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Biomedical subjects

B Stein

Publications and source records attributed to B Stein.

At least 163 records · Page 9Linked to original sources

The effect of exogenous gonadotropic hormones on the endometrium of the rat.

This investigation examined the effects of hyperstimulation on the uterine endometrium of rats. Female rats were injected, out of cycle, with FSH followed by hCG and mated. Control rats were mated during oestrus. Animals were killed at 5.5 days of pregnancy. The endometrium was examined by light and electron microscopy. Hyperstimulation resulted in an increase in the length and number of microvilli and a deficiency of the glycocalyx of surface epithelial cells. Stromal cells failed to undergo decidualization. These alterations in morphology may interfere with attachment and implantation of the embryo.

Animals↗

[Control of the ultrafiltration rate as the main component of a new balancing system in continuous hemofiltration].

In 27 patients undergoing continuous pump-driven hemofiltration during intensive care, a new balancing device was used to control transmembrane pressure difference, and thus ultrafiltration rate, by means of an elastic reservoir and an infusion pump. The simultaneous infusion of substitution fluid by a second pump working independently of the former provided exactly and automatically the intended fluid balance. In only 0.7% of the total hemofiltration time (5519 h) could the preset ultrafiltration rate not be achieved. The simple components and installation of this device recommend its application in every intensive care unit that uses continuous arteriovenous or continuous pump-driven hemofiltration, relieving the staff and reducing unwanted and unnoticed deviations of intravascular volume and fluid balance.

Acute Kidney Injury↗

Thrombosis/platelets and other blood factors in acute coronary syndromes.

We support the concept of a common anatomic and physiologic link between the acute coronary syndromes, which consists of plaque fissuring or rupture, leading to exposure of the circulating blood to collagen, lipids, and smooth muscle cells. This, in turn, results in marked platelet activation and the initiation of the coagulation sequence, both of which lead to thrombus formation. What determines the clinical outcome in these patients is the suddenness of coronary occlusion, the completeness of blood flow deprivation, and most importantly, its duration. In unstable angina, either plaque disruption resulting in an abrupt change in its morphologic configuration with reduction of coronary blood flow or increased myocardial oxygen demand are associated with increased exertional symptoms. In rest angina, two events may take place: formation of a transient and labile thrombus due to platelet and clotting activation, or vasospasm associated with the release of platelet-derived vasoconstrictive substances or loss of endothelial relaxing properties. As a result, transient myocardial ischemia occurs, which may be intermittent and recurrent and may progress to myocardial infarction or sudden death. In myocardial infarction, plaque rupture is usually more severe, leading to the formation of an occlusive or near-occlusive thrombus which may be more persistent and fixed to the arterial wall. The duration of coronary blood flow deprivation needs to be sufficiently long in order to produce myocardial cell death. Moreover, the difference between Q-wave and non-Q-wave infarction is probably determined by the duration of blood flow obstruction, being longer in the former. The presence of a functionally adequate collateral circulation will, in part, determine the survival of the area of myocardium at jeopardy. The coronary events that take place in ischemic sudden death are probably similar to those in unstable angina, namely plaque rupture with thrombus formation. In sudden death, the resulting myocardial ischemia may precipitate fatal ventricular arrhythmias. Alternatively, platelet microemboli from ulcerated arterial plaques may produce multiple areas of myocardial necrosis which can result in electrical instability and ventricular fibrillation.

Angina Pectoris↗

Novel halogenated dihydropyridine derivatives with high vascular selectivity.

Calcium channel antagonists of the dihydropyridine type exhibit preferential vasodilator properties. To study whether this vascular selectivity is due to distinct steric modifications or may be influenced by the physicochemical nature of these drugs, contractility in guinea pig heart isolated papillary muscles, vasodilator properties in isolated rabbit femoral arteries and the lipophilicity of some novel halogenated dihydropyridines have been examined. All newly synthesized derivatives exhibited dose-dependent negative inotropic and vasodilator effects. The negative inotropic potency of all the halogenated derivatives was weaker than that of the parent compound nitrendipine. In contrast, compared to nitrendipine the vasodilator potency of the ester substituted derivatives was slightly increased, while halogen substitution in position 2 and 6 of the dihydropyridine nucleus decreased the vasodilator potency. As a result of the different influence on cardiac and vascular smooth muscle an improved vascular selectivity of the drugs was attained. The ester-substituted dihydropyridine derivatives showed a 9 times (3-bromoethyl-nitrendipine) or 11 times (3-chloroethyl-nitrendipine) higher vascular selectivity with respect to nitrendipine. Correlation of the lipophilicity with the physiological properties showed an increase in biological activity with decreasing lipophilicity. Within the ester-halogenated dihydropyridine derivatives an inverse trend was observed (increasing vasodilation with increasing lipophilicity), indicating a different influence of lipophilicity with the ester-substituted compounds on the different tissues examined. The improved vascular selectivity of the novel halogenated dihydropyridines may be at least in part a consequence of the different lipophilicity of the drugs. In addition, differences in the binding affinities of the dihydropyridines subordinate to distinct voltage dependent conformation states of the calcium channel may contribute.

Animals↗

"Intermittent" and transient ST-segment elevation following direct current cardioversion.

Transient ST-segment elevation immediately following direct current cardioversion is a clearly documented occurrence in a small percentage of cases. Two main explanations have been suggested: myocardial injury or coronary vasospasm. We report two cases of "intermittent" and transient ST-segment elevation after cardioversion. Such intermittent elevation of the ST segment has not been reported previously. We hypothesize that this electrocardiographic observation is explained by a timing difference induced by electroshock in the action potential between the epicardium and endocardium.

Action Potentials↗

Antithrombotic therapy after myocardial reperfusion in acute myocardial infarction.

The problem of post-thrombolytic reocclusion can be approached in several ways. 1) Better thrombolytic agents with longer duration of effects and more powerful properties aimed at enhanced clot lysis and anticoagulation are under study. 2) The combination of high dose heparin and low dose aspirin is proposed for all patients with an acute myocardial infarction treated with thrombolytic agents. 3) Peptide inhibitors of thrombin and monoclonal antibodies against platelet glycoprotein receptors and adhesive macromolecules are potentially effective inhibitors of platelet aggregation and thrombus formation during or after thrombolytic therapy.

Coronary Disease↗

Reduction or loss of HLA-A,B,C antigens in colorectal carcinoma appears not to influence survival.

Primary colorectal carcinomas of an unselected group of 159 patients 126 of whom could be curatively resected were examined for the expression of MHC class I antigens with monoclonal antibody W6/32 directed against a non-polymorphic determinant of HLA-A,B,C heavy chain. One hundred and nine (68.6%) were found to express HLA-A,B,C antigens in normal quantities, 33 (20.8%) showed a substantial reduction in expression, while 17 (10%) lacked these antigens either completely or incompletely. The loss of HLA-A,B,C was inversely correlated with the degree of differentiation. The tendency of mucinous carcinomas to lack class I antigens was statistically not significant. Tumours with distant metastatic spread at the time of operation tended to be normal with respect to HLA-A,B,C expression. Within the curatively resected group, poor differentiation and mucus production were risk factors for survival as could be shown by life table analysis after a maximum follow-up of 39 months. In contrast, the mode of HLA-A,B,C expression of the primary tumour did not influence survival within this time of observation. We conclude that in spite of increasing experimental data suggesting the contrary, the presence or absence of MHC class I antigens does not seem to profoundly modify tumour biology, at least in human colorectal carcinoma.

Adenocarcinoma↗

Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor.

The promoter regions of several phorbol diester-(TPA-) inducible genes (collagenase, stromelysin, hMT IIA, and SV40) share a conserved 9 bp motif. Synthetic copies of these closely related sequences conferred TPA inducibility upon heterologous promoters. Footprinting analysis indicated that these TPA-responsive elements (TREs) are recognized by a common cellular protein: the previously described transcription factor AP-1. A point mutation that eliminated the basal and induced activity of the TRE also interfered with its ability to bind AP-1. Treatment of cultured cells with TPA led to a rapid 3- to 4-fold increase in TRE binding activity, by a posttranslational mechanism. These results strongly suggest that AP-1 is at the receiving end of a complex pathway responsible for transmitting the effects of phorbol ester tumor promoters from the plasma membrane to the transcriptional machinery.

Animals↗

Influence of microsurgical reanastomosis of the fallopian tube on luminal pH and PO2 and on the fertilization rate and embryo development in the rabbit oviduct.

The luminal pH and PO2 were measured in rabbit oviducts to evaluate the influence of microsurgery on the environment within the fallopian tube before and after resection of a 1 cm ampullary portion with subsequent tubal reanastomosis. While the oxygen tension showed no difference between the operated oviduct (56 +/- 16 mmHg, n = 8) and the control side (53 +/- 13 mmHg, n = 8), there was a significant pH decrease in the oviducts after microsurgery (7.94 +/- 0.10, n = 8, versus 7.75 +/- 0.16, n = 8, p less than 0.0025). In the second part of the experiment the operated animals were induced to ovulate by hCG injection, and artificial insemination was performed at the same time. The number of fertilized and unfertilized oocytes and the stages of embryonic development (64 h post hCG) were compared between the operated and control oviducts. From the operated oviducts a lower number of ova were recovered and a lower rate of fertilization was observed. The data indicate that microsurgery of the rabbit fallopian tube does not disturb the luminal oxygen tension but may cause a lower pH. Ultimately a reduced rate of fertilization and impaired early development were observed.

Animals↗

12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5'-flanking region.

Genomic clones coding for human fibroblast collagenase were isolated. By constructing and transfecting mutants with 5' and 3' deletion mutations of the 5' control region of the gene into human or murine cells, we delimited a 32-base-pair sequence at positions -73 to -42 which is required for the induction of transcription by the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. The DNA element behaves as a 12-O-tetradecanoyl-phorbol-13-acetate-inducible enhancer: it mediates the stimulation of transcription to the heterologous herpes simplex virus thymidine kinase promoter and acts in a position- and orientation-independent manner. Differences in enhancer efficiency in different cell lines are interpreted to indicate differences in the activity of a trans-acting factor.

Adult↗

The classification of disturbed personality functioning in early adolescence.

This study describes disturbed personality functioning in early adolescence. A non-clinical sample of 63 thirteen year olds underwent a semi-structured psychiatric interview as part of a longitudinal study investigating the relationship between competence in personality functioning and development. The presence of personality disturbance was determined by two psychiatrists who rated the adolescents on a personality functions scale. The raters then described the type of disturbance using Axis II of DSM-III as a guideline. Forty-six percent of the sample were found to have some degree of disturbed personality functioning. Of these, over one-half fell into a cluster comprised of avoidant, dependent, compulsive, or passive-aggressive types, while another third were characterized by antisocial tendencies. Severity of disturbance was not related to type of disturbance. Ratings of behaviour by teachers and parents supported the division of subjects with personality dysfunction into two broad groups: an anxious, fearful, "quiet" cluster; and a group of more "acting out", disturbing individuals. However, parents and teachers could not distinguish the "quiet" group from teenagers who were free of disturbed personality functioning. These data indicate that it is possible to classify a segment of a non-clinical population of young adolescents who had personality dysfunction using Axis II of DSM-III as a guideline. Furthermore, such a group of teenagers is not homogeneous. They distribute themselves into internalizing and externalizing clusters.

Adolescent↗

Immunocytochemical localization of hFSH as an index of Sertoli cell function in the human testis.

The FSH receptor in the human testis has not been well characterized in vivo. Using an immunoperoxidase technique we have attempted the immunocytochemical localization of FSH in testicular tissue from patients with a variety of disorders including oligo- or azoospermia (N = 6), cryptorchidism (N = 3), and prostatic carcinoma (N = 3). Specific staining for hFSH was observed inside the seminiferous tubule, generally near the basal membrane in all except the cryptorchid patients. Specific staining was also localized in the luminal area of the seminiferous tubule. In most cases, FSH-positive cells were also found in the interstitium, with a minority of the cells being macrophages. The latter were more prevalent in the undescended testes and in orchiectomy specimens from patients with prostatic cancer. The pattern of FSH localization observed in this study probably represents receptorbound hormone, and may reflect damage to the Sertoli cell and its tight junctions. Further study of the changes in receptor distribution as an indication of Sertoli cell malfunction, may be helpful in our understanding of human testicular disorders.

Adult↗