De novo insertion of an intron into the mammalian sex determining gene, SRY

Two theories have been proposed to explain the evolution of introns within eukaryotic genes. The introns early theory, or “exon theory of genes,” proposes that introns are ancient and that recombination within introns provided new exon structure, and thus new genes. The introns late theory, or “insertional theory of introns,” proposes that ancient genes existed as uninterrupted exons and that introns have been introduced during the course of evolution. There is still controversy as to how intron–exon structure evolved and whether the majority of introns are ancient or novel. Although there is extensive evidence in support of the introns early theory, phylogenetic comparisons of several genes indicate recent gain and loss of introns within these genes. However, no example has been shown of a protein coding gene, intronless in its ancestral form, which has acquired an intron in a derived form. The mammalian sex determining gene, SRY, is intronless in all mammals studied to date, as is the gene from which it recently evolved. However, we report here comparisons of genomic and cDNA sequences that now provide evidence of a de novo insertion of an intron into the SRY gene of dasyurid marsupials. This recently (approximately 45 million years ago) inserted sequence is not homologous with known transposable elements. Our data demonstrate that introns may be inserted as spliced units within a developmentally crucial gene without disrupting its function.     

Do psychiatric patients need greater protection than medical patients when they consent to treatment?

It is commonly assumed that psychiatric patients require greater protection than medical patients when they make health care decisions. A review of the literature reveals that there is meager evidence for this belief and that both groups have significant capacity problems. Many factors other than psychiatric illness have been shown to impede understanding of informed consent information in health care settings. These include powerful emotional states, lack of a high school education, the presence of a severe medical illness, and increasing age. Clinicians can help patients become more adequate decision makers by taking such steps as providing adequate disclosure and inquiring about patient understanding. Even then, setting a realistically lenient standard of capacity seems the most practical approach. If screening for capacity is important for a specific health care decision, all vulnerable groups should be targeted.     

Effects of thyroxine on infant development of undernourished rats

The rehabilitative effects of exogenous thyroxine on infant development of undernourished animals were examined. Thyroxine injection accelerated the rate of body growth, age at eye opening, tooth eruption, and several emitted behaviors in undernourished infant animals. The data indirectly support previous findings that undernutrition induces hypothyroidism and that exogenous thyroxine might be an effective rehabilitative agent.     

Multiple sclerosis: Oligoclonal IgG, ξ-λ light chain distribution and measles antibodies in brain extracts

The presence of measles antibodies in white and grey brain material and in 8 demyelination plaques from 6 patients affected with multiple sclerosis was investigated with the hemagglutination inhibition (HI) and complement fixation (CF) techniques.White and grey matter of 5 controls were run in parallel. No measles antibodies could be detected, except for one plaque, where the answer could be considered as doubtful. The immunoglobulin G (IgG) content and the ξ/λ light chain ratios of all the samples were evaluated. No unique monoclonal immunoglobulin population could be detected, but ξ or λ predominant oligoclonal populations appeared in controls as well as in MS IgG.     

High-dose continuous infusion plus pulse interleukin-2 and famotidine in metastatic kidney cancer

High-dose continuous infusion interleukin-2 (IL-2) regimens generate a higher degree of lymphokine activated killer cell (LAK) cytotoxicity when tested against tumor cells in vitro and a higher rebound lymphocytosis in vivo than do bolus IL-2 regimens. Lymphocytes initially activated by continuous infusion IL-2 have increased cytotoxicity against cancer cells when they are subsequently pulsed with additional IL-2. Famotidine may enhance LAK cytolytic ability. Six patients with kidney cancer have been treated with a combination of famotidine 20 mg intravenous bid and continuous infusion IL-2 (18 MIU/sq m/24 hours) for 72 hours, followed by a 24-hour rest, then IL-2 18 MIU/sq m over 15-30 minutes. The most common metastatic sites were the lung, lymph node, and bone. Median number of cycles received = 5 (range, 3-8). The most common toxicities were fever, rigors, nausea/emesis, hypophosphatemia, hypotension, elevated creatinine, and metabolic acidosis. There were no treatment-related deaths, and no patients required intensive care admission. Two partial responses (33% response rate) have been seen. Median survival has not been reached at greater than 8 months. The combination of high-dose continuous infusion plus pulse IL-2 and famotidine is active in metastatic kidney cancer. An accrual of additional patients is needed to better assess the response rate.     

Effects of marital transitions on changes in dietary and other health behaviours in US women

BACKGROUND: Previous studies have indicated that married people have lower mortality and are generally healthier. Most previous studies have been cross-sectional and few studies investigated the effect of marital transition on health. With a prospective design and repeated measures of variables, we sought to analyse the temporal relation between marital transition and change in health behaviours. METHODS: We followed up 80 944 women aged 46-71 for 4 years (1992-1996). All information was self-reported. We used multivariate-adjusted linear and logistic regression models to examine the impact of changes in marital status on concomitant changes in health behaviours, controlling for potential confounders and baseline health behaviours. RESULTS: Compared with women who remained married, women who divorced/widowed had body mass index (BMI) decreases of 0.65 kg/m(2) (P < 0.001) and 0.44 kg/m(2) (P < 0.001), respectively. Compared with women who remained unmarried, women who remarried had an increase in mean BMI of 0.41 kg/m(2) (P < 0.001). Women who divorced increased physical activity by 1.23 metabolic equivalent hours (MET)/week (P = 0.07) compared with women who stayed married. Among non-smokers and past smokers, women who divorced/widowed had more than a twofold increased risk of relapsing/starting smoking (OR = 2.47, 95% CI: 1.56, 3.89; OR = 2.08, 95% CI: 1.56, 2.76, respectively) than women who stayed married. Divorced and widowed women had decreased vegetable intake relative to women who stayed married (-2.93 servings/week [P < 0.001] and -1.67 servings/week [P < 0.001], respectively). CONCLUSIONS: These patterns suggest both health-damaging and health-promoting changes accompanying divorce and widowhood, and generally health-promoting changes following remarriage.     

The beneficial effects of recipient-derived vascular endothelial growth factor on graft survival after kidney transplantation

BACKGROUND: Vascular endothelial growth factor (VEGF) is crucial for preservation of microvasculature and contributes to cytoprotection of the graft after kidney transplantation. METHODS: The authors investigated the influence of VEGF single-nucleotide polymorphism (SNP) on graft survival after renal transplantation. The SNP at positions -2578, -1154, and, -7 were analyzed in 306 donors and 387 recipients of renal transplants. RESULTS: The authors observed no effect of those recipient or donor SNP on acute rejection. However, graft survival was associated with recipient SNP at position -2578 C/A. Recipients with a genetic basis for high production of VEGF had significantly better graft survival compared with recipients with low production of VEGF. Homozygotes for the A allele (low producers of VEGF) had worse graft survival compared with high producers, the heterozygotes and homozygotes for C allele (P=0.03). Multivariate analysis in which the effects of donor age, recipient race, cold ischemia time, donor origin, and number of human leukocyte antigen mismatches were included showed that the status of noncarriers of -2578 C allele of recipients was an independent factor for graft failure (odds ratio, 1.8; 95% confidence interval, 1.0-3.0; P=0.03). CONCLUSIONS: The authors conclude that homozygote recipients for the -2578 A allele, the low producers of VEGF, are more vulnerable to tissue injury, resulting in worse graft survival.     

Anti-CD2 monoclonal antibody and tacrolimus in adult liver transplantation

BACKGROUND: Blockade of costimulation and adhesion signaling is an attractive approach to interfere with graft rejection METHODS: Between January 1997 and May 1999, forty adults having benign liver diseases were included in a prospective, randomized study comparing tacrolimus plus low-dose short-term steroids without (n=20, TAC group) or with a 10-day course of antihuman CD2 monoclonal antibody (n=20, BTI group). RESULTS: At day 7, histological rejection expressed by mean Banff scores (2.3+/-1.6 vs. 5.4+/-1.6 in the TAC group; P<0.0001) and incidence of moderate to severe rejection (score>or=6) (0 vs. 10 [50%] in the TAC group; P<0.001) were significantly lower in the BTI group. Rejection was treated in 10% (two patients) of BTI patients during the first 3 months and in 15% during the whole follow-up and in 25% (five patients) of TAC patients (P=NS). None of the BTI-patients presented with an adverse event. Three-month, 1-year, and 5-year actual patient survival rates were 100%, 95%, and 95% in the BTI group and 100%, 100%, and 85% in the TAC group. Graft survival rates were 100%, 90%, and 90% in the BTI group and 95%, 95%, and 80% in the TAC group (P=NS). The mAb had no negative impact on infectious or tumor events. CONCLUSIONS: Antihuman CD2 monoclonal antibody is a safe immunosuppressive drug which has a favorable impact on early immunological follow-up of liver transplanted patients. The antibody had no impact on late patient and graft survival.     

Relation between blood lead levels and childhood anemia in India

Lead pollution is a substantial problem in developing countries such as India. The US Centers for Disease Control and Prevention has defined an elevated blood lead level in children as > or = 10 microg/dl, on the basis of neurologic toxicity. The US Environmental Protection Agency suggests a threshold lead level of 20-40 microg/dl for risk of childhood anemia, but there is little information relating lead levels <40 microg/dl to anemia. Therefore, the authors examined the association between lead levels as low as 10 mug/dl and anemia in Indian children under 3 years of age. Anemia was divided into categories of mild (hemoglobin level 10-10.9 g/dl), moderate (hemoglobin level 8-9.9 g/dl), and severe (hemoglobin level <8 g/dl). Lead levels <10 mug/dl were detected in 568 children (53%), whereas 413 (38%) had lead levels > or = 10-19.9 microg/dl and 97 (9%) had levels > or = 20 microg/dl. After adjustment for child's age, duration of breastfeeding, standard of living, parent's education, father's occupation, maternal anemia, and number of children in the immediate family, children with lead levels > or = 10 microg/dl were 1.3 (95% confidence interval: 1.0, 1.7) times as likely to have moderate anemia as children with lead levels <10 microg/dl. Similarly, the odds ratio for severe anemia was 1.7 (95% confidence interval: 1.1, 2.6). Health agencies in India should note the association of elevated blood lead levels with anemia and make further efforts to curb lead pollution and childhood anemia.     

Health promotion and disease prevention for older adults: Intervention themes and strategies used in Quebec local community health centres and seniors' day centres

OBJECTIVE: Despite the considerable potential of disease prevention and health promotion (DPHP) among older adults, extant data suggest that this field of intervention is still underdeveloped. To shed further light on this issue, this paper presents the results of an inventory of DPHP interventions for older adults conducted in local community health centres (CLSCs) and seniors' day centres in the province of Quebec. METHODS: All CLSCs (N=147) and day centres (N=124) were invited to participate (response rates: 74% and 79%). Data were collected through telephone interviews. Interventions were coded according to type of intervention strategies and target themes. RESULTS: Awareness-raising and health education strategies emerged as the most frequently-cited type of intervention strategies, reported by 77% of CLSCs and 95% of day centres, respectively. The two themes reported by a majority of CLSCs were physical health (87%) and community issues (58%). Lifestyle habits (92%) and social issues (92%) were the two most frequently-cited themes in day centres. DISCUSSION: DPHP for older adults is substantially well developed in terms of intervention offerings in the two types of organizations under study. However, the range of available interventions requires expansion to increase the potential of DPHP programs to tackle the numerous challenges posed by the aging of the population.