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Biomedical subjects

C Haller

Publications and source records attributed to C Haller.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cytotoxicity of radiocontrast agents on polarized renal epithelial cell monolayers.

OBJECTIVE: Radiocontrast-induced nephropathy is a clinically important complication of coronary angiography. The cellular mechanisms of radiocontrast-induced renal dysfunction are not clear. Since tubular transport functions depend on the polarity of renal epithelial cells, we investigated the effects of radiocontrast agents on polarized tubular cells in vitro. METHODS: We studied the effects of iso-iodine concentrations (37 and 74 mg iodine/ml) of an ionic (diatrizoate) and a non-ionic (iopamidol) monomeric radiocontrast agent and of hyperosmolal mannitol control solutions on filter-grown renal epithelial cell (MDCK, LLCPK) monolayers in vitro. The cytotoxicity was assayed by measurement of cell viability, transepithelial resistance, inulin permeability and (polarized) cellular enzyme release. The polarized MDCK cell phenotype was assessed by transmission electron microscopy and indirect immunofluorescence microscopy using monoclonal antibodies against specific apical (gp135) and basal (gp60, uvomorulin) MDCK surface markers. RESULTS: The radiocontrast agents reduced cell viability to a greater extent than hyperosmolal mannitol solutions in both cell lines; diatrizoate was more toxic than iopamidol. LLCPK cells were more susceptible to radiocontrast cytotoxicity than MDCK cells. This cytotoxicity was associated with an alteration of MDCK cell polarity as assessed by the redistribution of surface marker proteins. CONCLUSIONS: Diatrizoate is more toxic than iopamidol, which is partly related to its higher osmolality. The cytotoxicity of radiocontrast agents induces a redistribution of polarized membrane proteins which could contribute to the pathophysiology of radiocontrast-induced nephropathy.

Animals↗
PubMed1997

Pro-thymocyte expansion by c-kit and the common cytokine receptor gamma chain is essential for repertoire formation.

Growth factors have been implicated in thymocyte development, but mutants lacking cytokines, or their receptors, have failed to reveal essential roles for growth/differentiation factors in the thymus. Mutations in the receptor tyrosine kinase c-kit and the common cytokine receptor gamma chain (gamma c) reduce cellularity, but are permissive for thymocyte development. We now report that thymocyte development is completely abrogated in mice lacking both c-kit and gamma c (c-kit-gamma c-). Thymic hypocellularity is so severe that the T cell receptor repertoire fails to form except for monoclonal or oligoclonal beta chain DJ rearrangements. B lymphopoiesis is only mildly reduced in c-kit-gamma c- as compared with c-kit+gamma c- mice, and hematological values are identical comparing c-kit-deficient and c-kit-gamma c- mice. These experiments reveal essential, overlapping, and synergistic functions for two distinct signaling pathways, one utilizing c-kit and the other cytokine receptor gamma c complexes coupling to Janus kinases and signal transducers and activators of transcription.

Animals↗
PubMed1997

AE anion exchanger mRNA and protein expression in vascular smooth muscle cells, aorta, and renal microvessels.

Intracellular pH (pHi) is an important regulator of vascular smooth muscle cell (VSMC) tone, contractility, and intracellular Ca2+ concentration. Among the multiple transport processes that regulate VSMC pHi, Na(+)-independent Cl-/HCO3- exchange is the major process that acidifies VSMCs in response to an alkaline load. Here, we characterize, in native and cultured VSMCs, the expression of the AE family of band 3-related anion exchangers, the best studied of these Cl-/HCO3- exchangers. A 4.2-kb AE2 mRNA was present in aorta and in all cultured VSMCs tested. Cultured VSMCs and aorta both expressed a approximately 165-kDa AE2 polypeptide, but a approximately 115-kDa polypeptide was the major AE2-related protein in aorta. AE3 mRNA levels in VSMCs and in arterial tissue were significantly lower than those for AE2, but AE3 or related polypeptides were readily detected by immunoblot and immunolocalization experiments. The approximately 125-kDa AE3 polypeptide was present in an immortalized aortic VSMC line, but the predominant AE3 epitope in aorta and most cultured cells was associated with a polypeptide of M(r) approximately 80 kDa. These data demonstrate the expression in native arteries and in VSMCs of products of the AE2 and AE3 genes, which may contribute to Na(+)-independent Cl-/HCO3- exchange activity in these tissues and cells.

Animals↗
PubMed1996

Evidence that induction of tolerance in vivo involves active signaling via a B7 ligand-dependent mechanism: CTLA4-Ig protects V beta 8+ T cells from tolerance induction by the superantigen staphylococcal enterotoxin B.

Co-stimulation through CD28 is thought to be necessary for the activation of unprimed CD4+ T cells, which are otherwise rendered tolerant. However, we previously found that CD4+ T cell priming was normal or augmented in mice which overexpressed a soluble form of CTLA4 where co-stimulation through CD28 was abrogated. To investigate this CD4+ T cell response, we exploited the capacity of the superantigen staphylococcal enterotoxin B to stimulate T lymphocytes bearing V beta 8+, which represent approximately 30% of all CD4+ T cells. In litter-mate controls of CTLA4-Ig transgenic mice, immunization with staphylococcal enterotoxin B leads to expansion, followed by deletion of V beta 8+ T cells, and the remaining cells are tolerant when stimulated in vitro. Comparable expansion and deletion of V beta 8 T cells occurs in CTLA4-Ig transgenic mice. However, in contrast to normal mice, the remaining V beta 8+ T cells from CTLA4-Ig transgenic mice are not anergic and remain responsive to superantigen in vitro.

Abatacept↗
PubMed1995

Refractory oedema in congestive heart failure: a contributory role of loop diuretics?

We report a patient with congestive heart failure (CHF) who presented with massive oedema resistant to therapy with maximal doses of loop diuretics, despite an adequate renal function. After a diuretic pause and dietary salt restriction, a conventional dose of furosemide in combination with distally active diuretics induced a prompt weight loss exceeding 30 kg with stable renal function. We suggest that the 'refractory' oedema in this patient was due to a combination of CHF and inappropriate (loop) diuretic therapy in conjunction with a high dietary sodium intake. We conclude that in the absence of hyponatremia and renal failure, even severe oedema may not represent a negative prognostic indicator. The recognition of diuretic-associated mechanisms complicating cardiac oedema is essential to avoid the vicious circle of worsening oedema whilst escalating therapy with loop diuretics.

Adult↗
PubMed1995

Regional and segmental localization of AE2 anion exchanger mRNA and protein in rat kidney.

Chloride/base exchange activity has been detected in every mammalian nephron segment in which it has been sought. However, in contrast to the Cl-/HCO3- exchanger AE1 in type A intercalated cells, localization of AE2 within the kidney has not been reported. We therefore studied AE2 expression in rat kidney. AE2 mRNA was present in cortex, outer medulla, and inner medulla. Semiquantitative polymerase chain reaction of cDNA from microdissected tubules revealed AE2 cDNA levels as follows [copies of cDNA derived per mm tubule (+/- SE)]: proximal convoluted tubule, 688 +/- 161; proximal straight tubule, 652 +/- 189; medullary thick ascending limb, 1,378 +/- 226; cortical thick ascending limb, 741 +/- 24; cortical collecting duct, 909 +/- 71; and outer medullary collecting duct, 579 +/- 132. AE2 cDNA was also amplified in thin limbs and in inner medullary collecting duct. AE2 polypeptide was detected in all kidney regions. AE2 mRNA and protein were also detected in several renal cell lines. The data are compatible with the postulated roles of AE2 in maintenance of intracellular pH and chloride concentration and with its possible participation in transepithelial transport.

Animals↗
PubMed1993

Nonpolarized surface distribution and delivery of human CD7 in polarized MDCK cells.

Madin-Darby canine kidney (MDCK) cells grown on permeable supports have served as the most common experimental system for in vitro studies of the generation and maintenance of epithelial surface polarity. Protein targeting to the apical and basolateral plasmalemmal domains of these and other polarized epithelia has been suggested to rely on targeting sequences. Two simple sorting models for MDCK cells have proposed active sorting to a single domain, with "default" movement to the other domain. Examples of both apical and basal sorting signals have been found to support each hypothesis, but the idea of a default pathway has remained in question. Indeed, all endogenous and heterologous wild-type proteins so far studied in MDCK cells achieve polarized distributions at steady state. It is not known whether these selected proteins are representative of all surface membrane proteins or represent only a subset. We report here the apparent absence of sorting by MDCK cells of the transmembrane protein of T-cells, CD7. CD7 is expressed at similar density in apical and basolateral membranes of MDCK cells as assessed by both immunocytological and biochemical criteria. Furthermore, CD7 appears to be directly sorted to both surfaces at similar rates and turns over at both surfaces at similar rates. The nonpolarized distribution of CD7 appears independent of its level of expression. CD7 may identify a "bulk-flow" default pathway for plasma membrane proteins expressed in polarized MDCK cells.

Animals↗
PubMed1993

[Population genetics, immunologic evaluation and Buerger's disease. Projection through a personal study comprising 127 cases of juvenile arteriopathy].

The analysis of anamnestic, clinical and arteriographic parameters in 127 young patients with arterial disease of the lower limbs allowed a definite distinction between thromboangiitis obliterans (TAO) and early-onset atheroma, even if the etiopathogenic of TAO is still obscure. The HLA gene frequency has been determined in 54 patients (14 TAO, 40 early atheroma) and has been compared with local blood donors and with caucased subjects from the IXth Workshop. The results (higher frequency of HLA A28, AX, B53 and BX in the TAO group) have, however, a dubious significance. Furthermore, there were no differences between TAO and early atheroma in a comparative study of immunological parameters (anti-nuclear antibodies, circulating immune complexes, C3, C4 and CH50, cryoglobulin) in 72 patients (22 TAO, 50 early atheroma). So, neither a genetic predisposition nor a dysimmunity could be involved in the pathogenesis of TAO.

Adult↗
PubMed1990

Effect of gamma-hydroxybutyrate on local and global glucose metabolism in the anesthetized cat brain.

This study addresses three topics in the chloralose-anesthetized cat: (a) distribution of local CMRglc: values ranging from 5 to 109 mumols/100 g/min were found in 37 brain structures and the mean CMRglc over all examined structures was 30.6 mumols/100 g/min; (b) effect of gamma-hydroxybutyrate (GHB, 250 mg/kg i.v.) on local CMRglc, which was significantly (p less than 0.05) depressed in 16 of 37 structures, most prominently in the auditory system, and the mean CMRglc over all structures after GHB was 20.4 mumols/100 g/min; and (c) global values of CMRglc, CMRO2, and CBF before and after GHB: in these experiments, a modified Kety-Schmidt technique was employed measuring saturation/desaturation of inhaled H2 and concentrations of glucose and oxygen in aortic and sagittal sinus blood. CBF and CMRO2 were not altered after GHB, whereas CMRglc was significantly decreased from 35.7 to 28.8 mumols/100 g/min. The values of CMRglc obtained with both techniques (autoradiography and the Kety-Schmidt technique) are concordant, especially when considering the different sampling areas of both methods. The main finding of the present study is a reduction in cerebral glucose consumption after GHB, irrespective of the technique of measurement. This reduction occurs at an unchanged CMRO2 and CBF.

Animals↗
PubMed1987

Effect of the muscarinic agonist carbachol on pial arteries in vivo after endothelial damage by air embolism.

Reactions of pial arteries to the muscarinic agonist carbachol were tested in vivo in chloralose anesthetized cats before and after endothelial damage. Moderate endothelial damage was induced by arterial air embolism and verified by electron microscopy for the vessels tested. The experiments had three phases; First, the normal reactivity of pial arteries to carbachol (10(-7) to 10(-5) M) was tested using the microapplication technique, then, after air embolism, the reactivity was reinvestigated at the same vessel. Finally, pial arteries were taken out for scanning electron microscopy. The results show carbachol (10(-6) and 10(-5) M) induced significant dilations under control conditions, also after repetition at the same vessel. After air embolism, the reactions to carbachol were abolished. Morphologic data revealed that whereas control pial arteries showed intact endothelium, the embolized vessels revealed various degrees of endothelial alterations. All showed flattening of endothelial nuclei, to a greater or lesser degree, and in many cases, the endothelium had a wrinkled appearance; several arteries showed severe degradation of the intercellular junctions. It is concluded that (a) carbachol-induced muscarinic vasodilatation of pial arteries in vivo can be abolished after a morphologically verified endothelial lesion--thus confirming in vitro studies in larger arteries and (b) disturbed vascular function does not require rubbing of the endothelium, but occurs already with moderate endothelial damage.

Animals↗
PubMed1987

Moderate hypoxia: reactivity of pial arteries and local effect of theophylline.

The reactivity of pial arteries to the perivascular microapplication of artificial cerebrospinal fluids with mounting concentrations of adenosine (10(-11)-10(-3) M), K+ (0-10 mM), and H+ (pH 5.1-7.6) was determined in chloralose-anesthetized ventilated cats during normoxic control conditions and during moderate normocapnic arterial hypoxia (arterial Po2 47 Torr). Hypoxia induced a significant mean pial arterial dilatation of 18-29% in the various types of experiments. The pial arterial reactivity to each of the tested factors remained unchanged during hypoxia compared with normoxia. The hypoxic vasodilatation could not be reduced by the perivascular microapplication of theophylline (10(-5) and 5 X 10(-5) M). Systemic theophylline (50-75 mumol/kg, iv), regardless of whether given during or before hypoxia, did not attenuate the hypoxic vasodilatation, although it blocked dilatations induced by the perivascular microapplication of adenosine during normoxia. The present study shows that 1) local metabolic factors are vasoactive during moderate hypoxia; therefore they could mediate the hypoxic dilatation of brain vessels; 2) systemic theophylline can block vascular adenosine receptors; 3) since local theophylline had no effect on the hypoxic dilatation of pial arteries, adenosine may not be the main causative factor for the hypoxic hyperemia.

Adenosine↗
PubMed1986

Effect of gamma-hydroxybutyrate on the reactivity of pial arteries before and after ischemia.

The effect of gamma-hydroxybutyrate (GHB) on the reactivity of pial arteries to local metabolic factors was tested in chloralose-anesthetized cats before or after a period of transient ischemia induced by air embolism. The vascular reactions were determined during the perivascular microapplication of artificial CSFs with increasing concentrations of adenosine (10(-11)-10(-3) M), H+ (pH 5.1-7.6), or K+ (0-10 mM). During nonischemic conditions the pial arterial reactivity to adenosine and H+, but not to K+, was significantly increased by GHB (250 mg/kg i.v.) when compared with the control reactivity. After cerebral ischemia the reactivity to adenosine was abolished with and without the administration of GHB prior to air embolism. The reactivity to K+ was partly preserved but not increased by GHB when compared with previous results without GHB. In contrast GHB improved the postischemic reactivity to perivascular H+ that had been found to be abolished in previous experiments without GHB. The perivascular microapplication of GHB showed no influence of GHB on the vascular diameter. An important finding of the present study is the demonstration of an increase in cerebrovascular reactivity, which may give scope for therapeutic improvement of the regulation of CBF in pathophysiological conditions.

Adenosine↗