In ovarian neoplasms, BRAF, but not KRAS, mutations are restricted to low-grade serous tumours

Genes of the RAF family, which mediate cellular responses to growth signals, encode kinases that are regulated by RAS and participate in the RAS/RAF/MEK/ERK/MAP-kinase pathway. Activating mutations in BRAF have recently been identified in melanomas, colorectal cancers, and thyroid and ovarian tumours. In the present study, an extensive characterization of BRAF and KRAS mutations has been performed in 264 epithelial and non-epithelial ovarian neoplasms. The epithelial tumours ranged from adenomas and borderline neoplasms to invasive carcinomas including serous, mucinous, clear cell, and endometrioid lesions. It is shown that BRAF mutations in ovarian tumours occur exclusively in low-grade serous neoplasms (33 of 91, 36%); these included serous borderline tumours (typical and micropapillary variants), an invasive micropapillary carcinoma and a psammocarcinoma. KRAS mutations were identified in 26 of 91 (29.5%) low-grade serous tumours, 7 of 49 (12%) high-grade serous carcinomas, 2 of 6 mucinous adenomas, 22 of 28 mucinous borderline tumours, and 10 of 18 mucinous carcinomas. Of note, two serous borderline tumours were found to harbour both BRAF and KRAS mutations. The finding that at least 60% of serous borderline tumours harbour mutations in two members of the ERK-MAP-kinase pathway (BRAF 36%, KRAS 30%) compared with 12% of high-grade serous carcinomas (BRAF 0%, KRAS 12%) indicates that the majority of serous borderline tumours do not progress to serous carcinomas. Furthermore, no BRAF mutations were detected in the other 173 ovarian tumours in this study.     

Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients

In this study we have investigated a group of 29 Brazilian patients, who had been diagnosed with the lysosomal storage disorder, Mucopolysaccharidosis type I (MPS-I). MPS I is caused by a deficiency in the lysosomal hydrolase, alpha-L-iduronidase. Ninety percent of the MPS I patients in this study were genotyped and revealed 10 recurrent and thirteen novel IDUA gene mutations. Eight of these new mutations and three common mutations W402X, P533R, and R383H were individually expressed in CHO-K1 cells and analyzed for alpha-L-iduronidase protein and enzyme activity. A correlation was observed between the MPS I patient clinical phenotype and the associated mutant alpha-L-iduronidase protein/enzyme activity expressed in CHO-K1 cells. This was the first time that Brazilian MPS I patients had been thoroughly analyzed and highlighted the difficulties of mutation screening and clinical phenotype assessment in populations with high numbers of unique mutations.     

Comparison of contact and spatial repellency of catnip oil and N,N-diethyl-3-methylbenzamide (deet) against mosquitoes

Nepetalactone, the primary component of catnip oil, was compared with the repellent N,N-diethyl-3-methylbenzamide (deet) for its ability to affect the host-seeking ability of Aedes aegypti (L.). A triple cage olfactometer was used to bioassay each substance and to assess its attraction inhibition (spatial repellent) attributes when combined with the following attractants: carbon dioxide, acetone, a blend of L-lactic acid and acetone, and human odors. Repellent tests were conducted with each substance against female Ae. aegypti, Anopheles albimanus Weidemann, and Anopheles quadrimaculatus Say. Catnip oil and deet were both weakly attractive to Ae. aegypti, catnip oil was the better spatial repellent, whereas deet was a more effective contact repellent in tests with all three species of mosquitoes.     

Brain regions and their dynamics in prospective memory retrieval: a MEG study.

We measured brain activity using magnetoencephalography in five participants during ongoing tasks that included prospective memory, retrospective memory, and oddball trials. Sources were identified in the hippocampal formation and posterior parietal and frontal lobes. Posterior parietal cortex activation had an earlier onset in the prospective memory condition than retrospective memory or oddball conditions, a higher level of theta activity in the retrospective condition, and higher levels of upper alpha in the prospective and oddball conditions. Activation of the hippocampal formation had a longer duration in the retrospective memory and prospective memory conditions than the oddball condition, but prominent alpha and theta band activity was present in all three conditions. We interpret the early (87 ms) onset of activity in parietal cortex as evidence for an initial noticing of appropriate conditions for a PM response. Hippocampal activity may reflect a subsequent memory search for the intended action.     

Correlation of human decidual and cord blood mononuclear cell cytokine production

Human decidua has been shown to produce a number of cytokines. We hypothesized that decidual cytokine production influences cord blood mononuclear cell (CBMC) cytokine production and that cytokine profiles of decidua from allergic women differ from those of decidua from nonallergic women. Using enzyme-linked immunosorbent assay, we measured unstimulated and concanavalin A/phorbol myristate acetate-stimulated production of interleukin-4 (IL-4), IL-5, IL-10, IL-13 and interferon- gamma (IFN-gamma) by decidual explants from 59 healthy women delivered by unlabored cesarean section and from corresponding CBMCs in 39 of the 59. Except for IL-10, there was little or no unstimulated cytokine production. There was a strong correlation between stimulated decidual and stimulated CBMC IFN-gamma production (p = 0.01). In allergic women the ratio of IL-13 to IL-4 production was increased in stimulated explants (p = 0.03). Stimulated CBMCs from infants of allergic mothers were more likely to produce detectable levels of IL-5 than those from infants of nonallergic mothers (p = 0.04) and had a tendency toward higher IL-13 levels as well (p = 0.07). These results suggest that maternal and fetal IFN-gamma production is closely linked and that maternal allergy appears to influence cytokine production in the neonate for IL-5 and possibly IL-13.     

A prevalence study of antenatal depression among Chinese women

BACKGROUND: There has thus far been no empirical research on the occurrence of antenatal psychiatric morbidity in Chinese population. Epidemiological studies in western societies generally show that depressive episodes occur in 10-20% of pregnant women. Longitudinal studies have demonstrated that antenatal depression is one of the most powerful predictors of postnatal depression. There is also a growing literature that shows that antenatal psychological distress can adversely affect maternal and foetal well being. METHODS: At 38 weeks of pregnancy, 238 consecutive women were invited to return for psychiatric assessment. The participants were interviewed using the non-patient version of the Structured Clinical Interview for DSM-IV (SCID-NP). RESULTS: Seventy women (29%) declined to participate, and another 11 (5%) defaulted the SCID interview. Among the 157 women interviewed, the 1-month prevalence of antenatal depression was 4.4%. The 1-month prevalence of all psychiatric diagnoses was 6.4%. The prevalence of antenatal depression and all psychiatric diagnoses for the entire pregnancy was 6.4% and 8.3%, respectively. LIMITATIONS: About a third of eligible subjects did not participate in the study. CONCLUSIONS: A significant proportion of Chinese women suffer from psychiatric morbidity during pregnancy. Depressive disorders are by far the commonest morbidity in the study population. Given the scope of the morbidity and the potential impact on obstetric and neonatal outcomes, early screening and treatment are warranted.     

Ultrasonic vocalizations and maternal-infant interactions in a rat model of fetal alcohol syndrome

When isolated from their dams and littermates, rat pups emit ultrasonic vocalizations to elicit attention and retrieval from their dams. This study examined the effects of perinatal alcohol exposure on ultrasonic vocalizations and maternal-infant interactions. Alcohol was administered throughout gestation to the dams and during the early postnatal period to the pups. Control groups consisted of a nontreated control and an intubated, pair-fed control. Ultrasonic vocalizations were measured on postnatal day (PD) 5 under varying conditions of isolation. Maternal behaviors were examined on PD2, 4, 6, 8, and 10. Maternal behaviors were not significantly affected by prior alcohol administration to either the dams or the pups. However, ethanol-exposed rat pups vocalized more on PD5 than controls regardless of condition. The heightened vocalization response of the ethanol-exposed pups might be an underlying factor in the persistent effects of perinatal ethanol exposure on social behavior.     

Epstein-Barr viral load as a marker of lymphoma in AIDS patients

Epstein-Barr virus (EBV) is implicated in the pathogenesis of acquired immunodeficiency syndrome (AIDS) lymphoma, and viral DNA is present within the malignant cells in about half of affected patients. We examined the extent to which EBV viral load is elevated in the plasma of AIDS lymphoma patients compared to AIDS patients with opportunistic infections. Sixty-one AIDS patients were studied including 35 with lymphoma (24 non-Hodgkin, six Hodgkin, and five brain lymphoma) and 26 with various opportunistic infections. In situ hybridization revealed EBV encoded RNA (EBER) expression in the malignant cells of 17/28 AIDS lymphomas (61%). In 232 serial plasma samples from 35 lymphoma patients and in 128 samples from AIDS controls, EBV viral load was assayed by quantitative-polymerase chain reaction (Q-PCR) using a TaqMan probe targeting the BamH1W sequence. EBV was detected in plasma from all 17 EBER-positive AIDS lymphoma patients, with viral loads ranging from 34 to 1,500,000 copies per ml (median 3,210). Viral load usually fell rapidly upon initiation of lymphoma therapy and remained undetectable except in two patients with persistent tumor. In 11 AIDS patients, whose lymphoma lacked EBER expression, and in 26 control patients without lymphoma, levels of EBV in plasma were usually low or undetectable (range 0-1,995 and 0-2,409, median 0 and 0, respectively). There was no association between EBV viral load and human immunodeficiency virus (HIV) load or CD4 count. In conclusion, EBV viral load shows promise as a tool to assist in diagnosis and management of EBV-related lymphoma patients.     

Obesity and upper body fat distribution in Mexican American children from families with a diabetic proband

Upper and centralized body fat distribution is associated with non-insulin dependent diabetes mellitus (NIDDM). Few studies have focused on anthropometric characteristics of preadults from families in which there is a diabetic (NIDDM) proband. This study explores the prevalence of upper and centralized body fatness in Mexican American children from the Diabetes Alert study (1981–1983) in Starr County, Texas. Anthropometric data on 165 males and 224 females 9–19 years include measures of adiposity such as skinfold thicknesses and the body mass index (BMI), a measure of overweight. They show rates of obesity two to three times that of White children of comparable age and sex from National Health Surveys. In comparison with U.S. White subjects, Mexican American adults are shorter, have more adiposity and arm muscle mass and have sitting heights and body breadths at the mean of these dimensions for the U.S. population. Children from Diabetes Alert families show only marginal excess of severe obesity (> 95th percentile of BMI) when compared to the general population of children surveyed in Starr County schools. Girls from these families, but not boys, have excess fatness in the BMI compared to Mexican American children from the Hispanic Health and Nutrition Examination Survey (HHANES); suprailiac skinfold thicknesses are also greater in children of the Diabetes Alert study than in HHANES children. From 1972 through 1982, Mexican American children in South Texas showed an increase in average stature, weight, and the BMI. These data together suggest that excessive obesity exists and may be increasing in children in populations at risk for NIDDM. The prevention of NIDDM in the Mexican American population may be more effective if educational and promotional interventions include the school aged population. © 1993 Wiley-Liss, Inc.     

Hypoxia promotes murine bone-marrow-derived stromal cell migration and tube formation

Recent evidence indicates that bone-marrow-derived stromal cells (MSCs) have a histology coherent with endothelial cells that may enable them to contribute to tumor angiogenesis through yet undefined mechanisms. In this work, we investigated the angiogenic properties of murine MSCs involved in extracellular matrix degradation and in neovascularization that could take place in a hypoxic environment such as that encountered in tumor masses. MSCs were cultured in normoxia (95% air and 5% CO(2)) or in hypoxia (1% oxygen, 5% CO(2), and 94% nitrogen). We found that hypoxic culture conditions rapidly induced MSC migration and three-dimensional capillary-like structure formation on Matrigel. In vitro, MSC migration was induced by growth-factor- and cytokine-enriched conditioned media isolated from U-87 glioma cells as well as from MSCs cultured in hypoxic conditions, suggesting both paracrine and autocrine regulatory mechanisms. Although greater vascular endothelial growth factor levels were secreted by MSCs in hypoxic conditions, this growth factor alone could not explain their greater migration. Interestingly, matrix metalloproteinase (MMP)-2 mRNA expression and protein secretion were downregulated, while those of membrane-type (MT)1-MMP were strongly induced by hypoxia. Functional inhibition of MT1-MMP by a blocking antibody strongly suppressed MSC ability to migrate and generate capillary-like structures. Collectively, these data suggest that MSCs may have the capacity to participate in tumor angiogenesis through regulation of their angiogenic properties under an atmosphere of low oxygen that closely approximates the tumor microenvironment.