The Ohio Midlife Women's Study

The Ohio Midlife Women's Study was longitudinal with measurements occurring at three, 9-month intervals. Our purpose in doing this research was to examine predictors, moderators, and outcome variables associated with the transition to midlife in Caucasian and African American women. Predictor variables included loss and gain of resources. Moderators included menopause symptoms, menopausal status, attitude toward menopause, coping, and demographic characteristics. Outcome variables included anxiety, depression, and health promoting activities. To obtain the proposed final sample of 160 midlife women, an initial sample of 103 African American and 105 Caucasian "healthy" women were recruited in the community. Consistent predictors of anxiety were loss of resources, coping effectiveness, and education. Consistent predictors of depression were loss of resources and education. Health promoting activities were consistently predicted by attitude toward menopause and coping effectiveness. Stress is a better predictor of negative health outcomes than menopausal status.     

Docetaxel and carboplatin as second-line chemotherapy for metastatic non-small cell lung cancer

The aim of this pilot study was to evaluate the activity and toxicity of docetaxel plus carboplatin as second-line treatment in patients with metastatic non-small cell lung cancer (NSCLC). Patients received docetaxel 75 mg/m(2) followed by carboplatin AUC 5 on day 1 every 3 weeks in an out-patient setting. Twenty-six patients were enrolled; 23 patients were diagnosed stage IV disease and three patients had a IIIB disease with malignant pleural effusion. The median interval from first to second-line treatment was 3.5 months (range 1-13). Patients received a total of 101 cycles with a median number of four cycles per patient (range 1-6). Five patients achieved a partial remission (19.23%; 95% confidence interval (CI) 6.55-39.35%), 11 had stable disease (42.31%) and ten progressed (38.46%) after initiation of second-line therapy. Median survival was 243 days (95% CI 182-336 days), the median progression-free survival was 118 days (95% CI 89-170 days), and the 1-year survival rate was 25.98% (95% CI 6.33-45.63%). Moderate haematological and mild nonhaematological toxicities were observed. No treatment-related death occurred. In conclusion, docetaxel plus carboplatin as second-line regimen has a reasonable activity with good tolerance and encouraging survival data.     

The CD24/P-selectin binding pathway initiates lung arrest of human A125 adenocarcinoma cells

Carbohydrates on tumor cells have been shown to play an important role in tumor metastasis. We demonstrated before that CD24, a Mr 35,000-60,000 mucine-type glycosylphosphatidylinositol-linked cell surface molecule, can function as ligand for P-selectin and that the sialylLex carbohydrate is essential for CD24-mediated rolling of tumor cells on P-selectin. To investigate the role of both antigens more closely, we transfected human A125 adenocarcinoma cells with CD24 and/or fucosyltransferase VII (Fuc TVII) cDNAs. Stable transfectants expressed CD24 and/or sialylLex. Biochemical analysis confirmed that in A125-CD24/FucTVII double transfectants, CD24 was modified with sialylLex. Only double transfectants showed rolling on P-selectin in vivo. When injected into mice, double transfectants arrested in the lungs, and this step was P-selectin dependent because it was strongly enhanced in lipopolysaccharide (LPS) pretreated wild-type mice but not in P-selectin knockout mice. CD24 modified by sialylLex was required on the tumor cells because the LPS-induced lung arrest was abolished by removal of CD24 from the cell surface by phosphatidylinositol-specific phospholipase C. A125-FucTVII single transfectants expressing sialylLex but not CD24 did not show P-selectin-mediated lung arrest. The sialylLex epitope is abundantly expressed on human carcinomas, and significant correlations between sialylLex expression and clinical prognosis exist. Our data suggest an important role for sialylLex-modified CD24 in the lung colonization of human tumors.     

Differential expression of a recombinant adeno-associated virus 2 vector in human CD34+ cells and breast cancer cells

The use of autologous hematopoietic stem cell (HSC) grafts after high-dose chemotherapy protocols may be hampered by contamination of the grafts with tumor cells. Because epithelial cells seem to be the natural hosts of adeno-associated virus 2 (AAV-2), we speculated that epithelial tumor cells in HSC grafts might be selective targets for AAV-2-based vectors. To test this hypothesis, the breast cancer cell lines T47D and MCF-7 were infected with a recombinant AAV-2 vector expressing the green fluorescent protein (GFP) gene; in addition, human CD34+ mobilized peripheral progenitor cells were infected with the same vector. At a multiplicity of infection of 100, only 1.39% +/- 0.51% CD34+ cells expressed the GFP gene whereas, 36.06% +/- 6.53% of the infected T47D cells and 41.52% +/- 3.16% of the infected MCF-7 cells expressed the transduced GFP gene. After further optimizing the transduction procedure by using higher multiplicities of infection (100-500) and preincubation of samples with the tyrosine kinase inhibitor genistein, up to 82.52% and 85.35% GFP+ T47D and MCF-7 cells, respectively, were observed. The GFP fluorescence intensity in transduced mammary tumor cells was up to 3 logs higher than that of transduced CD34+ cells. The differential expression of recombinant AAV-2 vectors in hematopoietic and epithelial tumor cells warrants further research with this vector system, including the use of suicide genes for the purging of autologous HSC grafts.     

Differential effects of inhibitors of monoamine oxidase Types A and B on the adrenergic system of the rabbit iris.

Topical instillation of inhibitors of monoamine oxidase Types A and B into the rabbit eye, followed by the administration of a releaser of monoamines (Ro 4-1284), induces strong and sustained dilation of the iris. The mydriatic pattern differs markedly with A- and B-inhibitors and with the duration of the inhibitor treatment. The Type B inhibitor, deprenyl, prevents the degradation of exogenous 2-phenylethylamine and possibly of the endogenous amine X capable of releasing monoamines from a compartment less accessible to Ro-1284.     

Chemotherapy of autochthonous leukemias induced by 7,12-dimethylbenz(a)anthracene in long evans rats

Summary A total of 111 autochthonous (primary) acute rat leukemias of the diffuse-hepatic type which had been induced by 7,12-dimethylbenz(a)anthracene were treated with mono- and combination chemotherapy. The survival time of treated rats increased significantly compared to untreated controls. A combination of vincristine (VCR), adriamycin (ADR), and cytosine arabinoside (Ara-C) was superior to a combination of VCR and ADR as well as to a monotherapy with Cyclophosphamide, BCNU, VCR, ADR, and Ara-C.     

Regional myocardial dysfunction: evaluation of patients with prior myocardial infarction with fast CT

A prototype ultrafast cine computed tomographic (CT) scanner, designed specifically for cardiac imaging, was used to evaluate a preliminary series of patients with prior myocardial infarction (n = 21) and a control group without coronary artery disease (n = 5). Multilevel 50-msec CT scan exposures were obtained during peripheral intravenous bolus injections of contrast medium. A comparison was made between cine-CT scans and standard left ventriculographic images in assessing segmental left ventricular motion. Results indicate that cine CT, performed at sufficiently rapid speeds (20 scans per second) to allow useful analysis of regional ventricular wall motion, can provide adequate image quality. Analysis of 110 segments revealed a good correlation (90.9%) between the two techniques in characterizing normal from abnormal regional wall motion. Cine CT, based on this initial study, demonstrates considerable potential for evaluating not only cardiac chamber dimensions but also segmental wall dynamics.