Concomitant T-cell receptor alpha and delta gene rearrangements in individual T-cell precursors.

A debate has recently surfaced concerning the degree of precommitment attained by alpha beta and gamma delta T-cell precursors prior to T-cell receptor (TCR) gene rearrangement. It has been suggested that precursors may be precommitted to rearrange either alpha or delta genes, but not both, thus giving rise to alpha beta- and gamma delta-producing T cells, respectively. Alternatively, the precursors may be flexible with regard to potential TCR gene rearrangements. To address this controversy, the gene rearrangements among a group of T-cell hybridomas from fetal, newborn, and early postnatal mouse thymi were examined. Six probes spanning the delta and alpha loci were used in Southern blot analyses to characterize the rearrangements which occurred on homologous chromosomes in each cell. Although homologous chromosomes often rearranged in synchrony within the alpha locus, a number of hybridomas were found which had retained a delta rearrangement on one chromosome and an alpha rearrangement on the second. Results show that a precommitment by T cells to rearrange delta or alpha genes in a mutually exclusive manner is not an absolute feature of mouse thymocyte development.     

Disability,depression and somatization in a low back pain population

Objective: The aim of this study was to determine the prevalence of low back pain (LBP) in a primary care setting population and examine its association with the symptoms of depression and somatization. Methods: This is a cross‐sectional study, utilising a survey carried out in primary health care clinics (PHCs) in Al‐Ain, United Arab Emirates (UAE). A multistage stratified sampling design was used and a representative sample of 1304 UAE nationals aged 18–65 years who attended PHC clinics for any reason were included and 1103 (84.5%) subjects agreed to participate and responded to the questionnaire during a period from June 2001 to January 2002. A specially designed questionnaire with three parts was used for the data collection: socio‐demographic information of the studied subjects, modified version of the Roland‐Morris scale for evaluating back‐related functional disability and SCL‐90 R for depression and somatization subscales was used to assess depressive and somatic symptoms. Results: Of the total number of subjects surveyed (1103), 586 (53.1%) were men and 517 (46.9%) women. The mean age was 34.9 ± 13.4 years for men and 33.5 ± 11.8 years for women. The prevalence of LBP in the studied subjects was 64.7% (95% CI, 60.7–68.5] with 46.7% among men and 53.3% among women. There were a significant differences between the subjects with LBP and without LBP with respect to gender (P < 0.001), body mass index (BMI) (P < 0.001), occupational status (P < 0.001) and living environment (P = 0.016). Functional disability was higher in patients with LBP. Young patients in aged 15–34 years, patients with preparatory/secondary educational level and students showed higher depressive symptoms. A similar pattern was found in patients with somatic symptoms. Factor analysis revealed a strong association between depression and somatization in LBP patients. Conclusions: Functional disability was higher in with LBP. Furthermore, symptoms of depression and somatization are prevalent among LBP patients.     

Effort reward imbalance, and salivary cortisol in the morning

Background

Effort reward imbalance (ERI) is suggested to increase risk for stress and is hypothesized to increase cortisol levels, especially the awakening cortisol response, ACR.

Methods

In 2006 and 2008, 480 individuals collected saliva samples at awakening and 30 min post-awakening. Mixed effects models with subject as a random effect and appropriate covariates were used to evaluate associations between the Effort Reward Model, and salivary cortisol at awakening (S0), and ACR.

Results

ERI was negatively and significantly associated with S0 for women and positively associated with ACR. S0 and ACR increased significantly from 2006 to 2008.

Conclusion

ERI was significantly associated with cortisol levels at awakening (inverse association) for women, and positively associated with ACR. The population experienced a significant increase in morning cortisol levels and ACR from 2006 to 2008, which may originate in a re-organization of the included work places.     

Effort reward imbalance is associated with vagal withdrawal in Danish public sector employees

Objectives

The current study analyzed the relationship between psychosocial work environment assessed by the Effort Reward Imbalance Model (ERI-model) and heart rate variability (HRV) measured at baseline and again, two years later, as this relationship is scarcely covered by the literature.

Methods

Measurements of HRV during seated rest were obtained from 231 public sector employees. The associations between the ERI-model, and HRV were examined using a series of mixed effects models. The dependent variables were the logarithmically transformed levels of HRV-measures. Gender and year of measurement were included as factors, whereas age, and time of measurement were included as covariates. Subject was included as a random effect.

Results

Effort and effort reward imbalance were positively associated with heart rate and the ratio between low frequency (LF) and high frequency power (HF) and negatively associated with total power (TP) and HF. Reward was positively associated with TP.

Conclusion

Adverse psychosocial work environment according to the ERI-model was associated with HRV, especially in the form of vagal withdrawal and most pronounced in women.     

PRIME: impact of previous mental health problems on health-related quality of life in women with childbirth trauma

We investigated the impact of pre-existing mental ill health on postpartum maternal outcomes. Women reporting childbirth trauma received counselling (Promoting Resilience in Mothers' Emotions; n?=?137) or parenting support (n?=?125) at birth and 6 weeks. The EuroQol Five dimensional (EQ-5D)-measured health-related quality of life at 6 weeks, 6 and 12 months. At 12 months, EQ-5D was better for women without mental health problems receiving PRIME (mean difference (MD) 0.06; 95 % confidence interval (CI) 0.02 to 0.10) or parenting support (MD 0.08; 95 % CI 0.01 to 0.14). Pre-existing mental health conditions influence quality of life in women with childbirth trauma.     

Age‐dependent differences in morphine‐induced taste aversions

Adolescence is a developmental period of particular importance given the host of neurobiological changes that occur during this stage of development. Drug use and abuse is said to be a function of the balance of its rewarding and aversive effects, and any age‐dependent differences in morphine's aversive effects could impact drug intake. The present experiments examined the ability of morphine sulfate (0, 3.2, 10, and 18 mg/kg) to induce taste aversions in adolescent and adult rats under high (20‐min fluid access each day; Experiment 1A/B) and low (50% of ad libitum access; Experiment 2A/B) deprivation conditions. In both studies, adolescent and adult rats were given a novel saccharin solution to drink and were subsequently injected with morphine. Independent of the deprivation condition, adults acquired stronger aversions than adolescents and did so at a faster rate. On a subsequent two‐bottle aversion test, all morphine‐injected subjects drank a significantly lower percentage of saccharin than vehicle‐injected controls with adults exhibiting stronger aversions than adolescents. These age‐dependent differences in morphine‐induced CTAs extend the findings with other drugs of abuse for which adolescents exhibit weaker aversions. The possible basis for and implications of these differences were discussed. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 415–428, 2013     

α-Galactosylceramide Promotes Killing of Listeria monocytogenes within the Macrophage Phagosome through Invariant NKT-Cell Activation

α-Galactosylceramide (α-GalCer) has been exploited for the treatment of microbial infections. Although amelioration of infection by α-GalCer involves invariant natural killer T (iNKT)-cell activation, it remains to be determined whether macrophages (Mφ) participate in the control of microbial pathogens. In the present study, we examined the participation of Mφ in immune intervention in infection by α-GalCer using a murine model of listeriosis. Phagocytic and bactericidal activities of peritoneal Mφ from C57BL/6 mice, but not iNKT cell-deficient mice, were enhanced after intraperitoneal injection of α-GalCer despite the absence of iNKT cells in the peritoneal cavity. High levels of gamma interferon (IFN-γ) and nitric oxide (NO) were detected in the peritoneal cavities of mice treated with α-GalCer and in culture supernatants of peritoneal Mφ from mice treated with α-GalCer, respectively. Although enhanced bactericidal activity of peritoneal Mφ by α-GalCer was abrogated by endogenous IFN-γ neutralization, this was only marginally affected by NO inhibition. Similar results were obtained by using a listeriolysin O-deficient strain of Listeria monocytogenes. Moreover, respiratory burst in Mφ was increased after α-GalCer treatment. Our results suggest that amelioration of listeriosis by α-GalCer is, in part, caused by enhanced killing of L. monocytogenes within phagosomes of Mφ activated by IFN-γ from iNKT cells residing in an organ(s) other than the peritoneal cavity.Listeria monocytogenes, a Gram-positive facultative intracellular bacterium, is the causative agent of listeriosis, with an overall mortality rate of 30% (76). A major virulence factor of L. monocytogenes is listeriolysin O (LLO), a 58-kDa protein encoded by the hly gene (26, 42, 65). LLO promotes intracellular survival of L. monocytogenes in professional phagocytes such as macrophages (Mφ) by promoting listerial escape from the phagosome into the cytosol (10, 22, 26, 42, 62, 65). Cells of the innate immune system play a pivotal role as a first line of defense against L. monocytogenes infection and among these, mononuclear phagocytes are critical (56, 61). Activation of Mφ by gamma interferon (IFN-γ) is mandatory for elimination of L. monocytogenes (31, 35). Nitric oxide (NO) synthesized by inducible NO synthase, which is localized in the cytosol of professional phagocytes, participates in killing of L. monocytogenes (48, 52, 69, 71). Similarly, reactive oxygen intermediates (ROI) play a role in killing of L. monocytogenes within the phagosome (52, 53, 59).Natural killer T (NKT) cells represent a unique T-lymphocyte population expressing NKR-P1B/C (NK1.1; CD161), which is a type 2 membrane glycoprotein of the C-type lectin superfamily (6). In the mouse, the majority of NKT cells express an invariant T-cell receptor (TCR) α chain encoded by Vα14/Jα18 gene segments and a TCRVβ highly biased toward Vβ8.2, Vβ7, and Vβ2 (invariant NKT [iNKT] cells) (6). In contrast to conventional T cells, which recognize antigenic peptides presented by polymorphic major histocompatibility complex class I or class II molecules, iNKT cells recognize glycolipid antigens, including α-galactosylceramide (α-GalCer), a synthetic glycolipid originally isolated from a marine sponge, presented by the nonpolymorphic antigen presentation molecule CD1d (6, 40). iNKT cells are highly versatile and promptly produce both type 1 and type 2 cytokines, such as IFN-γ and interleukin-4 (IL-4), respectively, upon activation through their TCRs (1, 15-17, 79). IL-15 is an essential growth factor of both iNKT cells and NK cells and, hence, both cell populations are absent in IL-15-deficient (IL-15^−/−) mice (58). The numbers of iNKT cells are also markedly reduced in SJL mice because of a large deletion in their TCRVβ genetic region (5, 78).In vivo administration of α-GalCer causes prompt release of various cytokines by iNKT cells, which are involved in the control of various diseases, e.g., tumor rejection and prevention of autoimmune diseases (33, 41, 67, 70). Although α-GalCer has been reported to enhance host resistance to some microbial pathogens (27-29, 37, 39, 44, 55, 64), its potential role in protection against intracellular bacterial infections remains enigmatic.We have recently described that α-GalCer ameliorates murine listeriosis, which is, in part, caused by accelerated infiltration of inflammatory cells into the liver (18), although iNKT cells themselves exacerbate disease (19). Because Mφ play a central role in the elimination of L. monocytogenes, we considered the possibility that Mφ participate in enhanced resistance to L. monocytogenes infection caused by α-GalCer treatment. In the present study, we examined the influence of α-GalCer on listericidal activities of Mφ using a virulent and an avirulent strain of L. monocytogenes.