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Biomedical subjects

B Stein

Publications and source records attributed to B Stein.

At least 127 records · Page 7Linked to original sources
PubMed1991

Importance of experimental models for the development of clinical trials on thromboatherosclerosis.

Experimental models of vascular injury have enhanced our understanding of the pathophysiological process leading to vascular obstruction in both spontaneous and accelerated atherosclerosis. Based on experimental findings, we present and discuss a pathological classification of vascular injury or damage and its role in the pathogenesis of various vascular diseases. In addition, these animal models have provided insights into the roles of platelets and lipid metabolism in the evolution and progression of atherosclerosis and have suggested potential therapeutic applications. Thus, based on studies in the pig models, antiplatelet agents have been shown for the first time to have a beneficial effect in preventing the formation and progression of coronary atherosclerotic lesions in humans. Similarly, our findings in high density lipoprotein plasma fractions regarding inhibition and even reversal of the process of atherosclerosis in a hypercholesterolemic rabbit model have added new insights to an explosive field of lipoprotein research and provided new avenues of therapeutic strategies. our in vivo and ex vivo pig models of an extracorporeal perfusion chamber mimicking the various coronary conditions have aided in the understanding of the pathophysiology of the acute coronary syndromes and intensified our search for the ideal antithrombotic regimen in these high-risk patients. Finally, a carotid pig model of balloon angioplasty, a dog model of saphenous vein grafting, and a pig model of heart transplantation not only have provided insights into the pathophysiological process of accelerated atherosclerosis but also are allowing development of new antithrombotic and antiproliferative approaches for the prevention of these accelerated vascular diseases. In summary, we are entering an exciting era in vascular research. Significant advances in our understanding of vascular injury or damage as well as the interactions of blood cells and lipids with the vascular wall have allowed us to formulate new experimental strategies with subsequent clinical application in the prevention and progression of these vascular diseases.

Animals↗
PubMed1990

A novel function of the transforming domain of E1a: repression of AP-1 activity.

Adenovirus E1a represses transcription of the collagenase gene via the phorbol ester-responsive element (collTRE). The mechanism involves inhibition of the trans-activating function of the transcription factor AP-1 without reduction of its synthesis and without any apparent change in DNA binding or composition. The ability of E1a to downmodulate AP-1 is a unique property among dominant oncogenes. This repression depends on conserved region 1, one of the transforming domains of E1a, indicating that it is an integral feature of adenovirus transformation.

Adenovirus Early Proteins↗
PubMed1990

Antithrombotic therapy in cardiac disease: an approach based on pathogenesis and risk stratification.

An approach to the management of thrombosis and embolism in various cardiovascular disorders is discussed. This approach is based on current knowledge of pathogenesis and risk of thromboembolism. Rational therapeutic guidelines are formulated along the lines of anatomic location (arterial circulation, cardiac chambers or prosthetic valves), pathophysiology (activation of platelets or the coagulation system, or both), and degree of thromboembolic risk. With clear understanding of these factors, it may be possible to determine the most suitable platelet inhibitor or anticoagulant regimen for the individual patient, and whether these agents should be given singly or in combination.

Anticoagulants↗
PubMed1990

No difference in basal ganglia mineralization between schizophrenic and nonschizophrenic patients: a quantitative computerized tomographic study.

The role of iron in schizophrenia (SC) has aroused attention because of its modulatory effect on the dopamine receptor and its role as a cofactor for tyrosine hydroxylase. In addition, several postmortem studies suggest that increased mineralization (especially iron) of the basal ganglia is a possible clinicopathological correlate of schizophrenia. In order to quantitate the in vivo mineral content in the basal ganglia of patients with SC, a protocol was developed to analyze CT scans films with a LOATS computer analysis system. A total of 725 consecutive CT scans (275 SC, 450 nonSC) from a psychiatric population were reviewed. Eighteen scans (2.3%) revealed basal ganglia mineralization of which 7 cases carried a diagnosis of SC and 11 had other psychiatric disorders. All subjects had received neuroleptics, and 8 of the 11 patients in the nonschizophrenic group were demented. Both the SC and nonSC patients exhibited a prevalence (2.5%) of basal ganglia mineralization similar to that found in a postmortem series of the general population.

Adult↗
PubMed1990

Radiation-induced activation of transcription factors in mammalian cells.

In mammalian cells radiation induces the enhanced transcription of several genes. The cis acting elements in the control region of inducible genes have been delimited by site directed mutagenesis. Several different elements have been found in different genes. They do not only activate gene transcription in response to radiation but also in response to growth factors and to tumor promoter phorbol esters. The transcription factors binding to these elements are present also in non-irradiated cells, but their DNA binding activity and their transactivating capability is increased upon irradiation. The signal chain linking the primary radiation-induced signal (damaged DNA) to the activation of transcription factors involves the action of (a) protein kinase(s).

Animals↗
PubMed1990

Influence of continuous haemofiltration on haemodynamics and central blood volume in experimental endotoxic shock.

In order to assess the influence of continuous haemofiltration (HF) on haemodynamics and central blood volume in endotoxic shock, endotoxinaemia was invoked in 20 swine (28-32 kg). 15 min after doubling the mean pulmonary pressure, the animals were randomly assigned to receive either a zero-balanced veno-venous HF with an ultrafiltration and replacement rate of 600 ml/h (HF group, n = 10) or to observe the spontaneous course (E group, n = 10) under a constant infusion of endotoxin for 4 h. A trend to a higher survival rate in the HF group (6/10 vs. 3/10; E group) during the observation period was evident, but not statistically significant. Early initiation of HF during endotoxic shock modifies the haemodynamic response, lowering the pulmonary artery pressure (PAP), PCWP, pulmonary (PVR) and systemic vascular resistance (SVR), compared to the spontaneous course, whereas the decrement of central blood volume was comparable in both groups. These changes cannot be explained by effects of the HF on the volume status, but supports and additional effect by the filtration of small and medium-sized molecules.

Animals↗
PubMed1990

Appearance during chick embryogenesis of vitamin D-dependent calcium-binding protein (calbindin-D28K).

The appearance of the vitamin D-dependent calcium-binding protein (calbindin-D28K) in embryonic chick tissues was determined using a sensitive immunohistochemical assay to elucidate the possible role of calbindin-D28K during embryogenesis. This protein first occurs in renal, cerebellar and intestinal cells during the final stages of maturation and/or differentiation. It is during this period of their development that these tissues become functional. On the basis of our observations, we suggest that the onset of cell function may be coupled with the appearance of calbindin-D28K.

Animals↗
PubMed1990

[Effect of stress incontinence surgery on urodynamic parameters. 2. Are various surgical methods comparable?].

This study examines the pre- and postoperative clinical data of 215 women operated on during 1983-87 at the University Hospital of Freiburg for stress incontinence. The following procedures were used: Anterior colporrhaphy (n = 27), anterior colporrhaphy in combination with a ventral levator plasty (n = 61), sling procedure with the Lyodura sling (n = 44), and a colposuspension within the total abdominal concept (n = 83). All the procedures, with the exception of anterior colporrhaphy, were followed by a decrease in maximum urethral pressure. The functional urethral length was not changed by any of the methods. Colposuspension showed a marked postoperative improvement of urethral stress profile parameters in the proximal and midurethra, the sling had a steep, unphysiological increase of pressure transmission ratio in the proximal urethra. The vaginal methods did not improve pressure transmission to the proximal section of the urethra, their effect was only measurable in the mid section. The urodynamic effects of different types of surgery were very individual, a fact which may be helpful in the selection of the surgical approach.

Adult↗
PubMed1990

Differential effects of the adenovirus E1A oncogene on members of the AP-1 transcription factor family.

The adenovirus early region 1A (E1A) oncogene interferes with the expression level and activity of the AP-1 transcription factor family. E1A abolished the transactivating function of AP-1 (Jun/Fos), which binds to the 12-O-tetradecanoylphorbol-13-acetate-responsive element of the collagenase gene (collTRE). In contrast, the activity of another member of the AP-1 family that binds to the c-junTRE was not repressed. The mRNA expression of the c-jun gene was, in fact, strongly elevated in various cell types expressing the E1A gene of either adenovirus type 5 (Ad5) or Ad12. The regulation of the junB gene by adenovirus E1A, on the other hand, depended both on the cell type and on the transforming adenovirus serotype. The fact that E1A-induced alterations in the repertoire of AP-1 transcription factors depend on its transforming domain in conserved region 1 suggests that the effects are relevant for the transformation process.

Adenovirus Early Proteins↗
PubMed1990

Focal headache during balloon inflation in the internal carotid and middle cerebral arteries.

Although a number of reports are available on the occurrence of headache in patients with ischemic cerebrovascular disease, most studies have recorded the frequency but not the specific sites of the pain. We report 18 patients who underwent balloon inflation in the distal internal carotid artery and middle cerebral artery stem during embolization therapy for intracerebral arteriovenous malformations. Eleven patients had reproducible patterns of headache during balloon inflation. Inflation in the proximal middle cerebral artery stem produced pain primarily in the ipsilateral temple, that in the middle of the middle cerebral artery stem produced pain referred primarily retro-orbitally, and inflation in the distal middle cerebral artery stem produced pain referred primarily to the forehead. Experimental studies have demonstrated similar patterns of referred pain. The fact that these areas of referred pain are so reproducible is of potentially great clinical importance in the approach to management of patients with cerebrovascular disease.

Adult↗
PubMed1990

Differential antagonism by 1,3-dipropylxanthine-8-cyclopentylxanthine and 9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo(1,5-c)quinazolin-5-im ine of the effects of adenosine derivatives in the presence of isoprenaline on contractile response and cyclic AMP content in cardiomyocytes. Evidence for the coexistence of A1- and A2-adenosine receptors on cardiomyocytes.

The antagonism by the A1-adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and the A2-adenosine receptor antagonist [9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo (1,5-c)quinazolin-5-imine] (CGS 15943A) of the effects of the A1-adenosine receptor agonist (-)-N6-phenylisopropyladenosine (R-PIA) and the A2-adenosine receptor agonist 5'-N-ethyl-carboxamideadenosine (NECA) in the presence of isoprenaline on contractile response and cyclic AMP (cAMP) content in cardiomyocytes from guinea pig cardiac ventricles were studied. In electrically driven (1 Hz) guinea pig ventricular cardiomyocytes R-PIA concentration-dependently (0.0001-100 microM) reduced the stimulatory effects of isoprenaline (0.01 microM) on contractile response and on cAMP content. The A1-adenosine receptor antagonist DPCPX (0.3 microM) antagonized the effects of R-PIA on contractile reponse and on cAMP content, whereas the A2-adenosine receptor antagonist CGS 15943A (0.01 microM) was ineffective. NECA (0.0001-100 microM) reduced the effects of isoprenaline (0.01 microM) on contractile response to about the same extent as R-PIA. However, NECA did not change cAMP content. DPCPX (0.3 microM) antagonized the effects of NECA on contractile response and evoked a cAMP-increasing effect of NECA, which was 38% of the isoprenaline value at most. In contrast, CGS 15943A did not affect the reduction of contractile response induced by NECA, whereas CGS 15943A revealed a cAMP-decreasing effect of NECA (0.1-10 microM). This study provides functional evidence that both, cAMP-decreasing A1- and cAMP-increasing A2-adenosine receptors are present on ventricular cardiomyocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1990

Atherosclerotic plaque rupture and thrombosis. Evolving concepts.

Rupture of an atherosclerotic plaque associated with partial or complete thrombotic vessel occlusion is fundamental to the development of ischemic coronary syndromes. Plaques that produce only mild-to-moderate angiographic luminal stenosis are frequently those that undergo abrupt disruption, leading to unstable angina or acute myocardial infarction. Plaques with increased lipid content appear more prone to rupture, particularly when the lipid pool is localized eccentrically within the intima. Macrophages appear to play an important role in atherogenesis, perhaps by participating in the uptake and metabolism of lipoproteins, secretion of growth factors, and production of enzymes and toxic metabolites that may facilitate plaque rupture. In addition, the particular composition or configuration of a plaque and the hemodynamic forces to which it is exposed may determine its susceptibility to disruption. Exposure of collagen, lipids, and smooth muscle cells after plaque rupture leads to the activation of platelets and the coagulation cascade system. The resulting thrombus may lead to marked reduction in myocardial perfusion and the development of an unstable coronary syndrome, or it may become organized and incorporated into the diseased vessel, thus contributing to the progression of atherosclerosis. In unstable angina, plaque disruption leads to thrombosis, which is usually labile and results in only a transient reduction in myocardial perfusion. Release of vasoactive substances, arterial spasm, or increases in myocardial oxygen demand may contribute to ischemia. In acute myocardial infarction, plaque disruption results in a more persistent thrombotic vessel occlusion; the extent of necrosis depends on the size of the artery, the duration of occlusion, the presence of collateral flow, and the integrity of the fibrinolytic system. Thrombi that undergo lysis expose a highly thrombogenic surface to the circulating blood, which has the capacity of activating platelets and the coagulation cascade system and may lead to thrombotic reocclusion. Measurements aimed at reversing the process of atherosclerosis via cholesterol reduction and enhanced high density lipoprotein activity are encouraging. Active research is being focused on the development of new antithrombotic tools, such as inhibitors of thrombin, thromboxane, and serotonin receptor antagonists, and monoclonal antibodies aimed at blocking platelet membrane receptors or adhesive proteins. These compounds may prove useful when immediate and potent inhibition of the hemostatic system is desired. Intensive research is still needed in the areas of pathogenesis and therapeutic intervention in atherosclerosis.

Acute Disease↗