B-lymphocyte alloantigens in Caucasians

Human B lymphocytes have been shown to have at least five polymorphic specificities defined by 32 antisera. The antisera were produced by absorption with pooled platelets to remove HLA activity and were selected out of over 400 tested sera. The sera that defined the five specificities had high correlation coefficients within a group (generally in the range of 0.6-0.9). As shown by the fit in the Hardy-Weinberg equilibrium, the five specificities appear to be determined by alleles at one genetic locus. No association between these specificities and HLA was noted.     

The associations of voluntary counseling and testing acceptance and the perceived likelihood of being HIV-infected among men with multiple sex partners in a South African township

This paper examines the socio-demographic factors and sexual risk behaviors (condom use, number of sexual partners, STI symptoms) associated with voluntary counselling and testing (VCT) acceptance and self-perceived risk of being HIV-infected among black men with multiple and younger sex partners in a South African township outside of Cape Town. Using respondent driven sampling, we interviewed 421 men, of whom 409 (97.3%) consented to provide a dried blood spot, 12.3% were HIVinfected (95% confidence intervals [CI.] 8.3, 16.9) and 47.2% (CI. 41.1, 53.6) accepted on site VCT. Twenty six percent (CI. 20.2, 30.7) reported having an HIV test in the past year. Few men perceived themselves as very likely to be infected with HIV (15.6%; CI. 10.4, 20.5). VCT acceptance was significantly associated with being older, married or living with a partner, having higher education, having four to six partners in the past three months and testing HIV positive. Self-perceived likelihood of being HIV infected was significantly associated with low condom use and having seven or more partners in the past three months, and testing HIV positive. These findings indicate that men correctly understand that engaging in certain HIV risk behaviors increases the likelihood of HIV-infection. However, those who perceive themselves at high risk of having HIV do not seek testing. Further investigation into the psychological and cultural barriers to reducing risky sexual behaviors and accessing VCT and other HIV services is recommended.     

Emerging natural killer cell immunotherapies: large-scale ex vivo production of highly potent anticancer effectors

Natural killer (NK) cell therapies are emerging worldwide as promising anticancer treatments, exploiting the fast cytolytic action of NK effectors and their potentially broad applicability against a wide range of malignancies. Until recently, clinical protocols have mainly involved freshly isolated NK cells or short- term activated NK cells or lymphokine-activated killer (LAK) cells. However, overall effector numbers and their anticancer potencies remained restricted, which poses a limiting factor to clinical efficacy. Recent developments in the field aim to improve clinical trial designs by increasing effector to target cell ratios in vivo and by application of superior cytotoxic NK effectors. Large-scale production of clinical grade NK cells through long-term activation in ex vivo cultures are another novel means in achieving these goals. However, such procedures require compliance with the strict Good Manufacturing Practice (GMP) regulations to ensure quality and safety of the NK cell product. Although the overall number of new protocols still remains comparably low, some of the protocols are already translated into clinical use. Also striking is the diversity of the different protocols proposed. We highlight in this review the most recent developments in the NK cell field with a focus on long-term NK cell expansion. Critical issues relating to this novel and promising type of therapy are highlighted and discussed.     

HPA-axis regulation at in-patient admission is associated with antidepressant therapy outcome in male but not in female depressed patients

A concatenation of data implicates a hyperactivity of the hypothalamus pituitary adrenal (HPA)-axis in the pathogenesis of depression and its normalization as a necessary predecessor of clinical response to antidepressant drugs. In addition, regulation of the HPA-axis has been shown to be dependent on sex hormones. We therefore investigated gender differences in HPA-axis regulation in depression and its normalization during remission of clinical symptoms. We used the combined dexamethasone suppression/CRH stimulation (Dex-CRH) test to evaluate the degree of HPA-axis dysregulation in 194 in-patients with unipolar depression from the Munich Antidepressant Response Signature (MARS) study at both admission and discharge. The Hamilton Depression (HAM-D) Rating Scale was used to monitor clinical response to antidepressant treatment. For both genders, we observed a normalization of HPA-axis dysregulation in remitters but not in non-remitters, both after 5 weeks of treatment and at discharge. The pattern of HPA-axis normalization with remission of depressive symptoms, however, showed gender-specific differences. In male patients, remission after 5 weeks of in-patient treatment was associated with a significantly higher cortisol response in the Dex-CRH test at admission. In female patients, 5-week remitters and non-remitters had a comparable cortisol response at admission. Cortisol response at admission was not correlated with gonadal steroid levels at this time point and the results were similar for pre-menopausal women vs. post-menopausal women. Gender-associated biological characteristics, likely independent of circulating gonadal steroids, thus seem to influence HPA-axis regulation in depression. In male patients, a single measure of HPA-axis dysregulation at admission may serve as a predictor of response to antidepressant treatment in addition to the previously reported repeated measure of the Dex-CRH test.     

Changes in the hypothalamic-pituitary-adrenal axis and leptin levels during antidepressant treatment

BACKGROUND: In depressed patients, overstimulation of the hypothalamo-pituitary-adrenocortical (HPA) system, probably caused by glucocorticoid receptor resistance, is the most consistent neurobiological finding. Glucocorticoids themselves are reported to increase leptin synthesis and secretion in humans. METHODS: We examined alterations in plasma levels of leptin as well as changes in the HPA system function using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test on admission and at discharge in 74 depressed inpatients. RESULTS: Mean leptin concentration did not change significantly between admission and discharge. However, changes in ACTH response and partial cortisol response to the combined dex/CRH test between admission and discharge were significantly correlated with leptin levels at discharge. CONCLUSIONS: Leptin levels at discharge rise as the HPA axis normalizes. These findings may be explained by an improvement in glucocorticoid receptor sensitivity among depressed patients during antidepressant therapy and a consecutively increased influence of glucocorticoids on leptin levels via the glucocorticoid receptor.     

Clinical characteristics and treatment outcome in a representative sample of depressed inpatients - findings from the Munich Antidepressant Response Signature (MARS) project

Depression is a common and often difficult-to-treat clinical condition with a high rate of patients showing insufficient treatment response and persistence of symptoms. We report the characteristics of a representative sample of depressed inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Eight hundred and forty-two inpatients admitted to a psychiatric hospital for treatment of a major depressive episode, recurrent or bipolar depression were thoroughly characterized with respect to demographic factors, clinical history, and the degree of HPA-axis dysregulation evaluated by means of combined dex/CRH tests, and the predictive value of these factors for treatment outcome is investigated. 80.8% of patients responded to treatment (i.e., improvement in symptom severity of at least 50%) and 57.9% reached remission (i.e., near absence of residual depressive symptoms) at discharge after a mean treatment period of 11.8 weeks. Regression analysis identified early partial response (within 2 weeks) as the most important positive predictor for achieving remission. Previous ineffective treatment trials in the current episode and presence of a migration background are potent negative predictors for treatment outcome. In addition, remitters were characterized by a more pronounced normalization of an initially dysregulated HPA-axis. We could show that a large majority of inpatients suffering from depression benefits from antidepressant treatment during hospitalization. However, a considerable number of patients failed to achieve remission. We demonstrated that this subgroup can be characterized by a set of demographic, clinical and neuroendocrine variables allowing to predict unfavorable outcome at an early stage of treatment.