygen consumption. We therefore investigated the effects of acetazolamide, furosemide, hydrochlorothiazide, and amiloride, known to preferentially inhibit sodium reabsorption at different segments of the nephron, on hypoxia-induced EPO formation in mice. Those drugs that are considered to act mainly in the loop of Henle, distal tubule, and collecting duct (furosemide, hydrochlorothiazide, and amiloride) did not impair EPO formation. Acetazolamide on the other hand, which is thought to act predominantly at the proximal tubular site, significantly reduced EPO formation in response to normobaric hypoxia (8 and 14% O2) and functional anemia (0.1% carbon monoxide). This inhibitory effect of acetazolamide was dose dependent and correlated with the natriuresis induced. It appeared not to depend on the metabolic acidosis induced by the drug, since the simultaneous administration of sodium bicarbonate, which restored standard bicarbonate levels to normal, did not diminish the inhibitory effect of acetazolamide on EPO production. In conclusion the data suggest that the regulation of EPO production is likely to be related to proximal tubular function.

Animals↗

Rate of erythropoietin formation in humans in response to acute hypobaric hypoxia.

This study was carried out to investigate the early changes in erythropoietin (EPO) formation in humans in response to hypoxia. Six volunteers were exposed to simulated altitudes of 3,000 and 4,000 m in a decompression chamber for 5.5 h. EPO was measured by radioimmunoassay in serum samples withdrawn every 30 min during altitude exposure and also in two subjects after termination of hypoxia (4,000 m). EPO levels during hypoxia were significantly elevated after 114 and 84 min (3,000 and 4,000 m), rising thereafter continuously for the period investigated. Mean values increased from 16.0 to 22.5 mU/ml (3,000 m) and from 16.7 to 28.0 mU/ml (4,000 m). This rise in EPO levels corresponds to 1.8-fold (3,000 m) and 3.0-fold (4,000 m) increases in the calculated production rate of the hormone. After termination of hypoxia, EPO levels continued to rise for approximately 1.5 h and after 3 h declined exponentially with an average half-life time of 5.2 h.

Adult↗

[Regulation of erythropoietin synthesis].

The main regulatory hormone for the control of erythropoiesis is erythropoietin (EPO). This glycoprotein has a molecular weight of 34,000 daltons, about 40% of which is represented by carbohydrates. EPO leads to an enhanced mitosis and differentiation of erythroid precursors (colony-forming unit erythroid) in the bone marrow by binding to specific receptors. The major stimulus for EPO formation in the kidney is hypoxia. The tubular parts that are intimately involved in this O2-sensing mechanism are the proximal tubular cells as can be inferred from the use of site-specific transport inhibitors. The minimal time necessary for a hypoxic signal to induce EPO formation was found to be 30 min, including wash out of oxygen stores, activation of the EPO gene and equilibration of the EPO distribution space. About 1.5 h after the onset of hypoxia, EPO mRNA was found to accumulate in the kidney, thus pointing toward the possibility of an oxygen-regulated transcription or oxygen-dependent regulation of the stability of EPO mRNA. Possibly, a decrease in the intracellular calcium concentration is involved in this signalling process.

Animals↗

[Erythropoiesis and serum erythropoietin concentrations before and after kidney allotransplantation].

Hematological parameters and serum erythropoietin (EPO) levels were measured before and sequentially after grafting in 50 consecutive cadaver renal transplant recipients. EPO was estimated using a sensitive radioimmunoassay. Values for nonanemic controls were 15-25 mU/ml. Mean hematological values before transplantation were as follows: hemoglobin 9.7 +/- 2.4 g/dl; hematocrit 29 +/- 8%; corrected reticulocytes count 15 +/- 8% and EPO 29 +/- 23 (11-131) mU/ml. In the entire studied population, 35 patients had inadequate low EPO levels for their degree of anemia. In the whole population, there was a significant positive exponential correlation between EPO and hematocrit (r = 0.31; p less than 0.05). In the subset of patients with underlying cystic kidney disease and in hemodialysis patients treated with recombinant human EPO, hemoglobin, hematocrit and EPO levels were higher when compared to hemodialysis or CAPD patients with other kidney diseases. Following successful renal transplantation, EPO increased to 45 +/- 31 mU/ml at 1 month and then decreased to 25 +/- 18, 18 +/- 7 and 19 +/- 4 mU/ml at 3,6 and 9 months, respectively. Within the 1st month after transplantation there was a 4-fold increase in reticulocytes from 9 +/- 5 to 38 +/- 14%, followed by a slow decrease over the next several months to 23 +/- 11% at 9 months. In contrast, the hematocrit level rose more gradually from 28 +/- 7 to 44 +/- 6% at 9 months. In 25 of 36 patients with a functioning graft who were followed for more than 6 months, anemia was corrected and 11 patients remained slightly anemic with a mean hematocrit level of 36 +/- 4%.

Erythropoiesis↗

Insulin-like growth factor I increase glomerular filtration rate and renal plasma flow in man.

Recombinant IGF-I was infused seal at a dose of 20 micrograms-kg 1-h 1 to 2 healthy subjects during a total of 79 h. Serum levels of IGF-I rose from 93 and 177 to 502 and 616 micrograms/l, respectively. Fasting blood glucose remained normal. During the infusion glomerular filtration rate increased by 31%, in subject No. 1 and by 32% in subject No.2. Concomitantly, renal plasma flow increased by 26% and 22%, respectively. Proximal and distal tubular reabsorption of fluid and sodium as determined by lithium clearance was elevated to a similar extent. When determined again one week after the end of the IGF-I infusion, all parameters of renal function had returned to baseline. Sodium excretion, body weight and blood pressure did not change. We conclude that IGF-I infused at pharmacological doses has marked effects on kidney function. Future studies will necessary to define the clinical potential of recombinant IGF-I in the treatment of diseases characterized by impaired renal perfusion and filtration.

Adult↗

[Critical aspects in determining total radioactivity of biological samples].

During measurements of radioactivity in some milk samples with liquid scintillation counter (about one year after the nuclear accident of Chernobyl) we have observed an increase of the values of scintillation fluid with the passing of time. Although this enhancement is absolutely small (about 2 c.p.m. in 500 min), it is very important for an exact measurement of samples at low counting, as those tested. Our protocol of measure provides for insertion of alternate blanks and samples in the automatic sample-holders of liquid scintillation counter. The values of measurement of samples are taken during the increase phase subtracting the value of blank interpolated on the increasing straight line from c.p.m. of sample. Finally, we report the collected values of the whole radioactivity in some milk samples: at least 5-6 nCi/L contrary to about 1 nCi/L of 137Cs reported by USL. In our opinion it is important to consider the whole radioactivity as measure of the overall biological danger of radioactive samples. In fact, this measurement takes into account also biologically very dangerous radionuclides as 3H, 14C, 90Sr.

Animals↗

Evaluation of the stability of human erythropoietin in samples for radioimmunoassay.

Radioimmunoassays for erythropoietin are limited so far to a few specialized laboratories and this requires transport and storage of samples. We therefore tested the stability of immunoreactive erythropoietin in serum and plasma samples obtained from a uremic and a nonuremic anemic patient. No significant change in the concentration of immunoreactive erythropoietin was found in either serum or plasma samples for up to 14 days of storage. This type of stability was observed no matter whether the samples were stored at room temperature, 4 degrees C, or -20 degrees C. There was no difference between the estimates of erythropoietin in serum and heparinized plasma. Validity of the radioimmunoassay used in this study was demonstrated by parallelism of dilution curves of test specimens and the 2nd International Reference Preparation for erythropoietin and by a close correlation between the immunoreactivity and the bioactivity of the hormone, as assessed in the same samples by the exhypoxic polycythemic mouse bioassay. In conclusion the data obtained clearly indicate that the necessity of storage and transport of clinical samples does not limit the practicability of the radioimmunoassay for erythropoietin.

Anemia, Aplastic↗

Cerebrospinal fluid antibodies to myelin basic protein in acute idiopathic optic neuritis.

Free and bound levels of anti-myelin basic protein (anti-MBP) antibodies were measured by radioimmunoassay in the cerebrospinal fluid of 20 patients with acute idiopathic optic neuritis, 133 patients with multiple sclerosis (MS) divided into three clinical subgroups, and 76 normal control subjects. Patients with idiopathic optic neuritis had elevated levels of anti-MBP predominantly in free form, resulting in an elevated (above unity) free/bound anti-MBP ratio similar to that of MS patients with acute relapses. These data suggest that acute idiopathic optic neuritis, like active MS, is associated with anti-MBP.

Autoantibodies↗

Expression of a cloned beta-glucanase gene from Bacillus amyloliquefaciens in an Escherichia coli relA strain after plasmid amplification.

Amino acid starvation of cells of the Escherichia coli relA strain, CP79, which cannot accumulate guanosine tetraphosphate (ppGpp) in response to amino acid limitation, increased the pEG1 plasmid content about 5- to 7-fold in comparison with exponentially growing cells (pEG1:pBR322 with an insertion of Bacillus amyloliquefaciens DNA coding for beta-glucanase). In contrast, no pEG1 amplification occurred in E. coli CP78, the stringently controlled counterpart, after amino acid starvation. In order to verify these results, the plasmid DNA content was monitored by measuring the expression of pEG1-encoded beta-glucanase from B. amyloliquefaciens both before and after plasmid amplification. When amino acid starved CP79 cells were given an additional dose of amino acids, a more than 10-fold increase in pEG1-encoded beta-glucanase activity (per cell mass) was measured. This increase in enzyme activity correlates with pEG1 amplification during amino acid limitation. Under comparable conditions the activity of beta-glucanase was not increased in strain CP78, which did not amplify the plasmid. We suggest that the replication of pEG1 in amino acid starved E. coli cells is somehow under negative control by ppGpp. Moreover, we found the Bacillus beta-glucanase in E. coli relA cells to be excreted into the growth medium after starvation and overexpression.

Amino Acids↗

Besnoitia besnoiti: studies on the definitive host and experimental infections in cattle.

Domestic cats, 11 other species of carnivorous mammals, 6 species of snakes, and white-backed vultures were tested for their possible role as definitive hosts of Benoitia besnoiti by feeding with cystic material from chronically infected bovines. None of the species tested is a definitive host; hence, the life cycle of this parasite remains obscure. In attempts to produce clinical cases of besnoitiosis by experimental infection, bovines were inoculated IV, SC, and IP with cystozoites or tachyzoites. Immunosuppression of the animals was essential for the development of severe cases and skin lesions; cystozoites proved to be more pathogenic than tachyzoites.

Animals↗

In vivo induction of gliadin-mediated enterocyte damage in rats by the mannosidase inhibitor, swainsonine: a possible animal model for celiac disease.

Simultaneous feeding of gliadin and swainsonine, an inhibitor of alpha-D-mannosidases, in rats disturbed enterocytic maturation as shown by a marked loss of activities of alkaline phosphatase and gamma-glutamyltransferase. Morphologically, simultaneous treatment with gliadin and swainsonine caused destruction and decreased density of microvilli, as shown by electron microscopy. Neither gliadin nor swainsonine when given alone had significant effects on enterocytic enzyme activities or enterocytic morphology. Binding of enterocytic glycoproteins to both gliadin-Sepharose and concanavalin A-Sepharose was significantly increased in rats treated with swainsonine. Because swainsonine causes the formation of hybrid-type oligosaccharides with a high binding affinity to mannose-specific lectins, the observed alterations of enterocytic maturation and morphology are presumably caused by the increased binding of gliadin to enterocytic glycoproteins. A possible analogy in the etiology of celiac disease is discussed.

Alkaline Phosphatase↗

EDTA affects cytochrome P450-dependent biotransformation reactions during incubations for the liver microsomal assay.

In order to optimize the condition of the liver microsomal assay (LMA), studies were carried out to determine the effects of EDTA on mixed-function oxidase activity and its stability under the exact incubation conditions for the LMA. Aminopyrine N-demethylase (APD) and p-nitroanisole O-demethylase (p-NAD) activities as well as lipid peroxidation development (LP) in S9 liver fractions from beta-naphthoflavone and sodium phenobarbital (beta-NF + PB)- or Aroclor 1254 (AC)-treated mice were examined during a period of preincubation with EDTA ranging from 1 to 40 mM. At 5 mM EDTA, we obtained a strong inhibition of the microsomal LP as well as the greatest value of the mean specific activity (Asp) for both APD and pNAD activities. In agreement with the biochemical data, the presence of 5 mM EDTA in the incubation mixtures for the LMA significantly increased the mitotic gene conversion, mitotic crossing-over and point-reverse mutation of the well-known premutagen cyclophosphamide (30 mM) on the diploid D7 strain of Saccharomyces cerevisiae as the outcome of a greater metabolic activity. We concluded that the systematic use of 5 mM EDTA in LMA mixtures could improve the reliability and sensitivity of such a test.

Aminopyrine N-Demethylase↗

Prevalence of Eimeria leuckarti (Flesch, 1883) and intensity of faecal oocyst output in a herd of horses during a summer grazing season.

The prevalence of Eimeria leuckarti infection and the intensity of faecal oocyst output were determined in a herd of 14 mares and their foals in northwest Germany using a sedimentation technique at weekly intervals during a summer grazing season from May to September. None of the mares, but all foals shed oocysts on at least one occasion. The patent periods lasted up to 16 weeks. The mean intensity of oocyst output (0.1-33 o.p.g.) was very low. No clinical signs of gastrointestinal disorder were noticed in any of the foals during this study.

Animals↗