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Biomedical subjects

R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 325 records · Page 18Linked to original sources
PubMed1993

[Mobilization of hematopoietic stem cells in peripheral blood by leukapheresis].

To improve the separation results of peripheral blood stem cells (PBSC), cytokines (GM-CSF, G-CSF or IL3) can be administered to patients. The most important prerequisites for successful PBSC separation are daily monitoring of CD-34-positive cells to determine the separation days and the use of optimized separation programs. To improve the performance of the cell separation, we increased the process volume to more than patients' blood volume and obtained increased MNC and CFU recoveries. In most cases, we collected more cells than the preseparation number of circulating cells. We therefore conclude that large-volume PBSC separation itself mobilizes hematopoietic progenitor cells.

Antigens, CD↗
PubMed1993

[Optimizing leukocytapheresis for collection of circulating hematopoietic stem- and precursor cells by multiparameter flow cytometry].

Peripheral blood stem cells are an alternative to bone marrow-harvested stem cells. We report on the feasibility of predicting optimal timing for leukapheresis by means of blood monitoring for CD34-positive cells by flow cytometry. In addition to monitoring, determinations of CD34-positive cells also are predictive for the hemopoietic potency of cells harvested by leukapheresis, as close correlations of numbers of CFU-GM and of CD34-positive cells, respectively, in leukapheresis samples are determined. Our data are indicating that flow-cytometrical determinations of CD34-positive cells are helpful in the setting of blood stem cell harvesting by leukapheresis, both for optimal timing of the procedure and for real-time estimation of the hemopoietic potency of cells harvested.

Antigens, CD↗
PubMed1993

Activation of neutrophils in the microvasculature of the ischaemic and reperfused myocardium.

In 11 rats, the microcirculation of the repeatedly ischaemic (stunned) left ventricular myocardium was studied using in vivo fluorescence microscopy. Stunning was provoked by six subsequent 10 min ligations of the left anterior descending coronary artery, each of them followed by a 20 min reperfusion period. In the stunned myocardium showing hypokinetic wall motion, myocardial blood flow dropped by 55%; in this region, leukocytes often appeared in slow-flow capillaries plugging capillary branches. Closely linking to leukocyte adherence, a rise of microvascular permeability was documented by extravascular clouds of fluorescent dextran. After nifedipine treatment, in ischaemic regions marked dilatation of larger A1 and A2 arterioles was noted, in addition to the ischaemia-induced dilatation of smaller A3 and A4 arterioles. Furthermore nifedipine and nisoldipine reduced the number of adherent leukocytes in post-capillary venules and capillaries of the repeatedly ischaemic myocardium. In 12 patients with coronary one-vessel disease and without previous transmural myocardial infarction, elective coronary angioplasty (PTCA) was performed (balloon inflation for 2 min). After elective PTCA of the LAD, a significant rise in the proportion of activated neutrophils was noted. After elective 2 min PTCA of the LAD, coronary sinus blood samples showed a marked rise of FMLC stimulated superoxide anion production, whereas passive deformability decreased considerably. Furthermore, an increase in chemotactic activity in coronary sinus blood samples was observed.

Angioplasty, Balloon, Coronary↗
PubMed1993

Water birth--is it safe?

Water births have gradually become more popular in industrialized countries during the last decade. People advocating this form of delivery argue that the buoyancy in water helps the mother to relax and that the warmth helps reduce pain, meaning that the whole labor process and experience is positively influenced and even accelerated. Due to the sitting position and lower pressure gradient, there are supposedly fewer injuries to the birth canal, and delivery is also claimed to be easier on the child. However there is a great lack of scientific data. We have found only one publication in a peer reviewed journal with some 100 water births described. In a case controlled study not published the authors found fewer birth canal injuries and less use of analgesics but the difference was only slight. There was no difference in the length of labor. Several neonatal deaths are reported during uncontrolled water births. Based on the knowledge available to date, physiologic and general considerations (e.g. risk of infections, risk of hypoxia, risk of aspiration), water births must be classified as a type of obstetrical management, whereby the risks are still too undetermined to be said to be a safe form of birth. Water births should, thus, be restricted to centers with adequate medical assistance, and only in randomized, controlled studies who fulfill the Declaration of Helsinki. In any other setting water births should be rejected, since too little is known about the safety of this method.

Animals↗
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

Doppler ultrasound examination of fetal renal arteries.

This study used color Doppler imaging to establish the normal values of the pulsatility index in the fetal renal arteries in a group of 304 uncomplicated singleton pregnancies. The measurements were taken between 26 and 42 weeks of gestation. The median was 2.79 (95% confidence interval: 2.72-2.86) for 26 weeks' gestation, and it then fell linearly to 1.96 (95% confidence interval: 1.92-2.00) at 40 weeks. Compared with values published so far in the literature, the range was clearly smaller. These normal values could be used as a basis for further investigations on these vessels.

Journal Article↗
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↗