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Biomedical subjects

C Bauer

Publications and source records attributed to C Bauer.

At least 19 recordsLinked to original sources
PubMed1992

Inhibitory effect of zinc on stimulated erythropoietin synthesis in HepG2 cells.

The effect of zinc on erythropoietin (EPO) synthesis in HepG2 cells was investigated. The increase in EPO synthesis induced by Co2+ (50 microM), Ni2+ (300 microM) or oxygen (1% O2) was inhibited by the presence of ZnCl2 (50-150 microM) in the tissue-culture medium, whereas basal EPO synthesis was unaffected. The effect was reflected by corresponding changes in the EPO mRNA level. These effects of zinc on EPO synthesis could not be mimicked by CdCl2 (less than or equal to 2 microM). Addition of FeCl3 to the medium appeared to decrease the inhibitory effect of zinc on hypoxia-induced EPO synthesis, implying that zinc may interfere with an iron-dependent step in EPO regulation.

Blotting, Northern↗
PubMed1992

Intracellular distribution of endothelin-1 receptors in rat liver cells.

We studied the binding of (125I)-endothelin-1 as well as that of the vasopressin analogue (125I)-[8-phenylpropionyl]-LVP to purified plasma membranes, Golgi cisternae and cell nuclei from rat liver. Cell organelles were isolated by differential centrifugation and discontinuous sucrose gradients. Endothelin-1 exhibited specific binding to plasma membranes, Golgi cisternae and nuclei, while the binding of (125I)-[8-phenylpropionyl]-LVP was restricted to the plasma membranes. The number of receptors (Bmax) and the binding constants (Kd) were determined by Scatchard analysis of competition binding studies. In all cases only one class of Et-1 binding sites could be detected. The presence of Et-1 receptors on the Golgi complex either indicates that the receptor is glycosylated within the cisternae or alternatively, there exists a recycling pathway. The unexpected finding of Et-1 receptors on highly purified nuclei suggests that this peptide may exert part of its biological functions intracellularly via the nucleus.

Animals↗
PubMed1992

Inhibition of N-acetylglucosamine kinase and N-acetylmannosamine kinase by 3-O-methyl-N-acetyl-D-glucosamine in vitro.

During the search for inhibitors of N-acetylneuraminic acid biosynthesis, it was shown that 3-O-methyl-N-acetylglucosamine competitively inhibits the N-acetylglucosamine kinase of rat liver in vitro with a Ki value of 17 microM. N-Acetylmannosamine kinase is inhibited non-competitively with a Ki value of 80 microM. In a human hepatoma cell line (HepG2), 3-O-methyl-N-acetyl-D-glucosamine (1 mM) inhibits the incorporation of 14C-N-acetylglucosamine and 14C-N-acetylmannosamine into cellular glycoproteins by 88% and 70%, respectively.

Acetylglucosamine↗
PubMed1992

Inhibition of the biosynthesis of N-acetylneuraminic acid by metal ions and selenium in vitro.

In liver homogenate the biosynthesis of N-acetylneuraminic acid using N-acetylglucosamine as precursor can be followed stepwise by applying different chromatographic procedures. In this cell-free system 16 metal ions (Zn2+, Mn2+, La3+, Co2+, Cu2+, Hg2+, VO3-, Pb2+, Ce3+, Cd2+, Fe2+, Fe3+, Al3+, Sn2+, Cs+ and Li+) and the selenium compounds, selenium(IV) oxide and sodium selenite, have been checked with respect to their ability to influence a single or possibly several steps of the biosynthesis of N-acetylneuraminic acid. It could be shown that the following enzymes are sensitive to these metal ions (usually applied at a concentration of 1 mmol l-1): N-acetylglucosamine kinase (inhibited by Zn2+ and vandate), UDP-N-acetylglucosamine-2'-epimerase (inhibited by Zn2+, Co2+, Cu2+, Hg2+, VO3-, Pb2+, Cd2+, Fe3+, Cs+, Li+, selenium(IV) oxide and selenite), and N-acetylmannosamine kinase (inhibited by Zn2+, Cu2+, Cd2+ and Co2+). Dose dependent measurements have shown that Zn2+, Cu2+ and selenite are more efficient inhibitors of UDP-N-acetylglucosamine-2'-epimerase than vanadate. As for the N-acetylmannosamine kinase inhibition, a decreasing inhibitory effect exists in the following order Zn2+, Cd2+, Co2+ and Cu2+. In contrast, La3+, Al3+ and Mn2+ (1 mmol l-1) did not interfere with the biosynthesis of N-acetylneuraminic acid. Thus, the conclusion that the inhibitory effect of the metal ions investigated cannot be regarded as simply unspecific is justified.

Acetylglucosamine↗
PubMed1992

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) methods for the detection of anthelmintic resistance in nematodes of veterinary importance.

Methods have been described to assist in the detection of anthelmintic resistance in strongylid nematodes of ruminants, horses and pigs. Two tests are recommended, an in vivo test, the faecal egg count reduction test for use in infected animals, and an in vitro test, the egg hatch test for detection of benzimidazole resistance in nematodes that hatch shortly after embryonation. Anaerobic storage for submission of faecal samples from the field for use in the in vitro test is of value and the procedure is described. The tests should enable comparable data to be obtained in surveys in all parts of the world.

Animals↗
PubMed1992

Isolation of plasma membranes from keratinocytes: a newly developed method allows the sensitive detection of the membrane antigen pattern in normal and psoriatic skin.

Distinct differences of proteins in the plasma membranes have been described in psoriatic keratinocytes as compared with normal epidermis. These changes are presumably involved in the pathogenesis of psoriasis. To identify and distinguish glycosylated proteins of the plasma membranes of keratinocytes, a method for mild preparation was developed that avoids the use of degrading or digestive enzymes. After cell lysis, three steps of centrifugation were performed, including the use of a sucrose step gradient. A fine-vesicular membrane fraction was obtained. Using marker enzymes for cell compartments, no contamination of cell nuclei or mitochondria and only 0.4% of endoplasmic reticulum was detectable in the final membrane fraction. Based on this preparation, disc-polyacrylamide-gel electrophoresis, followed by Western blotting, were performed. Staining with five different lectins to visualize glycosylated proteins allowed 75 different membrane glycoproteins to be distinguished. The patterns of normal, transformed (HaCaT), foreskin and psoriatic keratinocytes after cell culture with one passage were compared. Up to six proteins per lectin staining were expressed differently in psoriatic as compared to normal keratinocytes. Psoriatic cells shared similarities with highly proliferative foreskin cells, but not with transformed HaCaT cells. Main alterations of glycosylation were detected in the fucose content. In conclusion, the method developed for isolation of plasma membranes allows selective and sensitive examination of plasma membranes of normal and pathological keratinocytes. The glycosylation patterns observed suggest that distinct membrane proteins may be involved in the pathogenesis of psoriasis.

Antigens, Surface↗
PubMed1992

Insulin-like growth factors decrease oxygen-regulated erythropoietin production by human hepatoma cells (Hep G2).

We examined the effects of insulin-like growth factors (IGFs) and insulin on erythropoietin (EPO) production by human hepatoma cells (Hep G2). Compared with normoxia (20% O2), EPO production by Hep G2 cells during a 72-h incubation was stimulated fivefold by exposure to low oxygen tension (1% O2) and nearly threefold by exposure to cobalt chloride (100 microM). IGF-I caused a concentration-dependent attenuation of EPO formation under normoxic conditions and inhibited (maximally 50%) EPO production stimulated by either low oxygen tension or cobalt [half-maximal effect (ED50) approximately 5 nM]. The increase of EPO mRNA levels in response to hypoxia was significantly reduced by IGF-I. Similarly to IGF-I, IGF-II (ED50 approximately 8 nM) and insulin (ED50 approximately 80 nM) also inhibited EPO formation in Hep G2 cells. IGF-I (100 pM-100 nM) stimulated the incorporation of radiolabeled alanine as a measure for total protein synthesis, 3H-labeled thymidine incorporation into DNA, and glycogen synthesis at 20 and 1% O2 in a concentration-dependent fashion. IGF-I exhibited a high affinity for the IGF-I receptor (apparent Kd approximately 3 nM). Unlabeled insulin was greater than 100-fold less potent than IGF-I in competing for 125I-IGF-I binding (apparent Kd approximately 360 nM). Conversely, insulin bound to the insulin receptor with high affinity (apparent Kd approximately 0.3 nM), whereas IGF-I was less than 1% as potent in competing for 125I-insulin binding. In summary, IGFs and insulin exert a negative control function on oxygen-regulated EPO production in Hep G2 cells. The inhibitory effect of IGFs and insulin on EPO formation appears to be mediated via the IGF-I receptor.

Animals↗
PubMed1992

Age-dependent expression of the erythropoietin gene in rat liver and kidneys.

Using RNAse protection, we have made quantitative measurements of erythropoietin (EPO) mRNA in liver and kidneys of developing rats (days 1-54), to determine the relative contribution of both organs to the total EPO mRNA, to monitor changes which occur with development, and to compare the hypoxia-induced accumulation of EPO mRNA with the changes in serum EPO concentrations. To determine whether developmental and organ-specific responsiveness is related to the type of hypoxic stimulus, normobaric hypoxia was compared with exposure to carbon monoxide (functional anemia). Under both stimuli EPO mRNA concentration in liver was maximal on day 7 and declined during development. In contrast, EPO mRNA concentration in kidney increased during development from day 1 when it was 30-65% the hepatic concentration to day 54 when it was 12-fold higher than in liver. When organ weight was considered the liver was found to contain the majority of EPO mRNA in the first three to four weeks of life, and although, in stimulated animals, the hepatic proportion declined from 85-91% on day 1, it remained approximately 33% at day 54 and was similar for the two types of stimuli. When normalized for body weight the sum of renal and hepatic EPO mRNA in animals of a particular age was related linearly to serum hormone concentrations. However, the slope of this regression increased progressively with development, suggesting age-dependent alterations in translational efficiency or EPO metabolism.

Age Factors↗
PubMed1992

[Use of anthelmintics for nematode control in sheep in West Germany: results of a survey].

A survey by questionnaires was performed on 543 (0.9% of all) sheep flocks in western Germany in 1988/89 to obtain informations about deworming practices against gastrointestinal nematodes. The major informations are: Anthelmintic treatments were associated with the reproductive status of ewes and the breeding of lambs in most of the flocks. They were performed at an epidemiologically appropriate time in many cases but were not accompanied by essential management practices. (Pro)benzimidazole compounds were the anthelmintics most frequently used by more than 95% of the farmers; 22% and 13% of the farmers additionally or exclusively administered levamisole/pyrantel and ivermectin, respectively. On average, treatment of ewes and lambs against nematodes was performed 2.5 times and 2.8 times a year, respectively. The mean frequency of deworming differed regionally and was generally greater in pedigree breeding flocks than in commercial breeding flocks; it was significantly affected by the husbandry system, the number of ewes per flock, the size of available pasture and the class of anthelmintics employed. The results of this survey revealed that many German sheep farmers obviously lack an awareness of the rationale of preventive and economic control practices against gastrointestinal nematodes.

Animals↗
PubMed1992

HIV-1 seroprevalence in pregnant women testing positive on serologic screening for syphilis.

Epidemic increases in active syphilis have been reported in the geographic areas hit hard by acquired immunodeficiency syndrome. Although both epidemics have been associated with illicit substance abuse, the extent to which recent increases in syphilis are linked to the human immunodeficiency virus (HIV-1) epidemic is uncertain. In order to define the frequency of syphilis and HIV-1 coinfection in the pregnant patients seen at City Hospital Center at Elmhurst, we saved syphilis-positive serologic specimens from obstetrical patients for anonymous HIV-1 antibody testing. Of 120 women who tested positive for syphilis, 7/120 (5.8%) had antibodies to HIV-1; of the 44 women with VDRL titers greater than or equal to 1:16 (suggestive of a recent infection), 1/44 (2.3%) had antibodies to HIV-1.

Female↗
PubMed1991

Distribution of glycosyltransferases among Golgi apparatus subfractions from liver and hepatomas of the rat.

Glycosyltransferase activities of highly purified fractions of Golgi apparatus, plasma membrane and endoplasmic reticulum, all from the same homogenates, were analyzed and compared. Additionally, Golgi apparatus were unstacked and the individual cisternae separated into fractions enriched in cis, median and trans elements using the technique of preparative free-flow electrophoresis. Golgi apparatus from both liver and hepatomas were enriched in all glycosyltransferases compared to endoplasmic reticulum and plasma membranes. However, Golgi apparatus from hepatomas showed both elevated fucosyltransferase and galactosyltransferase activities but reduced sialyltransferase and dipeptidyl peptidase IV (DPP IV) activities compared to liver. Activity of N-acetylglucosaminyltransferase was approximately the same in both liver and hepatoma Golgi apparatus. With normal liver, sialyl- and galactosyltransferase activities and DPP IV showed a marked cis-to-trans gradient of activity. Fucosyltransferase was concentrated in two regions of the electrophoretic separations, one corresponding to cis cisternae and one corresponding to trans cisternae. N-Acetylglucosaminyltransferase activity was more widely distributed but the endogenous acceptor activity was predominantly cis. With hepatoma Golgi apparatus, the pattern for DPP IV was similar to that for liver but those of sialyl- and galactosyltransferases differed markedly from liver. Instead of activity increasing cis to trans, the activities for sialyl- and galactosyltransferases decreased. For fucosyltransferases, activity dependent on exogenous acceptor was medial whereas with endogenous acceptor, two activity peaks, cis and trans, still were observed. For N-acetylglucosaminyltransferase the pattern for hepatoma was similar to that for liver. The results indicate alterations in the distribution of glycosyltransferase activities within the Golgi apparatus in hepatotumorigenesis that may reflect altered cell surface glycosylation patterns.

Animals↗
PubMed1991

19F nuclear magnetic resonance imaging of drug distribution in vivo: the disposition of an antifolate anticancer drug in mice.

The application of 19F nuclear magnetic resonance imaging to the study of drug distribution in vivo is discussed. CB3988 (C2-desamino-C2-methyl-N10-propargyl-2'-trifluoromethyl-5,8-dideazafolic acid) is a fluorinated representative of a class of quinazoline antifolates which act as inhibitors of thymidylate synthase and which are being evaluated for the treatment of human cancer. 19F images were obtained in vivo from the abdomen of mice following intravenous injection of CB3988 (500 mg/kg). Time resolutions of 4 and 20 min were achieved for two- and three-dimensional imaging, respectively. These images were consistent with the presence of high concentrations of drug (up to 26 mg/ml) in the gall bladder, urinary bladder, and small intestine, as confirmed ex vivo by extraction and HPLC analysis. The results indicate the potential value of 19F NMR imaging in pharmacokinetic studies.

Animals↗
PubMed1991

Oxygen-dependent erythropoietin production by the isolated perfused rat kidney.

In this study we have investigated the role of oxygen delivery and of classic second messengers on erythropoietin production by the isolated perfused rat kidney. We found that the rat kidney was capable of de novo synthesis of erythropoietin. The erythropoietin production rate was inversely related to the oxygen pressure in the perfusate and increased from 0.17 to 1.85 U erythropoietin h-1 g kidney-1 when arterial PO2 was lowered from 500 mmHg to 30 mmHg. Addition of forskolin (10 microM) and 8-bromo-cGMP (100 microM) to the perfusate elicited significant effects on the renal vascular resistance, but had no significant effect on erythropoietin production. Hypoxia-induced erythropoietin formation, however, was blocked by calmidazolium (1 microM) and W-7 (10 microM), two structurally different putative calmodulin antagonists. Calmidazolium and W-7 had no effect on other functional parameters of the isolated perfused rat kidney such as flow rate, glomerular filtration rate or sodium reabsorption. Our findings suggest that the oxygen-sensing mechanism that controls renal erythropoietin production is primarily located in the kidney itself. A calcium/calmodulin-dependent cellular reaction could be involved in the signal transduction process.

Animals↗
PubMed1991

Sigma receptor ligands alter concentrations of corticosterone in plasma in the rat.

Both BMY-14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-butanol hydrochloride) and gevotroline (WY-47384; 8-fluoro-2,3,4,5-tetrahydro-2-[3-(3-pyridinyl)-propyl]-1H-pyrido[4,3-b] indole hydrochloride) are known to antagonize the psychotomimetic action of N-allyl-normetazocine (NAN; SKF-10047) and exhibit a high affinity for the sigma receptor. Unexpectedly, the putative antagonists BMY-14802 and gevotroline acted like the agonist NAN and increased activity in the hypothalamic-pituitary-adrenal axis to elevate levels of corticosterone in plasma. During the acrophase (peak) of the effects of the circadian rhythm on the hypothalamic-pituitary-adrenal axis, the ED50 was 6.5 mmol/kg for BMY-14802 and 9.6 mmol/kg for gevotroline. The ED50s for BMY-14802 and gevotroline during the low activity phase were 15.8 and 21.2 mmol/kg, respectively. The efficacies during both phases of the circadian rhythm were similar for each drug. Additive effects on the levels of corticosterone in plasma were observed when the animals were pretreated with doses above the respective ED50 values and then subjected to a rotational stress, but a small dose of BMY-14802 (0.5 mg/kg) had the opposite effect and completely inhibited the stress-related increases in corticosterone in plasma. Neither drug, at large doses, altered the increase in levels of corticosterone in plasma generated by the circadian rhythm, but at smaller doses BMY-14802 did lower circadian-related levels of corticosterone. Pretreatment with dexamethasone blocked the gevotroline-related increase in corticosterone in plasma, but not the BMY-14802-related increase. These data suggest that central sigma receptor mechanisms are involved in the regulation of the hypothalamic-pituitary-adrenal axis and that therapeutic agents that affect these receptors may alter the activity in this axis.

Animals↗
PubMed1991

Effects of maximal and submaximal exercise under normoxic and hypoxic conditions on serum erythropoietin level.

This study was carried out to investigate the influence of different exercise regimens on serum immunoreactive erythropoietin concentration (EPO). The same untrained male subjects performed bouts of maximal and submaximal exercise (60 min at 60% of maximal performance) under normoxia (n = 10) and normobaric hypoxia (PIO2 92 mmHg, n = 9). Five of them were exposed to hypoxia for 90 min under resting conditions (RTH). [EPO] was unchanged up to five hours after maximal (MEN) and submaximal (SEN) exercise under normoxia. After RTH, [EPO] increased after 3 hours by 5.0 mU/ml (p less than 0.01). Submaximal exercise under hypoxia (SEH) led to a similar increase in [EPO] (after 3 hours: + 5.5 mU/ml), which remained elevated the following days (after 24 h: + 6.1 mU/ml, 48 h: + 5.3 mU/ml; ANOVA p less than 0.001). Maximal exercise under hypoxia (MEH) had no significant effect. The results indicate that exercise has no immediate effect on serum [EPO], whereas the higher EPO level one and two days after SEH could result from the occurring hemodilution as is indicated by a slight negative correlation between [EPO] and Hct (r = 0.59, p less than 0.001). The number of reticulocytes increased after all hypoxic experiments and after MEN without any correlation to [EPO].

Adult↗