Factors affecting contrasting results between self-reported and performance-based levels of physical limitation

Molecular electrostatic potential (MEP) maps of certain 3-methoxy flavone derivatives having different anti-picornavirus activities have been studied. Geometries of the molecules were optimised and charge distributions computed using the AM1 molecular orbital method. Hybridization displacement charges (HDC) were combined with the L?wdin charge distributions to compute the MEP maps. Reliability of the method of computing MEP maps was tested by studying certain other molecules for which ab initio MEP results are available. The anti-picornavirus activities of the flavones have been shown to be related with negative MEP values in two regions, one near the 3-methoxy group and another in a diagonally opposite region near the substituent attached to the C7 atom of the molecules.     

Reduced growth factor requirements and accelerated cell-cycle kinetics in adult human melanocytes transformed with SV40 large T antigen

Melanomas develop with high frequency in transgenic mice in which oncogenic sequences of the SV40 DNA tumor virus have been specifically targeted to melanocytes. To investigate the role of SV40 in melanomagenesis, cultured human melanocytes were transformed with a retroviral shuttle vector encoding the SV40 large T antigen and examined for changes in cell-cycle kinetics and growth-factor dependence. Colonies expressing the viral oncogene were morphologically indistinguishable from their non-T-antigen-transformed counterparts. Also like normal melanocytes, the infected cells remained anchorage dependent and non-tumorigenic in nude mice. However, T-antigen-positive cultures exhibited significantly accelerated population doubling times, increased saturation densities with highly confluent monolayers and a three- to fourfold extended life span. Most interestingly, cell-cycle analysis revealed a measurable shift from quiescent to cycling cells in T-antigen-expressing cultures and an acquired ability to progress more rapidly through G1. Moreover, T-antigen-positive melanocytes proliferated in the absence of PMA and required markedly reduced levels of exogenous bFGF. These studies indicate that the viral oncogen of simian virus 40 provides melanocytes with distinct growth advantages that may render these cells unusually susceptible to additional environmental challenges necessary for full expression of the malignant phenotype.     

Epithelioid sarcoma: a clinicopathologic review of 55 cases

OBJECTIVE: To identify any clinical and pathologic features of treatment modalities that are predictive of outcome in patients with epithelioid sarcoma, a rare slow-growing soft tissue tumor most commonly occurring in the distal extremities of young adults. DESIGN: We reviewed the institutional files for cases of epithelioid sarcoma for the period 1956 to 1991 and analyzed the effect of various factors on survival. MATERIAL AND METHODS: Fifty-five cases of epithelioid sarcoma were found, and the relevant clinical, pathologic, treatment, follow-up, and outcome features were assessed. RESULTS: All tumors were treated initially by operative resection. The recurrence rate progressively decreased with increasing aggressiveness of the initial operation; however, no difference was noted in metastatic rate. Overall, the recurrence rate was 38% and the metastatic rate was 47%. At the end of a mean follow-up of 102 months, 69% of patients had no evidence of disease, 27% had died of the disease, and 4% were alive with disease. Increasing tumor size, necrosis of more than 30%, and vascular invasion correlated significantly with a worse prognosis. CONCLUSION: Epithelioid sarcoma should be considered a malignant neoplasm with a significant potential for aggressive behavior, and close follow-up of affected patients should be maintained for many years. Initial treatment should be aggressive in an attempt to prevent recurrence.     

Serum lipids and incidence of coronary heart disease. Findings from the Systolic Hypertension in the Elderly Program (SHEP)

BACKGROUND: The association of serum lipids with coronary heart disease has been studied extensively in middle-aged men and, to a lesser extent, in similar women. Less well defined are lipid variables predictive of CHD in individuals of age > or = 60 years. METHODS AND RESULTS: The Systolic Hypertension in the Elderly Program recruited 4736 persons (mean age, 72 years; 14% were black; and 43% were men). Mean systolic and diastolic blood pressures were 170 and 77 mm Hg, respectively. Baseline mean total cholesterol was 6.11 mmol/L (236 mg/dL); HDL cholesterol, 1.39 mmol/L (54 mg/dL); and non-HDL cholesterol, 4.72 mmol/L (182 mg/dL). Triglyceride levels were 1.62 mmol/L (144 mg/dL) for fasting participants and 1.78 mmol/L for the total group. LDL cholesterol, estimated in fasting samples with triglycerides of < 4.52 mmol/L, averaged 3.98 mmol/L (154 mg/dL). Mean follow-up was 4.5 years. In multivariate Cox regression analyses, baseline total, non-HDL, and LDL cholesterol levels and the ratios of total, non-HDL, and LDL to HDL cholesterol were significantly related to CHD incidence. HDL cholesterol and triglycerides were not significant in these analyses. In fasting participants with triglyceride levels of < 4.52 mmol/L, a 1.03 mmol/L (40 mg/dL) higher baseline total, non-HDL, or LDL cholesterol was associated with a 30% to 35% higher CHD event rate. CONCLUSIONS: The results of this study support the concept that serum lipids are CHD risk factors in older Americans.     

Preference of invasive cytotrophoblast for maternal vessels in early implantation in the macaque

The interaction of cytotrophoblast with maternal endometrium, especially endometrial blood vessels, was examined in macaque gestational stages between 2 and 8 days after the onset of implantation. Serial sectioning of these early implantation sites allowed immunostaining of consecutive sections with a number of different antibodies, facilitating cell identification. In the earliest implantation site, immunostaining showed that antibody to cytokeratin stained cytotrophoblast, syncytial trophoblast, epithelial plaque and endometrial gland cells. However, only those cytotrophoblast cells near the maternal-fetal border and within vessels showed surface staining for neural cell adhesion molecules and only syncytial trophoblast showed SP1 reactivity. Even at this early stage cytotrophoblast filled the lumen of superficial arterioles, whereas dilated venules contained only a few cytotrophoblast cells. In later stages endovascular cytotrophoblast not only plugged many spiral arterioles but also migrated into the walls of these arterioles, and progressed into deeper coils. Displacement of endothelial cells and disruption of vessel walls were illustrated with antibody to factor VIII, TGF alpha, and desmin. Clusters of cytotrophoblast cells at the fetal-maternal interface tended to bypass clusters of epithelial plaque cells and larger clusters of maternal fibroblasts, but readily entered all vascular spaces. Consequently the vascular system constituted a major pathway of invasion, although the arterioles were the only component substantially invaded beyond the trophoblastic-shell/endometrial border.     

Hormonal profile during the follicular phase in cycles stimulated with a combination of human menopausal gonadotrophin and gonadotrophin-releasing hormone antagonist (Cetrorelix)

A third generation gonadotrophin-releasing hormone antagonist (Cetrorelix) was used during ovarian stimulation in 32 patients undergoing assisted reproduction, in order to prevent the premature luteinizing hormone (LH) surge. In all patients, ovarian stimulation was carried out with two or three ampoules of human menopausal gonadotrophin (HMG), starting on day 2 of the menstrual cycle. In addition, 0.5 mg of Cetrorelix was administered daily from day 6 of HMG treatment until the day of ovulation induction by human chorionic gonadotrophin (HCG). A significant drop in plasma LH concentration was observed within a few hours of the first administration of Cetrorelix (P < 0.005). Moreover, no LH surge was detected at any point in the treatment period in any of the 32 patients. A mean oestradiol concentration of 2111 +/- 935 ng/l was observed on the day of the HCG administration, indicating normal folliculogenesis. Like LH, progesterone concentration also dropped within a few hours of the first administration of Cetrorelix (P < 0.005). A 0.5 mg daily dose of Cetrorelix prevented a premature LH surge in all the 32 patients treated.     

Tripartite hemolysin BL from Bacillus cereus. Hemolytic analysis of component interactions and a model for its characteristic paradoxical zone phenomenon

This study describes the use of the microdialysis technique to elucidate specific properties of the circadian pacemaking system in the hypothalamus, by measurement of melatonin production in the pineal gland. Melatonin has appeared to be a reliable marker of the pacemaker activity, which is influenced by the light/dark cycle. A phase shift in the light/dark cycle was applied to perturb the rhythm generating system. An 8-h phase advance resulted in the disappearance of melatonin production over two days, with basal levels comparable to normal daytime levels. In the subsequent return of rhythmic melatonin production, new clock characteristics could be revealed, due to the high time-resolution measurements of microdialysis. While half of the animals still did not show any rhythmicity, the other half of the animals regained rhythmicity with entrained onset of melatonin production, while the offset was variable and not stably entrained to lights on. Ten days after the shift, the system had completely recovered and all animals regained normal rhythmicity, in phase with the new light/dark cycle. The results are interpreted in terms of the two-oscillator model, with one oscillator reacting with a phase advance and the other with a phase delay to adapt to the phase shift.