Oral administration of muscle derived small molecules inhibits tumor spread while promoting normal cell growth in mice

Tumor metastases are extremely rare in striated muscles. This is surprising given the fact that this tissue constitutes 60% of body weight. The present study focuses on small molecules produced and secreted by muscle cells which possess anti-cancer activity in vivo. Recently we have shown that a low molecular weight fraction (<1000 Dalton) of skeletal muscle cell conditioned medium (muscle factor-MF), markedly inhibits the proliferation of carcinoma, sarcoma or melanoma cell lines in vitro. The MF exerts a cytostatic effect on tumor cell growth and arrests the cells in the G0/G1 of the cell cycle. However, normal cell proliferation, such as bone marrow and fibroblasts, was stimulated following incubation with MF. In this study, the effect of orally administered MF on melanoma and sarcoma growth was examined in mice. The administration of MF to mice inoculated intravenously with melanoma (B16–F10) or sarcoma (MCA-105) cells, resulted in a statistically significant inhibition of metastatic lung foci. In a different model, melanoma was induced in the foot pad and after development of a local lesion, the leg was amputated. A prolonged survival time was observed in the MF treated groups. Since the MF stimulated bone marrow cell proliferation in vitro, we decided to test its efficacy as an inhibitor of the myelotoxic effect exerted by chemotherapy, in vivo. MF, administered after chemotherapy, restored the number of white blood cells and yielded an increased percentage of neutrophils compared with the decline in these parameters after administration of chemotherapy alone. Thus, it is indicated that MF exerted a systemic anti tumor and chemoprotective effect when given orally. It can be concluded that it is bioavailable and is not biodegradable in the digestive system. MF may be considered as a potential therapy for the prevention of tumor spread. This revised version was published online in July 2006 with corrections to the Cover Date.     

Continued maturation of thymic emigrants in the periphery

Developing thymocytes are selected for recognition of molecules encoded by the major histocompatibility complex, purged of self-reactive cells and committed to either the CD4 or CD8 lineage. The 1% of thymocytes that complete these tasks emigrate and join the population of peripheral lymphocytes. Whether T cell maturation is complete at the time of thymic exit has been a subject of debate. Using mice transgenic for green fluorescent protein driven by the recombination activating gene 2 promoter to identify recent thymic emigrants, we now show that T cell differentiation continues post-thymically, with progressive maturation of both surface phenotype and immune function. In addition, the relative contribution of CD4 and CD8 recent thymic emigrants was modulated as they entered the peripheral T cell pool. Thus, T cell maturation and subset contribution are both finalized in the lymphoid periphery.     

Improved detection of amyloid in fat pad aspiration: an evaluation of Congo red stain by fluorescent microscopy

Amyloid fat pad aspiration specimens for cases with a clinical suspicion of amyloid typically are stained with Congo red and examined by brightfield microscopy. Congophilia with apple-green birefringence by polarization microscopy (PM) is considered diagnostic for amyloid. Examination of Congo red-stained slides by fluorescent microscopy (FM) is considered by some to be a more sensitive detection method. In this study, we assessed the utility of this technique in cytopathology archival slides from abdominal fat pad aspirations previously stained with Congo red dye. Seventy-eight cases of abdominal fat pad aspirations collected during the last 5 yr and stained with the Congo red procedure were obtained from archival files. Additionally, 20 adipose tissue material slides prepared from the surgical pathology specimens were examined as controls. One representative smear was examined in each case using FM equipped with rhodamine excitation/absorption (540/570 nm) filters. Relevant clinical information was obtained in all cases. Twelve cases (15.4%) of the 78 fat pad aspiration cases were reported originally as positive by Congo red stain using polarization and apple-green birefringence as diagnostic criteria. On review, four cases were deemed unsatisfactory. By FM examination 29 of the 74 (39.2%) cases were reclassified as positive for amyloid. The results were confirmed by immunohistochemical stain for amyloid P protein and electron microscopy. A number of similar distinct fluorescence and immunohistochemical patterns were recognized in the positive cases. Minimally weak fluorescence in the adipose tissue was observed in the control cases. The use of FM in Congo red-stained fat pad smears can improve the detection of amyloid in cytology preparations.     

Immunization with cholinergic cell bodies induces histopathological changes in rat brains

We have previously shown that sera from patients with Alzheimer’s disease (AD) contain antibodies to the cell bodies (perikarya; PK) of purely cholinergicTorpedo neurons, and that repeated immunization of rats with this neuronal preparation for over a year induces learning and memory impairments. In the present study, we examined the brain morphology of cholinergic PK immunized rats relative to controls. Immunohistochemical studies of the brains of these rats revealed the accumulation of IgG in specific areas, such as, the hippocampus. Parallel histochemical studies demonstrated significant changes in the hippocampus, and in white matter areas. They included large vacuoles and necrotic nuclei in the granular layer of the dentate gyrus, tangle-like appearance in some pyramidal neurons of the hippocampus, and vacuolar degeneration accompanied by oligodendroglia hypertrophy in white matter tracts, such as, the corpus callosum and fimbria. In contrast, immunization withTorpedo cholinergic nerve terminals, that has no cognitive effects on the rat, also did not induce brain morphological changes. These findings suggest that the learning and memory deficits induced by immunizing rats with cholinergic PK are related to the observed brain morphological changes, and support the hypothesis that the antibodies to cholinergic neurons found in the sera of AD patients may play a role in neuronal degeneration in this disease.     

Stigmatization, self-esteem, and coping among the adolescent children of lesbian mothers

Purpose: To examine perceived stigma, coping, disclosure, and self-esteem among adolescents with lesbian mothers.

Method: Interviews were conducted with 76 adolescents ages 11–18 years. Standardized measures of self-esteem and coping skills were used. A measure of stigma was adapted for this study and a measure of disclosure was developed. The relationship between perceived stigma and self-esteem was examined. General coping skills and level of disclosure about the adolescents’ mothers’ sexual orientation were assessed as potential moderators of the relationship between perceived stigma and self-esteem.

Results: Adolescents who perceived more stigma had lower self-esteem in five of seven self-esteem areas, compared to those who perceived less stigma. In addition, coping skills moderated the effect of stigma on self-esteem in three self-esteem areas. However, only one subtype of coping skills, that of decision-making coping, was found to moderate the relationship of perceived stigma and self-esteem in such a way that adolescents using more decision-making coping had higher self-esteem in the face of high perceived stigma. For social support coping, in the face of high perceived stigma, the adolescents with more effective coping skills had lower self-esteem. In the face of high perceived stigma, adolescents who disclosed more about their mother’s sexual orientation had higher self-esteem in the subscale of close friendship than those who disclosed less.

Conclusions: Results suggest that stigma is related to self-esteem among the adolescent children of lesbian mothers. The results indicate that this relationship is moderated by coping skills. These results have implications for intervention and prevention of stigmatization by the establishment of effective coping skills as well as through educational efforts to eradicate stigmatizing attitudes.     

Is obesity a risk factor for psychopathology among adolescents?

BACKGROUND: Although several studies have documented the existence of psychopathology in obese adolescents, disagreement remains regarding the extent and nature of this psychopathology. The aim of the present study was to explore the type and frequency of psychopathology in a clinical as well as a non-clinical sample of obese adolescents, and in a normal weight control group. METHODS: The study sample consisted of a clinical study group of 30 obese adolescents, a non-clinical obese group of 30 obese adolescents, and a control group of 30 normal weight adolescents. Psychological assessment was performed using a non-structured psychiatric interview, the Child Behavior Checklist (CBCL), Children Depression Inventory (CDI), Rosenberg Self-esteem scale (SES) and the Eating Attitude Test (EAT). RESULTS: More than half of the clinical obese adolescents (16/30) had a DSM-IV diagnosis, often involving major depressive disorder (n = 10). The mean scores of anxiety-depression, social problems, social withdrawal and total problem in the CBCL scale of the clinical obese group were significantly higher than the non-clinical obese group and the normal weight control group. The mean total scores of the SES and the CDI of the clinical obese group were higher than the normal weight control group. The mean total score of EAT of the clinical obese group was significantly higher than the normal weight control group, and the mean score of EAT of the non-clinical obese group was significantly higher than the normal weight control group. CONCLUSIONS: The results support previously published reports which show a higher ratio of psychopathology (depression, behavioral problems, low-esteem) among clinical obese adolescents than among non-clinical obese adolescents. Findings provided evidence for a psychosocial at-risk population in a subgroup of obese adolescents.