Identification of a novel pre-TCR isoform in which the accessibility of the TCR beta subunit is determined by occupancy of the 'missing' V domain of pre-T alpha

We have identified a novel pre-TCR isoform that is structurally distinct from conventional pre-TCR complexes and whose TCR beta chains are inaccessible to anti-TCR beta antibodies. We term this pre-TCR isoform the MB (masked beta)-pre-TCR. Pre-T alpha (pT alpha) subunits of MB-pre-TCR complexes have a larger apparent mol. wt due to extensive modification with O:-linked carbohydrates; however, preventing addition of O-glycans does not restore antibody recognition of the TCR beta subunits of MB-pre-TCR complexes. Importantly, accessibility of TCR beta chains in MB-pre-TCR complexes is restored by filling in the 'missing' variable (V) domain of pT alpha with a V domain from TCR alpha. Moreover, the proportion of pre-TCR complexes in which the TCR beta subunits are accessible to anti-TCR beta antibody varies with the cellular context, suggesting that TCR beta accessibility is controlled by a trans-acting factor. The way in which this factor might control TCR beta accessibility as well as the physiologic relevance of TCR beta masking for pre-TCR function are discussed.     

In vitro immunomodulatory properties of tucaresol in HIV infection

The immunomodulatory properties of tucaresol (compound 589C80) were tested on in vitro antigen- and mitogen-stimulated proliferation and cytokine production by peripheral blood mononuclear cells (PBMC) of HIV-infected individuals and healthy controls (HC). Results showed that tucaresol: (1) increases influenza A virus-, gp 160 peptide-, and HLA alloantigen-stimulated proliferation as well as interleukin (IL)-2 and interferon gamma (IFN gamma) production by PBMC of HIV-infected individuals with higher CD4 counts (>500/microl) but had only a marginal immunomodulatory effect on PBMC of patients with lower CD4 counts (<500/microl); (2) did not modify IL-10 production; (3) augmented CD25 expression on mitogen-stimulated T cells of HC but not of HIV-infected individuals; and (4) marginally increased CTL activity. The immunomodulatory properties of tucaresol were confirmed by PCR analyses; additional data showed that tucaresol costimulated CD3-dependent triggering of T cells and that this stimulation was independent of CD28 costimulation. The immunomodulatory effects of tucaresol on T cell functions are characterized by a bell-shaped dose response curve; the action of the compound is optimal in the 100 to 300 microM range. Analyses of mitogen-stimulated apoptosis demonstrated that the lack of effect of tucaresol at higher doses is not the result of increased cell death, suggesting a role of functional impairment. These data confirm that tucaresol can stimulate T helper cell function and enhance the production of type 1 cytokines, thus eliciting cell-mediated immunity, and warrant its potential utility in the therapy of HIV infection.     

Selective Breeding for Increased Home Cage Physical Activity in Collaborative Cross and Hsd:ICR Mice

Selective breeding experiments for increased wheel running and open field behavior have identified genetic and neurobiological factors associated with increased voluntary physical activity in mice, but no previous study has directly selected for increased distance traveled in the home cage. Therefore, within-family selection was applied to increase home cage activity as measured by continuous video tracking using two different starting populations, G2:F1 Collaborative Cross (CC) and Hsd:ICR mice. Genetic correlations with distance traveled on running wheels and in the open field were evaluated by mid-parent offspring regression. A significant response to selection was observed in CC but not Hsd:ICR. Wheel running was heritable in both populations but not significantly genetically correlated with home cage activity. Open field was not heritable in either population. We conclude that different genes and neural circuits influence physical activity in the home cage as compared to wheel running or open field. Selective breeding for home cage activity in CC mice warrants further exploration.     

Perceptual asymmetries influence task choice: The effect of lateralised presentation of hierarchical stimuli

The current study examined how hemispheric asymmetries in perceptual processing affect control processes associated with voluntary task choice during multitask behaviour. In a voluntary task-switching paradigm, where participants are free to choose which task to perform on each trial, participants identified either the global-or local-level features of hierarchical stimuli presented to either the left or right visual field. Hemispheric asymmetries in perception of lateralised hierarchical stimuli were evident in reaction times. Importantly, participants were more likely to categorise the stimulus in line with the processing efficiency of the hemisphere to which it was initially presented: the global task for left visual field presentation and the local task for right visual field presentation. Perceptual processing characteristics influence control processes associated with task choice in multitask environments.     

脊柱骨巨细胞瘤误诊1例

发生于骶骨以上的脊柱骨巨细胞瘤罕见[1],关于其CT表现仅见零星个案报道。我院误诊1例,报告如下。患者男性,20岁。胸背部疼痛2月,加重伴双下肢麻木10天入院。病史中无明显咳嗽、潮热、盗汗现象。外院X线及CT提示第5胸椎体结核伴椎旁冷脓肿形成。专科检查:胸椎活动受限,尤以屈曲位为明显,第5胸椎处叩压痛明显,局部无明显畸形及包块,剑突平面以下痛觉略减退,双下肢踝阵挛阳性,双膝反射、踝反射亢进。实验室检查:肝功、肾功、电解质、CEA、AFP及血、尿常规均无异常,入院时ESR:41mm/h,1周后复查ESR:16mm/h,2周后复查ESR:37mm/h。影像表…     

Effect of human lymphoblastoid interferon on insulin synthesis and secretion in isolated human pancreatic islets

Summary Human islets of Langerhans were isolated from the pancreas removed from a 13-year-old female transplant donor. The islets were incubated in a culture medium for 24 h in the presence of human lymphoblastoid interferon (1000 units/ml). Insulin secretion, proinsulin biosynthesis, total protein biosynthesis and total insulin content were assessed at various concentrations of glucose in the presence of interferon. In interferon-treated islets glucose-stimulated insulin secretion was unaltered from that of control islets; however, glucose-stimulated proinsulin biosynthesis was specifically inhibited by interferon (48%, p<0.025). Total protein biosynthesis and total insulin content were not significantly affected by interferon.     

In vitro synthesis of RNA that contains polyadenylate by virion-associated RNA polymerase of vesicular stomatitis virus

The RNA synthesized in vitro by the virion-associated RNA-instructed RNA polymerase of purified vesicular stomatitis virus contains polyadenylate sequences. These have been demonstrated by their partial resistance to pancreatic and T(1) ribonucleases and their capacity to bind to poly(U) filters and oligo(dT)-cellulose. The polyadenylate sequences range in apparent size from 50 to 200 bases, similar to the size of the poly(A) in mRNA from vesicular stomatitis virus-infected cells. Possible mechanisms of polyadenylylation of the in vitro RNA product are discussed.     

HLA‐C/KIR genotypes in oral lichen planus patients infected or non‐infected with hepatitis C virus

Oral Diseases (2011) 17 , 309–313 Objectives: Oral Lichen Planus (OLP) is associated with hepatitis C virus (HCV) infection and resembles graft‐versus‐host disease (GVHD) both clinically and histologically. The killer cell immunoglobulin‐like receptor (KIR) genes encode a family of receptors expressed on NK and T cells and are supposed to play a significant role in GVHD and HCV infection. The aim of this study was to analyze the association among OLP, HCV infection and variants in KIR gene expression. Methods: A total of 81 patients with OLP (36 HCV+ve and 45 HCV?ve) and 217 healthy controls (HCV?ve) were typed for the presence of eight KIR genes and of HLA‐Cw* alleles by polymerase chain reaction‐sequence specific primer. Results: There were no significant differences in the frequency of the KIR genes and HLA‐C1/C2 group alleles between cases and controls. We only found a significant difference in the frequency of the gene KIR2DL2 between HCV+ve and HCV?ve OLP patients. Conclusions: The present data suggest that OLP is not associated with particular KIR genes or with HLA‐Cw* alleles in patients without HCV infection. Contrarily, the role of the genes in OLP‐HCV+ve patients remains unclear and might warrant further researches.     

Effect of right ventricular anatomy on the cardiopulmonary response to exercise. Implications for the Fontan procedure

Incorporation of the right ventricle (RV) into the pulmonary circulation of patients with tricuspid atresia undergoing a Fontan procedure has been advocated. The consequences of this approach on the exercise function of these patients was studied by examining the effects of progressive and steady-state bicycle exercise tests performed by 11 patients with right atrial (RA)-RV Fontan anastomoses, seven patients with RA-pulmonary artery (PA) Fontan anastomoses, 13 patients after repair of tetralogy of Fallot, and 34 normal control patients. All patients were in New York Heart Association class I. The exercise function of the patients undergoing RA-RV and RA-PA Fontan procedures were similar. The achieved peak work loads 60% and 67% of control and peak oxygen consumptions 60% and 64% of control, respectively. Both groups also displayed excessive ventilation, elevated dead space/tidal volume ratios, and depressed cardiac output during steady-state exercise. In contrast, tetralogy of Fallot patients achieved peak work loads and oxygen consumptions 83% of control and maintained normal cardiac outputs and dead space/tidal volume ratios during steady-state exercise. These results suggest that the presence of an RV within the pulmonary circulation of the Fontan patient does not result in improved exercise function. This may be due to the development of obstructive gradients across the RA-RV conduits during exercise or to the RV's negative effect on left ventricular compliance. Moreover, in contrast with the postoperative tetralogy of Fallot patient, the hypoplastic RV of tricuspid atresia may not have sufficient myocardium to assume the active pumping function required by exercise.     

A serum-free culture method for myeloma progenitors in vitro: proliferative and immunophenotypic characteristics

Methods for forming multiple myeloma (MM) colonies are difficult because nonproliferative, but viable, plasma cells can survive for several weeks in culture and because MM cells tend to clump readily, forming pseudo-colonies. The present study describes a method for growing pure myeloma colonies in serum-free conditions in which genuine myeloma growth is unequivocally demonstrated. Growth was observed in 17 of 32 MM bone marrow samples. After a delay of 3-5 weeks, during which most cells died, Ig light-chain-restricted colonies emerged, expanded for approximately 3 weeks, and then showed no evidence of further proliferation. Cell doubling time was 8-10 days, and a significant number of cells in all cultures expressed Ki-67, having earlier lacked this nuclear proliferation antigen. In addition, colony formation was abrogated by irradiation, and two of eight cultures were successfully replated in 0.8% methylcellulose. Phenotypic analysis revealed a mixed population of plasma cells (RFD6+) and B-lymphocytes (CD19+, CAL-LA-), and cells were consistently Epstein-Barr virus negative. Culture of myeloma bone marrow by this serum-free method will allow appraisal of the role of various recombinant growth factors.