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Biomedical subjects

C Bauer

Publications and source records attributed to C Bauer.

At least 235 records · Page 13Linked to original sources
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↗
PubMed1990

Role of erythropoietin in adaptation to hypoxia.

The glycoprotein hormone erythropoietin (EPO) counteracts tissue hypoxia by increasing the systemic oxygen-carrying capacity. It induces augmentation of red blood cell mass by stimulating the formation and differentiation of erythroid precursor cells in the bone marrow. EPO production is increased under various forms of diminished oxygen supply such as anemic or hypoxic hypoxia. In the adult organism, the kidneys are the major source of EPO. The precise nature of the cells responsible for renal EPO production, however, has not yet been elucidated. Most likely, peritubular cortical cells, e.g. interstitial or endothelial cells, are involved in the elaboration of the hormone. From the observation that isolated perfused rat kidneys produce EPO in an oxygen-dependent fashion we conclude that the 'oxygen sensor' that controls hypoxia-induced EPO synthesis is located in the kidney itself. Within the kidneys, the local venous oxygen tension which reflects the ratio of oxygen supply to oxygen consumption is measured and transformed into a signal that regulates the formation of EPO. However, the mechanism by which a decrease of oxygen delivery to the kidneys is linked to an enhanced EPO gene expression is not yet known. Two possible mechanisms of regulation are discussed: First, renal hypoxia could lead to enhanced formation of metabolic mediators, for example prostaglandins or adenosine, which might stimulate EPO gene transcription by increasing cellular levels of second messenger molecules. Second, some kind of molecular 'oxygen receptor' such as a heme protein, that controls EPO formation by an oxygen-dependent conformational change, could mediate signal transduction.

Animals↗
PubMed1990

Role of excretory graft function for erythropoietin formation after renal transplantation.

To examine the role of renal excretory function for erythropoietin (EPO) formation we have determined the kinetics of plasma immunoreactive EPO (irEPO) in patients with end-stage renal disease undergoing renal allotransplantation (RTX). In 13 patients with immediate excretory graft function (imGF) and stable haemoglobin (Hb) concentrations (median Hb 9.5 g dl-1 and median irEPO 18 mU ml-1 before RTX) irEPO increased significantly on day 4 after RTX to a median value of 29 mU ml-1 and 2 days later reached a plateau of 34.4 +/- 3.3 mU ml-1 (mean +/- SD of daily median values during days 6-20). In patients with imGF having acute blood loss and subsequently receiving transfusions, irEPO responded in an inverse fashion to changes in Hb concentrations. In 12 patients with delayed graft function (dGF) (median Hb 8.8 g dl-1 and median irEPO 15 mU ml-1 before RTX) irEPO levels during the period of excretory failure remained either unchanged or displayed marked variations with peak values greatly exceeding those of patients with imGF. These variations were not related to changes in Hb concentrations and irEPO levels did not change following alterations in Hb concentrations. Upon recovery of excretory function irEPO approached the values found in patients with imGF. The results suggest that an intact excretory renal function is not a prerequisite for the capability to produce EPO, but correlates with the oxygen-dependent regulation of EPO formation.

Adolescent↗
PubMed1990

Triggering of erythropoietin production by hypoxia is inhibited by respiratory and metabolic acidosis.

Erythropoietin (EPO) production in response to hypoxic hypoxia is known to be attenuated by simultaneous hypercapnia. This study aimed to investigate whether this inhibitory effect of hypercapnia is 1) a direct effect of carbon dioxide or mediated by changes in pH or bicarbonate, 2) affects also carbon monoxide hypoxia, and 3) influences either the synthesis and release of EPO or the mechanisms by which hypoxia triggers an increase in EPO production rate. We found that EPO formation in mice exposed to normobaric hypoxia (8% O2) or to carbon monoxide (0.1%) was reduced by 30 and 42% when animals were simultaneously exposed to hypercapnia (7% CO2), by 35 and 38% when subjected to metabolic acidosis (NH4Cl), and unchanged when subjected to metabolic alkalosis (NaHCO3). In animals exposed to brief hypoxia (15 min) and subsequent normoxia (2 h), metabolic acidosis did not affect EPO levels when initiated after the hypoxic period. The results indicate that acidosis inhibits hypoxia-induced triggering of EPO formation independently of PCO2 and HCO3 levels. Because this inhibitory effect is also present during carbon monoxide hypoxia, it appears not solely due to potentiated hyperpnea. Alternatively, it may result from a facilitated intrarenal oxygen release or a direct effect at the EPO production sites.

Acid-Base Equilibrium↗
PubMed1990

Decline of erythropoietin formation at continuous hypoxia is not due to feedback inhibition.

Serum erythropoietin (EPO) levels in response to hypoxia are known to decline before an increase in blood oxygen carrying capacity. To define the possible mechanisms underlying this phenomenon, we have investigated 1) how renal EPO mRNA content and EPO production rate underlying the early kinetics of serum EPO levels change under different degrees of normobaric hypoxia, and 2) if a feedback inhibition of either EPO formation or EPO survival in the circulation exists by the hormone itself. We found that serum immunoreactive EPO levels in rats peaked after 12-h exposure to 7.5 or 9% oxygen (2,949 +/- 600 and 756 +/- 108 mU/ml, respectively, mean +/- SE) and declined to 29 and 64% of peak levels, respectively, after 36 h of hypoxia. EPO levels in response to 11.5% oxygen showed no consistent change between 12 (122 +/- 21 mU/ml, mean +/- SE) and 36 h (182 +/- 35 mU/ml) of hypoxia. The decline in EPO levels under severe hypoxia (7.5% O2) was paralleled by a marked reduction in renal EPO mRNA content, indicating that it was primarily a result of diminished hormone production. The observed reductions in serum EPO after 36 h corresponded to preceding declines of calculated EPO production rates from 163- to 62-fold (7.5% O2) and 36- to 25-fold (9% O2) basal values. Application of 50 IU recombinant human EPO to rats 12 h, 6 h, or immediately before hypoxic exposure to mimic the early increase in EPO levels did not affect endogenous EPO formation during a subsequent hypoxic exposure of 12 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Unchanged in vivo P50 at high altitude despite decreased erythrocyte age and elevated 2,3-diphosphoglycerate.

We measured hematological and erythrocyte O2 transport parameters in whole blood and density-separated erythrocytes in 11 mountaineers before and during 5 days of exposure to high altitude (4,559 m). We determined the in vivo (arterial pHblood and PCO2) and standard (pHblood = 7.4, PCO2 = 40 Torr) O2 tension at 50% O2 saturation of hemoglobin and (P50,vv and P50,st) and Bohr coefficients (BC) for fixed acid (H+) and CO2 and examined the contribution of the altered average age of circulating erythrocytes due to the stimulation of erythropoiesis on whole blood 2,3-diphosphoglycerate (2,3-DPG) and P50,st. At altitude, whole blood P50,vv remained almost unchanged, whereas P50,st and 2,3-DPG increased significantly (+4 Torr; 3.5 mumol/g hemoglobin). BCCO2 was elevated significantly at altitude. Serum erythropoietin increased transiently fourfold, iron utilization increased, and serum iron decreased by 66%. Reticulocyte counts increased, but other hematological parameters were unchanged. In density-separated erythrocytes, P50,st and 2,3-DPG increased with decreasing cell density but were higher in fractions with comparable reticulocyte counts in cells prepared at altitude than in those from control studies. Our data show that, despite the increase in 2,3-DPG and the decrease in average erythrocyte age, the in vivo hemoglobin-O2 affinity remains unchanged. P50,st values reflect the elevation of 2,3-DPG, and approximately 50% of the increase in both parameters can be ascribed to the increase in the number of reticulocytes and young erythrocytes.

2,3-Diphosphoglycerate↗
PubMed1989

Renal mesangium is a target for calcitonin gene-related peptide.

Rat calcitonin gene-related peptide (CGRP alpha; EC50, 1 nM) was shown to stimulate cAMP formation in cultured rat renal mesangial cells. CGRP concentration dependently (EC50, 1 nM) also inhibited contraction of mesangial cells by angiotensin II (10 nM). Angiotensin II (10 nM) caused a transient increase of the intracellular calcium concentration from 140 nM to 480 nM in the mesangial cells, but these calcium transients were not altered by CGRP. CGRP (10 nM) decreased vascular resistance in the isolated rat kidney perfused at constant pressure (100 mm Hg; P less than 0.01). The decreased vascular resistance was accompanied by a rise of the glomerular filtration fraction. CGRP, moreover, attenuated the effects of angiotensin II on renal vascular resistance and glomerular filtration (P less than 0.01). In conclusion, CGRP causes relaxation of renal mesangial cells and decreases renal vascular resistance. As a result CGRP raises glomerular filtration and the filtration fraction. The effect may be linked to cyclic AMP formation. Thus, regulation of renal vascular and glomerular function may represent a novel action of CGRP apart from its cardiovascular effects.

Angiotensin II↗
PubMed1989

[Perioperative anxiety behavior of IVF patients and a suitable simplified analgo-sedation procedure in transvaginal follicle puncture].

In the present prospective study, perioperative anxiety was investigated in 52 patients, who underwent transvaginal follicular centesis for IVF treatment. Also the surgical and anaesthesiological procedures are described. The mean age of the patients was 32.2 years, and the mean period of desire for children 9.1 years. On average, six stimulation cycles were carried out. In an operation with a duration of approx. 20 minutes, an average of six oocytes were collected. As an alternative to general anaesthesia, an analgosedation, given intravenously with midazolam (0.1 mg/kg) and fentanyl (2 micrograms/kg) has been described. This necessitates continuous anaesthesiological monitoring due to respiratory depression, induced by the risk of medication. In our study, IVF patients who had a long history of desire for children, in some cases with several previous operations, show a low to moderate anxiety level before the operation. "Hospital routine" has evidently led to this low anxiety level, which is maintained after the operation.

Adult↗