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R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 253 records · Page 14Linked to original sources
PubMed1995

Residual 201Tl activity in irreversible defects as a marker of myocardial viability. Clinicopathological study.

BACKGROUND: The objective of the present study was to characterize the relation between the residual 201Tl activity in irreversible perfusion defects and the extent of irreversible myocardial damage indicated by the volume fraction of myocardial interstitial fibrosis in patients with chronic coronary artery disease. METHODS AND RESULTS: Stress planar 201Tl scintigraphy with tracer reinjection at rest was performed in 37 patients with > or = 75% stenosis of the left anterior descending coronary artery, and anteroseptal 201Tl activity was quantified by computer-assisted placement of regions of interest from the serial myocardial images. During coronary artery bypass grafting (performed within 6 +/- 3 weeks after scintigraphy), two transmural biopsy specimens were taken from the anterior wall of the left ventricle and the amount of interstitial fibrosis was assessed by use of light microscopic morphometry. A wide spectrum of interstitial fibrosis was obtained, ranging from 15 vol% to 60 vol%. Interstitial fibrosis was similar in patients with reversible (n = 11) or irreversible (n = 15) tracer defects in conventional stress-redistribution images. However, interstitial fibrosis was significantly lower in patients who had enhanced regional 201Tl activity after tracer reinjection compared with those who did not have enhancement of tracer activity after reinjection (28 +/- 8 vol%, n = 7, versus 41 +/- 12 vol%, n = 8; P = .031). The correlation between relative poststenotic 201Tl activity and interstitial fibrosis after tracer reinjection was significantly improved compared with conventional redistribution images (r = -.622 versus r = -.851, n = 15; P < .01). CONCLUSIONS: The present data demonstrate that the level of regional 201Tl activity in redistribution and, in particular, reinjection images is significantly related to the mass of preserved viable myocytes in poststenotic left ventricular myocardium. Therefore, the residual 201Tl activity provides information about viability within irreversible perfusion defects and may itself serve as marker of myocardial viability.

Biopsy↗
PubMed1995

Enzyme assembly after de novo synthesis in rabbit reticulocyte lysate involves molecular chaperones and immunophilins.

The folding kinetics of two luciferases were studied after synthesis in reticulocyte lysates to investigate whether molecular chaperones and/or folding catalysts are involved in the folding reactions. Two bacterial luciferases were used as model proteins: heterodimeric Vibrio harveyi luciferase (LuxAB), and a monomeric luciferase fusion protein (Fab2). Data indicate that folding of these enzymes to the native state occurs in the translation system, and that the extent of folding can be quantified. It was found that (i) folding of LuxAB and Fab2 can clearly be separated in time from synthesis, (ii) folding of Fab2 and LuxAB is slow because it involves either transient (Fab2) or permanent (LuxAB) interaction of polypeptides, (iii) preservation of the assembly competent state of LuxA and/or LuxB and folding of Fab2 depend on ATP-hydrolysis, (iv) folding of Fab2 and LuxAB is partially sensitive to cyclosporin A (CsA) and FK506, i.e. inhibitors of two distinct peptidylprolyl cis/trans-isomerases. Thus, bacterial luciferases provide a unique system for direct measurement of the effects of ATP-dependent molecular chaperones on protein folding and enzyme assembly in reticulocyte lysates. Furthermore, these two luciferases provide the first direct evidence documenting the involvement of peptidylprolyl cis/trans-isomerases in protein biogenesis in a eukaryotic cytosol.

Adenosine Triphosphate↗
PubMed1995

Elevated alpha-fetoprotein and human chorionic gonadotropin as a marker for placental trisomy 16 in the second trimester?

In a series of 2961 consecutive cases with second-trimester biochemical triple screening for Down's syndrome and neural tube defect (NTD), ten (0.3 per cent) showed an apparent increased risk for both conditions. Three cases had chromosomal abnormalities, namely trisomy 16 confined to the placenta. Since placental trisomy 16 as well as cases with increased alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) are associated with (intrauterine growth retardation (IUGR), oligohydramnios, and fetal demise, at least some cases with this atypical biochemical profile could be explained by this chromosomal abnormality. From our results we recommend that in cases with increased risk for both Down's syndrome and NTD, fetal karyotyping should preferably be done on a placental biopsy, especially when ultrasound in the absence of anomalies demonstrates early IUGR.

Adult↗
PubMed1995

Altered gene transcription following brief episodes of coronary occlusions.

This study was designed to elucidate whether previously observed enhanced mRNAs were due to accelerated transcription, enhanced mRNA stability or both mechanisms. We employed the nuclear run-on technique on myocardial nuclei and found the transcriptional induction of several genes, especially nuclear protooncogenes, Ca2+ regulating and heat shock protein genes.

Animals↗
PubMed1995

Response of magnesium-deficient saplings in a young, open stand of Picea abies (L.) Karst. to elevated soil magnesium, nitrogen and carbon.

A decline in a Picea abies L. (Karst.) stand in the Fichtelgebirge, NE-Bavaria, FRG has been attributed to a nutritional disharmony-a seasonal imbalance between a high supply of nitrogen, caused by high nitrogen deposition, and a low supply of soil magnesium, caused by soil acidification (Oren et al., 1988a). The nutritional disharmony hypothesis was tested on ten-year-old P. abies saplings in an adjacent stand growing on identical soil. The supply rate of magnesium relative to nitrogen was continuously increased or decreased during three successive growing seasons. Increasing the nitrogen or carbon supply resulted in a small increase in foliar nitrogen concentrations. Magnesium or carbon addition slightly raised the concentration of magnesium in the foliage. Reduction in crown leaf-area did not result in any appreciable changes in nutrient concentrations. Increased N supply decreased foliar Mg concentrations. In spite of the changes in the nutritional status of the needles, gas-exchange rates, pigment concentrations, needle characteristics and growth of twigs and stems did not differ among treatments. It appears that the growth of saplings was unimpaired at the foliar magnesium concentration at which the growth of adjacent mature trees was reduced. Moreover, it was not possible to promote nutritional disharmony in the saplings, including those receiving three times the annual nitrogen input. The study demonstrates that in young, relatively open stands of P. abies, much of the deposited nitrogen is not absorbed by the roots of saplings. Thus, the conceptual model of nutritional disharmony cannot explain forest decline if nitrogen uptake does not increase with deposition. Identifying the processes which control the uptake relative to the supply of all nutrients, and quantifying the rates of nutrient uptake are essential steps in using the conceptual model to explain specific decline symptoms.

Journal Article↗
PubMed1995

Extracellular matrix deposition in hypertensive hearts antifibrotic effects of ramipril.

Hypertension induced in rats by suprarenal banding has a blood pressure elevating effect that is accompanied by the occurrence of cardiac hypertrophy and fibrosis. This phenomenon is already present at 2 weeks after banding and persists up to 1.5 years. The increase in cardiac weight is mostly due to the development of fibrosis, since myocytes are only slightly increased in size. The fibrotic tissue consists mainly of fibronectin and collagen and contains numerous cellular elements. The occurrence of fibrosis can be completely inhibited by the administration of the specific ACE inhibiting drug, ramipril, which indicated that angiotensin II may directly stimulate fibroblasts to produce fibronectin and collagen. The antifibrotic effect of ramipril was also present in a low dosage that did not lower blood pressure, confirming the hypothesis that angiotensin II has a direct effect on connective tissue cells and their ability to produce extracellular matrix proteins. The direct effect of the renin-angiotensin system on the activity of interstitial cells was further proven by molecular biology techniques showing an upregulation of transcription for collagen I and III which is prevented by ACE inhibition.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Preservation of myocardial blood flow by calcium antagonists does not prevent attenuation of regional myocardial function after repetitive brief periods of myocardial ischaemia in the rat heart.

The aim of this study was to assess the effect of two different calcium channel blockers on myocardial blood flow and function in a rat model of myocardial 'stunning' by repeated short episodes of ischaemia ('repetitive ischaemia'). In an open chest rat model, the left anterior descending coronary artery was ligated for 10 min followed by 15 min reperfusion. In total, five periods of ischaemia and reperfusion were performed. Myocardial blood flow was assessed by the hydrogen clearance technique and systolic thickening fraction by pulsed Doppler. After five episodes of ischaemia, myocardial blood flow adn myocardial thickening in the ischaemic area were reduced by 60 +/- 8% and 52 +/- 7% (n=9), respectively, as compared to baseline. Continuous intravenous infusion of the calcium channel blockers nifedipine (n=6) and gallopamil (n=6), started 20 min prior to onset of ischaemia, attenuated the ischaemia-induced decrease of myocardial perfusion. Nifedipine was the most effective with only 5 +/- 2% reduction in blood flow after five ischaemic episodes, whereas reduction of myocardial blood flow was 30 +/- 4% in the presence of gallopamil. However, neither nifedipine nor gallopamil were able to prevent regional ventricular dysfunction induced by repetitive ischaemia. Despite the preservation of myocardial blood flow following repetitive ischaemia, calcium channel blockers do not prevent ischaemia-induced reduction of myocardial function in the ischaemic area.

Animals↗
PubMed1995

rhEPO treatment of postpartum anemia.

Postpartum hemorrhage is a continuing problem occurring in 5-10% of all deliveries. Due to recent problems with blood transfusion, heterologous blood is nowadays restricted to life-threatening indications. As a consequence the clinician is faced with many patients suffering from overt symptoms of anemia. We therefore investigated the effect of recombinant human erythropoietin (rhEPO) in combination with adequate iron supplementation as an alternative for blood transfusion in postpartum anemia. In a pilot study we could show that rhEPO can enhance the effect of endogenous erythropoietin on erythropoiesis. These data could be confirmed in a larger randomized trial. In another study we could show that rhEPO given s.c. is as effective as i.v. Measurement of the iron stores, however, demonstrated low values at the end of pregnancy indicating that iron is a limiting factor for erythropoiesis in postpartum anemia. In a next study i.v. iron combined with rhEPO showed a greater increase in Hb compared to i.v. iron alone. The chosen dose of i.v. iron, however, was too small as shown by the low ferritin levels. We concluded from these previous studies that rhEPO enhances endogenous erythropoiesis, but so far the effect was only slight (ca 1 g/dl within 14 days); all treated patients developed overt iron deficiency in terms of low ferritin levels despite oral and i.v. iron supplementation; no major side-effects were seen. A further study in healthy non pregnant volunteers demonstrated an effect on erythropoiesis lasting for 3-4 days after a single dose of 300 U/kg rhEPO.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗
PubMed1995

Insulin-like growth factor I is involved in inflammation linked angiogenic processes after microembolisation in porcine heart.

OBJECTIVE: Angiogenesis in the porcine heart can be induced by myocardial ischaemia following vascular occlusions. This process is characterised by increased numbers of monocytes/macrophages, known to be potent producers of various mitogens such as insulin-like growth factors (IGF) and interleukins (IL). The aim of the study was to examine gene expression of these factors by means of northern blot hybridisation, slot blot analysis, and in situ hybridisation in a porcine model of coronary angiogenesis. METHODS: Experimental ischaemia and subsequent focal necroses were induced by selective injection of 25 microns microspheres into the left circumflex artery. The hearts were excised after 3-168 h of microembolisation, and tissue was collected from a non-ischaemic control area and the circumflex region of the same heart for further analysis. RESULTS: IGF-I was constitutively transcribed in normal porcine myocardium mainly by myocytes. Following microembolisation, IGF-I mRNA expression was significantly increased in the experimental region (1.8-fold) after 72 h and to a lesser extent after 168 h. In the ischaemic region, characterised by capillary sprouting, numerous mononuclear cells contained IGF-I mRNA. In contrast, IGF-II mRNA levels, constitutively produced by porcine myocytes, were not altered by microembolisation. IL-1 alpha, IL-1 beta, and IL-4 mRNA expression was undetectable in our animal model, whereas IL-6 was constitutively transcribed in normal and ischaemic heart and remained insensitive to microembolisation and focal necrosis. CONCLUSION: After microembolisation, increased IGF-I mRNA expression occurred by infiltrating monocytes in areas of microsphere induced focal necrosis, where capillary sprouting can be detected, suggesting that IGF-I is involved in inflammation linked angiogenic processes.

Animals↗
PubMed1995

Insulin-like growth factor II is an experimental stress inducible gene in a porcine model of brief coronary occlusions.

OBJECTIVE: Previous observations have shown that myocardium activates many adaptive processes after brief ischaemia. The aim of this study was to determine whether insulin-like growth factors (IGF) as well as their receptors and binding proteins (IGFBP), which control the activity of the IGF, may play an important role during these processes. METHODS: Ischaemia was induced in anaesthetised open chest pigs by two 10 min occlusions of the left anterior descending coronary artery, separated by 30 min of reperfusion, and followed by reperfusion up to 210 min. Tissue from the ischaemic area and from a non-ischaemic control region of the same heart was examined by means of northern blot, slot blot, and in situ hybridisation. RESULTS: IGF-I, IGF-II, the type I receptor, the insulin receptor, and IGFBP-2-6 are constitutively expressed in porcine myocardium. In situ hybridisation showed that IGF-I and IGF-II are mainly transcribed by myocytes. Ischaemia/reperfusion led to an early and significant increase in IGF-II mRNA compared to non-sham controls but not in comparison with sham operated animals, which already showed a (not significantly) enhanced IGF-II expression. In each case the IGF-II mRNA levels are equal in the control and the experimental region of the same heart. Whereas IGF-II expression was already increased by experimental stress, IGFBP-5 mRNA was enhanced only by ischaemia/reperfusion. The expression of IGF-I, the receptors, and IGFBP-2, 3, 4, and 6 remained unchanged during the experimental protocol. IGFBP-1 was neither expressed nor induced in our model. CONCLUSIONS: IGF-II acts like a stress-response gene activated by the experimental conditions (surgery, anaesthesia) and remains induced during following episodes of ischaemia/reperfusion. A possible interaction of IGFBP-5 with other components of the IGF system may contribute to the preconditioning response.

Animals↗
PubMed1995

Biotin in vitro translation, nonradioactive detection of cell-free synthesized proteins.

In vitro translation of mRNAs into proteins is frequently used to study the coding capacity of RNAs or cDNAs and the functional effects of mutations. In vitro translation assays have traditionally been monitored by following the incorporation of a radiolabeled amino acid into newly synthesized protein. We have optimized an alternative nonradioactive biotin-labeling method. tRNALys is first aminoacylated with lysine, which is then chemically labeled with biotin. When biotin-lysine-tRNALys is added to translation systems, the biotinylated lysine is incorporated into the growing polypeptide chain. After electrophoresis and transfer to a blotting membrane, the biotin-labeled translation products are detected by a chemiluminescent reaction of luminol/iodophenol with streptavidin-coupled horseradish peroxidase. This nonradioactive method yields results equivalent to those obtained using the radioactive method. Biotin-labeled translation products are also biologically functional: (i) biotinylated precursor proteins are transported and processed correctly by dog pancreas microsomes; (ii) transcription factors synthesized by biotin in vitro translation bind specifically to their DNA recognition sequence; and (iii) biotin-modified luciferase keeps its enzymatic activity. The major advantage of the biotin in vitro translation system is that no radioactivity is required, and the method is easy, economical, reproducible and fast--the whole nonradioactive procedure, from translation to detection, can be completed within six hours.

Animals↗
PubMed1995

Pharmacokinetics and tolerability of factor XIII concentrates prepared from human placenta or plasma: a crossover randomised study.

The pharmacokinetics and tolerability of factor XIII (FXIII) from plasma were compared with those of FXIII from placenta in a randomised, double-blind, crossover study involving 13 patients with congenital FXIII deficiency. Both FXIII activity and FXIII antigen were monitored. No difference was seen in the mean half-lives of the two preparations (9.3 days and 9.1 days for plasma and placenta FXIII activity, respectively). Response was similar for both preparations, but was slightly greater for FXIII from plasma (1.6 ormula: see text] vs 1.5 [formula: see text]). Similar results were found for recovery (65% vs 60%). The area under the data completed by extrapolation was significantly higher for FXIII from plasma. No differences between preparations in terms of efficacy or tolerability were observed. It can be concluded that treatment with FXIII concentrate from plasma is as efficient as with FXIII concentrate from placenta in terms of recovery and half-life. Both preparations were equivalent in terms of safety during the observation period. With the administration of monthly injections of approximately 30 U/kg serious bleeding events were prevented and no other serious adverse events occurred.

Adolescent↗
PubMed1995

[Cardiac gene expression after brief coronary occlusion].

In the pig short coronary occlusions induce molecular damage on the protein level in the myocardium, which elicit repair mechanisms by increased transcription and translation, including the activation of potential transcription factors (protooncogenes), genes involved in repair processes (heat shock genes) or calcium-binding genes. Additionally, some growth factors like insulin-like growth factor II show increased transcription in accordance with their function as trophic factors for reversibly injured myocardium. Changes in mRNA levels mostly are due to increased transcription rates and rarely due to prolonged half-life of the mRNA. However, at present our data do not allow us to conclude which genes are causative for myocardial stunning and/or ischemic preconditioning.

Animals↗
PubMed1995

[Cutaneous larva migrans, autochthonous in France. Apropos of a case].

INTRODUCTION: Cutaneous larva migrans is rarely contracted in temperate countries. CASE REPORT: When his house became flooded, he had to stand for a long period of time with mud up to the thigh. Some days later, he developed multiple erythematous, serpiginous pruritic tracts moving 1-2 cm per day over preexisting lesions of the right leg. Local and systemic treatment with thiabendazole led to rapid and definitive cure. DISCUSSION: Cutaneous larva migrans results from the migration of hookworm larvae in the dead-end human host. It is mainly an imported disease and native cases in Europe as reported here are rare. This case demonstrates that the conditions leading to the development of cutaneous larva migrans are rarely found simultaneously in temperate zones.

Adult↗