Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia.

Background: A diagnosis of chronic lymphocytic leukemia (CLL) requires a count of over 5000 circulating CLL-phenotype cells per cubic millimeter. Asymptomatic persons with fewer CLL-phenotype cells have monoclonal B-cell lymphocytosis (MBL). The goal of this study was to investigate the relation between MBL and CLL.

Circumcision among adolescent boys in rural northwestern Tanzania.

Objective: Male circumcision reduces risk of HIV among heterosexual men by about 60%. Modelling the impact of circumcision on HIV transmission, and planning service expansion, relies on self-reported circumcision status. We investigated the validity of self-reported status.

Children of the sug: a study of the daily lives of street children in Khartoum, Sudan, with intervention recommendations.

Objectives: The study examines street children's daily lives in Khartoum, Sudan to recommend ways to improve their conditions and to successfully assist them off the streets.

Methods: In 2000-2001, eight researchers conducted participant observation for 7 weeks; 20 groups of children engaged in role-plays and drawing activities; over 500 children participated in qualitative group and individual interviews; and 872 current and former street children were surveyed.

Results: Approximately half of children were 14 years old or younger.

International correlation between human papillomavirus prevalence and cervical cancer incidence.

Data from population-based human papillomavirus (HPV) surveys in regions of low, intermediate, and high cervical cancer incidence were used to study the ecologic correlation between high-risk HPV prevalence and cervical cancer incidence. All the surveys were conducted by the IARC according to a standardized protocol for the collection of female population samples and detection of HPV DNA using PCR assay in a central laboratory. Cervical cancer incidence data were extracted, when available, from a cancer registry covering the surrounding or nearby area of the prevalence survey.

Genetic polymorphisms in mediators of inflammation and gastric precancerous lesions.

Chronic inflammation induced by Helicobacter pylori is a key process in gastric carcinogenesis. We hypothesized that genetic polymorphisms in important mediators of H. pylori-induced inflammation may influence the risk of developing various grades of precancerous lesions.

Atherosclerotic lesion formation and triglyceride storage in obese apolipoprotein AI-deficient mice.

Obese leptin-deficient (ob/ob) mice have increased levels of high-density lipoprotein (HDL) and a unique lipoprotein referred to as low-density lipoprotein (LDL)/HDL1. When crossed onto an apolipoprotein AI (apoAI)-deficient (-/-) background, ob/ob;apoAI-/- mice accumulate LDL/HDL1 in the absence of traditional HDL. To determine the role of LDL/HDL1 in atherosclerosis, C57BL/6, apoAI-/-, ob/ob and ob/ob;apoAI-/- mice were placed on butterfat diet.

Penalized loss functions for Bayesian model comparison.

The deviance information criterion (DIC) is widely used for Bayesian model comparison, despite the lack of a clear theoretical foundation. DIC is shown to be an approximation to a penalized loss function based on the deviance, with a penalty derived from a cross-validation argument. This approximation is valid only when the effective number of parameters in the model is much smaller than the number of independent observations.

Macrophage-derived apolipoprotein E ameliorates dyslipidemia and atherosclerosis in obese apolipoprotein E-deficient mice.

Previous studies have demonstrated that macrophage-derived apolipoprotein E (apoE) reduces atherosclerotic lesion formation in lean apoE-deficient ((-/-)) mice. apoE has also been demonstrated to play a role in adipocyte differentiation and lipid accumulation. Because the prevalence of obesity has grown to epidemic proportions, we sought to determine whether macrophage-derived apoE could impact atherosclerotic lesion formation or adipose tissue expansion and inflammation in obese apoE(-/-) mice.

Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies.

Background: Combined oral contraceptives are classified by the International Agency for Research on Cancer as a cause of cervical cancer. As the incidence of cervical cancer increases with age, the public-health implications of this association depend largely on the persistence of effects long after use of oral contraceptives has ceased. Information from 24 studies worldwide is pooled here to investigate the association between cervical carcinoma and pattern of oral contraceptive use.

B-cell chronic lymphocytic leukaemia cells show specific changes in membrane protein expression during different stages of cell cycle.

The proliferating component in chronic lymphocytic leukaemia (CLL) is usually small (<1%) and restricted to a specific micro-environmental niche. To characterize the proliferating component, CLL cells from bone marrow or lymph nodes of 23 patients were assessed for expression of up to 66 surface antigens in combination with nuclear Ki-67/MCM6. Ki-67 expression was associated with step-wise increases in CD23/CD95/CD86/CD39/CD27 and decreases in CD24/CD69/CXCR4/CXCR5.

4-anilino-5-carboxamido-2-pyridone derivatives as noncompetitive inhibitors of mitogen-activated protein kinase kinase.

A new series of MEK1 inhibitors, the 4-anilino-5-carboxamido-2-pyridones, were designed and synthesized using a combination of medicinal chemistry, computational chemistry, and structural elucidation. The effect of variation in the carboxamide side chain, substitution on the pyridone nitrogen, and replacement of the 4'-iodide were all investigated. This study afforded several compounds which were either equipotent or more potent than the clinical candidate CI-1040 (1) in an isolated enzyme assay, as well as murine colon carcinoma (C26) cells, as measured by suppression of phosphorylated ERK substrate.

ECOLOGY: The Other H's.

Fisheries scientists have long identified the factors implicated in salmon decline as the "four H's": hydropower dams, harvesting, habitat degradation, and hatchery misuse. According to a new plan by nine federal agencies, known as the "All-H Paper," improvements in the other three H's will provide benefits that are more certain and widespread than those from dam breaching. But addressing the other H's may be even more costly than breaching dams.

Helicobacter pylori cytotoxin-associated genotype and gastric precancerous lesions.

Background: Helicobacter pylori infection is associated with the development of gastric cancer. Although infection with an H. pylori strain containing the cytotoxin-associated (cag A) gene (a marker for a pathogenicity island) may increase the risk of atrophic gastritis and gastric cancer, the relationship of variants in pathogenic H.

Biological and behavioural impact of an adolescent sexual health intervention in Tanzania: a community-randomized trial.

Objective: The impact of a multicomponent intervention programme on the sexual health of adolescents was assessed in rural Tanzania.

Design: A community-randomized trial.

Methods: Twenty communities were randomly allocated to receive either a specially designed programme of interventions (intervention group) or standard activities (comparison group).

The glial or neuronal fate choice of oligodendrocyte progenitors is modulated by their ability to acquire an epigenetic memory.

The identity of any cell type is determined by the specific pattern of gene expression. We show here that the ability of oligodendrocyte progenitors to acquire the identity of myelin-expressing cells or choose alternative fates is dependent on the activity of histone deacetylases. Using gene expression profiling, electrophysiological recordings, transplantation studies, and pharmacological inhibition, we demonstrate that specified NG2+ oligodendrocyte progenitors are plastic cells, whose decision to initiate an oligodendrocytic rather than astrocytic or neuronal program of gene expression requires the establishment of an epigenetic identity that is initiated by histone deacetylation.

A randomized controlled trial of a peer support intervention targeting antiretroviral medication adherence and depressive symptomatology in HIV-positive men and women.

Objective: To determine the efficacy of a peer-led social support intervention involving support groups and telephone contacts compared with standard clinical care to enhance antiretroviral medication adherence.

Design: Randomized controlled trial with follow-up. Participants were 136 HIV-positive indigent mainly African American and Puerto Rican men and women recruited from an outpatient clinic in the Bronx, New York.

Developmental and activity-dependent regulation of ARMS/Kidins220 in cultured rat hippocampal neurons.

Neurotrophin activation of Trk receptors elicits diverse effects on neuronal survival, differentiation, and synaptic plasticity. One of the central questions is how specificity is encoded in neurotrophin receptor signaling and actions. A unique downstream protein is the Ankyrin-Repeat Rich Membrane Spanning (ARMS)/Kinase D-interacting substrate-220 kDa (Kidins220), a very abundant scaffold protein in the hippocampus.

A 2-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion.

Background: Cervical cancer is caused by persistent infection with human papillomavirus (HPV). Most infections and associated lesions clear spontaneously. It is important to define the determinants and timing of clearance, so that viral persistence can be recognized and managed.

Hypothermia in patients with chronic spinal cord injury.

Design: Retrospective analysis of medical records.

Background/objectives: To determine frequency and degree of hypothermic episodes in patients with chronic spinal cord injury (SCI).

Setting: Veterans Administration Medical Center.

Quadrivalvular marantic endocarditis (ME) mimicking acute bacterial endocarditis (ABE).

Marantic endocarditis (ME) is defined by noninfectious valvular vegetations. The most common disorders associated with ME are malignancy with or without hypercoagulable state, intercardiac instrumentation, residual vegetations from previously treated infective endocarditis (IE), renal insufficiency, and burns. Another important cause of ME is systemic lupus erythematosus when accompanied by vegetations, that is, Libman-Sacks endocarditis.

Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population.

Background: Gastric cancer is one of the most common malignancies worldwide. Histopathologic studies have identified a sequence of changes in the gastric mucosa that mark the slow progression from normal tissue to carcinoma. Epidemiologic evidence suggests that a diet rich in fresh fruit and vegetables could be a protective factor against this disease.

Single-cell characterization of retrograde signaling by brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) is a key regulator of hippocampal synaptic plasticity in the developing and adult nervous system. It can be released from pyramidal neuron dendrites in an activity-dependent manner and has therefore been suggested to serve as a signal that provides the retrograde intercellular communication necessary for Hebbian plasticity and hippocampal-dependent learning. Although much has been learned about BDNF function by field stimulation of hippocampal neurons, it is not known whether moderate action potential-independent depolarization of single cells is capable of releasing sufficient BDNF to influence transmission at individual synapses.

Polymorphisms in genes related to bacterial lipopolysaccharide/peptidoglycan signaling and gastric precancerous lesions in a population at high risk for gastric cancer.

As Helicobacter pylori (HP) is a Gram-negative bacterium, we investigated the associations between several functional polymorphisms in genes involved in lipopolysaccharide (LPS) signaling and the prevalence of various stages of gastric premalignant lesions in a Venezuelan population. The two NOD2 polymorphisms, del3020insC and Gly908Arg, were too infrequent to study their associations with gastric lesions. The risk of intestinal metaplasia (IM) was significantly increased among subjects with the CD14 T-260 allele compared to those without this allele.

Solvent density effects on the solvation behavior and configurational structure of bare and passivated 38-atom gold nanoparticle in supercritical ethane.

In exploring the effects of solvent density on the mode and the degree of solvation of the bare and passivated 38-atom gold particle in supercritical ethane, we have extended the molecular dynamics simulations of the system, reported previously,(34) to cover a range of isotherms in the T > T(c) regime, where T(c) is the critical temperature of the solvent. Consonant with our previous observations, the modes of solvation of the bare and the passivated particle, deduced from the radial distribution of the solvent about the metal core center of mass, are found to be vastly different from each other at all solvent densities: while the molecules solvating the bare particle form a well-defined, two-region layer around it, those solvating the passivated particle are loosely dispersed in the passivating layer. For the bare particle, the degree of solvation (vartheta) as a function of solvent density passes through a maximum occurring in the close vicinity of the critical point, consistent with our previous results and in agreement with Debenedetti's theoretical analysis,(22,23) which predicts a solvation enhancement effect in the critical region for systems where the unlike solvent/solute interaction is much stronger than the solvent/solvent interaction.

Brain-derived neurotrophic factor rapidly increases NMDA receptor channel activity through Fyn-mediated phosphorylation.

Brain-derived neurotrophic factor (BDNF) is a potent modulator of hippocampal synaptic plasticity. Previously, we found that one of the targets of BDNF modulation is NR2B-containing NMDA receptors. Furthermore, exposure to the trophin rapidly increases NMDA receptor activity and enhances tyrosine phosphorylation of NR2B in cortical and hippocampal postsynaptic densities (PSDs), potentially linking receptor phosphorylation to synaptic plasticity.