Evidence for alpha-helical conformation of an essential N-terminal region in the human Bcl2 protein

A region occupying approximately 24 amino acids near the N terminus of human Bcl2 is essential for this cytoplasmic membrane protein's ability to inhibit apoptosis. Systematic mutagenesis of this N-terminal region indicates that only five hydrophobic and aromatic residues within it are specifically required for function. Computerized secondary structure prediction, together with circular dichroism spectroscopy of synthetic peptides, indicates that the region encompassing these five residues has the propensity to take on an alpha-helical conformation in the presence of SDS micelles, which presumably mimic the hydrophobic surfaces of cellular membranes or polypeptides. The five critical residues are predicted to be clustered on one face of this putative helix, where they might serve to mediate protein-protein contacts involved in the multimerization of Bcl2 or in the interaction of Bcl2 with other, as yet unidentified components of the apoptotic pathway. Apparent structural homologues of this helical motif are also present in at least some other anti-apoptotic proteins from the Bcl2 family but not in those family members that tend to potentiate, rather than inhibit, apoptosis.     

The clomipramine test and subtypes of depression

OBJECTIVE: Neuroendocrine challenge paradigms have been used to assess serotonergic system in depression but limitations in the specificity of many of these tests have been noted. In this study, the neuroendocrine responses to acute intravenous administration of the serotonin (5-HT) reuptake inhibitor clomipramine were assessed in patients with Major Depression with Melancholia (DMM) and matched subjects with Major Depression (DM) (without Melancholia) and Dysthimic disorder (TD). METHOD: 10 patients who met DSM III-R criteria of DMM, 10 patients with DM and 10 with DD matched for age and sex received 12.5 mg of intravenously administered clomipramine. Prl, Cortisol and GH were measured during the next 135 minutes. RESULTS: The DMM patients had significant blunting prolactin responses to clomipramine compared with the other patients. CONCLUSIONS: These data support the hypothesis that DMM patients have abnormal neuroendocrine responses to the intravenous administration of the 5-HT reuptake inhibitor clomipramine and that they are different from the DM and TD patients.     

Massive infarcts involving the territory of the anterior choroidal artery and cardioembolism

BACKGROUND AND PURPOSE: At neuropathological examination, the territory of the anterior choroidal artery is frequently found to be involved in massive infarcts of the internal carotid artery territory. The aim of our study was to analyze the clinical spectrum, the course, and the mechanism of these massive infarcts compared with the rare infarcts involving only the anterior choroidal artery territory. METHODS: Retrospective clinical examination and pathological study were performed in 35 patients with cerebral infarcts affecting at least the territory of the anterior choroidal artery. RESULTS: In no patient had the involvement of the anterior choroidal territory infarcts been recognized clinically, nor had the triad of clinical signs (hemiplegia, hemianesthesia, and hemianopsia) classically seen in infarcts restricted to this territory been found alone. Impairment of consciousness, cognitive disorders, or oculomotor palsies had been found in addition to one or more signs of the triad. This was probably related to the involvement of other territories (94%), especially the middle cerebral artery territory (68%) and the posterior cerebral artery territory (20%). The concomitant involvement of several territories was due most frequently to an occlusion of the internal carotid artery, which was found at autopsy in 74% of the patients. These occlusions were often associated with cardioembolism (54%). In contrast, artery-to-artery embolism (17%) and small-artery disease (6%) were seldom found. Only two cases of infarcts restricted to the anterior choroidal artery territory were observed. CONCLUSIONS: The involvement of the territory of the anterior choroidal artery in massive infarcts was due mainly to a cardioembolic occlusion of the internal carotid artery.     

Unusual attendance at Hospital Emergency Services for asthma and chronic obstructive pulmonary disease and SO2 air pollution in Cartagena (Spain)

BACKGROUND: The objective of this investigation is to determine the influence of air pollution (SO2 and particulate matter) on the existence of days of unusual attendance at emergency services for asthma and chronic obstructive pulmonary lung disease (COPD). A registry of attendances for these diseases and the daily mean concentrations of SO2 and particles were used (1989-1991). RESULTS: Unusual attendance days are establish by the fortnightly movable mean of the period that has that day as central one, under the hypothesis of a Poisson distribution with equal mean as the calculated one. In the logistic regression model, Odds Ratio (OR) between an excess of attendance of cases for asthma and SO2 levels greater than 80.60 m/m3 was 3.6 (CI95%: 1.1-11.7). For COPD, SO levels ten days before were introduced, and OR for SO2 levels more than 56.5m/m was 4.7 (CI95%: 1.5-15.1). CONCLUSIONS: High SO2 levels are related with the appearances of days with an excessive use of emergencies for Asma and EPOC.     

Recanalization of totally occluded saphenous vein grafts using local urokinase delivery with the Dispatch catheter

Current techniques for the percutaneous revascularization of totally occluded vein grafts are limited by a low initial success rate, a significant incidence of distal embolization, and a high rate of early graft reclosure. This case report describes two patients in whom graft recanalization was attempted with the combined use of balloon angioplasty/intra-graft stent placement and local urokinase delivery using a new angiotherapy catheter. Successful recanalization was achieved in both patients without major complications, in spite of a large thrombus burden as demonstrated by angiography.