The effects of chronic trimipramine treatment on biogenic amine metabolism and on dopamine D2, 5-HT2 and tryptamine binding sites in rat brain

1. Two week chronic administration of trimipramine increased the brain concentration and metabolism of dopamine and 5-hydroxytryptamine. 2. The treatment also produced a reduction in dopamine D2 and 5-hydroxytryptamine 5-HT2 receptors but no change in tryptamine binding was observed. 3. These findings suggest that trimipramine induces adaptive changes in dopamine and 5-hydroxytryptamine neurotransmission.     

Genetic association analyses of non-synonymous single nucleotide polymorphisms in diabetic nephropathy

Aims/hypothesis  Diabetic nephropathy, characterised by persistent proteinuria, hypertension and progressive kidney failure, affects a subset of susceptible individuals with diabetes. It is also a leading cause of end-stage renal disease (ESRD). Non-synonymous (ns) single nucleotide polymorphisms (SNPs) have been reported to contribute to genetic susceptibility in both monogenic disorders and common complex diseases. The objective of this study was to investigate whether nsSNPs are involved in susceptibility to diabetic nephropathy using a case-control design. Methods  White type 1 diabetic patients with (cases) and without (controls) nephropathy from eight centres in the UK and Ireland were genotyped for a selected subset of nsSNPs using Illumina’s GoldenGate BeadArray assay. A χ ² test for trend, stratified by centre, was used to assess differences in genotype distribution between cases and controls. Genomic control was used to adjust for possible inflation of test statistics, and the False Discovery Rate method was used to account for multiple testing. Results  We assessed 1,111 nsSNPs for association with diabetic nephropathy in 1,711 individuals with type 1 diabetes (894 cases, 817 controls). A number of SNPs demonstrated a significant difference in genotype distribution between groups before but not after correction for multiple testing. Furthermore, neither subgroup analysis (diabetic nephropathy with ESRD or diabetic nephropathy without ESRD) nor stratification by duration of diabetes revealed any significant differences between groups. Conclusions/interpretation  The nsSNPs investigated in this study do not appear to contribute significantly to the development of diabetic nephropathy in patients with type 1 diabetes. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Isolation and characterization of subgenomic DNAs encapsidated in "single" T = 1 isometric particles of Maize streak virus

"Single" T = 1 isometric particles of Maize streak virus (MSV) have been isolated from infected maize leaves. Biochemical and genetic characterizations show that these particles contain subgenomic (sg) MSV DNA encapsidated by the MSV coat protein. The largest sg DNA is 1.56 kb, slightly larger than half genome size, although sg DNAs as small as 0.2 kb were also cloned. The sg DNAs are not infectious, and they do not appear to play a role in the pathogenicity of MSV. This is the first report of sg DNAs for MSV and, to our knowledge, the first time that encapsidated sg DNAs have been characterized at the sequence level for any geminivirus. These data will assist in our investigations into the role of genomic DNA in the formation of the unique geminate capsid architecture of the Geminiviridae.     

Neisserial outer membrane vesicles bind the coinhibitory receptor carcinoembryonic antigen-related cellular adhesion molecule 1 and suppress CD4+ T lymphocyte function

Pathogenic Neisseria bacteria naturally liberate outer membrane "blebs," which are presumed to contribute to pathology, and the detergent-extracted outer membrane vesicles (OMVs) from Neisseria meningitidis are currently employed as meningococcal vaccines in humans. While the composition of these vesicles reflects the bacteria from which they are derived, the functions of many of their constituent proteins remain unexplored. The neisserial colony opacity-associated Opa proteins function as adhesins, the majority of which mediate bacterial attachment to human carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). Herein, we demonstrate that the Opa proteins within OMV preparations retain the capacity to bind the immunoreceptor tyrosine-based inhibitory motif-containing coinhibitory receptor CEACAM1. When CD4(+) T lymphocytes were exposed to OMVs from Opa-expressing bacteria, their activation and proliferation in response to a variety of stimuli were effectively halted. This potent immunosuppressive effect suggests that localized infection will generate a "zone of inhibition" resulting from the diffusion of membrane blebs into the surrounding tissues. Moreover, it demonstrates that OMV-based vaccines must be developed from strains that lack CEACAM1-binding Opa variants.     

Gay men, social support and HIV disease: a study of social integration in the gay community

As part of a large study of the effects of HIV and AIDS on gay male sexual behaviour, we investigated the extent to which gay men in the UK have access to social support and informal care at times of illness. The study sample (n = 502) demonstrated high levels of willingness to disclose sexuality to others, sociability and social integration. Over 90% reported that they had access to people whom they could turn for practical help at times of temporary incapacity. Between 42% and 46% have known a person, or persons, with HIV symptomatic disease, AIDS or someone who has died of AIDS, although men recruited in larger towns and cities were more likely to know people at every stage of HIV infection and AIDS than those from smaller towns. Twenty-five per cent had provided practical help and support to at least one person with AIDS; men in this situation were more likely to have had a close friend, lover or former lover who had died of AIDS. It is argued that it is not possible to expect the gay community to provide fully for the non-medical care of its members and, whilst some needs can be fulfilled on an informal care basis, the demands of long-term serious illness are such that adequate support services should be available in the community.     

Guidelines for microplate techniques in liquid-phase blood grouping and antibody screening

Summary. This document is an introduction to microplate serology prepared at a time of very active research and development. Antibody detection techniques are expected to improve during the lifetime of this document. Approximately 25% of hospital blood banks are ABO and D grouping by microplate techniques. Antibody screening by microplate techniques is only being carried out by a small percentage of hospital blood banks but there is likely to be a change to antiglobulin tests by microplate procedures as soon as the methods have been thoroughly tested and approved. There are one or two weak links in these procedures which could give rise to serious errors:— (1) Antiglobulin reagents standardized for spin-tube tests may be subject to prozones in liquid phase microplate tests. Each new batch of antiglobulin reagent must be standardized by the microplate procedure in use to show that the reagent is at its optimum anti-IgG dilution for use. However dilutions greater than 1:2 may seriously compromise the anti-complement activity of the reagent. (2) Automated cell washers for microplates are currently under development and should be evaluated by replicate tests with weak anti-D sensitized cells. (3) The combination of diluted anti-IgG and poor washing procedures may lead to neutralization of anti-IgG and cause false negative errors. Future development for improved antiglobulin tests in microplates by a solid phase system is now well advanced and workers proposing to change to antibody screening by microplates are advised to bear this in mind. It is hoped that microplate methodology will move towards standardization based on national guidelines using standard antibody reagents for the validation of new microplate procedures.     

Survival after neonatal myocardial infarction

These are case reports of two children with structurally normal hearts and with normal coronary arteries, who survived myocardial infarction in the early neonatal period. They are only the third and fourth reported survivors of neonatal myocardial infarction and the first in which hypercholesterolemia is postulated to have played an important role. The most likely cause of the myocardial infarction was thrombosis or thromboembolism. Changes in hemostatic function associated with hypercholesterolemia may be relevant.     

A randomized controlled trial of intracameral lidocaine during phacoemulsification under topical anesthesia

OBJECTIVE: To test the hypothesis that adjunctive intracameral 1% lidocaine reduces intraoperative pain during phacoemulsification using topical anesthesia. DESIGN: Prospective, double-masked, randomized, controlled trial. PARTICIPANTS: A total of 200 patients undergoing routine phacoemulsification under topical 1% tetracaine were studied. INTERVENTION: Randomization to 0.5 ml intracameral, unpreserved, epinephrine-free 1% lidocaine or placebo was conducted. MAIN OUTCOME MEASURE: Intraoperative pain was quantified by the patients using a 0-10 visual analog pain scale. RESULTS: Intraoperative pain scores (+/- standard deviation) for the lidocaine and control groups were 1.29 +/-1.24 and 1.44 +/- 1.33, respectively (P > 0.35). CONCLUSIONS: In a rigorously double-masked, prospective, randomized, controlled trial there was no significant reduction in intraoperative pain when intracameral 1% lidocaine was used during phacoemulsification under topical anesthesia.     

Centration of donor trephination in human corneal transplantation

PURPOSE: To develop and evaluate a new method to quantify centration of the trephined donor cornea relative to the limbus. METHODS: After human donor corneas were trephined for penetrating keratoplasty, the remaining corneoscleral discs were stained and subjected to image analysis. The centration of the excised donor cornea relative to the limbus was calculated by measuring their centroids from the "captured" images. RESULTS: Fifty-two corneoscleral discs were analyzed. The average deviation from the centre was 0.32 mm (SD, 0.18 mm). Neither surgeon nor the type of trephine significantly influenced the mean centroid deviation. CONCLUSION: We have developed and evaluated a method to quantify centration of human donor cornea. In a small series, decentration did not correlate significantly with either the surgeon or the trephine.