HIV-1 gp120 Binding to Dendritic Cell Receptors Mobilize the Virus to the Lymph Nodes,but the Induced IL-4 Synthesis by FcεRI+ Hematopoietic Cells Damages the Adaptive Immunity – a Review,Hypothesis, and Implications

HIV-1 is equipped with the envelope gp160 glycoprotein for interaction with Langerhans cells (LCs) and dendritic cells (DCs), the members of the innate immune system, which confront the virus at the portal of virus entry in the human body. These cells are equipped with receptors by which they bind and endocytose the virus. The gp120 glycoprotein is used for binding to CD4 receptor and CCR5 co-receptor of T helper 2 (Th2) cells and the virions shed gp120 is able to induce FcepsilonRI+ hematopoietic cells to produce IL-4, which inactivate the host adaptive immune response. The properties of gp120s various functional domains are analyzed together with the regulatory viral proteins, which are involved in the damage to T and B cells during HIV-1 replication. The interaction of HIV-1 virions through their gp120 with LCs and DCs at the portal of virus entry will be discussed. A hypothesis will be presented that the understanding of the role of the different functional domains of gp120 in the life cycle of the virus and during AIDS will help in the design of approaches to prevent and abrogate HIV-1 infection and AIDS.     

Neurocognitive basis of impaired empathy in schizophrenia

Patients with schizophrenia show impaired emotional and social behavior, such as lack of theory of mind and misinterpretation of social situations. However, there is a paucity of work focusing on the empathic abilities of these patients. The present study was designed to examine the degree of impairment in cognitive and affective empathy in schizophrenia and to evaluate the contribution of executive prefrontal functions to empathy in these patients. To explore the neurocognitive processes that underlie the empathic ability in schizophrenic patients, the relationship between empathy scores and the performance on a cognitive flexibility task that assesses dorsolateral and orbitofrontal functioning (set shifting and reversal, respectively) was examined in 26 patients with schizophrenia and 31 healthy control subjects. Results indicated that patients with schizophrenia were significantly impaired in both cognitive and affective empathy compared with healthy control subjects. The degree of impaired empathy related to the severity of negative symptoms. In addition, patients showed impaired performance on measures of both shifting and reversal. However, while cognitive empathy was particularly related to measurements of orbitofrontal (rather than dorsolateral) functioning, affective empathy was related to measures of social functioning.     

A randomized controlled feasibility and safety study of deep transcranial magnetic stimulation

OBJECTIVE: The H-coils are a new development in transcranial magnetic stimulation (TMS) research, allowing direct stimulation of deeper neuronal pathways than does standard TMS. This study assessed possible health risks, and some cognitive and emotional effects, of two H-coil versions designed to stimulate deep portions of the prefrontal cortex, using several stimulation frequencies. METHODS: Healthy volunteers (n=32) were randomly assigned to one of four groups: each of two H-coil designs (H1/H2), standard figure-8 coil, and sham-coil control. Subjects were tested in a pre-post design, during three increasing (single pulses, 10 Hz, and 20 Hz) stimulation sessions, as well as 24-36 h after the last stimulation. RESULTS: The major finding of the present study is that stimulation with the novel H-coils was well tolerated, with no adverse physical or neurological outcomes. Computerized cognitive tests found no deterioration in cognitive functions, except for a transient short-term effect of the H1-coil on spatial recognition memory on the first day of rTMS (but not in the following treatment days). On the other hand, spatial working memory was transiently improved by the H2-coil treatment. Finally, the questionnaires showed no significant emotional or mood alterations, except for reports on 'detachment' experienced by subjects treated with the H1-coil. CONCLUSIONS: This study provides additional evidence for the feasibility and safety of the two H-coil designs (H1/H2). SIGNIFICANCE: The H-coils offer a safe new tool with potential for both research and clinical applications for psychiatric and neurological disorders associated with dysfunctions of deep brain regions.     

Estrogen receptor alpha gene polymorphisms are associated with the angiographic extent of coronary artery disease

CONTEXT: Sequence variants in the estrogen receptor alpha gene (ESR1) may alter the atheroprotective effects of estrogens, and be associated with the severity of coronary artery disease (CAD). OBJECTIVE: This study seeks to investigate the association between the ESR1 haplotype created by the c.454-397 T>C and c.454-351 A>G polymorphisms, the length of the (TA)n repeats, and the angiographic extent of CAD. DESIGN: Consecutive subjects with age younger than or equal to 55 yr who had undergone coronary angiography between November 2003 and January 2004 were included in the study. SETTING: The study was conducted in a referral center. PATIENTS: One hundred five subjects with age younger than or equal to 55 yr (87 males, 18 females) participated in the study. MAIN OUTCOME MEASURES: The angiographic extent of CAD was graded by number of: 1) major coronary vessels with more than 50% narrowing (NMCV); 2) narrowed major coronary vessels and/or their second-order branch (NCV); and 3) coronary segments with any narrowing (NN). Analysis of covariance was used to test the effect of haplotype and (TA)n length on the angiographic extent of CAD with gender and number of CAD risk factors (hyperlipidemia, diabetes, hypertension, obesity, smoking, and family history of CAD) as covariates. RESULTS: The ESR1 haplotype c.454-397C and c.454-351G was associated with NCV and NN (P = 0.008 and 0.02, respectively). Carriers of two copies of haplotype C-G had a higher number of NCV compared with subjects with one or no copies combined (3.5 +/- 2.2 vs. 2.3 +/- 1.9, P = 0.012, respectively). A longer (TA)n repeat was associated with NCV (P = 0.04). CONCLUSIONS: The ESR1 c.454-397C and c.454-351G haplotype and longer (TA)n repeats are associated with the extent of CAD in young subjects, independent of the known CAD risk factors.     

The association of genetically determined serum glycine with cardiovascular risk in East Asians

Background and aimsGlycine is involved in a wide range of metabolic pathways and increased circulating glycine is associated with reduced risk of cardio-metabolic diseases in Europeans but the genetic association between circulating glycine and cardiovascular risk is largely unknown in East Asians.Methods and resultsWe conducted a genome-wide association study (GWAS) in Singaporean Chinese participants and investigated if genetically determined serum glycine were associated with incident coronary artery disease (CAD) (711 cases and 1,246 controls), cardiovascular death (1,886 cases and 21,707 controls) and angiographic CAD severity (as determined by the Modified Gensini score, N = 1,138).ConclusionOur study, a first in East Asians, suggest a protective role of glycine against CAD.     

Chronic granulomatous disease: Clinical,functional, molecular,and genetic studies. The Israeli experience with 84 patients

Chronic granulomatous disease (CGD) is an innate immunodeficiency with a genetic defect of the nicotinamide adenosine dinucleotide phosphate, reduced, oxidase components. This leads to decreased reactive oxygen species (ROS) production, which renders patients susceptible to life‐threatening infections. Over the course of 30 years, we diagnosed CGD in 84 patients from 61 families using functional, molecular, and genetic studies. The incidence of CGD in Israel is 1.05 per 100,000 live‐births in the Jewish population and 1.49 in the Israeli Arab population. We diagnosed 52 patients (62%) with autosomal recessive inheritance (AR‐CGD) and 32 (38%) with X‐linked recessive inheritance (XLR‐CGD). Consanguinity was detected in 64% of AR‐CGD families (14% in Jews and 50% in Israeli Arabs). We found 36 different mutations (23 in XLR‐CGD and 13 in AR‐CGD patients), 15 of which were new. The clinical spectrum of CGD varied from mild to severe disease in both XLR and AR forms, although the AR subtype is generally milder. Further, residual ROS production correlated with milder clinical expression, better prognosis and improved overall survival. Patients with recurrent pyogenic infections developed fibrosis and hyperinflammatory states with granuloma formation. The management of CGD has progressed substantially in recent years, evolving from a fatal disease of early childhood to one of long‐term survival. Our present cohort displays an encouraging 81% overall long term survival. Early hematopoietic stem cell transplantation is advisable before tissue damage is irreversible. Successful transplantation was performed in 18/21 patients. Therapeutic gene modification could become an alternative cure for CGD. Am. J. Hematol. 92:28–36, 2017. © 2016 Wiley Periodicals, Inc.     

Induction and repair of DNA damage in normal and ataxiatelangiectasia skin fibroblasts treated with neocarzinostatin

Cells from patients with the hereditary multisystem disorderataxia-telangiectasia (A-T) are hypersensitive to the cytotoxicaction of DNA-breaking agents, such as X-rays, bleomycin andneocarzinostalin (NCS). A defect in the repair of a certainDNA lesion induced by all three agents may underlie this hypersensitivity.This DNA lesion may be a certain type of DNA strand break. Mostof the previous experiments done with X-rays and bleomycin failedto show any retardation in the rejoining of DNA strand breaksin A-T cells. However, since both A-T homozygous and heterozygouscells are particularly hypersensitive to NCS, we studied thetime course of strand breakage induction and repair in A-T skinfibroblast strains treated with NCS, using the sensitive methodof alkaline or neutral elution. A linear dose response was obtainedfor the induction by NCS of single-strand breaks and double-strandbreaks. A-T cells did not respond with a higher initial extentof strand breakage compared with normal cells. NCS is an appropriateagent for studying the kinetics of rejoining strand breaks,due to its rapid action in the cells; this action, which iscompleted within 2–4 min, was studied by monitoring strandbreak induction, inhibition of DNA synthesis and decrease incellular survival. The time course of strand break rejoiningfound after NCS treatment was very similar to that found followingX-irradiation: with both single- and double-strand breaks, arapid phase of rejoining was first noticed (t 5 min for single-strandbreaks and 20–25 min for double-strand breaks). This wasfollowed by a second, slow phase that continued for severalhours. No difference could be detected between normal and A-Tcells either with regard to the time course of rejoining orthe fraction of non-rejoined breaks remaining several hoursafter treatment.     

The Jerusalem Perinatal Study cohort, 1964-2005: methods and a review of the main results

The Jerusalem Perinatal Study recorded information on population-based cohorts of 92 408 live- and stillbirths in 1964-76, and their parents, with active surveillance of infant deaths and birth defects. Data on maternal conditions, obstetric complications and interventions during labour and delivery were recorded for 92% of the births. Subsets were surveyed with antenatal interviews in 1965-68 (n = 11 467), paediatric admissions to hospital (n = 17 782) and postpartum interviews in 1975-76 (n = 16 912). Data from some offspring were linked to records of a health examination at age 17. The offspring, mothers and fathers have been traced recently, their vital status assessed, and the data linked to Israel's Cancer Registry and Psychiatric Registry. This paper describes the different types of data available, their sources, and some potential biases. Characteristics of this unique population are shown. Findings from the study are reviewed and a list of references is provided. The cohorts provide a unique source of data for a wide variety of studies.     

Deep TMS add-on treatment for intractable Tourette syndrome: A feasibility study

Objectives. In a considerable minority of patients who suffer from Tourette syndrome (TS) the disorder persists into adulthood and is associated with severe symptoms and limited therapeutic options. Repetitive transcranial magnetic stimulation (rTMS) to the supplementary motor area (SMA) has shown promising therapeutic results. Deep rTMS is a novel technology that enables deeper non-invasive cortical stimulation. This open-label pilot study is the first to examine the possible role of deep rTMS as add-on treatment for intractable TS. Methods. Twelve patients were recruited in order to examine bilateral SMA inhibition via deep TMS using the HBDL coil, as a possible treatment for adult TS treatment-resistant patients. Two patients did not complete the 20-day study protocol. Results. There were no significant side effects. While tics did not improve among the group as a whole, the subgroup of six patients with combined TS and OCD (obsessive compulsive syndrome) showed significant improvement in tic severity (P = 0.037). Conclusions. These findings support the safety of deep rTMS for treating TS. The results also highlight the importance of studying the different TS syndromes separately (e.g., with or without OCD comorbidity) when evaluating deep rTMS protocols for TS patients.