Latent membrane protein-1 of Epstein-Barr virus inhibits cell growth and induces sensitivity to cisplatin in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma is closely associated with Epstein-Barr virus (EBV) and the EBV encoded latent membrane protein-1 expression (LMP1) is commonly found in the tumour cells. LMP1 has been shown to be involved in modulation of cell growth in B cells but the biological properties of LMP1 expression in nasopharyngeal carcinoma cells are less defined. In this study, a full length LMP1 gene was introduced into an EBV negative nasopharyngeal carcinoma cell line, CNE2, and five LMP1-expressing clones were isolated. Expression of LMP1 did not confer cell growth advantage in CNE2 cells; instead, it induced growth inhibition both in vitro and in vivo. In addition, the LMP1 transfected cells were more susceptible to cisplatin-induced cell death and showed 1.4-4.0-fold increased sensitivity to cisplatin compared to the vector infected control clones. The effect of LMP1 on the balance of Bcl-2 and Bax ratio may play a role in inducing susceptibility to cisplatin-induced cell death. These results demonstrated that LMP1 did not confer growth advantage in CNE2 cells, suggesting that expression of LMP1 may not be crucial in sustaining cell growth in established cell lines. Alternatively, LMP1 alone may not be sufficient to facilitate nasopharyngeal carcinoma cell growth and additional oncogenic factors may be needed along with LMP1 in modulating the malignant property of nasopharyngeal carcinoma.     

Lifestyles and social class: implications for primary care

Data from the Oxford healthy life survey were used to explore social class variations in beliefs about the determinants of health, willingness to contemplate behaviour change and experience of lifestyle advice in primary care.While the association between lifestyle factors and health was well-recognized by all social groups, those in social classes 1 and 2 were more likely than others to stress the importance of smoking, diet and exercise, while those in social classes 4 and 5 were more likely than middle class people to emphasize the effect of socioeconomic influences on health such as unemployment, income, pollution and housing. Members of all social classes attributed considerable importance to psychosocial influences on health. In all social classes a substantial proportion of overweight people expressed a desire to reduce their weight, smokers to modify their smoking habits and sedentary people to increase the amount of exercise they took. However, there was less interest in dietary change or reduction of alcohol consumption. One third of the smokers and of those who were overweight had received advice from health professionals about behaviour modification, but less than 10% of those in the other risk groups reported receiving advice. There was a high demand for advice on health; 44% of all respondents said they would be interested in receiving advice on a healthier lifestyle.     

Isolation of Neisseria lactamicus from the nasopharynx

During 1971 and 1972, 71 cultures of neisseriae that attacked lactose were received by this laboratory. All strains except one from an eye swab were from the nasopharynx of healthy subjects. Nineteen similar strains from the nasopharynx were isolated in this laboratory.The characteristics of these strains were compared with those of Neisseria meningitidis, Neisseria pharyngis, Neisseria catarrhalis, and Neisseria lactamicus. The 90 strains under investigation closely resembled Neisseria meningitidis but could be differentiated by production of acid from lactose and beta-galactosidase activity and were therefore classified as Neisseria lactamicus.     

High and low frequency transcutaneous electrical nerve stimulation inhibits nociceptive responses induced by CO2 laser stimulation in humans

The aim of the study was to evaluate the effects of transcutaneous electric nerve stimulation (TENS) on CO(2) laser evoked potentials (LEPs) in 16 normal subjects. The volar side of the forearm was stimulated by 10 Hz TENS in eight subjects and by 100 Hz TENS in the remainder; the skin of the forearm was stimulated by CO(2) laser and the LEPs were recorded in basal conditions and soon after and 15 min after TENS. Both low and high frequency TENS significantly reduced the subjective rating of heat stimuli and the LEPs amplitude, although high frequency TENS appeared more efficacious. TENS seemed to exert a mild inhibition of the perception and processing of pain induced by laser Adelta fibres activation; the implications of these effects in the clinical employment of TENS remain to be clarified.     

Investigation of de novo variation in pediatric cardiomyopathy

Pediatric cardiomyopathies can be caused by variants in genes encoding the sarcomere and cytoskeleton in cardiomyocytes. Variants are typically inherited in an autosomal dominant manner with variable expressivity. De novo variants have been reported, however their overall frequency is largely unknown. We sought to determine the rate of de novo, pathogenic and likely pathogenic (P/LP) variants in children with a diagnosis of hypertrophic, dilated, or restrictive cardiomyopathy (HCM, DCM, or RCM), and to compare disease outcomes between individuals with and without a de novo variant. A retrospective record review identified 126 individuals with HCM (55%), DCM (37%), or RCM (8%) ≤18 years of age who had genetic testing. Overall, 50 (40%) had positive genetic testing and 18% of P/LP variants occurred de novo. The rate of de novo variation in those with RCM (80%) was higher than in those with HCM (9%) or DCM (20%). There was evidence of germline mosaicism in one family with RCM. Individuals with de novo variants were more likely than those without to have a history of arrhythmia (p = .049), sudden cardiac arrest (p = .024), hospitalization (p = .041), and cardiac transplantation (p = .030). The likelihood of de novo variation and impact on family risk and screening should be integrated into genetic counseling.     

Homologues of insecticidal toxin complex genes in Yersinia enterocolitica biotype 1A and their contribution to virulence

Yersinia enterocolitica is an enteric pathogen that consists of six biotypes: 1A, 1B, 2, 3, 4, and 5. Strains of the latter five biotypes can carry a virulence plasmid, known as pYV, and several well-characterized chromosomally encoded virulence determinants. Y. enterocolitica strains of biotype 1A lack the virulence-associated markers of pYV-bearing strains and were once considered to be avirulent. There is growing epidemiological, clinical, and experimental evidence, however, to suggest that some biotype 1A strains are virulent and can cause gastrointestinal disease. To identify potential virulence genes of pathogenic strains of Y. enterocolitica biotype 1A, we used genomic subtractive hybridization to determine genetic differences between two biotype 1A strains: an environmental isolate, Y. enterocolitica IP2222, and a clinical isolate, Y. enterocolitica T83. Among the Y. enterocolitica T83-specific genes we identified were three, tcbA, tcaC, and tccC, that showed homology to the insecticidal toxin complex (TC) genes first discovered in Photorhabdus luminescens. The Y. enterocolitica T83 TC gene homologues were expressed by Y. enterocolitica T83 and were significantly more prevalent among clinical biotype 1A strains than other Yersinia isolates. Inactivation of the TC genes in Y. enterocolitica T83 resulted in mutants which were attenuated in the ability to colonize the gastrointestinal tracts of perorally infected mice. These results indicate that products of the TC gene complex contribute to the virulence of some strains of Y. enterocolitica biotype 1A, possibly by facilitating their persistence in vivo.     

Complement studies in membranoproliferative glomerulonephritis

Detailed studies of the complement system were carried out in fifteen patients with membranoproliferative glomerulonephritis. The findings of reduced levels of C3 and C7 and of circulating breakdown products of C3 in fresh plasma suggested in vivo complement activation. Low C3 levels were associated with the presence of a serum factor (the C3 nephritic factor C3NeF) which was capable of breaking down C3 in normal serum in vitro. Metabolic studies using radioactive iodine labelled C3 showed no evidence of accelerated in vivo breakdown of parenterally administered C3 suggesting that hypocomplementaemia is either maintained by diminished C3 synthesis or that accelerated catabolism is occurring in a pool that does not freely exchange with parenterally given C3. The C3 nephritic factor has so far only been identified in patients with membranoproliferative nephritis and is therefore of major diagnostic significance in patients with glomerular disease.     

Histamine activates suppressor cellsin vitro using a coculture technique

Aliquots of human blood mononuclear cells were culturedin vitro in the absence or presence of varying concentrations of histamine (10^–3–10^–8 M) for 24 hr, mitomycin treated, washed, and cocultured with autologous indicator cells that were then stimulated by PHA. The degree of suppression of thymidine uptake was measured in the presence of histamine-activated cells. The results demonstrated that histamine, in a dose-dependent fashion (10^–3 and 10^–4 M), significantly suppressed the PHA proliferative response. A minimum of 2 hr was required to activate cells by histamine to express suppressor function. While initial studies were carried out with a 1:1 suppressor:indicator cell ratio, it was found that maximum suppression resulted with lower rations (1:2 or 1:5) in some experiments, and was dependent somewhat on the concentration of histamine used. That the suppressor cells expressed histamine receptors was shown by the finding that histamine-Sepharose columns (but not control columns) depleted the histamine-reactive cells. In addition, Con A-reactive suppressor cells also adhered to histamine columns. Based on experiments with H₁ and H₂ antagonists and agonists, the histamine-responsive cell was apparently activated through its histamine type-2 receptor.