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R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 379 records · Page 21Linked to original sources
PubMed1990

Ribonucleoparticle-independent transport of proteins into mammalian microsomes.

There are at least two different mechanisms for the transport of secretory proteins into the mammalian endoplasmic reticulum. Both mechanisms depend on the presence of a signal peptide on the respective precursor protein and involve a signal peptide receptor on the cis-side and signal peptidase on the trans-side of the membrane. Furthermore, both mechanisms involve a membrane component with a cytoplasmically exposed sulfhydryl. The decisive feature of the precursor protein with respect to which of the two mechanisms is used is the chain length of the polypeptide. The critical size seems to be around 70 amino acid residues (including the signal peptide). The one mechanism is used by precursor proteins larger than about 70 amino acid residues and involves two cytosolic ribonucleoparticles and their receptors on the microsomal surface. The other one is used by small precursor proteins and relies on the mature part within the precursor molecule and a cytosolic ATPase.

Amino Acid Sequence↗
PubMed1990

[Normal pressure hydrocephalus. An evaluation 25 years following the initial description].

A quarter of a century after the first description of a condition known as "normal pressure hydrocephalus", there no longer exists serious doubt about the existence of this disease nor about the possibility of treating it surgically with success. Nevertheless, there is still no general agreement on the exact definition of this condition, nor is there confirmed knowledge regarding its pathogenesis. Approximately half of the cases still are designated "idiopathic" in as much as physicians have no clear concept of its etiology. Some progress has been reached concerning the indication for operation: the "resistance to outflow" of cerebrospinal fluid can be measured now exactly by fluid infusion tests and seems to be a valuable predictor of outcome after shunting procedures. Reviewing world literature of the past 25 years reveals: the most important symptom of normal pressure hydrocephalus is not dementia, but disturbances of gait. Patients suffering from dementia, but not from gait-disturbances, do not gain from cerebrospinal fluid shunting and do not need to be investigated by invasive diagnostic procedures. In patients who suffer from gait-disturbances with or without dementia, with or without urinary incontinence, and in whom computed tomography reveals enlargement of ventricles without pronounced cortical atrophy, there should be a measurement of intracranial pressure and of the resistance to cerebrospinal fluid outflow.

Cerebrospinal Fluid Shunts↗
PubMed1990

Influence of melatonin on the sleep-independent component of prolactin secretion.

Sleep has a stimulatory effect on prolactin secretion. Recent studies in the human suggest the hypothesis that prolactin has also an endogenous sleep-independent rhythm, which can be influenced by endogenous melatonin. To investigate this hypothesis, the prolactin response to nighttime exposure to bright light was studied in eight women in detail. Light exposure induces a decrease in nocturnal melatonin secretion. It was demonstrated that exposure to bright light for 2 h at night caused a decrease in prolactin secretion, which surpassed significantly the decline one would expect by sleep deprivation only (P less than 0.01). This was associated with a similar decline in melatonin secretion. Fall and rise of prolactin secretion under these conditions were always preceded by decrease and rise in melatonin levels in all eight women studied. Based on these observations, it is concluded that melatonin is associated with an endogenous circadian component of prolactin secretion. As specific melatonin receptors have been identified in the human nucleus suprachiasmaticus, which is the "master" circadian pacemaker, the observed phenomenon might be mediated through this structure. An alternative explanation of our findings could be based on the fact that melatonin influences dopamine metabolism, which in turn alters prolactin secretion. It can also not be ruled out that melatonin might act via the opioid system, which then could affect prolactin secretion. The total secretory activity for both hormones (area under the curve) did not change under experimental conditions, when compared to a control group. This suggests that acute light exposure and sleep deprivation influence the secretory process rather than the synthesis of these two hormones. This is in agreement with the observation that changes in natural light exposure throughout the year do alter the amplitude, but not the total amount of melatonin secreted. Further studies are needed to answer the question of melatonin storage definitively, as it is commonly believed that melatonin is immediately released after synthesis. It is concluded that melatonin through its external modulator light might entrain the circadian sleep-independent component of prolactin secretion and via its action on prolactin could modulate reproductive processes.

Adult↗
PubMed1990

Activation and decreased deformability of neutrophils after intermittent claudication.

This study investigated local alterations in neutrophil activation and deformability after intermittent claudication. In 17 patients with one-sided peripheral arterial occlusive disease, neutrophil count, proportion of activated neutrophils (by nitro blue tetrazolium test), and neutrophil filterability as a measure of passive deformability were assessed in the femoral arterial and venous blood of the diseased leg and in the femoral venous blood of the healthy leg (n = 10). The values were obtained at rest, immediately after claudication, and 10 minutes after claudication induced by repetitive toe stands. Immediately after exercise, the arterial and venous blood differences in the diseased leg were 1) neutrophil count, 9% (95% confidence interval [CI], 5-14%; relative increase in the venous blood compared with arterial blood); 2) the proportion of activated neutrophils, 26% (CI, 10-42%); and 3) the neutrophil filterability, -10% (CI, -4% to -15%). At rest and 10 minutes after exercise, neutrophil parameters did not differ significantly between the femoral arterial and venous blood. Furthermore, no arterial and venous blood differences in the neutrophil parameters were found in the healthy leg. In addition to local changes, systemic changes occurred immediately after exercise. In the femoral arterial blood, the total neutrophil count had risen by 13% (CI, 8-18%), the proportion of activated neutrophils had risen by 41% (CI, 25-58%), and average neutrophil rigidity had risen 17% (CI, 11-22%) compared with the values obtained before exercise. At 10 minutes after exercise, all neutrophil parameters were still elevated. We conclude that even short periods of ischemia, as in intermittent claudication, cause local alterations in neutrophil function and distribution.

Arteries↗
PubMed1990

Development of a dedicated two-dimensional gel electrophoresis system that provides optimal pattern reproducibility and polypeptide resolution.

The development of a dedicated two-dimensional gel electrophoresis system is described that provides superior performance in terms of high resolving power and enhanced gel-to-gel reproducibility. Isoelectric focusing is performed in a 1-mm capillary tube with a 0.08-mm thread, optimized for this application, incorporated along its length prior to polymerization of the gel matrix. The isoelectric focusing gel is 4% T, 2.6% C to minimize sieving of proteins and promote adhesion of the gel to the thread. The thread incorporated in the isoelectric focusing matrix prevents gel stretching and breakage during its application to the second dimension. An optimum ampholyte pH range has been defined based on 1600 polypeptides present in a transformed fibroblast cell lysate and verified using a variety of other cell types. The length of time required to complete an electrophoretic separation in the second dimension was found to depend on buffer conductivity establishing the importance of high quality electrophoresis grade reagents devoid of contaminating salts. To ensure reproducibility of electrophoretic separations, it is critical to maintain a strict control of temperature during the second dimension separation. This prevents altered migration of some polypeptides relative to neighboring polypeptides that have constant Rfs over a broad temperature range. It was also determined that to obtain the maximum information from a complex protein mixture it is critical to use a large format 22- x 22-cm two-dimensional electrophoretic system. Using the optimized two-dimensional electrophoretic system and computerized gel analysis, it was determined that molecular weight estimates of polypeptides differed by approximately 350 daltons between gels, while isoelectric point estimates differed by approximately 0.03 pH units between gels. Using the two-dimensional electrophoresis system described, approximately 1000 polypeptides can be routinely detected from silver-stained 10% polyacrylamide gels or 1600 polypeptides from autoradiographs of 35S-methionine-labeled polypeptides.

Autoradiography↗
PubMed1990

Role of cytosolic factors in the transport of proteins across membranes.

In a review article published in 1986 we emphasized that an unfolded conformation is a prerequisite for the transport of precursor proteins across membranes, and that cytosolic factors exist whose function is to maintain what we termed the transport-competent conformation of precursor proteins. Subsequent observations in a number of different in vitro systems related both the competent conformation and the cytosolic factors to the recent observations on the ATP-requirements for protein transport. Here we review the currently available data on such factors, and their ATP-requirements, for prokaryotic as well as eukaryotic organisms. Furthermore, we discuss possible models for their action and relate them to the so-called molecular chaperones. These were originally defined as being involved in the proper folding and assembly of oligomeric protein complexes, but have since been shown in addition to facilitate the transport of proteins across membranes.

Biological Transport↗
PubMed1990

Microcirculation in the hypertrophic and ischemic heart.

1. Myocardial hypertrophy, for instance in patients with hypertensive heart disease, is characterized by a reduction of coronary vascular reserve, even in the presence of normal coronary arteries. In hypertensive animals, on the microcirculatory level functional changes can be observed before the onset of any structural rarefications. In 10 rats with renal hypertension and pressure-induced left ventricular hypertrophy (LVH), the microcirculation of the left ventricular myocardium was studied using in vivo fluorescence microscopy and morphometric analysis. Renal hypertension was provoked by clipping of the left renal artery. After 8 weeks, systolic blood pressure in LVH rats averaged 172 +/- 8 mm Hg, compared to 91 +/- 2 mm Hg in 10 normotensive (NT) rats. In LVH rats, distances of plasma-perfused capillaries were significantly increased (NT = 17.7; LVH = 20 microns; p less than 0.001). Volume density, surface density, and length density of capillaries in LVH rats were reduced by 20% compared to NT rats. Capillary red cell content as measured by the ratio of capillaries filled with red cells to those containing plasma alone (Q) in LVH animals exceeded that in NT rats (LVH: Q = 0.83 +/- 0.04; NT: Q = 0.77 +/- 0.04; p less than 0.025). During hypoxia (H, 5% O2) capillary red cell recruitment in LVH rats (Q: control c = 0.83; H = 0.95) was diminished by 33% as compared to NT rats (Q: c = 0.77; H = 0.95). Thus, in addition to the decreased capillary density, the reduction of capillary red cell recruitment may be responsible for chest pain in patients with LVH and normal coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Protein C deficiency with recurrent infarct of the small intestine].

Protein C and antithrombin III represent main inhibitors of the plasmatic coagulation system. Due to the lack of practicable assays the clinical importance of protein C was only established during the last six years. In familial protein C deficiency 77% of patients present with recurrent venous thromboses, half of them below the age of 30. In addition to recurrent superficial thrombophlebitis more serious manifestations like deep vein thrombosis and pulmonary embolism have been described. Mesenteric vein thrombosis has been reported in only 5 cases all of which could be controlled by conservative treatment. In our patient protein C deficiency was discovered 10 years after the angiographic diagnosis of portal and mesenteric vein thrombosis. Thereafter, the patient complained of recurrent abdominal discomfort. Intestinal ischaemia due to mesenteric vein thrombosis required segmental resection twice. Postoperatively the patient was heparinized. After excluding a secondary protein C deficiency due to a lack in vitamin K, hepatic disease, or disseminated intravascular coagulation, long-term anticoagulation by dicumarol was implemented as therapy of first choice.

Female↗
PubMed1990

[Cardiopulmonary resuscitation of children and adolescents in the prehospital stage].

Between 1980 and 1988 52 children have been seen in Stuttgart after out-of-hospital cardiopulmonary resuscitation. In 31 children no circulation could be restored, 21 children could primarily be resuscitated, but only 10 children survived. Outcome was positively influenced if the emergency was witnessed, by immediate lay-person resuscitation, duration of resuscitation efforts under 20 min, and administration of no more than 2 doses of adrenalin.

Adolescent↗
PubMed1989

The reaction specificities of the thylakoidal processing peptidase and Escherichia coli leader peptidase are identical.

Proteins which are transported across the bacterial plasma membrane, endoplasmic reticulum and thylakoid membrane are usually synthesized as larger precursors containing amino-terminal targeting signals. Removal of the signals is carried out by specific, membrane-bound processing peptidases. In this report we show that the reaction specificities of these three peptidases are essentially identical. Precursors of two higher plant thylakoid lumen proteins are efficiently processed by purified Escherichia coli leader peptidase. Processing of one precursor, that of the 23 kd photosystem II protein, by both the thylakoidal and E. coli enzymes generates the correct mature amino terminus. Similarly, leader (signal) peptides of both eukaryotic and prokaryotic origin are cleaved by partially purified thylakoidal processing peptidase. No evidence of incorrect processing was obtained. Both leader peptidase and thylakoidal peptidase are inhibited by a synthetic leader peptide.

Amino Acid Sequence↗
PubMed1989

[In vivo effects of high density lipoprotein rich serum fractions (HDLF) in the human. 1. Modification of circulating thrombocyte aggregates, cardiovascular parameters and lipid metabolism by HDLF].

By means of the modified Cohn-method 6 Cohn-IV-1-fractions were prepared in the small pool technique as sterile, pyrogen-free and HDL-rich serum fractions (HDLF), the HDL-concentrations of which were 15-20 g/l. In in-vitro investigations they inhibited the spontaneous aggregation of erythrocytes as well as the ADP-induced aggregation of thrombocytes and activated the molar and fractional initial cholesterol estirification rates as well as the prostacyclin synthesis. From HDLF intravenously applied in people as immediate effects result significant decreases of the cardiac pre- and afterload, an increase of the cardiac ejection fraction as well as a complete dissolution of circulating aggregates of thrombocytes. In 35 patients with hyperlipidaemias after infusion of 100 ml HDLF up to the 5th day increasing and for 14 days remaining increases of concentration of biliary bile acids, total phospholipids and of cholesterol were observed in lithogenic indices remaining in the normal region. The plasmatic lipo- and apolipoproteins reacted with increases, decreases or constancy of concentration which might be based on the different ethryopathogeneses of the hyperlipoproteinaemias.

Cholesterol, HDL↗
PubMed1989

[In vivo effects of high density lipoprotein rich serum fractions (HDLF) in the human. 2. Effect of repeated HDLF infusions on atherogenic risk factors and arteriosclerotic vascular changes in patients with and without hyperlipoproteinemia].

10 patients with hyperlipoproteinaemia and 4 normolipaemic smokers with angiographically proved arteriosclerosis of different degrees of severity were infused in 2-week intervals 100 ml HDL-rich Cohn-IV-1 fractions each. After the infusion for 5 days essential phospholipids were injected and a permanent medication with cholestyramin and a choleretic drug were prescribed. In the patients with HLP increases of concentration, decreases of concentration, constancy of the plasma lipids and apoproteins independent of the phaenotype of the HLP as well as an improvement of the state of the antioxidant state were observed. In 6 of 10 patients in reproducible vascular areas regressions of athero- und arteriosclerotic findings could be made evident. Progressions were not observed also in extremely changed arteries in contrast to the normolipaemic smokers and the patients of the control group.

Arteriosclerosis↗
PubMed1989

Export of honeybee prepromelittin in Escherichia coli depends on the membrane potential but does not depend on proteins secA and secY.

Honeybee prepromelittin (70 amino acid residues), the precursor of an eukaryotic secretory protein, and a hybrid protein between prepromelittin and mouse dihydrofolate reductase (257 amino acid residues) were expressed in Escherichia coli and characterized with respect to their requirements for transport across the plasma membrane. Both precursor proteins are posttranslationally processed and exported into the periplasm, and they both depend on the membrane potential for this to occur. With respect to dependence on components of the export machinery, however, the two precursor proteins show striking differences: the small precursor protein prepromelittin does not require the function of proteins secA and secY; the large precursor protein prepromelittin-dihydrofolate reductase, on the other hand, depends on both components. The implications of these observations with respect to the mechanisms of protein export in E. coli and of protein import into the endoplasmic reticulum are discussed.

Animals↗