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R Schindler

Publications and source records attributed to R Schindler.

At least 73 records · Page 4Linked to original sources
PubMed1993

[31P-cardio-MR-spectroscopy in myocardial insufficiency].

The relative linear relationships of creatine phosphate/gamma-adenosine triphosphate (PCr/ATP) and of phosphodiester (PDE)/ATP were measured in 38 normals and 27 patients with cardiac insufficiency using cardiac 31P-MR-spectroscopy. There was no significant difference between normals and those with dilated cardiomyopathy (19 cases) and severe aortic valve lesions (8 cases), irrespective of the clinical stage of the cardiac abnormality. Within subgroups of insufficiency there was a correlation between PCr/ATP and the severity of the disease with significant differences between mild and severe cardiac insufficiency. In 6 patients a significant rise in PCr/ATP could be demonstrated following clinical improvement under drug therapy. There was no correlation between the relative linear relationship and the left ventricular ejection fraction.

Adult↗
PubMed1993

Plasma levels of bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP) during hemodialysis.

Several proteins modify the biological response to lipopolysaccharide (LPS). Both bactericidal/permeability-increasing factor (BPI), a protein stored in neutrophils, and the acute phase protein LPS-binding protein (LBP) bind to LPS; however, BPI inhibits while LBP enhances binding of LPS to leukocytes and subsequent induction of cytokines. We investigated plasma levels of BPI, LBP, elastase and C5a before, during and after hemodialysis (HD). Six patients were dialysed with Cuprophane (Cup) and polysulfone (PS) low-flux dialyzers on two consecutive HD sessions. There was a significant, 10.9 +/- 2.8-fold increase in BPI after 4-hour HD compared to predialysis and a 4.4 +/- 1.6-fold increase in elastase after 4-hour HD using Cup. Plasma levels of BPI and elastase decreased rapidly after the dialysis session. HD with PS resulted in a smaller, but still significant rise in BPI (3.7 +/- 1.6-fold at 4 hours) and elastase (1.69 +/- 0.2-fold at 4 hours). Levels for BPI and elastase were similar in the arterial and venous blood lines of the dialyzer. Plasma levels of LBP did not change during or after the HD session. These data indicate that BPI, but not LBP is released during HD with Cup and to a lesser extent with PS. Activation of neutrophils and release of BPI during HD may influence the biological response to bacterial products possibly introduced during HD.

Acute-Phase Proteins↗
PubMed1993

ERGIC-53, a membrane protein of the ER-Golgi intermediate compartment, carries an ER retention motif.

Overlapping cDNAs encoding the entire human ERGIC-53, a 53 kDa membrane protein of the ER-Golgi intermediate compartment, have been isolated and their nucleotide sequence determined. The isolated cDNA is about 2.7 kb in length. The deduced polypeptide chain for ERGIC-53 consists of 510 amino acids (M(r) 54217) including an N-terminal signal sequence of 30 amino acids, a single putative transmembrane segment of 18 amino acids, and a short cytoplasmic domain of 12 amino acids. Surprisingly, the cytoplasmic segment contains two lysines positioned three and four residues from the C-terminus. Such a double lysine motif is known to function as a retention signal for a group of membrane proteins associated with the ER. Expression of a full-length cDNA of ERGIC-53 in Vero cells revealed intracellular localization similar but not always identical to the endogenously expressed ERGIC-53. The presence of an ER retention motif in a protein of the ER-Golgi intermediate compartment has important implications for the retention mechanism mediated by this signal.

Amino Acid Sequence↗
PubMed1993

Dietary supplementation with n-3 fatty acids suppresses interleukin-2 production and mononuclear cell proliferation.

We studied the in vitro production of interleukin-2 in nine healthy volunteers who added 18 g/day of fish-oil concentrate rich in n-3 polyunsaturated fatty acids to their normal Western diet for a period of 6 weeks. Interleukin-2 synthesis from stimulated peripheral blood mononuclear cells was suppressed from 6.2 ng/ml at baseline to 2.2 ng/ml 10 weeks after the end of n-3 fatty acid supplementation (65% decrease; P = .04). At the same time phytohemagglutinin-induced proliferation of mononuclear cells was suppressed by 70% from the presupplement level. Interleukin-2 production returned to the premedication level at the end of the studies. The results suggest that the effect of dietary n-3 fatty acids in some diseases may be mediated in part by decreased production of interleukin-2 and decreased mononuclear cell proliferation.

Adult↗
PubMed1992

Fc gamma RIII activation is different in CD16+ cytotoxic T lymphocytes and natural killer cells.

The transmembrane protein CD16 (Fc gamma RIII) is detected on activated macrophages, natural killer (NK) cells and a small subset of T lymphocytes. From CD3-CD56+ CD16+bright NK cells and CD3+ CD56+ CD16+dim non-major histocompatibility complex (MHC)-restricted cytotoxic T lymphocyte (CTL) clones were generated reflecting the stable, but different, CD16 expression of the respective peripheral blood subpopulations. To compare the role of CD16 on NK cells and non-MHC-restricted CTL, Fc gamma RIII activation and its mechanisms were investigated using monoclonal antibodies (mAb). Cross-linking of CD16 induced Ca2+ influx in CD16+bright NK clones. In contrast, there was no Ca2+ mobilization after CD16 activation in CD16+dim CTL, which revealed a good response to cross-linking of CD3 antigen. Pretreatment with CD16 mAb alone or cross-linked CD16 mAb did not block the CD3 response of CD16+dim CTL. Again, CD16 cross-linking induced more interferon-gamma transcription in NK cell clones than in non-MHC-restricted CTL clones. Also a higher tumor necrosis factor-alpha production of NK clones after CD16 cross-linking compared to CD16+dim CTL could be observed. These data suggest that after CD16 activation CD16+dim CTL and CD16+bright NK cells use different second messengers. In addition, signal transduction via CD3 and CD16 appears to function independently in CD16+dim non-MHC-restricted CTL.

Antibodies, Monoclonal↗
PubMed1992

Direct measurement of spin-lattice relaxation times of phosphorus metabolites in human myocardium.

T1 values of phosphorus metabolites visible in human cardiac 31P-MR spectra were determined in 12 volunteers at 1.5 T. Consecutive spectra were acquired with varying pulse repetition time (TR) from 1.6 to 24 s; volume selection was achieved with ISIS. T1's of creatine phosphate (CP), [gamma-P], [alpha-P], and [beta-P]ATP, 2-3 diphosphoglycerate, and phosphodiesters were 6.1 +/- 0.5, 5.4 +/- 0.5, 5.5 +/- 0.5, 5.8 +/- 1.0, 7.6 +/- 1.0, and 5.0 +/- 1.0 s, respectively. CP/ATP ratios showed little change with varying TR; linear regression of CP/ATP vs TR was of borderline significance (r = 0.28, P = 0.06). T1's for CP and ATP were also determined in standard solution (20 mM CP, 10 mM ATP) yielding T1CP of 8.7 +/- 0.2 and T1[gamma-P]-ATP of 9.9 +/- 0.7 s. Thus, T1's for CP and ATP were similar at 1.5 T in both human heart and standard solution. In human cardiac 31P-MR spectra, CP/ATP ratios may need little correction for partial saturation.

2,3-Diphosphoglycerate↗
PubMed1992

Influence of antihypertensive therapy on renal function.

Antihypertensive therapy influences kidney function by different mechanisms depending on the mode of action of the drug used. The GFR is improved by calcium entry blockers and ACE inhibitors, unaffected by vasodilators, alpha-blockers and centrally acting sympatholytics and impaired by beta-blockers. The same is true for renal blood flow and is due to changes of renal vascular resistance. Renal sodium excretion is impaired mostly by vasodilators, by alpha-blockers, sympatholytics and beta-blockers; in contrast, calcium entry blockers and ACE inhibitors acutely induce natriuresis. The RAAS is stimulated by vasodilators, unaffected by alpha-blockers and sympatholytics and suppressed by beta-blockers. Plasma catecholamines are stimulated by vasodilators and suppressed by centrally acting sympatholytics and unaffected by the others. Induction of acute renal functional impairment is reported for ACE inhibitors under conditions of compromised renal perfusion pressure such as in renal artery stenosis. These data from the literature reviewed are supported by our own experimental data on sodium balance under different drugs and micropuncture data in experimental renal artery stenosis. To achieve effective antihypertensive treatment with a low profile of side effects, careful monitoring of renal function seems to be mandatory.

Animals↗
PubMed1992

[The direct measurement of the spin-grid-relaxation times of phosphorus metabolites in the human myocardium].

The T1 relaxation times of the phosphorus metabolites in human heart muscle measurable by 31P-MR spectra were determined in 12 individuals using a 1.5 Tesla system. Several spectra were recorded consecutively with a pulse repetition time of 1.6 s to 24 s. The T1 times of creatine phosphate (CP), of gamma-, alpha-, beta-adenosintriphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG) together with anorganic phosphate) and phosphodiester (PDE) showed mean measurements of 6.1 +/- 0.5, 5.4 +/- 0.5, 5.0 +/- 0.5, 5.8 +/- 1.0, 7.6 +/- 1.0, and 5.0 +/- 1.0 s (M +/- SE). The accuracy of the ISIS technique was tested with a special phantom. T1 times were also measured in standard solutions (20 mM CP, 10 mM ATP); CP was 8.7 +/- 0.2 s and gamma-ATP was 9.9 +/- 0.7 s. Corrections for partially saturated 31P-MR spectra--at least for CP/ATP ratios--are relatively small.

2,3-Diphosphoglycerate↗
PubMed1992

[MR tomographic volumetry of the subarachnoid space in HIV-associated brain atrophy].

The CSF volume of 45 patients with HIV infection was measured at various clinical stages and the results compared with 24 normals. 60% of all patients showed increased CSF spaces as an indication of cerebral atrophy. Serial measurements were particularly valuable during the early stages of atrophy since there is marked variation in the normal CSF volume. Conventional measurements, with the exception of the width of the third ventricle, were much less sensitive than these quantitative measurements. Classification of HIV infection according to the clinical stage was useful since CSF volume and volume increase correlated with the stage of HIV infection.

AIDS Dementia Complex↗
PubMed1992

31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Altered cardiac high-energy phosphate metabolism in heart failure.

BACKGROUND: The purpose of this work was to further define the value of cardiac 31P magnetic resonance (MR) spectroscopy for patients with coronary artery disease and dilated cardiomyopathy. METHODS AND RESULTS: Blood-corrected and T1-corrected 31P MR spectra of anteroseptal myocardium were obtained at rest using image-selected in vivo spectroscopy localization, a selected volume of 85 +/- 12 cm3, and a field strength of 1.5 T. Nineteen volunteers had a creatine phosphate (CP)/ATP ratio of 1.95 +/- 0.45 (mean +/- SD) and a PDE/ATP ratio of 1.06 +/- 0.53; in four patients with left anterior descending coronary artery (LAD) stenosis, six patients with chronic anterior wall infarction, and four patients with chronic posterior wall infarction, CP/ATP and phosphodiester (PDE)/ATP ratios did not differ from those in volunteers. Twenty-five measurements of 19 patients with dilated cardiomyopathy yielded a CP/ATP of 1.78 +/- 0.51 and a PDE/ATP of 0.98 +/- 0.56 (p = NS versus volunteers). When these patients were grouped according to the severity of heart failure, however, CP/ATP was 1.94 +/- 0.43 in mild (p = NS versus volunteers) and 1.44 +/- 0.52 in severe DCM (p < 0.05), respectively. No correlation was found between CP/ATP and left ventricular ejection fraction or fractional shortening, but correlation of CP/ATP with the New York Heart Association (NYHA) class was significant (r = 0.60, p < 0.005). Six patients with dilated cardiomyopathy were studied repeatedly before and after 12 +/- 6 weeks of drug treatment leading to clinical recompensation with improvement of the NYHA status by 0.8 +/- 0.3 classes. Concomitantly, CP/ATP increased from 1.51 +/- 0.32 to 2.15 +/- 0.27 (p < 0.01), whereas PDE/ATP did not change significantly. CONCLUSIONS: Cardiac high-energy phosphate metabolism at rest is normal in LAD stenosis and chronic myocardial infarction in the absence of heart failure. The CP/ATP ratio has low specificity for the diagnosis of dilated cardiomyopathy. However, CP/ATP correlated with the clinical severity of heart failure and may improve during clinical recompensation.

Adult↗
PubMed1992

Silences: helping elderly Holocaust victims deal with the past.

Persons who have faced severe crises such as the Holocaust in Nazi Germany confront painful memories, guilt, and the perceived irrationality of their own survival, which represses thoughts and memories. There is no language to share the dark and difficult years of the past. Silence is their only voice of expression. In later life, when friends are gone, the need to share with others becomes urgent; to bear witness is vital. Helping persons share these experiences is no easy task. To engage the elderly with reminiscences, memory, bereavement, and the working through of guilt provide unusual challenges for the helping professions. Significant family events are also important opportunities for sharing the past. It is the children and grandchildren's desire to know that also prompts the sharing of past horrors and future hopes. They often enable the deepest silences to be shared and it is the elderly that often welcome this opportunity. Being sensitive to these integenerational dynamics are important in helping elderly Holocaust victims deal with their past.

Adaptation, Psychological↗
PubMed1992

Present status of kidney transplantation.

Kidney transplantation today is the method of choice to treat end-stage renal disease (ESRD) in more than 50% of the ESRD-population. Due to major improvements in surgical handling, immunosuppressive therapy, and infection control, the one-year survival for patients and first grafts has reached nearly 90% in the recent years. In contrast no comparable achievements have been made in long-term graft survival. A constant number of grafts is lost yearly after the first postoperative year. In addition an increasing number of well functioning grafts is lost due to the death of the recipients caused mainly by cardiovascular and malignant disorders. The extension of kidney transplantation to all suitable recipients is nearly exclusively hampered by the organ shortage, which is further enhanced by failing grafts. This urges us to further improve the prognosis for patient and graft. This must include organ sharing on the basis of improved HLA-typing to achieve highly compatible grafts. The tools for differential diagnosis of acute and chronic graft dysfunction have to be improved. New immunosuppressive agents with higher immunosuppressive power and specificity but fewer nephrotoxic, metabolic and hemodynamic side effects are required at least for chronic rejection. The risk of infectious and malignant complications must be limited.

Cadaver↗
PubMed1992

Glomerular hemodynamics of the clipped kidney: effects of captopril and diltiazem.

Glomerular hemodynamics of the clipped kidney in two kidney-one clip Goldblatt-hypertensive rats were studied by micropuncture techniques after administration of either captopril (20 mg/kg of b.wt./day p.o.) or diltiazem (3 mg/kg of b.wt./hr i.v.). Both drugs decreased mean arterial and poststenotic renal arterial pressure to comparable levels. Total kidney glomerular filtration rate was not significantly different in the three groups (0.78 +/- 0.09 in hypertensive controls, 0.62 +/- 0.11 after captopril and 0.74 +/- 0.07 ml/min/g of kidney weight after diltiazem). Glomerular capillary pressure fell significantly in both treated groups but was lower in captopril-treated animals (60 +/- 2 in hypertensive controls, 45 +/- 2 after captopril and 53 +/- 1 mm Hg after diltiazem, both P < .05 vs. hypertensive controls). Afferent arteriolar resistance was lowered in both treatment groups to the same extent, whereas only captopril decreased efferent arteriolar resistance. Single nephron filtration rate of cortical nephrons was not altered significantly by captopril due to a 96% increase in the ultrafiltration coefficient and a 58% rise in glomerular plasma flow, whereas diltiazem increased ultrafiltration coefficient by 62% but did not affect glomerular plasma flow. These studies indicate that, despite of decreased effective filtration pressure, glomerular filtration rate is well preserved after converting enzyme inhibition. Captopril and diltiazem have different effects on glomerular hemodynamics within the stenosed kidney.

Angiotensin II↗
PubMed1991

Expression of interleukin-6 and interleukin-6 receptor in Hodgkin's disease.

Interleukin-6 (IL-6) is a multipotent lymphokine that can mediate differentiation of B cells into Ig-secreting cells, stimulate the growth of plasmacytomas, hybridomas, and T cells, and induce acute-phase proteins in liver cells. It has been suggested that IL-6 is involved in the pathogenesis of several diseases by autocrine or paracrine pathways. To examine whether IL-6 is possibly involved in the pathophysiology of Hodgkin's disease (HD), we analyzed the expression of IL-6 and IL-6 receptor mRNA and protein in cell lines and primary specimens from patients with HD. IL-6-specific transcripts were detected in three of six HD-derived cell lines by Northern blot analysis. In the culture supernatants of four HD-derived cell lines, IL-6 was detected by radioimmunoassay. Biologic activity of IL-6 was confirmed by proliferation of an IL-6-dependent cell line. In situ hybridization experiments showed IL-6-specific transcripts in Hodgkin (H) and Reed-Sternberg (RS) cells in primary tissues of two patients. In addition, mRNAs specific for the IL-6 receptor were detected in five HD-derived cell lines. Immunostaining experiments showed expression of IL-6 receptor molecules on H and RS cells in 8 of 16 cases with HD. Thus, our data suggest that IL-6 might be involved in the pathophysiology of HD.

Antibodies, Monoclonal↗
PubMed1991

Transcription, translation and secretion of interleukin 1 and tumor necrosis factor: effects of tebufelone, a dual cyclooxygenase/5-lipoxygenase inhibitor.

We examined the effect of tebufelone, a dual cyclooxygenase (CO)/5-lipoxygenase (LO) inhibitor, on the synthesis, secretion and gene expression of interleukin (IL) 1 beta and tumor necrosis factor (TNF)-alpha by human peripheral blood mononuclear cells (PBMC). Basal concentrations of immunoreactive IL 1 beta and TNF-alpha after 18-24 h, in the absence or presence of tebufelone (less than or equal to 12.5 microM), were near the limit of detection (100 pg/ml). By contrast, preincubation (1 h) of cells, in amounts of tebufelone which decrease the formation of leukotriene (LT) B4, markedly enhanced (up to 500%) the synthesis of IL 1 beta and TNF-alpha following lipopolysaccharide (LPS), heat-killed Staphylococcus epidermidis or concanavalin A stimulation. Moreover, a disproportionate amount of the overall increase in IL 1 (alpha and beta) was secreted in contrast to the amount which remained cell associated, an effect unrelated to cell damage or leakage as tebufelone had no effect on either lactate dehydrogenase release by PBMC, or mitochondrial dehydrogenases of adherent monocytes as detected by enzymatic cleavage of the substrate 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide. There was no inverse correlation between the changes in prostaglandin (PG)E2 levels and TNF-alpha or IL 1 beta synthesis, and when PG formation was maximally inhibited by preincubating the cells in indomethacin, tebufelone, added 1 h before the stimulus, continued to enhance the synthesis of IL 1 beta although not that of TNF-alpha. The addition of the CO/5-LO inhibitor 2 h after LPS stimulation, however, did not interfere with IL 1 beta synthesis, suggesting that tebufelone interacts with an early event(s) in the activation of PBMC. For IL 1 beta and TNF-alpha, basal and stimulated (4 h post LPS) mRNA levels were not increased by tebufelone, despite a concomitant increase in the synthesis of IL 1 beta. In conclusion, we have demonstrated that tebufelone enhances IL 1 (alpha and beta) and TNF-alpha synthesis at concentrations which suppress leukotriene formation. These findings argue against a role of 5-LO products as necessary intermediates of IL 1 (alpha and beta) and TNF-alpha synthesis.

Alkynes↗