Relationship of myoma cell size and menopausal status in small uterine leiomyomas

CONTEXT: Although myomas shrink after menopause, the cellular mechanism for this phenomenon has received little attention. It was recently demonstrated that fibrous degeneration is significantly associated with postmenopausal status in both small and large myomas. OBJECTIVE: The purpose of the present study was to evaluate whether reduction in myoma cell size is also associated with postmenopausal status in small myomas. DESIGN: Tumor size and patient age have also been related to fibrous degeneration in small (<1 cm) myomas. Therefore, in the present study, 10 pairs of premenopausal and postmenopausal small myomas were matched within 3 years for patient age, within 1 mm for size, and within 1 grade for degree of fibrous degeneration. Most of the women were in their 50s, the decade during which postmenopausal fibrous degeneration in small myomas is most prevalent. Myoma cell size was derived by morphometric evaluation of relative myoma cell area (correcting for percentage of stroma, as measured by point counting) and by direct counting of the number of myoma cells per unit area in trichrome-stained sections. RESULTS: Small myomas from postmenopausal women had significantly (P <.05) smaller cell sizes than did size-matched myomas from age-matched premenopausal women. Myoma cell sizes and nucleus-cell (N/C) ratios were highly variable, especially in premenopausal myomas. CONCLUSIONS: Reduction in myoma cell size is significantly associated with postmenopausal status in small uterine leiomyomas and may be an important mechanism for postmenopausal shrinkage of myomas. In addition, the high variability of myoma cell size and N/C ratio may further support the somatic mutation theory (ie, the theory that diverse mutations may account not only for variations in the growth potential of uterine myomas, but also for variations in their cellular details).     

Heritability and Expression of C-Reactive Protein in Type 2 Diabetes in the Diabetes Heart Study

Elevated C-reactive protein (CRP) levels are associated with both prevalent and incident cardiovascular disease. In this study, familial aggregation was estimated, and we tested for association between serum CRP levels and polymorphisms within the CRP and APOE genes in sib-ships with type 2 diabetes mellitus, a population at increased risk for cardiovascular disease. CRP levels were determined in 461 diabetes-affected subjects from 224 sibships from the Diabetes Heart Study (DHS). Heritability estimates of CRP levels were obtained using variance component models. Genetic influence on serum CRP levels by single nucleotide polymorphisms (SNPs) in the CRP and APOE genes was evaluated by association analysis using mixed models. Subjects were Caucasian American (84%) and African-American (16%), 53% female, and had an average age of 62.2 ± 9.2 years. The median CRP level was 3.3 mg/L (range 0 to 59.3 mg/L), and estimated heritability for CRP was approximately 40%. Estimates of heritability were significantly greater than zero (P < 0.0001) and relatively constant, despite adjustments for important modifiers (age, sex, ethnicity, diabetes duration, statin-use and anti-inflammatory use) of CRP. There was no significant evidence for association of CRP levels with CRP gene SNPs; however, consistent with previous reports, there was significant evidence of association of CRP levels with polymorphisms within the APOE gene. These data indicate CRP levels are significantly influenced by genetic (and/or environmental) factors that are shared within DHS families. While the APOE locus shows evidence of contributing to CRP levels, no evidence of CRP gene polymorphism association with CRP levels was observed.     

Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways

Macrophages are major targets for infection by human immunodeficiency virus type 1 (HIV-1). In addition to their role as productive viral reservoirs, inappropriate activation of infected and uninfected macrophages appears to contribute to pathogenesis. HIV-1 infection requires initial interactions between the viral envelope surface glycoprotein gp120, the cell-surface protein CD4, and a chemokine receptor CCR5 or CXCR4. Besides their role in HIV-1 entry, CCR5 and CXCR4 are G protein-coupled receptors that can activate multiple intracellular signaling pathways. HIV-1 gp120 has been shown to activate signaling pathways through the chemokine receptors in several cell types including lymphocytes, neurons, and astrocytes. In some cell types, these consequences may cause cellular injury. In this review, we highlight our data demonstrating diverse signaling events that occur in primary human macrophages in response to gp120/chemokine receptor interactions. These responses include K+, Cl-, and nonselective cation currents, intracellular Ca2+ increases, and activation of several kinases including the focal adhesion-related tyrosine kinase Pyk2, mitogen-activated protein kinases (MAPK), and phosphoinositol-3 kinase. Activation of the MAPK leads to gp120-induced expression of chemokines such as monocyte chemoattractant protein-1 and macrophage-inflammatory protein-1beta and the proinflammatory cytokine tumor necrosis factor alpha. These responses establish a complex cytokine network, which may enhance or suppress HIV-1 replication. In addition, dysregulation of macrophage function by gp120/chemokine receptor signaling may contribute to local inflammation and injury and further recruit additional inflammatory and/or target cells. Targeting these cellular signaling pathways may have benefit in controlling inflammatory sequelae of HIV infection such as in neurological disease.     

Long-term survival after autologous bone marrow transplantation for follicular lymphoma in first remission.

The role of autologous stem cell transplantation (ASCT) in the treatment of follicular lymphoma is still being defined in the era of antibody therapy. Here we report the long-term 12-year clinical outcomes of patients treated with autologous bone marrow transplantation (ABMT) for follicular non-Hodgkin's lymphoma (NHL) in first remission. Between 1988 and 1993, advanced-stage follicular NHL patients in need of initial therapy were enrolled in 2 consecutive prospective treatment trials of either standard-dose CHOP induction (83 patients) or high-dose CHOP plus granulocyte-colony stimulating factor (G-CSF) (20 patients). Patients who achieved an adequate remission with induction therapy underwent conditioning with cyclophosphamide and total body irradiation (TBI) followed by ABMT in first remission using bone marrow (BM) purged in vitro with anti-B cell monoclonal antibodies and rabbit complement (96 patients). At 12-year follow-up, 61% of the patients are alive and 43% remain in continuing complete remission. The only predictors of decreased progression-free survival proved to be histologic BM involvement at time of harvest (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.3-3.9, P<.004) and PCR detectable disease in the BM product after purging (HR 4.18, 95% CI 1.99-8.8, P=.0002). No significant predictors of overall survival were identified. These results at 12-year follow-up suggest that a subset of follicular lymphoma patients can experience prolonged survival with ABMT in first remission.     

The Athletic Prevention Programming and Leadership Education (APPLE) Model: Developing Substance Abuse Prevention Programs

Alcohol and other drug (AOD) abuse affects every sector of society, and student-athletes are no exception. Because many factors affecting athletes do not affect other students, athletic departments commonly approach prevention through AOD education. Different educational approaches are described in this article, particularly the Athletic Prevention Programming and Leadership Education (APPLE) model. Project APPLE is designed to enable an athletic department to systematically analyze its AOD prevention in seven areas: recruitment practices, expectations and attitudes, education and AOD programs, policies, drug testing, discipline, and referral and counseling. Because athletic trainers often are involved in this process, this article should help them to design more effective AOD programs.     

Skin testing in farmers' lung disease

Intradermal skin tests with a culture filtrate antigen of Micropolyspora faeni grown on a synthetic medium were performed on patients with farmers' lung disease (FLD) and well farmers with and without antibodies to a panel of FLD antigens. Seventy-five percent of the FLD patients, 79% of the well farmers with M. faeni antibody, and 5% of well farmers without M. faeni antibody had a 2+ or greater intradermal immediate skin-test reaction. Prausnitz-Küstner (P-K) reactions were positive using serum of M. faeni immediate skin test-positive FLD patients. IgG-rich fractions from a staphylococcal protein A-Sepharose column of such serum contained the sensitizing factor whereas IgG-depleted fractions did not. M. faeni—specific IgE could not be detected in serum by a polystyrene radioimmunoassay. Positive late-onset (6-hr) skin tests occurred only in FLD patients and farmers with precipitating antibody. Biopsy specimens of the 6-hr reactions revealed a generalized dermal and perivascular polymorphonuclear infiltrate with deposits of immunoglobulin and complement about blood vessels. The skin-sensitizing factor noted in FLD patients and well farmers with antibody is not disease specific. This factor appears to be associated with the IgG-rich fraction of serum, and its role in the pathogenesis of FLD is unclear.