The anti-ischemic properties of new specific bradycardic agents, derivatives of 2-mercaptobenzimidazole

Experiments on narcotized cats demonstrated that the derivatives of 2-mercaptobenzimidazole possessing the properties of specific bradycardic agents and coded as CM-251, CM-266, and CM-345, reduce the mean rise of segment ST on numerous leads of the epicardial electrogram during 5-min occlusion of the anterior descending branch of the left coronary artery. The agents stabilize the heart pumping and contracting functions under conditions of 30- and 60-min reperfusion of the coronary artery, respectively. It is concluded on the grounds of the obtained data that the 2-mercaptobenzimidazole derivatives possess a marked anti-ischemic action.     

A prognostic algorithm for complicated forms of measles

As many as 617 patients with measles were examined. Of these, 306 subjects presented with a complicated form of the condition. A way is suggested for the prognostication of complications, relying on clinical factors and on a method for non-uniform sequential statistical procedure. A correct prognosis involving a diagnostic table made up 61%.     

Uncoupling of stem cell inhibition from monocyte chemoattraction in MIP-1alpha by mutagenesis of the proteoglycan binding site

We have studied the role of proteoglycans in the function of Macrophage Inflammatory Protein-1 alpha (MIP-1alpha), a member of the proteoglycan binding chemokine family. Sequence and peptide analysis has identified a basic region within MIP-1alpha which appears to be the major determinant of proteoglycan binding and we have now produced a mutant of MIP-1alpha lacking the basic charges on two of the amino acids within this proteoglycan binding site. This mutant (Hep Mut) appears to have lost the ability to bind to proteoglycans. Bioassay of Hep Mut indicates that it has retained stem cell inhibitory properties but has a compromised activity as a monocyte chemoattractant, thus suggesting uncoupling of these two properties of MIP-1alpha. Receptor studies have indicated that the inactivity of Hep Mut on human monocytes correlates with its inability to bind to CCR1, a cloned human MIP-1alpha receptor. In addition, studies using proteoglycan deficient cells transfected with CCR1 have indicated that the proteoglycan binding site in MIP-1alpha is a site that is also involved in the docking of MIP-1alpha to the monocyte receptor. The site for interaction with the stem cell receptor must therefore be distinct, suggesting that MIP-1alpha utilizes different receptors for these two different biological processes.     

Stress increases the population of splenic macrophages, permissive for Langat virus, in mice

Cytogenetic study conducted after a single intraperitoneal injection of cyclophosphane in doses of 10, 20, and 40 mg/kg showed in 1.5-2-month-old male mice that the level of bone marrow cells damaged by the mutagen was significantly higher in NZW animals than in C57Bl/6 animals. The ability to produce active oxygen forms in response to addition of opsonized zymosan and phorbol myristate acetate was also higher in bone marrow suspensions of NZW mice. The higher sensitivity of NZW animals to pro-oxidant and clastogenic effects may be related to the genetically determined decrease of antioxidant protection in NZW animals.     

Composition and antibacterial activity of the essential oils of Helichrysum rupestre and H. ambiguum growing in the Balearic Islands (Part III)

The chemical compositions of the essential oils obtained from the aerial parts of Helichrysum rupestre and H. ambiguum were analysed by GC and GC/MS. From the forty-five identified constituents representing 90.21% and 93.90% of the two oils, respectively, manoyl oxide, dodecanal, nonanal, p-cymene, alpha-pinene, and 2,4,6-tris(1,1-dimethylethyl)benzoic acid, were found to be the major components. Furthermore, the oils were tested against six Gram (+/-) bacteria and it was found that one of them exhibited significant antibacterial activity.     

Spontaneous Clostridium septicum myonecrosis in congenital neutropaenia

Spontaneous Clostridium septicum myonecrosis is an uncommon disorder that has been described in association with malignancy, immunosuppression and neutropaenia. Typical clostridial myonecrosis develops without a visible portal of entry and mortality is high. The pathogenesis is not completely understood but the clostridia may gain access to the circulation via areas of ileo-caecal ulceration secondary to enterocolitis, antibiotics or neoplasms. A 5 year old boy with congenital neutropaenia presented with spontaneous Clostridium septicum myonecrosis in the thigh. Limb salvage was achieved using antibiotics, hyberbaric oxygenation and selective debridement. The portal of entry may have been the gastrointestinal tract as colonic ulceration may occur in neutropaenia, and pre-morbid clindamycin administration may have encouraged overgrowth of colonic clostridia.     

Allelic imbalance and instability of microsatellite loci on chromosome 1p in human non-small-cell lung cancer

The mapping of allelic loss on the short arm of chromosome 1 has been performed in non-small-cell lung cancer. We used a set of 11 microsatellite loci spanning 1p to examine the frequency of allelic imbalance in a panel of 58 tumours. Fifty-one of 58 (87.9%) cases have shown somatic allelic loss at one or more loci tested. The two shortest regions of the overlap (SRO) of the deletions have been identified: SRO 1 at 1p13.1 and SRO 2 at 1p32-pter. Allelic losses at these regions have been compared among adenocarcinoma and squamous cell carcinoma and no difference has been found. In contrast to SRO 1, deletions at SRO 2 significantly correlated with advanced stage of the disease as well as post-operative metastasizing and relapse. These data may suggest that SRO 1 and SRO 2 can harbour tumour-supressor genes (TSGs) involved in different stages of NSCLC development. SRO 2 is still quite large and its refined mapping should help attempts to clone and identify the putative TSG(s). Microsatellite instability (replication errors) affecting only 6 (10.3%) of 58 tumour samples is an infrequent genetic alteration at the loci tested.     

Methods development for epidemiologic investigations of the health effects of prolonged ozone exposure. Part I: Variability of pulmonary function measures

The acute and subacute effects of ambient concentrations of ozone on lung function have been studied extensively in a variety of settings. Such studies generally have focused on measures of function that reflect either lung volumes or flows that are influenced by the physiology of large and small airways (e.g., forced expiratory volume in one second [FEV1). Data from animal studies suggest that the effects of prolonged exposure to elevated ambient concentrations of ozone result in abnormalities in the centriacinar region of the lung; and dosimetry models for humans predict that long-term exposure to ozone could impact the same areas of the human lung. However, alterations in structure at this level of the lung are not well reflected by measuring FEV1 until substantial structural changes have occurred. Measures of the lung function that reflect the functional mechanics of airways smaller than 2 mm in diameter are considered to be more relevant. At least one epidemiologic study has provided evidence that small-airway functions may be relevant to effects of prolonged exposure to environments with high concentrations of oxidants. A considerable body of physiologic data has established that flow rates measured during the terminal portion of a maximum expiratory flow-volume (MEFV) curve are largely governed by airways smaller than 2 mm in diameter A similar interpretation has been given to changes in the slope of phase III (delta N2) of the single-breath nitrogen washout (SBNW) curve. Despite the attractiveness of these measures in relation to airway physiology, some data suggest that measurements of flow via the terminal portions of MEFV and SBNW curves have much greater within-subject variability than forced vital capacity (FVC and FEV1. The present study was undertaken as part of a larger feasibility study to develop methods to study the effects of prolonged exposure to elevated ambient ozone levels on lung function in adolescents. A convenience sample of 239 freshmen (ages 16-20 years) entering the University of California, Berkeley were recruited to participate in this protocol. All were lifelong residents of the San Francisco Bay Area or the Los Angeles Basin. Subjects were studied on two occasions five to seven days apart. At each test session, subjects performed up to eight forced expiratory maneuvers to produce three acceptable and reproducible MEFV curves by modified American Thoracic Society criteria. Tests of SBNW were then performed on the basis of detailed criteria for validity and reproducibility. Eight attempts to generate three curves were allowed. The delta N2 was obtained by a least-squares regression of nitrogen concentrations between the 750-mL and 1750-mL volume points. Instantaneous flow at 75% of expired volume (FEF75%), average flow between the 25% and 75% volume points (FEF25%-75%), and delta N2 were the principal outcomes. Variance components were estimated with a nested random effects model with adjustments for important covariates. The average within-subject coefficients of variation (+/-SD of distribution of means) for male subjects were: FEV1 1.2 (+/-0.8); FEF25%-75% 3.2 (+/-2.3); FEF75% 5.8 (+/-5.0); and delta N2 17.9 (+/-12.3); for female subjects they were: FEV1 1.4 (+/-0.9); FEF25%-75% 3.0 (+/-2.2); FEF75% 6.2 (+/-5.2); and delta N2 19.9 (+/-17.0). The variance attributed to test session was less than 1% for all measures. The percentages of variance due to within-subject variation for each measure (adjusted for sex, area of residence, ethnicity, and height) were: FVC 3.6%; FEV1 3.0%; FEF25%-75% 5.2%; FEF75% 8.9%; and delta N2 23.9%. Of all subjects tested, 234 (97.9%) could provide at least two acceptable MEFV curves, but only 218 (91.2%) could provide at least two acceptable SBNW curves. The results were unchanged by recent history of acute, respiratory illness.(ABSTRACT TRUNCATED)     

Kinetics of GaN radical-beam gettering epitaxy on GaAs substrates

The growth of thin GaN layers on single-crystal GaAs substrates during annealing in an atmosphere containing nitrogen atoms (radicals) has been analyzed in terms of a kinetic model. The nitridation of the surface of GaAs substrates has been studied by x-ray photoelectron spectroscopy. The results demonstrate that, at annealing temperatures below 500°C, both Ga-N and As-N bonds are formed on the substrate surface. Above 500°C, only Ga-N bonds are formed. The growth of GaN layers is shown to follow a quasi-epitaxial mechanism, in accordance with the proposed model.