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Biomedical subjects

R Joseph

Publications and source records attributed to R Joseph.

At least 145 records · Page 8Linked to original sources

Baseline and activated platelet cytoplasmic ionized calcium in acute ischemic stroke. Effect of aspirin.

We measured cytoplasmic ionized calcium concentrations [( Cai2+]) in aequorin-loaded gel-filtered platelets from 38 patients with acute occlusive stroke (12 treated with aspirin, 26 untreated) and 25 healthy controls. Compared with controls, baseline [Cai2+] was higher in untreated patients (p less than 0.002), maximal 36-72 hours after the onset of neurologic dysfunction (p less than 0.0001), in those patients with as well as those without major stroke risk factors. The increase in [Cai2+] after stimulation with 0.5 and 1.0 unit/ml thrombin (p less than 0.05), 2 and 4 micrograms/ml collagen (p less than 0.02), and 0.5 and 1.0 mM platelet activating factor (p less than 0.05) were also greater in untreated patients, but the profiles of these changes were parallel to those in controls. Even though the platelets of stroke patients are more sensitive to activation, they are functionally similar to those of controls. Aspirin treatment reduced baseline [Cai2+] as well as thrombin- and collagen-induced [Cai2+] changes. Platelet activating factor-induced increase in [Cai2+] was not altered by aspirin treatment. Our results suggest that the usefulness of aspirin in stroke is limited because aspirin does not suppress platelet responsiveness to all in vivo thrombogenic stimuli. Specific platelet activating factor antagonists may prove to be useful therapeutic agents in stroke.

Acute Disease↗

Platelet activity and selective beta-blockade in migraine prophylaxis.

Migraine is associated with increased platelet activity and an incidence of cerebrovascular ischemic events. Because cerebrovascular events might result from platelet aggregation, enhancing platelet activity further in the treatment of migraine is not desirable. beta-Adrenoceptor blockers effective in migraine prophylaxis include propranolol (nonselective) and metoprolol (beta 1-selective), but it is uncertain how beta-receptor subtype selectivity might influence platelet behavior in migraine. In 29 patients, comparable clinical responses were obtained with therapeutic doses during 1 month of treatment with propranolol, metoprolol, and the beta 2-selective Li 32-468. Propranolol increased and metoprolol decreased platelet aggregation and ATP release, and the effect of Li 32-468 could be related to that of propranolol. These actions can be largely explained in terms of what is known of platelet beta-receptors and therefore can be generalized to other effective beta-blockers. Since altered platelet activity does not account for the efficacy of these agents in migraine, the actions of beta-blockers on platelets should be considered as side effects. Those beta-blockers inhibiting platelet activity should be preferred in migraine treatment, assuming equal efficacy, which implies the use of beta 1-selective blockers.

Adenosine Diphosphate↗

Epithelial impedance analysis in experimentally induced colon cancer.

Epithelial impedance analysis was used to measure the alterations in resistance of the large bowel in a murine model of large bowel cancer. The technique was able to resolve the epithelial resistance from the total resistance of the bowel wall. A progressive decrease in resistance of the bowel epithelium occurs during carcinogenesis induced with dimethyhydrazine. About a 21% decrease in epithelial resistance from 22.0 +/- 1.3 omega.cm-2 to 17.5 +/- 1.1 omega cm-2 (p less than 0.025) was observed after 20 wk of carcinogen administration. The sensitivity of the technique in detecting altered epithelial resistance in premalignant bowel mucosa was improved by examining the impedance profile in a sodium-free Ringer's solution where the epithelium of control colons had a resistance of 24.4 +/- 1.8 omega.cm-2 compared with 19.0 +/- 1.1 omega.cm-2 (p less than 0.02) in colons from animals treated for only 4 wk with the carcinogen. Epithelial impedance analysis would seem to be a sensitive technique capable of identifying changes in the electrical properties or the large bowel early in disease states.

Animals↗

Migraine and the lupus anticoagulant. Case reports and review of the literature.

Lupus anticoagulants (LA) are antiphospholipid serum immunoglobulins generally associated with autoimmune conditions, especially systemic lupus erythematosus (SLE). They have recently been linked to thrombotic events, including stroke. A possible association of migraine with LA is now forwarded with the presentation of two cases and a literature review. Our two patients, both in their forties, had migrainous phenomena without SLE or thrombotic events. Eight other cases were found in the literature, suggesting more than a chance association. Relevance to migraine pathophysiology is discussed and may come from the ability of the LA to alter prostaglandins and platelet activity and to interact with neuronal phospholipids. Further, larger studies are needed to support this association.

Adult↗

The agarase gene (dag A) of Streptomyces coelicolor A3(2): affinity purification and characterization of the cloned gene product.

The coding and regulatory sequences of the agarase gene of Streptomyces coelicolor A3(2) were cloned in Streptomyces lividans 66 on the plasmid vector pIJ61, resulting in a several hundred-fold increase in the production of the secreted protein. Subcloning experiments localized the sequences required for agarase production and for the mediation of carbon catabolite repression to a segment of about 1.2 kb. A simple protein purification procedure that uses affinity binding of agarase to agarose beads was developed. Preliminary characterization of the enzyme, together with the results of in vitro transcription-translation studies, suggest that the intracellular form of agarase (about 34 kDa) possesses a signal sequence that is cleaved upon secretion across the cell membrane to produce an extracellular protein of about 29 kDa.

Chromatography, Affinity↗

Effect of inhibin on testosterone metabolism by rat ventral prostate in vitro.

Conversion of radiolabeled testosterone to 5 alpha-dihydrotestosterone (5 alpha-DHT) was determined in the rat ventral prostate in vitro, and the effect of inhibin on this conversion was demonstrated. The data revealed that the reduction of testosterone to 5 alpha-DHT was inhibited in a dose-related manner in the presence of inhibin as compared with the basal reduction. The percentage of testosterone reduced per 10-mg tissue also showed a similar trend. The ratio of radioactive counts for DHT and testosterone was also minimum at the highest dose of inhibin used. Inhibin can thus modulate the conversion of testosterone to 5 alpha-DHT in the rat ventral prostate, and therefore can autocrine-paracrine function can be attributed to the prostate.

5-alpha Reductase Inhibitors↗

Confabulation and delusional denial: frontal lobe and lateralized influences.

Various forms of confabulation, including denial of illness (e.g., paralysis, blindness), and conditions that often give rise to these disorders, such as cerebral disconnection, disinhibitory states, incomplete information reception, and "gap filling" are discussed. On the basis of clinical observation and a review of a number of studies, it appears that confabulatory states frequently are associated with cerebral damage that involves the right hemisphere, notably, the frontal (often bilaterally) and parietal lobes--areas intimately involved in arousal, attention, information regulation, and integration. With certain forms of injury, initially there appear disturbances in the organization, integration, and assimilation of ideas and associations, such that large gaps appear in the information transmitted to and received by the language axis of the left hemisphere. It is argued that in these instances, the language areas act so as to fill these "gaps" with information that, although inappropriate, is linked in some manner to the fragments received. In contrast, frontal lobe damage sometimes results in gross disinhibition and cortical overresponsiveness and, thus, speech release due to the flooding of the language axis (and other cortical regions) with tangential, fantastical, and grandiose associations. Other forms of confabulation also are reviewed briefly.

Adult↗

Involvement of prostate in the regulation of serum levels of FSH, LH, and prolactin in male rats.

Circulatory levels of LH and FSH were measured in serum of male rats (28, 35, 42, 63, 70, 77, and 207 days of age) 7 days following sham operation, castration (C), prostatectomy (P), and castration + prostatectomy (C + P). In C + P rats that were 49, 63, 70, 77, and 207 days of age, the plasma FSH was significantly elevated as compared to the C group. Administration of aqueous prostatic extract restored the circulatory FSH level in C + P animals to that observed in C animals, whereas in C animals FSH levels were suppressed, indicating inhibinlike activity. In rats 49 and 77 days of age, circulatory LH levels were significantly suppressed in C + P animals as compared to the C group. Both castration and prostatectomy alone suppressed circulatory prolactin levels. Administration of prostatic extract to castrated animals restored the prolactin levels to that of the sham-operated control animals. Results of the present study suggest a role of the prostate in feedback regulation of FSH and prolactin.

Animals↗