Hepatic vascular tumors, angiectasis in multiple organs, and impaired spermatogenesis in mice with conditional inactivation of the VHL gene

von Hippel-Lindau (VHL) disease is a multisystem inherited cancer syndrome characterized by the development of highly vascular tumors including hemangioblastomas of the retina and central nervous system, pheochromocytomas, and clear cell renal carcinoma, which result from somatic inactivation of the wild-type VHL allele in cells harboring a germ-line VHL mutation. Homozygous inactivation of the VHL gene in mice resulted in embryonic lethality. To produce a mouse model that closely mimics human VHL disease and avoids embryonic lethality, we used Cre/lox site-specific recombination technology. We generated mice carrying conditional VHL alleles and a cre transgene under the control of the human beta-actin promoter, which directs cre expression in a mosaic pattern in multiple organs. VHL(f/d)/Cre mice developed multiple, hepatic hemangiomas that led to premature death, as well as angiectasis and angiogenesis in multiple organs. Interestingly, testes of male VHL(f/d)/Cre mice were unusually small with severely reduced sperm count resulting in infertility. Loss of pVHL function in this VHL conditional knockout mouse model results in an extensive abnormal vascular phenotype in multiple mouse organs, which will provide a useful animal model for testing potential antiangiogenic therapies for VHL disease treatment. Importantly, the phenotypic defects in sperm development observed in these mice support a novel role for VHL in spermatogenesis. This VHL conditional knockout mouse model will provide an in vivo system for studying the functional requirement of the VHL gene in reproductive biology.     

Risk and protective factors for suicidal behavior in abused African American women.

This study examined risk and protective factors that differentiate low-income, abused African American women (N=200) who attempted suicide from those who had never made a suicide attempt. Results from multivariate analyses revealed that numerous and/or severe negative life events, a history of child maltreatment, high levels of psychological distress and depression, hopelessness about the future, and alcohol and drug problems were factors associated with attempter status. Protective factors associated with nonattempter status included hopefulness, self-efficacy, coping skills, social support, and effectiveness in obtaining material resources. Culturally competent intervention approaches for abused women should target increasing their protective factors and reducing their risk factors to decrease the likelihood that these women engage in suicidal behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

What is so bad about a little name-calling? Negative consequences of gender harassment for overperformance demands and distress.

Few studies have investigated why harassment has negative effects on women's well-being. The authors proposed that, for women working in traditionally male occupations, gender harassment (GH) causes overperformance demands (OPD), which lead to psychological distress. This mediated model was strongly supported for 262 female police officers but, as proposed, was not supported for male officers (N=315). For men, levels of GH and OPD were lower than for women, and GH was not a significant predictor of OPD. Harassing behaviors thus had different consequences for women and men. A lack of perceived support for equal deployment of women police was associated with OPD for women, and family → work conflict was a significant predictor of OPD for both men and women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amphetamine and morphine produce a conditioned taste and place preference in the house musk shrew (Suncus murinus).

Rats have been shown to avoid consuming a flavor, but prefer a location, previously paired with amphetamine or morphine. A series of 4 experiments evaluated the hedonic properties of amphetamine and morphine in the house musk shrew (Suncus murinus), an insectivore that (unlike rats) is capable of vomiting when exposed to toxins. Unlike rats, amphetamine (20 mg/kg) and morphine (20 mg/kg) produced both a conditioned sucrose (0.3 M) and saccharin (0.1%) preference in shrews (administered intraperitoneally), when measured by both a 1-and a 2-bottle test. At the same dose, both drugs also produced a place preference in shrews. These results suggest that the potential of rewarding drugs to produce taste avoidance may vary on the basis of the ability of the species to vomit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive motion extrapolation and cognitive clocking in prediction motion task

An interruption paradigm was used to measure judgments that rely on cognitive extrapolation of approach and lateral motion. In some conditions the pattern of errors was consistent with that obtained with time-to-contact (TTC) judgments measured with a prediction motion (PM) task. Also, the slope of the relationship between estimated and actual TTC in judgments of approaching objects decreased when visual information about the environment between the observer and the display was minimized. Moreover, the accuracy of relative duration judgments of visual (but not auditory) stimuli decreased when a PM task was performed concurrently. Results are consistent with the notion that PM tasks involve cognitive motion extrapolation rather than solely a clocking process that counts down TTC.     

Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women

This study sought to quantify influenza-related serious morbidity in pregnant women, as measured by hospitalizations for or death from selected acute cardiopulmonary conditions during predefined influenza seasons. The study population included women aged 15-44 years who were enrolled in the Tennessee Medicaid program for at least 180 days between 1974 and 1993. In a nested case-control study, 4,369 women with a first study event during influenza season were compared with 21,845 population controls. The odds ratios associated with study events increased from 1.44 (95% confidence interval (CI) 0.97-2.15) for women at 14-20 weeks' gestation to 4.67 (95% CI 3.42-6.39) for those at 37-42 weeks in comparison with postpartum women. A retrospective cohort analysis, which controlled for risk factors identified in the case-control study, identified 22,824 study events during 1,393,166 women-years of follow-up. Women in their third trimester without other identified risk factors for influenza morbidity had an event rate of 21.7 per 10,000 women-months during influenza season. Approximately half of this morbidity, 10.5 (95% CI 6.7-14.3) events per 10,000 women-months, was attributable to influenza. Influenza-attributable risks in comparable nonpregnant and postpartum women were 1.91 (95% CI 1.51-2.31) and 1.16 (95% CI -0.09 to 2.42) per 10,000 women-months, respectively. The data suggest that, out of every 10,000 women in their third trimester without other identified risk factors who experience an average influenza season of 2.5 months, 25 will be hospitalized with influenza-related morbidity.     

IL-12 modulates expression of hypersensitivity pneumonitis

The anticonvulsant compound felbamate (2-phenyl-1,3-propanediol dicarbamate; FBM) appears to inhibit the function of the N-methyl-D-aspartate (NMDA) receptor complex through an interaction with the strychnine-insensitive glycine recognition site. Since we have demonstrated previously that FBM inhibits the binding of [3H]5, 7-dichlorokynurenic acid (DCKA), a competitive antagonist at the glycine site, we assessed the ability of FBM to modulate the binding of an agonist, [3H]glycine, to rat forebrain membranes and human brain sections. In contrast to its ability to inhibit [3H]5,7-DCKA binding, FBM increased [3H]glycine binding (20 nM; EC50 = 485 microM; Emax = 211% of control; nH = 1.8). FBM, but not carbamazepine, phenytoin, valproic acid or phenobarbital, also increased [3H]glycine binding (50 nM; EC50 = 142 microM; Emax = 157% of control; nH = 1.6) in human cortex sections. Autoradiographic analysis of human brain slices demonstrated that FBM produced the largest increases in [3H]glycine binding in the cortex, hippocampus and the parahippocampal gyrus. Because various ions can influence the binding of glycine-site ligands, we assessed their effects on FBM-modulation of [3H]glycine binding. FBM-enhanced [3H]glycine binding was attenuated by Zn++ and not inhibited by Mg++ in human brain. These results suggest that FBM increases [3H]glycine binding in a manner sensitive to ions which modulate the NMDA receptor. These data support the hypothesis that FBM produces anticonvulsant and neuroprotective effects by inhibiting NMDA receptor function, likely through an allosteric modulation of the glycine site.     

A homology model for the human theta-class glutathione transferase T1-1

A manual threading approach is used to model the human glutathione transferase T1-1 based on the coordinates of the related Theta class enzyme T2-2. The low level of sequence identity (about 20%), found in the C-terminal extension in conjunction with a relative deletion of about five residues makes this a challenging modeling problem. The C-terminal extension contributes to the active site of the molecule and is thus of particular interest for understanding the molecular mechanism of the enzyme. Manual docking of known substrates and non-substrates has implicated potential candidates for the T1-1 catalytic residues involved in the dehalogenation and epoxide-ring opening activities. These include the conserved Theta class residues Arg 107, Trp 115, and the conserved GSTT1 subclass residue His 176. Also, the residue at position 234 is implicated in the modulation of T1-1 activity with different substrates between species.     

Human theta class glutathione transferase: the crystal structure reveals a sulfate-binding pocket within a buried active site

Depressive illness has been reported to interfere with effortful processing, which requires conscious attention. The aim of this study was to evaluate divided attention in depressed patients, as a function of the degree of difficulty of the task performed. Tasks designed to measure unimodal and bimodal reaction times were presented to 10 patients with major depression and 10 normal control subjects. Performance was evaluated both before treatment when the patients were depressed and after treatment when they had recovered. Unlike the unimodal trials, the bimodal reaction time tasks were designed to evaluate decision-making under conditions in which attention was divided between two perceptual channels. Reaction times were measured under two different conditions in order to assess the extent of the response delay induced by divided attention, modality shifting, and decision processing. During simple response tasks, the depressed patients displayed significantly greater lengthening of reaction times when their attention was divided between two perceptual channels. This cross-modal delay effect occurred both for stimuli of the same modality and when shifting between modalities. The cross-modal delay effect was evident only for the choice tests in both the depressed and the recovered patients, but only the recovered patients were as accurate as the control subjects. These results suggest that the need for decision processing in depressed patients results in a failure to allocate the mental resources required to complete interchannel shifting, when attention is divided between two perceptual channels. These data are consistent with the hypothesis that attentional regulation is impaired in major depression.     

Recognition by action: dissociating visual and semantic routes to action in normal observers

In this article the operation of a direct visual route to action in response to objects, in addition to a semantically mediated route, is demonstrated. Four experiments were conducted in which participants made gesturing or naming responses to pictures under deadline conditions. There was a cross-over interaction in the number of visual errors relative to the number of semantic plus semantic-visual errors in the two tasks: In gesturing, compared with naming, participants made higher proportions of visual errors and lower proportions of semantic plus semantic-visual errors (Experiments 1, 3, and 4). These results suggest that naming and gesturing are dependent on separate information-processing routes from stimulus to response, with gesturing dependent on a visual route in addition to a semantic route. Partial activation of competing responses from the visual information present in objects (mediated by the visual route to action) leads to high proportions of visual errors under deadline conditions. Also, visual errors do not occur when gestures are made in response to words under a deadline (Experiment 2), which indicates that the visual route is specific to seen objects.