Protective monoclonal antibodies define maturational and pH-dependent antigenic changes in Sindbis virus E1 glycoprotein

Monoclonal (MC) antibodies specific for either the EI or E2 glycoproteins of Sindbis virus (SIN) were used to probe for differences in the surface topography of SIN epitopes between infected cells and mature virions. Employing an enzyme-linked immunosorbent assay (ELISA) in which binding of individual peroxidase-labeled MC antibodies to immobilized (solid-phase) detergent-disrupted SIN was inhibited specifically by one or more unlabeled antibodies, viral epitopes could be grouped into six spatially distinct antigenic sites--five on E1, designated a through e, and one site on E2. All six sites were represented on the surfaces of SIN-infected cells as shown by the complement (C')-dependent lysis mediated by antibodies of the corresponding epitope specificities. In contrast, virus-neutralizing (NT) activity was restricted to antibodies specific for epitopes on E2 and on site c of E1, irrespective of the presence of added C' and an antiserum against mouse immunoglobulins. That E1 sites a, b, d, and e became inaccessible to antibody binding was shown by a competitive-inhibition ELISA. Whereas all MC antibodies were inhibited from binding to solid-phase SIN when premixed with detergent-treated virions, only those having NT activity could be competitively inhibited by intact virions. Sites E1-d and E1-e could be exposed not only by detergent disruption but also by lowering the virion pH from 7.2 to 6.0. These collective results indicate that a majority of immunologically relevant E1 epitopes present on SIN-infected cell surfaces become cryptic during SIN maturation and, except at low pH, remain undetectable on virion surfaces.     

Marfan syndrome: Absence of type I or III collagen structural defects in 25 patients

Summary The structure and metabolism of type I and III collagens were studied in fibroblast cultures and dermis from 25 unrelated patients including 23 with typical Marfan syndrome and two infants with a very severe clinical form of this syndrome. Electrophoretic analysis of collagen -chains, as well as one- and two-dimensional electrophoresis of collagen cyanogen bromide peptides, failed to show any evidence of primary structure defects or overmodification of lysine residues in these collagens. The proportion of hydroxylated prolyl residues in isolated 1(I) chains was also normal. There was a minimal increase in the proportion of type III collagen produced by nine cultures. The findings in this study indicate that the underlying molecular defects in the patients studied are unlikely to involve the structure of the main fibrillar type I and III collagens.     

Vitamin B12 and folate status in acute geropsychiatric inpatients: affective and cognitive characteristics of a vitamin nondeficient population

This chart review study examined the serum vitamin B12 and folate status of 102 geriatric patients newly admitted to a private psychiatric hospital. Only 3.7% were B12 deficient and 1.3% were folate deficient; 4% were anemic. Nevertheless, those with below-median values of both vitamins had significantly lower Mini-Mental State scores than patients higher in one or both vitamins. Patients with "organic psychosis" with a negative family history for psychiatric disorder had significantly lower B12 levels than those with a positive family history. In major depression, folate levels correlated negatively with age at onset of psychiatric illness and length of hospitalization. These data suggest that (1) biochemically interrelated vitamins such as B12 and folate may exert both a separate and a concomitant influence on affect and cognition; (2) poorer vitamin status may contribute to certain geropsychiatric disorders that begin at a later age and lack a familial predisposition.     

Evaluating clinical outcomes of respiratory infection

Evaluation of clinical outcomes of respiratory infection is essential to the audit of efficacy and safety of management practices. In order to examine the appropriateness of clinical outcome measurements in treated chronic respiratory infections, it is necessary to study a defined homogeneous population of treated patients. There is a fundamental difference between acute and chronic infection which governs the mode of antibiotic therapy. Understanding of the pathogenesis of chronic respiratory infection also allows more logical use of antimicrobial agents and more logical assessment of their efficacy, taking into account the tissue-damaging inflammation which might be controlled by anti-inflammatory combined with antibiotic therapy. This contrasts with acute infection in the immunocompetent host, in whom virulent bacteria overwhelm the host's immune defences temporarily so that a brief period of antibiotic therapy may reduce bacterial counts and host immune defences achieve killing of bacteria.     

An ethological analysis of the effects of chlordiazepoxide and bretazenil (Ro 16-6028) in the murine elevated plus-maze

The effects of chlordiazepoxide (2.5-15.0mg/kg), a full benzodiazepine receptor agonist, and bretazenil (5.0-30.0mg/kg), a partial benzodiazepine receptor agonist, were examined in the murine elevated plus-maze paradigm. Behaviours recorded comprised the traditional indices of anxiety as well as a number of ethologically derived measures. Results show that chlordiazepoxide (10-15mg/kg) and bretazenil (5-30mg/kg) not only decreased traditional indices of anxiety but also reduced risk assessment behaviours such as head-dipping and stretch attend postures from secure areas of the maze. Both compounds produced these effects without adversely affecting general activity levels. While traditional indices of anxiety did not clearly discriminate between the two compounds, some differences were apparent on the ethological measures. The dose-response curves for bretazenil were generally shallower than those for chlordiazepoxide, confirming its partial agonist profile. Together, these data support the view that benzodiazepine receptor partial agonists may have utility in the management of human anxiety disorders.     

The influence of stimulus parameters on the visual field indices by automated projection perimetry

The various stimulus parameters offered by two standard automated projection perimeters [Humphrey Field Analyser 630 (HFA) and Octopus 2011, namely, stimulus size and location and the interaction of adaptation level and stimulus duration, were compared in a sample of 20 patients attending a glaucoma clinic using the visual field indices mean defect (MD), loss variance (LV), short-term fluctuation (SF) and corrected loss variance (CLV). LV and SF were greater with Octopus program 32 compared with Octopus program G1 (P < 0.02). No difference in the indices was found between stimulus sizes I and III for HFA program 30-2. MD was greater for program 30-2 compared with program 32 (P < 0.002) when expressed in terms of log (L/L) whereas LV (P < 0.02) and SF (P < 0.02) were greater for program 32. All differences were considered to be negligible in the clinical sense.