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C Welsch

Publications and source records attributed to C Welsch.

At least 19 recordsLinked to original sources
PubMed2004

Mutations in the putative HCV-E2 CD81 binding regions and correlation with cell surface CD81 expression.

The hepatitis C virus (HCV) envelope (E)2 protein interacts with the cellular receptor CD81 leading to modulation of B and T cell function. Recently, a higher binding affinity of subtype 1a in comparison with 1b derived E2 proteins for CD81 in vitro was described. The importance of mutations within the putative CD81 binding regions of different HCV geno-/subtypes in correlation with CD81 expression is unknown. In the present study, CD81 expression on blood lymphocytes of patients with chronic hepatitis C infected with different HCV geno-/subtypes were analysed by fluorescence activated cell sorter analyses. In addition, the putative CD81 binding regions on the E2 gene comprising the hypervariable region (HVR)2 were analysed by direct sequencing. CD81 expression on CD8(+) T-lymphocytes from patients infected with subtype 1a (n = 6) was significantly higher in comparison with subtype 1b (n = 12) and 3 (n = 5) infected patients before and during antiviral therapy (P = 0.006; P = 0.021, respectively). Sequencing of the putative CD81 binding regions in the E2 protein comprising the HVR2 (codon 474-495 and 522-552 according to the HCV-1a prototype HCV-H) showed a highly conserved motif within HVR2 for subtype 1a isolates and an overall low number of mutations within the putative CD81 binding regions, whereas numerous mutations were detected for subtype 1b isolates (12.0 vs 23.6%). HCV-3 isolates showed an intermediate number of mutations within the putative binding sites (19.2%; P = 0.022). In conclusion, the highly conserved sequence within HVR2 and putative CD81 binding sites of subtype 1a isolates previously associated with a high CD81 binding affinity in vitro is correlated with high CD81 expression on CD8(+) T-lymphocytes in vivo.

Adult↗
PubMed1995

[Ramipril and cardiac and renal angiotensin converting enzyme].

The role of the angiotensin converting enzyme (ACE) in the regulation of local synthesis of angiotensin II has not been clearly defined. The authors investigated the local factors which might orientate the effects of ACE inhibitors to particular organs in the Wistar rat. The in vivo study of the effects of low doses of ramipril on the myocardium showed that cardiac ACE was significantly inhibited by the non-antihypertensive dose of 0.01 mg/kg whereas the inhibition only occurred from doses higher than 0.1 mg/kg in the other tissues studied. In the kidney: the affinity of 3H-ramiprilate for the brush borders of the proximal tubular cells was increased by high concentrations of chloride ions as observed in the renal parenchyma, the presence of esterases makes local activation of ramipril (diester) into ramiprilate (active diacid) possible, prolonged treatment with ramipril leads to a lowering of the concentration of ACE in the brush border of the proximal tubular cells, verified after the elimination of the ACE inhibitor fixed on the tissue. These data indicate that the myocardium and the kidney could be privileged targets of the action of ramipril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Effects of dietary protein and uninephrectomy on renal angiotensin converting enzyme activity in the rat.

This study examines the effects of dietary protein and of uninephrectomy on angiotensin converting enzyme (ACE) in the normotensive rat, with particular regard to the kidney. Male Wistar Kyoto rats were fed isocaloric diets containing 5, 16 or 50% protein for three weeks. Other groups of rats were subjected to either left unilateral nephrectomy or sham operations, and the rats were killed eight days after surgery. ACE activity was measured in the kidney medulla, cortex, proximal tubule brush border membrane and in the plasma, heart and lung. Renal cortex and brush border ACE activity increased in parallel with protein intake, whereas plasma and lung ACE activity decreased; heart and kidney medulla ACE activity did not vary significantly. Uninephrectomy also led to a high increase in brush border ACE activity in the contralateral kidney, with no effect in the renal medulla or in the other tissues. The increase in ACE activity in the brush border membrane corresponded to a similar increase in the maximum number of binding sites of 3H-ramiprilat. This suggested that the increase in ACE activity corresponded to an increase in ACE concentration. The increase in renal tubular ACE activity could result in higher angiotensin II levels, and could consequently play a role in the modification of sodium reabsorption and cellular growth which occurs in the proximal tubule in these experimental models.

Alkaline Phosphatase↗
PubMed1994

Effects of triiodothyronine and dexamethasone on plasma and tissue angiotensin converting enzyme in the rat.

In order to identify tissue specific regulation of angiotensin converting enzyme (ACE), the effects of dexamethasone (0.04 mg sc per day for 7 days) and triiodothyronine (T3) (0.5 mg/kg sc per day for 10 days) on ACE activity were investigated in different tissues in male Wistar rats. ACE activity was measured by fluorimetry in the plasma, heart, lung and kidney. In the kidney, ACE activity was measured in the medulla, cortex and brush border of proximal tubular cells and 3H-ramiprilat binding was used to characterise the changes in brush border ACE activity. Dexamethasone elicited a significant increase in lung ACE activity and a significant decrease in plasma ACE activity, but did not alter enzyme activity in the other tissues studied. T3 produced a significant decrease in lung ACE activity and an increase in ACE activity in the plasma and heart. In the kidney, ACE activity was not modified in the medulla whereas in the cortex and brush border ACE activity was doubled. This increase in ACE activity corresponded to a similar increase in the maximum number of binding sites of 3H-ramiprilat, suggesting that the increase in activity corresponded to an increase in the ACE level. The increased heart and kidney ACE activity in response to T3 may contribute to the cardiovascular effects of thyroid hormones through increased local angiotensin II generation. These results show that under dexamethasone or T3, ACE activity can vary from one tissue to another, suggesting that the ACE regulatory mechanism acts differently in each tissue.

Animals↗
PubMed1994

Plasma renin activity and changes in tissue angiotensin converting enzyme.

OBJECTIVES: Recent evidence suggests that tissue generation of angiotensins I and II depends on the level of the plasma components of the renin-angiotensin system and on tissue-specific processes. The present study was undertaken to clarify the possible relationship between plasma renin activity (PRA) and tissue angiotensin converting enzyme (ACE) activity in the heart, lung, kidney cortex and kidney medulla of Wistar-Kyoto rats. In the kidney cortex particular attention was focused on renal brush-border ACE. METHODS: Different experimental models known to have opposite effects on PRA were used: changes in salt intake, deoxycorticosterone acetate (DOCA) with or without salt supplements, and the Goldblatt two-kidney, one clip (2-K,1C) model. Two weeks after the start of the experiments the rats were killed, and PRA, and plasma and tissue ACE activity, were measured. RESULTS: At the end of the study the blood pressure in the treated rats was not significantly different from control. As expected, the PRA were highest in the 2-K,1C and depleted-salt groups and lowest in the DOCA, DOCA-salt and high-salt groups. ACE responses were different in different types of tissue, with no relationship between PRA and plasma or tissue ACE activity. For example, DOCA treatment led to increased ACE activity in the heart and the kidney only if the rats were maintained on a high salt intake. DOCA or salt alone failed to have this effect. In the 2-K,1C model the unclipped kidneys did not show any significant variation in ACE activity, but the clipped kidneys exhibited increased ACE activity compared with sham-operated rats. This increase, coupled with increased renal renin secretion, could play a role in the acceleration of local angiotensin II formation, and could thus initiate and sustain the development of hypertension in this model. CONCLUSION: The present results show that variations in ACE activity were organ-specific and were not linked either to hypertension or to changes in PRA.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Angiotensin converting enzyme variability in hypertensive and normotensive rats.

Recent data have revealed biological and genetic variability in normotensive Wistar-Kyoto rats, which are considered to be the most appropriate control strain for spontaneously hypertensive rats. To investigate the possibility that angiotensin converting enzyme activity could be affected by this variability, we measured plasma and tissue (lung, heart, renal cortex, renal medulla, and adrenal gland) angiotensin converting enzyme activity in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats from three commercial suppliers in France: Iffa-Credo, Janvier, and Charles River Laboratories. Angiotensin converting enzyme activity was measured in vitro with a fluorometric assay using carbobenzoxy-Phe-His-Leu as substrate. Angiotensin converting enzyme activity in both rat strains varied considerably from one supplier to another, and therefore, comparisons of spontaneously hypertensive rats and Wistar-Kyoto rats from the different suppliers produced conflicting results. For Wistar-Kyoto rats, angiotensin converting enzyme activity in the plasma, heart, kidney, and adrenal glands was highest in rats from Iffa-Credo and lowest in rats from Charles River. For spontaneously hypertensive rats, angiotensin converting enzyme activity in the plasma and tissues was highest in rats from Janvier, whereas no difference could be observed between rats from Iffa-Credo and Charles River. These data confirm the problem of how to interpret and compare studies that use spontaneously hypertensive and Wistar-Kyoto rat strains.

Adrenal Glands↗
PubMed1993

[Plasma renin activity and angiotensin converting enzyme of renal brush borders].

The present experiment was undertaken to examine the relationship between plasma renin activity and the concentration of angiotensin converting enzyme (ACE) in plasma and renal brush border of Wistar Kyoto rats. Different experimental models known to have opposite effects on plasma renin activity were used: changes in salt intake, the deoxycorticosterone acetate (DOCA) and DOCA-salt models and the two-kidneys one clip (2K1C) model. Two weeks after the start of these experimental series, the rats were killed. At this time, blood pressure did not differ from control group, even in the 2K1C and DOCA-salt groups. As expected, PRAs were highest in the 2K1C and depleted salt groups and lowest in the DOCA, DOCA-salt and high salt groups. No relationship between this wide variation in PRA and change of ACE activity in both plasma and renal brush border could be observed. In the plasma, ACE activity in sodium-depleted rats was slightly decreased whereas no change occurred in the other models. In the kidney, DOCA treatment led to increased ACE activity in the brush border only if the animals were maintained on a high salt intake. DOCA or NaCl alone failed to have this effect. In the 2K1C model, the clipped kidneys exhibited increased brush border ACE activity whereas the unclipped kidneys did not show any significant variation in ACE activity, when compared to sham operated rats. In summary, on one hand these findings show that variations in ACE activity were linked neither to hypertension nor to changes in PRA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Oncology nurse and physician attitudes toward aggressive cancer treatment.

Oncology nurses (n = 57) and oncology physicians (n = 40) employed in the same hospital completed the Cancer Attitude Questionnaire. Significant differences (p < or = .001) between nurse and physician attitudes were evident on the two major subscales addressing the issues of (a) aggressiveness of treatment/de-emphasis of socioemotional aspects of care and (b) the importance of patient-family attitudes. Physicians' attitudes were significantly more favorable on the first subscale; nurses' attitudes were significantly more favorable on the second. Implications of these findings as indicators of potential nurse-physician conflict are discussed.

Adult↗
PubMed1991

[3H]ramiprilat binding to the angiotensin-converting enzyme in rat renal brush-border membranes: the effect of chloride.

The [3H]ramiprilat binding to the angiotensin-converting enzyme (ACE) in rat renal brush-border membranes was studied. At pH 7.9, and in the presence of 50 mM NaCl, specific binding of [3H]ramiprilat was saturable with a dissociation constant KD = 5.05 nM and maximum number of binding sites of 1.52 pmol/mg prot. [3H]Ramiprilat binding was completely inhibited by specific inhibitors of ACE: ramiprilat, ramipril, enalaprilat, enalapril and captopril. [3H]Ramiprilat binding was Zn2(+)- and Cl(-)-dependent. In the presence of EGTA, which chelates Zn2+ ions, ramiprilat binding was inhibited, but the addition of Zn2+ restored the initial binding. Binding was maximum in the presence of 10 mM NaCl while higher NaCl concentrations decreased the binding, corresponding to a decrease in affinity. The association and dissociation kinetics were also NaCl-dependent. In the absence of NaCl, association and dissociation kinetics were rapid and monophasic. Two-step dissociation kinetics appeared in the presence of 10, 50 and 300 mM NaCl and dissociation time increased with the NaCl concentration. These results confirmed the role of Cl- in the isomerisation and the stability of the membrane-associated ACE-inhibitor complex.

Alkaline Phosphatase↗
PubMed1991

In vitro tissue potencies of converting enzyme inhibitors. Prodrug activation by kidney esterase.

The inhibition of angiotensin converting enzyme by ramipril, ramiprilat, enalapril, enalaprilat, and captopril was studied in the plasma and various tissues (lung, heart, renal cortex, renal medulla) of normotensive rats and spontaneously hypertensive rats. Displacement curves for [3H]ramiprilat were established on each tissue with the converting enzyme inhibitors, and their potencies were expressed as the concentration that inhibited 50% of the specific [3H]ramiprilat binding. In the plasma, lung, and heart, the order of activities was: ramiprilat greater than enalaprilat greater than captopril greater than ramipril greater than enalapril. This order was different in the kidney (cortex and medulla): ramiprilat greater than enalaprilat greater than ramipril greater than captopril greater than enalapril. For ramiprilat, enalaprilat, and captopril, there were no differences in their respective potencies between tissues or between rat strains. However, the two prodrugs ramipril and enalapril were 10-30 times more active in the kidney than in the other tissues in both groups of rats. This was due to the deesterification of the prodrugs: in the presence of an esterase inhibitor (diethyl nitrophenyl phosphate, 10 microM), the potencies of ramipril in the kidney were not different from that obtained in the lung, which was not affected by the presence of the esterase inhibitor. These results suggest that the variations in the tissue activities of an angiotensin converting enzyme inhibitor are probably not due to differences in tissue affinities of the angiotensin converting enzyme inhibitor but depend on the concentration of this angiotensin converting enzyme inhibitor in each tissue.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

[Changing factors of the activity of angiotensin converting enzyme of renal brush border in rats].

In the kidney, angiotensin I-converting enzyme (ACE) is present in the vascular endothelial cells and in the brush border of epithelial cells of the proximal tubule. In spite of this well-known distribution of ACE, little is known of its regulation. In order to elucidate the possible mechanisms of control for brush border ACE, the effects of dexamethasone (DM), (40 micrograms s.c. per day, for 7 days) and triiodothyronine (T3) 0.5 mg/kg s.c. per day, for 10 days) were investigated in male Wistar rats. Plasma and brush border ACE activities were measured by fluorimetry in the presence of an artificial substrate Cbz-Phe-His-Leu and brush border ACE was characterized with a binding assay using 3H-ramiprilat, a specific radiolabelled ACE inhibitor. DM elicited a significant decrease in plasma ACE activity (from 0.46 +/- 0.03 to 0.28 +/- 0.02 nmol His-Leu/min/mg protein) but did not alter enzyme activity in the brush border: 47.12 +/- 5.12 nmol His-Leu/min/mg protein (control, n = 6) and 47.78 +/- 5.63 (DM, n = 6). Administering T3 produced a marked increase in the brush border ACE activity (from 42.87 +/- 4.9 to 81.41 +/- 11.7 nmol His-Leu/min/mg protein). Similarly, the maximum number of 3H-ramiprilat-binding sites increased in the brush border, indicating a good correlation between ACE activity and the quantity of 3H-ramiprilat bound. Thus, the variation in tissue ACE activity corresponded to a change in the enzyme concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Age-related variations in tissue angiotensin converting enzyme activities: comparison between spontaneously hypertensive and Wistar-Kyoto rats.

Angiotensin converting enzyme (ACE) activity was measured by fluorimetry in the plasma, lung, heart, aorta and kidney (cortex and medulla) of 3-, 5-, 8- and 11-week-old spontaneously hypertensive rats (SHR) and compared with that of age-matched Wistar-Kyoto rats (WKY). In the plasma, lung and kidney (cortex and medulla), ACE activity was lower in SHR than in WKY. This was evident as early as the age of 3 weeks. In contrast, there were no differences between SHR and WKY in the aorta and the heart. Age-related variations in ACE activities differed in each tissue and in both groups of rats, but no major modifications were correlated with the development of hypertension. A binding assay was performed with [3H]ramiprilat; affinity (KD) and the maximum number of binding sites (Bmax) were determined in plasma and tissues of 3-week-old SHR and WKY. The KD values were identical in the two groups but Bmax was lower in all SHR tissues except in the heart; these results might be related to the decrease in ACE activity. Our results probably reflect genetic differences in ACE activity between SHR and WKY, and suggest that ACE regulatory mechanisms act differently in each tissue.

Aging↗
PubMed1989

Assay of tissue angiotensin converting enzyme.

The distinction between a circulating renin-angiotensin system and a tissue renin-angiotensin system led us to determine tissue angiotensin converting enzyme (ACE) activity. This study establishes the experimental conditions for a good reproducibility of the fluorimetric assay of ACE and describes the use of [3H]ramiprilat to characterize ACE. Angiotensin converting enzyme activity was determined in rat lung, heart, aorta, and kidney (cortex and medulla) and in rabbit kidney (cortex, medulla, tubules, and glomeruli). ACE activity and [3H]ramiprilat binding does not increase in a linear fashion with the protein content of tissue extracts. Linearity limits varied from 1.0 to 2.0 mg of protein/ml (fluorimetry) and from 0.4 to 1.0 mg of protein/ml [( 3H]ramiprilat binding). Comparing ACE activity, measured by fluorimetry, with the amount of [3H]ramiprilat bound shows that the two techniques yield similar results.

Animals↗
PubMed1988

Binding of loop diuretics to their renal receptors: use as a screening model for potential diuretic activity.

Loop diuretics of the benzoic acid and aryloxyacetic acid families inhibit Na+K+Cl- cotransport. The ranking order of potencies measured in the thick ascending limb of Henle's loop and the ranking order of affinities for [3H]piretanide receptors on renal plasma membranes are the same. Potencies and affinities correlate well (correlation coefficient r = 0.959 for the medulla and r = 0.951 for the cortex). Therefore, measurement of [3H]piretanide binding is proposed to facilitate screening for loop diuretic action.

Animals↗
PubMed1987

Tissue converting enzyme activity is low in the kidney of spontaneously hypertensive rats.

Angiotensin-converting enzyme (ACE) activity was measured in the plasma, the kidney, and other organs of 5-, 8-, and 11-week-old spontaneously hypertensive male rats (SHR) of the Okamoto-Aoki strain and compared with that of age-matched Wistar-Kyoto (WKY, bred by Iffa-Credo) or normotensive Wistar rats. ACE activity was measured spectrofluorometrically, using the artificial substrate N-CBZ-L-phe-L-his-L-leu. ACE activity was constantly lower in the plasma and renal cortex of SHR from 5 weeks on than in WKY rats. This difference in the renal cortex ACE activity persisted after 1 h of open circuit perfusion of the isolated kidney with Krebs-Henseleit medium. On the other hand, there lung, the brain occipital cortex, or the abdominal aorta of hypertensive or normotensive rats. The percentage inhibition of ACE activity provoked by 7 days of oral administration of ramipril (Hoe 498, 1 mg/kg/day) was analogous in the kidneys and lungs of WKY rats and SHR. Enalapril (MK 421, 30 mg/kg/day) was equipotent to ramipril in the kidney but had lower inhibitory effects on the pulmonary ACE activities of WKY rats and SHR.

Aging↗
PubMed1987

[Effects of conversion enzyme inhibitors on the synthesis of angiotensin II by the isolated rat kidney].

On the isolated perfused rat kidney, angiotensin-converting-enzyme activity was evaluated by two approaches: one, biochemical, through the measurements of the enzymatic activity on renal homogenate, the other, pharmacological, through the vasoconstrictor response to angiotensin I. Renal tissue angiotensin-converting-enzyme activity was not modified by setting the kidney under perfusion with a modified Krebs-Henseleit solution but was inhibited after addition of captopril into the perfusion medium (10(-5) M, 100 p. 100 inhibition) or after pretreatment of the animals with ramipril (10 mg/kg/day over 3 weeks, per os, 60 p. 100 inhibition). On the isolated perfused rat kidney, angiotensin I and angiotensin II induced a concentration dependent renal vasoconstriction (EC50 = 1.05 +/- 0.18 X 10(-8) and 0.11 +/- 0.05 X 10(-8) M) which was competitively antagonized by saralasin, an angiotensin II receptor antagonist. Addition of angiotensin-converting-enzyme inhibitors to the perfusion medium (captopril or ramiprilat, 10(-5) M) or pretreatment of the animals with ramipril (50 mg/kg, i.p. the day before or 10 mg/kg/day over 3 weeks, per os) only shifted the angiotensin I concentration-response curve to the right by a factor 3 to 4. The residual vasoconstrictor effect of angiotensin I was abolished by 10(-5) M saralasin and remains linked to a local generation of angiotensin II. Our results suggest that, on the isolated perfused rat kidney, besides the angiotensin-converting-enzyme, an iso-enzyme may also be able to generate angiotensin II.

Angiotensin I↗
PubMed1986

Effect of angiotensin converting enzyme inhibitors on the vasoconstrictor action of angiotensin I on isolated rat kidney.

On the isolated perfused rat kidney, the angiotensin converting enzyme (ACE) activity was evaluated with two approaches: one, pharmacological, through the vasoconstrictor response to angiotensin I (ANG I), and the other, biochemical, through the measurements of the enzymatic activity on renal homogenate. ANG I and angiotensin II (ANG II) induced a concentration-dependent renal vasoconstriction (EC50 = 10.5 +/- 1.8 X 10(-9) and 1.1 +/- 0.5 X 10(-9) M, respectively). Both responses were competitively antagonized by an ANG II receptor antagonist, saralasin (pA2 = 8.65 +/- 0.63 and 8.94 +/- 0.28, respectively). The effects of ACE inhibitors were studied in vitro after addition of captopril and ramiprilat (10(-5) M) directly to the perfusion medium, and ex vivo, after pretreatment of the rats with ramipril (50 mg/kg, i.p. the day before or 10 mg/kg/day, per os, over 3 weeks). In spite of the high doses of ACE inhibitors used, the ANG I concentration-response curve was only shifted to the right by a factor of 4, although renal tissue ACE activity was completely inhibited. Saralasin (10(-5) M) totally abolished the ANG I-induced vasoconstriction elicited in the presence of ACE inhibitors, this response being therefore linked to a generation of ANG II from ANG I. Our results suggest that, on the isolated perfused rat kidney, ANG II may be formed from ANG I by a peptidyl dipeptidase different from the ACE.

Angiotensin I↗