This experiment examined the impact of experimentally varied perceived self-efficacy in exercising control over stressors on components of the immunological system. Immunological changes while coping with phobic stressors were measured within an intrasubject control design that included a baseline phase, an efficacy-acquisition phase, and a maximal-efficacy phase. In each of these phases, perceived coping self-efficacy, level of autonomic and endocrine activation, and several components of the immunological system were measured. Development of strong perceived self-efficacy to control phobic stressors had an immunoenhancing effect. A slow growth of perceived self-efficacy, heart rate acceleration, and cortisol activation attenuated immunological system status during the efficacy-acquisition phase. Rapid growth of perceived self-efficacy also predicted maintenance of immunoenhancement during the maximal perceived self-efficacy phase.

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Oncogenic viruses demonstrating a strict tropism for the mammary gland provide special opportunities to study the susceptibility of this tissue to neoplasia. In rats, human adenovirus type 9 (Ad9) elicits mammary fibroadenomas that are similar to common breast tumors in women, as well as phyllodes-like tumors and mammary sarcomas. By constructing recombinant adenoviruses between Ad9 and Ad26 (a related nontumorigenic virus), it was shown that the Ad9 E4 region was absolutely required to produce these mammary tumors. This indicates that an adenovirus gene located outside the classic transforming region (E1) can significantly influence the in vivo oncogenicity of an adenovirus. Consistent with a direct role in mammary gland oncogenesis, the Ad9 E4 region also exhibited transforming properties in vitro. Therefore, the Ad9 E4 region is a viral oncogene specifically involved in mammary gland tumorigenesis.

Objective. To investigate the role of oxidative functions in human osteoarthritic (OA) chondrocytes and to investigate the presence of in vivo molecular markers of lipoxidation in OA cartilage.Methods. An in vitro model of cartilage collagen degradation was used. Lipid peroxidation activity and overall oxidative function in OA chondrocytes were monitored by cis-parinaric acid and dichlorofluorescein assays, respectively. In vivo molecular markers of lipoxidation in normal and OA cartilage were studied using immunohistochemistry to detect the presence of malondialdehyde and hydroxynonenal adducts.Results. Human OA chondrocytes showed a robust amount of 3 H-proline-labeled collagen degradation upon stimulation with lipopolysaccharide and calcium ionophore A21387, as compared with that in untreated OA chondrocytes. Primary OA chondrocytes showed both spontaneous and inducible levels of lipid peroxidation activity. However, lipid peroxidation activity was already maximally elevated in more than 50% of the OA chondrocyte samples. Overall, spontaneous and inducible oxidative activities were observed in all OA samples. Immunohistochemical analysis of control OA tissue sections that were not treated with monoclonal antibody showed little immunoreactivity. OA cartilage sections treated with monoclonal antibodies showed specific immunoreactivity on the cartilage surface, at sites of OA lesions, at the pericellular matrix, and at intra-and intercellular matrices. Normal cartilage sections showed faint surface reactivity.Conclusion. Our observations suggest that human OA chondrocytes demonstrate spontaneous and inducible cell-associated lipoxidative and nonlipoxidative activity. Lipoxidative activity appears to be enhanced in OA chondrocytes. The presence of molecular markers of in vivo lipid peroxidation was demonstrated in OA cartilage, suggesting its role in the pathogenesis of the disease.Osteoarthritis (OA) is the most common form of joint disease that affects humans. The incidence of OA increases during every decade of life, and by the age of 65 years, almost one-third of the population has OA of the knee joints. The economic burden attributed to the joint pain and disability of OA amounts to billions of dollars each year (1). As the population demographic in the US changes to a predominantly older generation, the increasing prevalence of OA will be a major public health problem.There is currently no treatment available that will prevent or cure OA. Pharmacologic and nonpharmacologic agents used for OA provide only symptomatic relief of pain. The lack of specific therapy for this disease is perhaps due to our limited understanding of its pathogenesis. Understanding the molecular mechanisms involved in the development of OA will help us to develop ways to prevent or reverse the degenerative process of the disease.Current concepts of the pathogenic mechanisms of OA suggest that there is a shift in the homeostatic balance between the destruction and synthesis of bone and cartilage, with a net progressive destruction of t...

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Plasma levels of soluble interleukin-2 receptors (sIL-2R) were measured by an enzyme-linked immunosorbent assay in 79 patients with systemic sclerosis (SSc). These levels were significantly elevated in SSc patients, compared with normal controls (mean 2 SEM 866.0 -t 63.6 unitshl versus 293.0 & 20.5; P < 0.001).Soluble IL-2R levels were highest in patients with generalized disease, were strongly associated with mortality (P < 0.001) and inversely correlated with disease duration (P = 0.003), but were not related to sex, age, specific visceral involvement, serologic status, peripheral lymphocyte count, or therapy. Levels of sIL-2R in the supernatants of peripheral blood mononuclear cells were low in patients and controls, and showed comparable increases following phytohemagglutinin stimulation. Exposure of peripheral blood mononuclear cells to laminin did not induce sIL-2R release. Circulating IL-2 levels were comparably low in patients and controls. Our findings suggest the presence of lymphocyte activation in SSc, and further suggest that measurement

Following subcutaneous inoculation of newborn Wistar-Furth rats with human adenovirus type 9 (Ad9), 16 of 16 female and 0 of 11 male rats developed mammary tumors. Tumor-positive animals usually developed tumors in multiple glands. Histopathological analyses indicated that three general categories of tumor could be identified. Mammary fibroadenomas were the most common tumor type encountered, but phyllodeslike tumors and solid sarcomas were also frequently found. In situ hybridization and immunohistochemical techniques established that benign fibroadenomas were derived from mammary fibroblasts (collagen type I-and vimentin-positive cells) and that malignant tumors were derived from myoepithelial cells (collagen type IV-, vimentin-, and muscle-specific actin-positive cells). The fact that mammary tumors were limited to female rats suggested that female hormones are essential for tumor growth and development. In this regard, ovariectomy of Ad9-infected female rats prevented tumor development, while subsequent diethylstilbestrol (DES) treatment elicited tumor formation. In addition, Ad9-infected and castrated male rats which received DES also developed mammary tumors. Established male mammary tumors regressed when DES treatment was stopped and reappeared after DES treatment was resumed. Together, these results indicate that estrogen is required for both initiation and maintenance of Ad9-induced mammary tumors. Southern blot analysis of high-molecularweight tumor DNA showed that mammary tumor cells contained single or multiple integrated copies of the entire Ad9 genome. RNase protection experiments established that estrogen receptor as well as Ad9 Ela and E4 mRNAs were expressed in mammary tumors, but Ad9 E3 and, surprisingly, Elb mRNAs were not expressed at detectable levels.

The development of high-grade, malignant B-cell lymphoma is a well-recognized complication of human immunodeficiency virus (HIV) infection. Plasma cell neoplasms, however, have been rarely encountered in HIV-infected people. This study presents the morphologic and immunologic features of an unusual plasma cell tumor occurring in a 31-year-old HIV-antibody-positive male. The malignancy was characterized by widespread dissemination and hypercalcemia at presentation and a clinically aggressive course. Immunoperoxidase staining of tumor tissue obtained from biopsy and at autopsy had positive results for IgM and lambda. In the patient's serum, only an IgG kappa paraprotein was detected, indicating that the tumor was nonsecretory. DNA analysis of autopsy-derived tumor tissues demonstrated clonal rearrangements of the immunoglobulin (Ig) heavy chain gene locus and rearrangements in both kappa and lambda light chain gene loci. Furthermore, DNA hybridization studies revealed the presence of Epstein-Barr virus (EBV) genomes in tumor tissue but not in nontumor tissue from this patient.