Reduced susceptibility to dextran sulphate sodium-induced colitis in the interleukin-2 heterozygous (IL-2) mouse

Summary Mice homozygous for an inactivation of the interleukin-2 (IL-2) gene develop a T-cell dependent colitis. Heterozygous (IL-2+/-) mice are clinically healthy but have been shown to express reduced levels of IL-2 in the colon. Splenocytes from the IL-2+/- mice had a poorer proliferative response to polyclonal T-cell activation and these mice have reduced numbers of intestinal regulatory T cells (CD4+ CD25+ cells) when compared to wild type mice. When exposed to dextran sulphate sodium (DSS) IL-2+/- mice showed a markedly reduced susceptibility to DSS-induced colitis. While DSS treatment caused a marked increase in both CD4+ and CD8+ colonic T cells expressing increased levels of IL-2, IL-4, and IL-10 in wild type mice none of these changes were seen in IL-2+/- mice. On the contrary, cytokine expression in intestinal T cells of IL-2+/- mice was actually reduced after DSS treatment. These results suggest that reduced levels of IL-2 leads to attenuated activation and function of intestinal T cells in IL-2+/- mice and a failure to react adequately to DSS exposure.     

Association of sleep duration with socio‐economic status and behavioural problems among schoolchildren

Aim: In this population‐based study, we aimed to determine the total sleep duration (TSD), its association with socio‐economic status (SES) and behavioural symptoms among schoolchildren. Methods: A cross‐sectional study was performed among schoolchildren in Istanbul. A structured questionnaire evaluating the sleep schedule variables was filled out by their parents. SES was determined according to the Turkish SES scale. Results:  The mean age of 2669 children was 8.2 ± 2.4 years, and 51% of the students were girls. The mean TSD was 10.20 ± 1.04, and the mean bedtime was 21.57 ± 0.56 (both in hours, minutes ± SD). Boys tended to go bed later (p = 0.004) and slept less than girls (p = 0.02). The duration of sleep disruptions increased (p < 0.001), whereas TSD decreased with age (p < 0.001). Multiple linear regression revealed that waking time and TSD decreased significantly (p < 0.05) with higher SES among both girls and boys. Sleep fragmentation was associated with habitual snoring, parasomnias, daytime sleepiness and conduct symptoms. Conclusion: Decreased total sleep duration is more prominent in boys, older children and children among higher socio‐economic status. Insufficient sleep attributed to shortened total sleep duration by age and higher socio‐economic status might have a negative effect on both sleep hygiene and psychological well‐being in schoolchildren.     

Single-cell analyses of CD4+ T cells from αβ T cell receptor-transgenic mice: a distinct mucosal cytokine phenotype in the absence of transgene-specific antigen

Development of distinct CD4⁺ T cell cytokine phenotypes may be conditioned by the anatomic site in which activation occurs. A double-label in situ hybridization technique was used to characterize co-expression of cytokine mRNA in antigen-specific responses of Peyer's patch (PP), lamina propria (LP), and splenic (SP) CD4⁺ T cells isolated from αβ T cell receptor-transgenic mice. Interleukin (IL)-2 was the dominant cytokine expressed by antigen-stimulated PP and SP populations, though it was expressed by a minority of the activated T cells. Cells that expressed interferon (IFN)-γ were less frequent, and IL-4, IL-5, and IL-10 were infrequent. In contrast, cells that expressed IFN-γ or IL-10 were most frequent in the LP population, with lower frequencies of IL-2, and few IL-4- and IL-5-positive cells. Co-expression of two cytokines by the same cell was the exception, regardless of the anatomic site from which the T cells were isolated. The surface phenotype of transgene-positive T cells isolated from each anatomic site was distinct, despite the absence of in vivo exposure to antigen for which the transgenic T cell receptor is specific. These data suggest that the cytokine responses of CD4⁺ T cells may be conditioned by the microenvironment, independently of specific antigen, and that the LP CD4⁺ T population has a distinct cytokine expression pattern with counter-regulatory properties that may be important for homeostasis in mucosal immune tissues.     

Expression of acyl-CoA synthetase 5 reflects the state of villus architecture in human small intestine

Several disorders of the small intestine are associated with disturbances in villus architecture. Thus, an understanding of the molecular mechanisms associated with the differentiation of villi represents an important step in the improvement of the understanding of small intestinal pathology. Screening of antibodies from a hybridoma library led to the identification of an acyl-CoA synthetase 5-specific monoclonal antibody. Protein synthesis, mRNA expression, and the enzyme activity of acyl-CoA synthetase 5 were studied by several methods in human small intestinal tissues with Crohn's disease or coeliac disease, respectively. Acyl-CoA synthetase 5 mRNA and protein levels were substantially reduced in injured small intestinal mucosa. Moreover, impaired synthesis of the acyl-CoA synthetase 5 protein was reflected by a decrease in intramucosal enzyme activity. Subtle changes of the acyl-CoA synthetase 5 pattern correlate with conversion of intestinal epithelial cells to a gastric phenotype. These results suggest that deranged acyl-CoA synthetase 5 expression, synthesis, and activity are closely related to the state of villus architecture and epithelial homeostasis in human small intestine.     

Lack of support for association between the copy number variants in the FCGR locus and schizophrenia: a case control study

The missing heritability of polygenic schizophrenia after genome-wide association studies (GWAS) can be potentially accounted for by the fact that most dynamic multiallelic copy number variants (CNVs) overlap segmental duplications (SDs). The FCGR locus covers this category of complex CNVs and it has long been postulated to harbor variants conferring the risk of schizophrenia. However, such association remains unproven. We used a case-control design to investigate CNV-based association with the disease. Data were obtained from 598 unrelated schizophrenia patients and 959 normal controls of Han ancestry from Shanghai. A total of four copy number (CN) probes in the FCGR locus were detected using TaqMan^® Copy Number Assay. SPSS version 16.0 was used for the statistical analyses. And the frequency distributions of target CN in FCGR locus were very similar between controls and cases, whereas the CNV frequency differed markedly among different target CN analyzed in the two cohorts. When compared with the predominant two copies per diploid genome, a distinct non-protein-coding CN deletion region containing regulatory sequences was detected by probe Hs04194069_cn. Taken together, we found no evidence of association of target CNVs in the FCGR locus with schizophrenia. However, our negative findings suggest that more detailed next generation sequencing-based association studies are needed to fully evaluate the contribution of this category of complex CNVs to the disease.     

Location and incidence of the zygomaticofacial foramen: An anatomic study

The location and incidence of the zygomaticofacial foramen (ZFF) was studied in 80 dry skulls (160 sides) of unsexed adult skulls of West Anatolian people. The average distances from the ZFF to the frontozygomatic suture, to the zygomaticomaxillary suture, and to the inferior orbital rim were found to be 26.2 ± 3.2 mm, 18.6 ± 3.14 mm, and 5.94 ± 1.43 mm, respectively. The zygomas were evaluated for the number of foramina on their facial aspects. There was none in 25 (15.6%), one in 71 (44.4%), two in 45 (28.1%), three in 10 (6.3%), four in seven (4.4%), and five in two (1.3%) sides. The ZFF was also studied for its distribution around the zygoma by dividing the surface into four anatomical areas. There was no statistical difference between the morphometrical results on both sides. Data regarding the location and variation in the number of the ZFF is important in avoiding zygomatic nerve and vessel injury during surgery, but by virtue of the great variability found, ZFF is an unreliable landmark for maxillofacial surgery. Clin. Anat. 22:559–562, 2009. © 2009 Wiley‐Liss, Inc.     

Neutrophil, monocyte and lymphocyte locomotion in rheumatic fever and rheumatoid arthritis

Neutrophil, monocyte and lymphocyte chemotaxis was investigated in 19 patients with active rheumatic fever (10 with carditis), in 15 patients with rheumatoid arthritis and in 20 healthy, age-matched controls. Chemotaxis assays were repeated in the rheumatic fever patients on the fifth day of therapy and two weeks after remission. Neutrophil and monocyte chemotaxis was found to be significantly decreased in the rheumatoid arthritis patients when compared with the controls and rheumatic fever patients. In contrast, neutrophil chemotactic activity was significantly higher in the rheumatic fever patients when compared with the healthy controls. Monocyte and lymphocyte chemotaxis in patients with rheumatic fever was not significantly different when compared with the controls. Neutrophil, monocyte and lymphocyte locomotion was found to be significantly decreased on the fifth day of salicylic acid or prednisolone treatment.     

Living with breast cancer - a challenge to expansive and creative forces

The aim of this qualitative case study is to obtain a deeper and more profound understanding of the life world of women living with breast cancer focusing particularly on changes in life perspective. The study is based on a series of interviews carried out within the space of one year and involving four women with breast cancer; each woman was interviewed four times. The participants were between 42 and 54 years of age; three of the four interviewed were in an advanced stage, with metastasis or recurrent breast cancer. There was an increased awareness of the relationship between life and death, which constituted a disclosure rather than an actual change in life perspective. The four women were 'opening up' to the beauty and the essentials in life and experienced an increased desire to live their life in accordance with their own values. Their revitalised view of life increased their desire for authenticity. When it proved impossible to live in accordance with new insights the women were particularly frustrated. From a caring perspective our findings suggest that an awareness of patients' increased openness to their own needs and desires is an important resource in the healing and rehabilitative process of breast cancer patients. The paradoxes and the struggles involved disguise a hidden potential for health.     

Review and meta-analysis of the phenomenology and clinical characteristics of mania in children and adolescents

OBJECTIVE: Using predetermined criteria for study quality and methods, a literature review and meta-analysis of seven reports about pediatric bipolar disorder (BPD) was conducted to determine if there is a consistent picture of the phenomenology and clinical characteristics of BPD in children and adolescents. METHODS: Searches were conducted in MedLine and PsycINFO using the terms mania, BPD, children and adolescents, and was limited to published articles in peer-reviewed journals. Seven reports were selected that met the following criteria: a systematic method for the elicitation and reporting of symptoms and clinical characteristics of subjects; subjects were interviewed by a trained researcher or clinician; ages 5-18 years; use of a diagnostic system, either DSM or RDC for categorization; a consensus method for the establishment of the diagnosis of BPD. RESULTS: Most DSM-IV symptoms of mania were common in the children and adolescents with BPD with the most common symptoms being increased energy, distractibility, and pressured speech. On average, four of five bipolar cases also showed threshold levels of irritable mood and grandiosity, and more than 70% of all cases showed elated/euphoric mood, decreased need for sleep, or racing thoughts. Roughly 69% of cases also showed poor judgment, whereas only half of bipolar cases demonstrated flight of ideas, and slightly more than one-third showed hypersexuality or psychotic features. CONCLUSIONS: The clinical picture that emerges is that of children or adolescents with periods of increased energy (mania or hypomania), accompanied by distractibility, pressured speech, irritability, grandiosity, racing thoughts, decreased need for sleep and euphoria/elation.