MHC class I genes in a New World primate, the cotton-top tamarin (Saguinus oedipus), have evolved by an active process of loci turnover

Lymphocytes of a New World primate, the cotton-top tamarin (Saguinus oedipus), express classical G-related major histocompatibility complex (MHC) class I molecules with unusually limited polymorphism and variability. Three G-related loci, an F locus, an E locus, and two pseudogenes (So-N1 and So-N3) have been identified by cDNA library screening and extensive PCR analysis of both cDNA and genomic DNA from the cotton-top tamarin. Furthermore, each genus of the subfamily Callitrichinae (tamarins and marmosets) appears to express its own unique set of MHC class I genes, likely due to a rapid turnover of loci. The rapid emergence of unique MHC class I genes in the Callitrichinae genera, resulting from an active process of duplication and inactivation of loci, may account for the limited diversity of the MHC class I genes in the cotton-top tamarin. To determine the nature of the entire complement of MHC class I genes in the cotton-top tamarin, we synthesized a genomic DNA library and screened it with MHC class I-specific probes. We isolated nine new MHC class I pseudogenes from this library. These newly isolated tamarin G-related MHC class I pseudogenes are not closely related to any of their functional counterparts in the tamarin, suggesting that they do not share a recent common ancestral gene with the tamarin's currently expressed MHC class I loci. In addition, these tamarin sequences display a high rate of nonsynonymous substitutions in their putative peptide binding region. This indicates that the genes from which they have derived were likely subject to positive selection and, therefore, were once functional. Our data support the notion that an extremely high rate of loci turnover is largely responsible for the limited diversity of the MHC class I genes in the cotton-top tamarin.     

Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia

BACKGROUND: Epidemiologic studies have demonstrated strong and consistent associations between the detection of human papillomavirus (HPV) type 16 DNA and the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. However, HPV16 is also the most common type of HPV in the normal population, and only a minority of women with HPV16 infection develop cervical cancer. Studies of genomic heterogeneity in HPV16 have demonstrated the presence of multiple variant forms in all human populations examined to date. It is conceivable that the natural variants of HPV16 in a given population may not have the same biologic behavior. PURPOSE: This study was designed to determine the association between natural variants of HPV16 and the risk of biopsy-confirmed CIN 2 or 3, the most important precancerous lesions of the uterine cervix. METHODS: Prospective studies were conducted among 1) women attending a university and 2) women presenting to a sexually transmitted disease clinic. Subjects were eligible for inclusion in this investigation if the initial cytologic findings did not reveal CIN 2-3 and HPV16 DNA was detected by means of a polymerase chain reaction (PCR)-based method in one or more cervical or vulvovaginal samples. Eligible subjects were followed every 4 months with cervical Pap smears and colposcopic examinations. Women were referred for biopsy if cytology or colposcopy suggested CIN 2-3. Two groups of HPV16 variants, prototype-like and nonprototype-like, were determined by means of single-strand conformation polymorphism (SSCP) analysis of PCR products from the noncoding region of the viral genome. Representative SSCP patterns from HPV16 variants were further characterized by direct DNA sequencing of the PCR products. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox regression analysis. RESULTS: Prototype-like variants accounted for 79% of the HPV16 detected in university students and 86% of the virus detected in patients presenting to the sexually transmitted disease clinic. CIN 2-3 was confirmed by biopsy in nine of 57 HPV16-positive women attending the university and in 10 of 66 HPV16-positive women presenting to the sexually transmitted disease clinic. Among university students, those with HPV16 nonprototype-like variants were 6.5 (95% CI = 1.6-27.2) times more likely to develop CIN 2-3 than those with prototype-like variants. A similar association was observed among women presenting to the sexually transmitted disease clinic (RR = 4.5; 95% CI = 0.9-23.8). CONCLUSIONS: This study suggests that the risk of developing CIN 2-3 is not the same with all variants of HPV16 and that nonprototype-like variants confer a greater risk compared with prototype-like variants. The important genomic differences underlying this increased risk of CIN 2-3 remain to be determined.     

Apomorphine-induced yawning in the rat: influence of fasting and time of day

Yawning behavior is an experimental tool to study physiological responses, to elucidate the mechanisms of action of some drugs and hormones, and it is also a paradigm for some diseases and for dopamine (DA) agonists' clinical use. In this study, the effects of 24- and 48-h fasting as well as the influence of the light-dark cycle on apomorphine (APO)-induced yawning were evaluated. Initially, control and 48-h-fasted adult male rats were tested for yawning induced by APO (50, 100, 150 micrograms/kg, SC). The most effective dose tested was 100 micrograms/kg. Fasting significantly lowered yawning in all doses tested. Comparison between 24- and 48-h-fasted rats for APO (100 micrograms/kg)-induced yawning showed no significant difference between groups. Ad lib-fed groups were tested for APO (100 micrograms/kg)-induced yawning in both the light and in the dark phases of the cycle. Total number of yawnings increased significantly in the dark period. The present data show that fasting reduces and dark period increases APO-induced yawning in rats, suggesting that these conditions modulate the expression of this behavior.     

Prediction of long-term mortality in patients with rheumatoid arthritis according to simple questionnaire and joint count measures

This study examined changes in employment status and quality of work in 109 chronic pain patients who underwent a cognitive-behavioural pain management course; 68% of patients were female, mean age was 45 years, mean pain chronicity 10.7 years, 70% had spinal pain, and mean impairment on the Sickness Impact Profile was 26%. Twenty-six per cent of patients were employed at pre-treatment; the remaining 74% had been unemployed for 4.3 years on average. Measures of work status and quality, mood, pain, self-efficacy and walking performance were taken before admission, and at 1-, 6-, and 12-month follow-ups. Among employed patients quality of work scores improved by 35% from pre- to post-treatment (p < 0.01). Thirty per cent of previously unemployed patients returned to work during the 1-year follow-up, although employment status fluctuated greatly during this period. Non-workers were generally more impaired than workers on most measures, but the same measures did not differentiate between those who successfully returned to work and those who remained unemployed.