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Biomedical subjects

R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 19 recordsLinked to original sources
PubMed1992

Structural requirements for transport of preprocecropinA and related presecretory proteins into mammalian microsomes.

The presecretory protein preprocecropinA (which comprises 64 amino acid residues) as well as a synthetic hybrid between preprocecropinA and dihydrofolate reductase (which comprises 252 amino acid residues) are processed by and transported into mammalian microsomes. Transport of both precursor proteins can take place cotranslationally, i.e. with the aid of ribosome and signal recognition particle, or posttranslationally, i.e. independently of these ribonucleoparticles (RNPs). We investigated the role of the precursor structure with respect to competence for RNP-independent transport by constructing deletion mutants and hybrid proteins. The results demonstrate that the signal peptide is essential for RNP-independent transport. Furthermore, the signal peptide is sufficient for translocation of preprocecropinA derivatives up to 85 amino acid residues in size. However, the conformation of the precursor protein is decisive in the case of larger hybrid proteins.

Amino Acid Sequence↗
PubMed1992

Decreased concentration of myofibrils and myofiber hypertrophy are structural determinants of impaired left ventricular function in patients with chronic heart diseases: a multiple logistic regression analysis.

OBJECTIVES: The aim of this study was to perform a multiple logistic regression analysis to identify independent structural determinants of impaired left ventricular function. BACKGROUND: The association between contractile failure and structural alterations of the myocardium has been demonstrated in several studies, and multiple interactions between myocardial structure and cardiac performance are likely. METHODS: Morphometric data assessed from 130 left ventricular biopsy specimens were analyzed. The endomyocardial specimens were obtained from 57 patients with normal coronary arteries (17 with normal left ventricular ejection fraction and 40 with impaired left ventricular function [dilated cardiomyopathy]), 15 patients with hypertrophic cardiomyopathy and 32 patients with aortic valve disease. Transmural biopsy specimens were assessed in 6 donor hearts before heart transplantation and in 20 patients with left anterior descending coronary artery disease whose specimens were obtained from the left ventricular anterior wall during aortocoronary bypass surgery. Global or regional left ventricular function was evaluated from left cineventriculograms. The volume fraction of cardiac fibrous tissue, intracellular volume fraction of myofibrils, volume fraction of myofibrils related to myocardial tissue (including fibrosis) and myofiber diameters were determined from semithin sections of the biopsy specimens with the use of light microscopic morphometry. RESULTS: Multiple logistic regression analysis revealed decreased volume fraction of myofibrils (p < 0.005) and increased fiber diameter (p < 0.002) as independent determinants of impaired left ventricular function. CONCLUSIONS: These data indicate that, independent of the underlying heart disease, both decreased concentration of contractile proteins and myocyte hypertrophy are independently associated with impaired left ventricular function.

Age Factors↗
PubMed1992

Hsp90 chaperones protein folding in vitro.

The heat-shock protein Hsp90 is the most abundant constitutively expressed stress protein in the cytosol of eukaryotic cells, where it participates in the maturation of other proteins, modulation of protein activity in the case of hormone-free steroid receptors, and intracellular transport of some newly synthesized kinases. A feature of all these processes could be their dependence on the formation of protein structure. If Hsp90 is a molecular chaperone involved in maintaining a certain subset of cellular proteins in an inactive form, it should also be able to recognize and bind non-native proteins, thereby influencing their folding to the native state. Here we investigate whether Hsp90 can influence protein folding in vitro and show that Hsp90 suppresses the formation of protein aggregates by binding to the target proteins at a stoichiometry of one Hsp90 dimer to one or two substrate molecule(s). Furthermore, the yield of correctly folded and functional protein is increased significantly. The action of Hsp90 does not depend on the presence of nucleoside triphosphates, so it may be that Hsp90 uses a novel molecular mechanism to assist protein folding in vivo.

Animals↗
PubMed1992

Myocardial scintigraphy with iodine-123 phenylpentadecanoic acid and thallium-201 in patients with coronary artery disease: a comparative dual-isotope study.

To characterise the clinical usefulness of serial myocardial scintigraphy with iodine-123 phenylpentadecanoic acid (IPPA) in comparison with thallium-201, dual-isotope investigations were performed in 41 patients with angiographically documented coronary artery disease. Both tracers were administered simultaneously during symptom-limited ergometry. Planar scintigrams were acquired immediately after stress, and delayed imaging was performed after 1 h for IPPA and 4 h for 201Tl. Scintigrams were evaluated both qualitatively and quantitatively using a newly developed algorithm for automated image superposition. Initial myocardial uptake of both tracers was closely correlated (r = 0.75, p < 0.001). Both tracers also revealed a similar sensitivity for the identification of individual coronary artery stenoses > or = 75% (IP-PA: 70.0%, 201Tl: 66.3%, P = NS) with identical specificity (69.8%). The number of persistent defects, however, was significantly higher with IPPA (P = 0.021), suggesting that visual analysis of serial IPPA scintigrams may overestimate the presence of myocardial scar tissue. On the other hand, previous Q wave myocardial infarction was associated with a decreased regional IPPA clearance (29% +/- 11% vs 44% +/- 11% in normal myocardium, P < 0.05). The data indicate that serial myocardial scintigraphy with IPPA is essentially as sensitive as scintigraphy with 201Tl for the detection of stress-induced perfusion abnormalities. Quantitative analysis of myocardial IPPA kinetics, however, is required for the evaluation of tissue viability.

Algorithms↗
PubMed1992

Silver-stained nucleolar organizer proteins in urothelial bladder lesions. A morphometric study.

The diagnostic value of image analysis of silver-stained nucleolar organizer regions (AgNORs) has been investigated in 170 urothelial bladder lesions obtained by transurethral biopsies in the same number of patients. According to the WHO classification 25 specimens showed a flat non-invasive growth pattern with simple hyperplasia or mild dysplasia (H/D1 = 10), as well as moderate (D2 = 10) to severe atypia (Cis = 5). 135 samples were of papillary and/or infiltrating type including polypoid cystitis (pC = 5), true papillomas (G0 = 7), and carcinomas of different malignancy grade (G1 = 30, G2 = 55, G3 = 38). 10 biopsies served as normal controls. Benign non-neoplastic urothelium (controls, H/D1, pC) exhibited few but large AgNORs (mean number [MNN] = 3.3 +/- 0.5, mean area [MNA] = 0.29 +/- 0.08 micron 2), whereas carcinomatous lesions (Cis, G1-G3) showed numerous small silver-stained dots within their nuclei (MNN = 6.9 +/- 1.1; MNA = 0.12 +/- 0.04 micron 2). Both parameters, MNN and MNA, were inversely correlated (r = -0.69, p less than 0.001); their quotient (NQ = MNN/MNA) revealed a clear cut difference in the AgNOR content of benign (control, H/D1:NQ = 12.8 +/- 2.5) and moderate to severe atypical flat urothelial lesions (D2, Cis: NQ = 44.2 +/- 12.8, p less than 0.001). This parameter also discriminated between G1 (NQ = 40.7 +/- 17.3), G2 (NQ = 57.5 +/- 18.8), and G3 carcinomas (NQ = 79.0 +/- 21.8, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Histocytochemistry↗
PubMed1992

Bone marrow processing with the Fresenius AS 104: initial results.

Prior to purging, cryopreservation, or ABO-incompatible bone marrow (BM) transplantation, we have concentrated 23 BM harvests using a modification of the "grancollect-protocol" and the recently available bone marrow stem cell (BMSC) protocol of the Fresenius AS 104 cell separator with the P1-Y set. Within 40-70 minutes, the initial marrow volume of 922 ml (+/- 408 ml) was processed two to three times. A mean of 59% (+/- 20%) of the initial mononuclear cells was recovered in a mean volume of 119 ml (+/- 31 ml). The recovery of clonogenic cells, measured by CFU-GM assays, was 98% (+/- 80%). Red blood cells in the BM concentrates were reduced to 8% (+/- 4%) of the initial number. The procedure was efficient and yielded a BM cell fraction suitable for purging, cryopreservation, and transplantation. All transplanted patients showed fast and sustained engraftments after autologous or allogeneic BM transplantation.

Bone Marrow Cells↗
PubMed1992

Transcranial Doppler sonography: effects of halothane, enflurane and isoflurane on blood flow velocity in the middle cerebral artery.

Systolic, diastolic, and mean blood flow velocity in the middle cerebral artery (Vs,mca; Vd,mca; Vm,mca) and pulsatility (Vs-Vd)/Vm of the waveform obtained were recorded in 51 patients before, during and after general anaesthesia. Transcranial Doppler (TCD) sonographic variables were measured in the awake patient and after induction of anaesthesia with thiopentone 5-6 mg kg-1. After tracheal intubation, 17 patients received 0.8% halothane and 66% nitrous oxide in oxygen for 30 min (15 min normoventilation; 15 min hyperventilation). The inspired halothane concentration was then increased to 1.6% for 45 min (15 min normoventilation; 15 min hyperventilation; 15 min normoventilation with nitrous oxide replaced by oxygen). Enflurane (1.7% for 30 min and 3.4% for 45 min) was given to another 17 patients; 17 other patients received isoflurane (1.2% and 2.4%). Mean arterial pressure (MAP), nasopharyngeal temperature, end-tidal carbon dioxide concentration, inspired and end-tidal anaesthetic agent concentrations, haemoglobin concentration, PVC and TCD variables were measured at the end of each 15 min period. After recovery from anaesthesia, TCD variables were measured again. There were no intergroup differences in changes in MAP, nasopharyngeal temperature, haemoglobin concentration and PCV. Halothane, enflurane and isoflurane at low doses and normoventilation had little influence on TCD variables compared with awake values. In large concentrations with nitrous oxide in oxygen and normoventilation, there were differences between the volatile agents. Halothane increased blood flow velocities, but enflurane and isoflurane caused little change. Hyperventilation always decreased blood flow velocities and increased pulsatility.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Reduction of myocardial ischemia by gallopamil: a dual-isotope study with thallium-201 and iodine-123 phenylpentadecanoic acid.

The present study was performed for characterizing the effect of chronic oral treatment with the calcium antagonist gallopamil on regional myocardial perfusion and free fatty acid utilization in poststenotic human myocardium. Twenty-two patients with angiographically documented coronary artery disease and stable angina pectoris underwent consecutive dual-isotope studies following simultaneous injection of 80 MBq thallium-201 and 200 MBq iodine-123 phenylpentadecanoic acid (IPPA) during a symptom-limited stress test. Radionuclide studies were performed after 1 week of placebo treatment (baseline), 4 weeks after oral treatment with 50 mg of gallopamil t.i.d. and again after 1 week of double-blind treatment with gallopamil or placebo. As compared to baseline, initial (poststress) uptake of both tracers in poststenotic myocardial segments was significantly improved after 4 weeks of treatment with gallopamil [thallium-201, +9.0%; p < 0.001; 95% confidence interval (CI), 4.3-13.6%; IPPA, +11.8%; p = 0.003; 95% CI, 4.2-19.3%]. Poststenotic IPPA-clearance was likewise significantly increased (+28.2%; p < 0.001; 95% CI, 12.4-44.0%) indicating a considerably enhanced myocardial fatty acid oxidation after treatment. In the final double-blind phase, myocardial uptake of both tracers as well as IPPA clearance remained enhanced in the subgroup of patients receiving gallopamil and returned to baseline values in patients receiving placebo. Thus, in poststenotic myocardium, chronic treatment with gallopamil provokes an improvement of both regional myocardial perfusion (as demonstrated by an increased tracer uptake in poststress scintigrams) and regional myocardial fatty acid utilization (as demonstrated by an increased uptake and clearance of IPPA).

Algorithms↗
PubMed1992

Autoantibodies in HIV-infected hemophilia patients against different epitopes on CD4+ lymphocytes and recombinant CD4.

We studied 684 sera obtained from 20 hemophilia patients with AIDS/AIDS-related complex (ARC), 89 asymptomatic HIV+, 76 HIV- hemophilia patients and 151 healthy controls for antibodies against recombinant CD4 (rCD4). Twenty-two percent of AIDS/ARC patients, 10% of asymptomatic HIV+ patients, 17% of HIV-patients, and 1% of healthy controls had anti-rCD4 antibodies. Purified anti-rCD4 antibodies did not react with human CD4+ lymphocytes. This may explain why formation of anti-rCD4 antibodies correlated neither with the occurrence of autoantibodies against CD4+ lymphocytes nor with a decrease in CD4+ cell counts. Antibodies that were eluted from CD4+ lymphocytes after sequential adsorption and elution with separated CD8+ and CD4+ cells reacted with CD4+ lymphocytes of only some healthy individuals, suggesting diversity of CD4 expression.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Anti-IgG autoantibodies in HIV-infected hemophilia patients.

Sera of 76 HIV-negative hemophilia patients, 103 HIV-positive (HIV+) hemophilia patients free of AIDS or AIDS related complex (ARC), and 32 HIV+ hemophilia patients with AIDS/ARC were tested for four different anti-IgG activities. IgG-anti-F(ab')2 gamma, IgM-anti-F(ab')2 gamma, and IgG-anti-Fc gamma serum activities were significantly associated with the clinical stage of HIV infection, whereas IgM-anti-Fc gamma was not. IgG-anti-F(ab')2 gamma activity was found to be caused by cross-reaction of anti-HIV antibody with an epitope within the constant CH1 domain of human IgG. HIV+ hemophilia patients with severe thrombocytopenia (less than 50,000/microliters platelet counts) had significantly higher IgM-anti-IgG activity than patients with greater than 50,000/microliters platelets. Because anti-IgG antibodies possess immunoregulatory properties, our results may serve as a possible explanation for the frequent B cell disorders encountered in HIV-infected patients.

AIDS-Related Complex↗
PubMed1992

Bone marrow purging prior to autologous transplantation.

Our data suggest that ex vivo bone marrow purging using monoclonal antibodies (MoAbs) and sheep-anti-mouse immunobeads (SAM beads) prior to autologous bone marrow transplantation (ABMT) allows satisfactory tumor cell reduction without critical stem cell losses. Nevertheless, there is only a reduction but no elimination of tumor cells. The consequences will have to be clinically discussed.

Antibodies, Monoclonal↗
PubMed1992

Effect of gallopamil on neutrophil function: experimental and clinical studies.

The purpose of the study was to investigate whether gallopamil interferes with neutrophil activation. In vitro, gallopamil caused a dose-dependent reduction in phorbol myristate acetate-stimulated superoxide anion production by neutrophils as measured by the superoxide dismutase inhibited reduction of cytochrome C [concentration of 50% inhibition (IC50) = 9.5 x 10(-6) mol/L]. Furthermore, gallopamil reduced the platelet-activating factor-induced loss of neutrophil deformation, which was assessed by filtrometry (IC50 = 4.3 x 10(-6) mol/L). The effect of gallopamil was assessed in 24 patients during elective balloon angioplasty. Gallopamil (0.4 mg) or placebo (double-blind conditions) was administered by intracoronary application during the 10-min interval between the first two balloon inflations. In the placebo group, blood samples obtained simultaneously from the coronary sinus and from the femoral artery revealed an increase in the proportion of activated neutrophils in the coronary sinus blood after the second balloon inflation [nitro blue tetrazolium (NBT) score, NBT test: 15 +/- 9% relative coronary sinus and arterial blood difference, p < 0.05]; these changes in NBT score were similar to those after the first balloon inflation. In the gallopamil-treated group, however, significant arterial and coronary sinus blood differences in NBT scores were not found after the second balloon inflation. Gallopamil may, thus, attenuate the local neutrophil activation during balloon angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1992

Intracoronary gallopamil during percutaneous transluminal coronary angioplasty.

The present study was designed to investigate the effect of the calcium-channel antagonist gallopamil on myocardial ischemia during percutaneous transluminal coronary angioplasty (PTCA). Twenty-four adult patients with coronary artery disease and significant proximal stenosis of the left anterior descending coronary artery (LAD) were randomly assigned to receive gallopamil or placebo under double-blind conditions. Patients with recent myocardial infarction, apparent collateralization of the LAD, myocardial failure, sinoatrial or atrioventricular block, severe hepatic disease, or renal failure were excluded from the study. PTCA was performed with use of at least two balloon inflations, each of 2 min in duration. Gallopamil (0.4 mg) or placebo (0.9% sodium chloride) was administered during the 10-min interval between the two inflations. For determination of myocardial lactate and hypoxanthine release, blood samples were taken simultaneously from the great cardiac vein and the femoral artery before and immediately after each inflation. Electrocardiogram changes were analyzed by measuring ST-segment deviations (80 ms after the J point) and maximal T-wave deviations of the leads I, II, III, and V2, V4, and V6. The most sensitive leads for identification of myocardial ischemia in the LAD area were V2 and V4. If compared to the first balloon inflation, the degree of ST-segment/T-wave changes induced by the second inflation was significantly reduced only in the presence of gallopamil. Furthermore, if compared to placebo, ischemia-induced lactate and hypoxanthine release was decreased in the presence of gallopamil. These results suggest that intracoronary application of gallopamil attenuates myocardial ischemia during PTCA.

Adult↗
PubMed1992

[Autologous blood donation and erythropoiesis].

Autologous blood donation before elective surgery has been widely endorsed as good transfusion practice. Although only 6% of patients undergoing elective orthopedic surgery are unable to donate 3 autologous units, 40% cannot donate 4 units because they become anemic. According to the results of our study this must be due to different problems of bone marrow dynamics, which cannot be overcome by unselected use of human recombinant erythropoietin.

Adult↗
PubMed1992

[Hemoglobin follow-up of orthopedic autologous blood transfusion patients].

Patients undergoing autologous donation prior to elective orthopedic surgery show better Hb values during the perioperative period compared to those without autologous donation, all patients in both groups receiving no homologous transfusion. The widely assumed improvement of Hb regeneration during the postoperative period according to an erythropoiesis stimulated by preoperative autologous donation is not supported by our data.

Adult↗
PubMed1992

[Acquired autoimmune hemolytic anemia after liver transplantation by "auto"-anti-A and "auto"-anti-P1].

A 47-year-old man (group A) received a cadaver liver from a group 0 donor. On day 8 after the transplant the recipient developed severe immune hemolysis and showed a positive direct antiglobulin test due to two antibodies (anti-A and anti-P1) of transplant donor origin. The possible mechanisms involved in "autoantibody" formation in the recipient are discussed.

ABO Blood-Group System↗