Saponins,IL12 and BCG adjuvant in the FML-vaccine formulation against murine visceral leishmaniasis

The FML antigen of Leishmania donovani, in combination with either Riedel de Ha?n (R), QuilA, QS21 saponins, IL12 or BCG, was used in vaccination of an outbred murine model against visceral leishmaniasis (VL). Significant and specific increases in anti-FML IgG and IgM responses were detected for all adjuvants, and in anti-FML IgG1, IgG2a and IgG2b and delayed type of hypersensitivity to L. donovani lysate (DTH), only for all saponins and IL12. The QS21-FML and QuilA-FML groups achieved the highest IgG2a response. QuilA-FML developed the strongest DTH and QS21-FML animals showed the highest serum IFN-gamma concentrations. The reduction of parasitic load in the liver in response to each FML-vaccine formulation was: 52% (P<0.025) for BCG-FML, 73% (P<0.005) for R-FML, 93% (P<0.005) for QuilA-FML and 79.2% (P<0.025) for QS21-FML treated animals, respectively. Protection was specific for R-FML and QS21-FML while the QuilA saponin treatment itself induced 69% of LDU reduction. The FML-saponin vaccines promote significant, specific and strong protective effects against murine visceral leishmaniasis. BCG-FML induced minor and non-specific protection while IL12-FML, although enhancing the specific antibody and IDR response, failed to reduce the parasitic load of infected animals.     

Segregation analysis of prostate cancer in 1,719 white,African-American and Asian-American families in the United States and Canada

Some data suggest that brothers of prostate cancer patients have higher disease risk than their fathers, supporting an X-linked or recessive mode of inheritance. However, higher observed frequencies in brothers than fathers may merely reflect the strong temporal changes in US incidence rates. Objectives: (a) to evaluate the fit of X-linked, recessive, and dominant modes of inheritance to prostate cancer incidence, specific for calendar year, age, and race, in population-based samples of US and Canadian families; and (b) to evaluate a simple multifactorial model for familial aggregation of prostate cancer due to shared low-penetrance variants of many genes or shared lifestyle factors. Methods: The data consist of reported prostate cancer incidence in first-degree relatives of 1719 white, African-American, and Asian-American men with and without prostate cancer at ages < 70 years. Model parameters were estimated by maximizing a pseudo-likelihood function of the data, and goodness of model fit was assessed by evaluating discrepancies between observed and expected numbers of pairs of relatives with prostate cancer. Results: After adjusting for temporal trends in prostate cancer incidence rates we found that the X-linked model fit poorly, underpredicting the observed number of affected father–son pairs. This also was true of the recessive model, although the evidence for poor fit did not achieve statistical significance. In contrast, the dominant model provided adequate fit to the data. In this model the race-specific penetrance estimates for carriers of deleterious genotypes were similar among African-Americans and whites, but lower among Asian-Americans: risk by age 80 years for carriers born in 1900 was estimated as 75.3% for African-Americans and whites, and 44.4% for Asian-Americans. None of the Mendelian models fit the data better than did the simple multifactorial model. Conclusions: The good fit of the multifactorial model suggests that multiple genes, each having low penetrance, may be responsible for most inherited prostate cancer susceptibility, and that the contribution of rare highly penetrant mutations is small.     

Carbohydrates and colorectal cancer risk among Chinese in North America.

Previous studies have analyzed total carbohydrate as a dietary risk factor for colorectal cancer (CRC) but obtained conflicting results, perhaps attributable in part to the embedded potential confounder, fiber. The aim of this study was to analyze the nonfiber ("effective") carbohydrate component (eCarb) separately and to test the hypothesis that effective carbohydrate consumption is directly related to CRC risk. The data (473 cases and 1192 controls) were from a large, multicenter, case-control study of Chinese residing in North America. Multivariate logistic regression was used to perform a secondary analysis controlling for age; sex; consumption of fat, fiber, calcium, and total kilocalories; body mass (Quetelet's) index; family history; education; and years in North America. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate risk among subgroups by sex and cancer site. A statistically significant positive association was observed between eCarb consumption and risk of CRC in both men (OR, 1.7 comparing highest with lowest tertile of eCarb consumption; 95% CI, 1.1-2.7) and women (OR, 2.7; 95% CI, 1.5-4.8). As expected, the ORs for total carbohydrate were somewhat lower than those for effective carbohydrate, but the differences were not large. A sex difference in risk by colorectal subsite was observed, with risk concentrated in the right colon for women (OR, 6.5; 95% CI, 2.4-18.4) and in the rectum for men (OR, 2.4; 95% CI, 1.2-4.8). These data indicate that increased eCarb and total carbohydrate consumption are both associated with increased risk of CRC in both sexes, and that among women, relative risk appears greatest for the right colon, whereas among men, relative risk appears greatest for the rectum.     

Acute effect of Bauhinia forficata on serum glucose levels in normal and alloxan-induced diabetic rats

Experimental diabetes was used to study the acute effect of the n-butanol fraction of Bauhinia forficata Link (Leguminosae) (BF) leaves on the serum glucose levels of rats. Body weight was measured on the day of diabetes induction and on the day of the experiment. Levels of glucose were determined at different doses and times following treatment with BF or with vehicle in normal, diabetic and hyperglycemic normal rats. Oral administration of n-BuOH fraction led to a significant blood glucose-lowering effect in normal and diabetic rats. However, in glucose-fed hyperglycemic normal rats, the maximum dose of this fraction failed to decrease blood glucose levels. The hypoglycemic effect was observed at doses of 500 and 600 mg/kg after 1 and 2 h treatment respectively, in normal rats. The maximum effect of BF was detected at 1 h with 800 mg/kg in diabetic animals and this profile was maintained for the next 3 h. Treatment of normal and alloxan-induced diabetic rats with BF decreased glucose levels, while this fraction was devoid of hypoglycemic effect in glucose-fed hyperglycemic normal rats.     

Dissociation in adolescent girls with anorexia: relationship to comorbid psychopathology

This study investigated the relationship between dissociation and psychological symptoms in adolescent girls with anorexia. First, the psychometric properties of the Adolescent Dissociative Experiences Scale (A-DES) were examined using data from 181 nonclinical adolescent boys and girls. Thereafter, A-DES scores and correlations with a range of psychological symptoms were compared across 20 girls with anorexia, 19 mixed clinical girls, and 86 nonclinical girls. The A-DES had a one-factor structure and good psychometric characteristics. Dissociation scores were significantly correlated with level of symptomatology for all groups. Although the group with anorexia did not have significantly higher dissociation scores than the other two groups, dissociation in the anorexic girls was related to psychopathology in a distinct way. Adolescent girls with anorexia appear to use dissociation specifically to avoid processing angry affect with an interpersonal basis, although it is also related to their use of somatization, and obsessive-compulsive features.     

Retrieval-induced forgetting in Alzheimer's disease

It is claimed that Alzheimer's disease (AD) patients show reduced inhibitory processing and this has been put forward as a reason why AD patients make intrusion errors at recall. However, the evidence to date has been equivocal, because non-inhibitory mechanisms can account for the pattern of findings. Recently, however, a paradigm has been developed that is claimed to give a purer measure of inhibitory processing in episodic memory, the retrieval-induced forgetting (RIF) paradigm [Inhibitory Processes in Attention, Memory and Language, Academic Press, San Diego, 1994, p. 265; J. Exp. Psychol.: Learning, Memory Cognition 20 (1994) 1063; Psychol. Rev. 102 (1995) 68]. Thus, we were interested whether AD patients would show a deficit in inhibitory processing using this procedure. Participants studied lists of category cue-exemplar pairs (e.g. fruit-orange) then practised retrieval for a subset of items from a subset of categories before taking a final memory test for all studied items. As in previous work, inhibition was measured as the difference between final memory performance for unpractised items from practised categories, and unpractised items from unpractised categories. The results show that AD patients showed normal levels of inhibition with both tests of cued recall and category generation (CG). This suggests that a deficit in inhibitory processes during retrieval is not behind the high levels of intrusion errors made in recall in AD.     

The fetal and neonatal brain protein neuronatin protects PC12 cells against certain types of toxic insult

The protein neuronatin is expressed in the nervous system of the fetus and neonate at a much higher level than in the adult. Its function is unknown. As a result of variable splicing, neuronatin mRNA exists in two forms, alpha and beta. Wild type PC12 cells express neuronatin-alpha. We have isolated a PC12 variant, called 1.9, that retains many of the neuron-like properties of wild type PC12 cells, but it does not express neuronatin and it exhibits markedly increased sensitivity to the toxic effects of nigericin, rotenone and valinomycin. Pretreatment of the 1.9 cells with alpha-methyltyrosine, which inhibits dopamine synthesis, had little effect on the cells' sensitivity to nigericin, rotenone or valinomycin indicating that dopamine-induced oxidative stress was not involved in the toxicity of these compounds. However, flattened cell subvariants of the 1.9 cells, which do not have any neuron-specific characteristics, did not exhibit increased sensitivity to nigericin indicating that some neuronal characteristic of the 1.9 cells contributed to the toxicity of nigericin. After the neuronatin-beta gene was transfected into and expressed in the 1.9 cells, they regained wild type PC12 levels of resistance to nigericin, rotenone and valinomycin. These studies suggest that the function of neuronatin during development could be to protect developing cells from toxic insult occurring during that period.