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81.
Properties and regulation of chloride channels in cystic fibrosis and normal airway cells 总被引:4,自引:0,他引:4
Karl Kunzelmann Hermann Pavenstädt Rainer Greger 《Pflügers Archiv : European journal of physiology》1989,415(2):172-182
The present study examines the properties of Cl–channels in cultured respiratory cells of cystic fibrosis (CF) patients and normal (N) individuals. In excised membrane patches the conductances for CF and N Cl– channels were larger at positive as compared to negative clamp voltages (V
c): 74±2.6 (V
c > 0) and 47±2.0 pS (V
c < 0) for CF (n= 57) and 69±3.6 (V
c > 0) and 45±2.3 pS (V
c < 0) for N (n=35). The open probability (P
o) of the channel increased markedly with depolarization. Both the voltage dependence of the conductance and of P
o contribute to the outward rectification of the channel. The time histogram analysis reveals two open and two closed time constants. The selectivity of the channel was Cl–=Br– =I– > NO
3
–
gluconate. The channel was inhibited reversibly by 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) at 10–7 mol/l to 10–5 mol/l. While Cl– channels were present in cell attached patches of N cells, they were absent in those of CF cells. The mean conductance for cell attached (N) Cl– channels was 76±3.2 pS for positive clamp voltages (V
c) and 46±3.9 pS for negative V
c (n=8). When the membrane patches were excised from CF cells Cl– currents appeared spontaneously (n=19). The immediate appearance (within 1 s) of Cl– channels after excision was observed at positive (n=6) as well as at negative clamp voltage (n=13). Excision activation of CF Cl– channels was observed at low (< 10–9 mol/l) or high (10–3 mol/l) calcium activities on the cytosolic side of the excised patch. Variation of the Ca+ activity (< 10–9–10–3 mol/l) or pH (6.5–8.5) on the cytosolic side exerted no effects on these Cl– channels. These results suggest that Cl– channels are present in the apical membrane of CF and N respiratory cells but they seem to be inhibited in intact CF cells. Excision of the patch and hence removal of the cytosolic inhibitor leads to an activation of Cl– channels. The Cl– channels in excised patches of N and CF cells have identical properties. 相似文献
82.
Acute and long-term humoral immunity following active immunization of rabbits with inacctivated spores of various Encephalitozoon species 总被引:1,自引:0,他引:1
Sobottka I Iglauer F Schüler T Schmetz C Visvesvara GS Albrecht H Schwartz DA Pieniazek NJ Bartscht K Laufs R Schottelius J 《Parasitology research》2001,87(1):1-6
Microsporidia of the genus Encephalitozoon are increasingly being reported as a cause of severe, often disseminated infections, mainly in patients with acquired immunodeficiency
syndrome (AIDS). Immunological identification of each of the three recognized species (E. cuniculi, E. hellem, and E. intestinalis) requires the availability of specific immune sera. All sera available thus far have been generated by direct inoculation
of rabbits with virulent microsporidian spores. This study demonstrates for the first time that subcutaneous immunization
with inactivated spores of E. cuniculi, E. hellem, or E. intestinalis is capable of generating highly active rabbit hyperimmune sera to the homologous antigens, with maximal titers being 1:5,120,
1:1,280, and 1:2,560, respectively, as determined by the indirect immunofluorescence technique (IIF). Broad cross-reactivity
of the rabbit antisera with all heterologous Encephalitozoon antigens was determined by IIF and immunogold electron microscopy; however, only the E. hellem immune serum strongly cross-reacted with spores of Enterocytozoon bieneusi. During the 35-month follow-up period the antibody titers to the homologous antigens declined to 1:640, 1:160, and 1:320,
respectively. The observed decay curves for antibody titers against E. cuniculi, E. hellem, and E. intestinalis were fitted using mathematical modeling, resulting in a predicted duration for specific immune responses of about 7 years
on average. Knowledge of the magnitude and duration of specific immune responses is a prerequisite for further evaluation
of the concept of using inactivated microsporidian spores in the quest for vaccines against microsporidian infections.
Received: 10 April 2000 / Accepted: 18 July 2000 相似文献
83.
Franz Dienstl Robert Gasser Heribert Rauch Rainer Henn 《Virchows Archiv : an international journal of pathology》1985,407(4):457-464
Summary 50 witnessed sudden cardiac deaths in the age group between 20–50 years have been studied at autopsy. The most remarkable findings were a high percentage of stenosis and arterioisclerosis of the descending branch of the left coronary artery and a large amount of three vessel disease. It is clear that severe stenosis and sclerosis of the coronary arteries are not essentially related to sudden cardiac death, but a high number of vessels with moderate stenoses and sclerosis has been found.The severity of vessel disease has been evaluated by a coronary score, which takes the haemodynamic effects of the injured coronary arteries on the myocardium into account. We also noted that patients below 35 years of age who died of sudden cardiac death showed a very low coronary score. 相似文献
84.
Schwarz C Hauser P Steininger R Regele H Heinze G Mayer G Oberbauer R 《Laboratory investigation; a journal of technical methods and pathology》2002,82(7):941-948
SUMMARY: In renal transplantation, postischemic acute renal failure (ARF) develops in more than 20% of patients. We investigated whether tubular epithelial cells obtained from donor kidneys without subsequent ARF express a different pattern of survival genes, compared with cells from kidneys exhibiting ARF. Donor kidney biopsy specimens were obtained before transplantation from eight recipients of cadaveric kidneys with primary graft function (CAD-PF), eight patients with biopsy-proven ARF without rejection (CAD-ARF), and eight recipients of living donor kidneys with primary graft function (LIV). One thousand proximal tubular epithelial cells per biopsy specimen were isolated by laser capture microdissection. Quantitative analysis of apoptosis and the apoptosis regulatory genes Bcl-2, Bcl-xL, and Bax were performed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling staining and real-time PCR, respectively. Primary cultures of human proximal tubular epithelial cells served as calibrator. The number of apoptotic cells was significantly higher in CAD-ARF compared with LIV and CAD-PF (1.5 +/- 1.1% [p < 0.05] vs. 0.3 +/- 0.2% vs. 0.4 +/- 0.2%; mean +/- SD). The apoptosis inhibitors Bcl-2 and Bcl-xL were significantly up-regulated in renal tubular cells of recipients without ARF compared with CAD-ARF. The ratios of Bcl-2/GAPDH normalized to calibrator were as follows: LIV 48 +/- 30, CAD-PF 38 +/- 55, and CAD-ARF 5 +/- 7 (p < 0.05). The corresponding ratios for Bcl-xL were as follows: LIV 6 +/- 6, CAD-PF 5 +/- 3, and CAD-ARF 1 +/- 1 (p < 0.05). No difference in the expression of the proapoptotic Bax could be observed. These data suggest that failure of proximal tubular cells to respond to injury by up-regulation of survival factors from the Bcl-2 family contributes to postischemic ARF in patients after cadaveric renal transplantation. 相似文献
85.
86.
Hans Oberleithner Florian Lang Rainer Greger Hans Sporer 《Pflügers Archiv : European journal of physiology》1979,379(1):37-41
In previous studies it has been demonstrated that a decline of plasma calcium concentration accounts for the decrease of phosphate reabsorption in thyroparathyroidectomized (TPTX) rats undergoing phosphate loading.Microinfusion studies were performed in TPTX rats in order to discriminate between a systemic effect of calcium an a direct renal effect.Thyroparathyroidectomized animals were infused with a phosphate solution continuously. When plasma calcium concentration fell below 1.30 mmol/l, proximal convoluted tubules were microinfused with a phosphate tracer solution for 42 min. After 18 min a calcium chloride-containing solution was applied superficially (superfused) to the area of the microinfused tubule. This elevation of peritubular calcium concentration led to an immediate increase of phosphate reabsorption up to 12% of the microinfused phosphate load within 24 min.In another series of experiments, the calcium specific ionophore A 23187 — a substance which is known to increase intracellular calcium — was superfused on the microinfused tubule. This resulted again in an increase of fractional phosphate reabsorption of about 15% after 24 min. In contrast, when calcium chloride-free as well as ionophore-free solutions were superfused fractional phosphate reabsorption decreased (7%).From these data we conclude that 1. calcium has a direct renal effect on phosphate reabsorption in the absence of parathyroid hormone and 2. intracellular calcium appears to be a major parameter in the regulation of renal phosphate transport under these conditions.This study was supported by Dr. Legerlotz StiftungParts of this study were presented at the fall meeting of the Nephrologische Gesellschaft in Bonn, 1977 and at the spring meeting of the Deutsche Physiologische Gesellschaft in Göttingen, 1978 相似文献
87.
Michael Steinhausen Frederick D. Dallenbach Rudolf Jäckh Niranjan Parekh Bernd Zimmerhackl Rainer Zimmermann 《Virchows Archiv : an international journal of pathology》1979,384(1):65-84
Summary After occlusion of the renal veins rats die quickly in progressive shock (within 4.5 h), but after ligating the renal hilum of both Kidneys they survive 27 h. To learn why renal vein occlusion is so rapidly lethal, and what substances are given off and by what method from the hemorrhagically infarcted kidneys, we studied eight groups of rats, each containing at least seven animals. The groups differed in the combination of hilar structures (renal veins, ureters, lymphatics) ligated. We compared: survival times, changes in blood pressure, blood volume, levels of plasma kinins, adenosine, and lactate, changes of blood pH, responses to Indomethacin, Trasylol®, and plasma expanders, tubular and capillary flow rates, histopathological changes in organs and cerebral blood flow and changes in the blood coagulation system. Our results suggest that the venous stasis, anoxia, and hemorrhagic necrosis caused by bilateral venous occlusion release into renal lymphatics toxic substances which reach the systemic circulation and induce irreversible shock. We have excluded prostaglandins and adenosine as the toxic substances inducing shock but could not rule out an action of the kallikrein-kinin-system. We postulate that the striking degenerative changes occurring in the arterioles of the brain after bilateral venous occlusion may mean these vessels are especially susceptible to high levels of lactic acid and that this may explain why these animals die so quickly. Our conclusions should help not only in understanding why high levels of lactate in shock portend a poor prognosis but also help in formulating appropriate therapy for circulatory failure of renal origin and for protracted hypotension after extensive tissue injury.The studies were supported by the German Research Foundation within the SFB 90 Cardiovasculäres SystemPresented in part: Jäckh and Steinhausen, 1976; Dallenbach et al., 1978; Zimmerhackl et al., 1979We dedicate this paper to Wilhelm Doerr, Dr. med., Professor of Pathology, University of Heidelberg on the occasion of his 65th birthday (August 25th, 1979) 相似文献
88.
Hematopoietic progenitor cells and cellular microenvironment: behavioral and molecular changes upon interaction 总被引:2,自引:0,他引:2
Wagner W Saffrich R Wirkner U Eckstein V Blake J Ansorge A Schwager C Wein F Miesala K Ansorge W Ho AD 《Stem cells (Dayton, Ohio)》2005,23(8):1180-1191
Cell-cell contact between stem cells and cellular determinants of the microenvironment plays an essential role in controlling cell division. Using human hematopoietic progenitor cells (CD34+/CD38-) and a stroma cell line (AFT024) as a model, we have studied the initial behavioral and molecular sequel of this interaction. Time-lapse microscopy showed that CD34+/CD38- cells actively migrated toward and sought contact with stroma cells and 30% of them adhered firmly to AFT024 stroma through the uropod. CD44 and CD34 are colocalized at the site of contact. Gene expression profiles of CD34+/CD38- cells upon cultivation with or without stroma for 16, 20, 48, or 72 hours were analyzed using our human genome cDNA microarray. Chk1, egr1, and cxcl2 were among the first genes upregulated within 16 hours. Genes with the highest upregulation throughout the time course included tubulin genes, ezrin, c1qr1, fos, pcna, mcm6, ung, and dnmt1, genes that play an essential role in reorganization of the cytoskeleton system, stabilization of DNA, and methylation patterns. Our results demonstrate directed migration of CD34+/CD38- cells toward AFT024 and adhesion through the uropod and that upon interaction with supportive stroma, reorganization of the cytoskeleton system, regulation of cell division, and maintenance of genetic stability represent the most essential steps. 相似文献
89.
Rick Galli Linda Merrick Michel Friesenhahn Rainer Ziermann 《Journal of clinical virology》2005,34(4):245-252
BACKGROUND: Plasma human immunodeficiency virus type 1 (HIV-1) RNA level is an important parameter for patient management, yet viral load assays from different manufacturers are not standardized. OBJECTIVES AND STUDY DESIGN: In this study, we evaluated the concordance between test results obtained for 1,000 plasma specimens collected from HIV-1-infected individuals measured with the VERSANT HIV-1 RNA 3.0 assay (bDNA) and the COBAS AMPLICOR HIV-1 MONITOR 1.5 test (PCR). We compared viral load values obtained by each of these assays throughout their dynamic ranges, with particular focus on samples with low viral load (i.e. 50-250 copies/mL), and calculated the estimated distribution of distinct plasma viral load levels for the entire study population modeled from the data observed in the study. RESULTS: We found that these two assays show excellent agreement, with a correlation (R(2)) of 0.957 and a slope of 1.004. The mean difference in viral load values between the two assays was less than 0.10-log(10) throughout the dynamic range and 98.2% of all samples had bDNA and PCR results within 0.5-log(10) of each other, a difference that is within the range considered to be a minimal change in plasma viremia. Moreover, the two assays show very similar results across all assay ranges tested. The estimated prevalence of samples with results <50 copies/mL, 50-250 copies/mL, and 250-500,000 copies/mL were 41.6%, 7.7%, and 49.7%, respectively, by the bDNA assay, and 42.4%, 6.9%, and 50.7%, respectively, by the PCR assay. CONCLUSION: Based on our findings from 1,000 clinical specimens, we do not see the need to re-establish a baseline value or apply a conversion factor when switching from one assay to the other. Since the majority of our patient population likely is infected with subtype B virus, it is unclear if our findings will apply to other patient populations with a greater incidence of infection with non-B subtypes. 相似文献
90.
Nafe R Gangnus R Glienke W Burgemeister R Haar B Pries A Schlote W 《Pathology, research and practice》2003,199(6):411-414
The technique of laser microdissection together with laser pressure catapulting (LMPC) is demonstrated in paraffin sections obtained from surgical specimens of brain tumors mounted on glass slides. A sufficient and precise application of microdissection techniques in tissue on glass slides is worthwhile, since it offers the possibility of a retrospective analysis of archived paraffin sections in histopathology. We could demonstrate a precise dissection of areas in tissues of different thicknesses (4 microm and 20 microm). Areas of tissue mounted directly on glass need to be dissected in a scanning mode in order to remove the total region in form of small tissue fragments row by row. This mode provided a precise microdissection of tissue areas of different sizes and shapes. A successful molecular biological analysis of the microdissected regions could be demonstrated. As an example for such an analysis, differential-PCR for detecting an amplification of the gene for the epidermal growth factor receptor (EGFR) was performed. 相似文献