Induction of apoptosis in granulosa cells by TNF alpha and its attenuation by glucocorticoids involve modulation of Bcl-2

Tumor necrosis factor alpha (TNF alpha) plays a role in mammalian ovarian follicular development, steroidogenesis, ovulation, luteolysis, and atresia, but the exact mechanism of TNF alpha action is not completely understood. Induction of apoptosis and suppression of steroidogenesis by TNF alpha in primary preovulatory rat and human granulosa cells, as well as, in human granulosa cells immortalized by mutated p53, were characterized in the present work. Dexamethasone (Dex) and hydrocortisone efficiently suppressed TNF alpha-induced apoptosis in granulosa cells. TNF alpha dramatically reduced intracellular levels of Bcl-2, while Dex abrogated this reduction. TNF alpha reduced considerably intracellular levels of StAR protein, a key regulating factor in steroidogenesis. This reduction can be explained only in part by elimination of cells through apoptosis, since loss of steroidogenic capacity was much higher and faster than the rate and extent of loss of cell viability induced by TNF alpha, suggesting independent mechanisms for TNF alpha-induction of apoptosis and TNF alpha-suppression of steroidogenesis.     

Correlations in global DNA methylation measures in peripheral blood mononuclear cells and granulocytes

Alterations in global DNA methylation levels have been associated with chronic diseases. Despite the increase in the number of studies measuring markers of global methylation, few have adequately examined within-individual differences by source of DNA and whether within-individual differences by source of DNA differ by age, race and other lifestyle factors. We examined correlations between peripheral mononuclear cell (PBMC) and granulocyte DNA methylation levels measured by the luminometric methylation assay (LUMA), and in LINE-1, Sat2, and Alu by MethyLight and pyrosequencing, in the same individual in 112 women participating in The New York City Multiethnic Breast Cancer Project. Levels of DNA methylation of Sat2 by MethyLight (r = 0.57; P < 0.01) and LINE-1 by pyrosequencing (r = 0.30; P < 0.01) were correlated between PBMC and granulocyte DNA of the same individuals, but LUMA and Alu levels were not. The magnitude of the correlations for Sat2 and LINE-1 varied when stratified by selected demographic and lifestyle factors, although the study sample size limited our comparisons across subgroups. These results lend further support to the importance of considering the source of DNA in epidemiologic studies of white blood cell DNA methylation. Results from studies that combine individuals with different available DNA sources need to be interpreted with caution.     

Monoclonal antibodies from mice bearing polyoma virus-induced tumor

Summary Monoclonal antibodies were produced by fusing NS1/1 myeloma cells with splenocytes from A. BY mice bearing syngeneic polyoma virus-induced SEYF-a tumors.From six separate fusion experiments 514 hybridomas were obtained, 45 of which were found to secrete SEYF-a-binding antibodies. The binding patterns of antibodies secreted by eight hybridomas to a panel of tumor cells and to normal mouse fibroblasts were analyzed by means of an indirect radioimmunoassay. Seven hybridomas were found to secrete antibodies that bound to all cell lines tested. This indicated that certain SEYF-a-associated antigens are widely distributed on a variety of seemingly nonrelated tumor cells.One hybridoma secreted antibodies that exhibited a high binding activity to SEYF-a cells, a low binding activity to two members of the tumor panel, and none at all against most of its constituents, including normal fibroblasts. The results of the binding experiments were further supported by absorption experiments.A subclass analysis of the immunoglobulins secreted by the various hybridomas revealed that three clones secreted IgG1; one clone secreted IgM; and three clones secreted IgG2a. Polyacrylamide gel electrophoresis of two of the secreted antibodies indicated a high degree of homogeneity of the heavy and the light chain of the corresponding antibodies, as would be expected from monoclonal products.The results of this study demonstrate the feasibility of obtaining anti-tumor monoclonal antibodies from tumor bearers, representing the immune response of the tumor bearer against antigens associated with his syngeneic tumor.     

A case study of virilizing adrenal tumor in an adolescent female elite tennis player--insight into the use of anabolic steroids in young athletes

A 14-year-old Caucasian girl was referred to the endocrine clinic for evaluation of voice deepening, facial hirsutism, and acne starting 2 years previously. She had been a competitive tennis player since age 7 years, practicing for 4-6 hours daily. On physical examination she was noticed to have a masculine appearance with mild facial acne and moderate hirsutism. Tanner stage was 1 for breast tissue and 5 for pubic hair. Her androgen levels (testosterone, androstenedione, dehydroepiandrosterone sulfate) were extremely elevated. Adrenal ultrasonography revealed a round left 4.6 × 5.3-cm adrenal mass. Laparoscopic left adrenalectomy was performed. The histologic findings were compatible with a benign adrenocortical tumor. Postoperatively, androgen levels dropped to within the normal range. Breast development proceeded normally, menarche occurred 2 months after tumor resection, and menses has been regular since then. Muscle strength of the dominant and nondominant upper and lower extremities was measured 1 month before surgery and 1 year later, using an isokinetic dynamometer (Biodex Systems II, Biodex, Shirley, NY, USA). There was no significant decrease in overall muscle strength after removal of the virilizing tumor and the marked drop in circulating androgens. In addition, the patient maintained her age category, number 1, national tennis ranking. The results suggest that even extremely high levels of tumor-related circulating androgens had no evident effect on muscle strength and competitive performance in a female adolescent tennis player. The lack of beneficial effect on performance in adolescents, combined with the potentially hazardous side effects of anabolic steroids, suggests that teenage athletes should avoid their use.     

Isolation and Characterization of Nonconverting Mutants of Bacteriophage ε34

epsilon(34) Is a converting bacteriophage which brings about a glucosylation of the O antigen in the E group salmonella, thus producing antigen 34. Uridine diphosphate glucose is the precursor of antigen 34 and a glucosyl-lipid is an essential intermediate in this process. Mutants of epsilon(34) which cannot produce antigen 34 have been isolated. Cells lysogenic for these mutants are of two types. Type 1 mutant lysogens cannot form the glucosyl-lipid intermediate; those of type 2 can form glucosyl-lipid but are unable to transfer glucose from the lipid to the O antigen.     

Aurora-A Breaks Symmetry in Contractile Actomyosin Networks Independently of Its Role in Centrosome Maturation

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Depression and Anxiety Disorders among Hospitalized Women with Breast Cancer

Purpose

To document the prevalence of depression and anxiety disorders, and their associations with mortality among hospitalized breast cancer patients.

Methods

We examined the associations between breast cancer diagnosis and the diagnoses of anxiety or depression among 4,164 hospitalized breast cancer cases matched with 4,164 non-breast cancer controls using 2006-2009 inpatient data obtained from the Nationwide Inpatient Sample database. Conditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CI) for the associations between breast cancer diagnosis and diagnoses of anxiety or depression. We also used binary logistic regression models to examine the association between diagnoses of depression or anxiety, and in-hospital mortality among breast cancer patients.

Results

We observed that breast cancer cases were less likely to have a diagnosis of depression (OR=0.63, 95% CI: 0.52-0.77), and less likely to have a diagnosis of anxiety (OR=0.68, 95% CI: 0.52-0.90) compared with controls. This association remained after controlling for race/ethnicity, residential income, insurance and residential region. Breast cancer patients with a depression diagnosis also had lower mortality (OR=0.69, 95% CI: 0.52-0.89) compared with those without a depression diagnosis, but there was no significant difference in mortality among those with and without anxiety diagnoses.

Conclusion

Diagnoses of depression and anxiety in breast cancer patients were less prevalent than expected based on our analysis of hospitalized breast cancer patients and matched non-breast cancer controls identified in the NIS dataset using ICD-9 diagnostic codes. Results suggest that under-diagnosis of mental health problems may be common among hospitalized women with a primary diagnosis of breast cancer. Future work may fruitfully explore reasons for, and consequences of, inappropriate identification of the mental health needs of breast cancer patients.     

Light,dark and growth regulator involvement in groundnut (Arachis hypogaea L.) pod development

Gynophore elongation and pod formation were studied in peanut plants (Arachis hypogaea L.) under light and dark conditions in vivo. The gynophores elongated until pod formation was initiated. Pod (3–20 mm length) development could be totally controlled by alternating dark (switched on) and light (switched off) conditions, repeatedly. Gynophore elongation responded conversely to light/dark conditions, compared to pods. In this study we aimed to correlate the light/dark effects with endogenous growth substances. The levels of endogenous growth substances were determined in the different stags of pod development. Gynophores shortly after penetration into the soil, ‘white’ gynophores, released twice the amount of ethylene as compared to the aerial green ones, or to gynophores bearing pods. Ethylene inhibitors had no effect on the percent of gynophores that developed pods, but affected pod size which were smaller compared to the control. A similar level of IAA was extracted from gynophore tips of green gynophores, ‘white’ gynophores and pods. ABA levels differed between the three stages and were highest in the green gynophores and lowest in the pods.     

Infectivity of Dengue Virus Serotypes 1 and 2 Is Correlated with E-Protein Intrinsic Dynamics but Not to Envelope Conformations

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