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.     

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.     

p53 expression in neurofibroma and malignant peripheral nerve sheath tumor. An immunohistochemical study of sporadic and NF1-associated tumors

OBJECTIVES--(1) to evaluate regional cerebral blood flow (rCBF) with single photon emission computed tomography and 99mTc-hexamethylpropyleneamine oxime in patients with the idiopathic adult hydrocephalus syndrome (IAHS); (2) to examine regional cerebral blood flow (rCBF), gait, and psychometric functions before and after CSF removal (CSF tap test); (3) to assess abnormalities in subcortical white matter by MRI. METHODS--Thirty one patients fulfilling the criteria for IAHS (according to history and clinical and neuroradiological examination) were studied. Quantified gait measurements, psychometric testing, and rCBF before and after removal of CSF were obtained. Pressure of CSF and CSF outflow conductance were investigated with a constant pressure infusion method. Brain MRI was used to quantify the severity of white matter lesions and periventricular hyperintensities. In IAHS a widespread rCBF hypoperfusion pattern was depicted, with a caudal frontal and temporal grey matter and subcortical white matter reduction of rCBF as the dominant feature. Removal of CSF was not accompanied by a concomitant increase in rCBF. Significant white matter lesions were detected only in a minority of patients by MRI. An altered CSF hydrodynamic state with a higher CSF pressure and lower conductance was confirmed. IAHS is characterised by an abnormal CSF hydrodynamic state, associated with a widespread rCBF reduction with preference for subcortical white matter and frontal-temporal cortical regions. Furthermore in most patients MRI did not show white matter changes suggestive of a coexistent subcortical arteriosclerotic encephalopathy. At least in the idiopathic group of patients with AHS, measurements of rCBF before and after temporary relief of the CSF hydrodynamic disturbance will not provide additional information that would be helpful in the preoperative evaluation but is suggestive of a preserved autoregulation of rCBF.     

RAP46 is a negative regulator of glucocorticoid receptor action and hormone-induced apoptosis

RAP46 was first identified by its ability to bind the glucocorticoid receptor. It has since been reported to bind several cellular proteins, including the anti-apoptotic protein Bcl-2, but the biological significance of these interactions is unknown. Here we show that RAP46 binds the hinge region of the glucocorticoid receptor and inhibits DNA binding and transactivation by the receptor. We further show that overexpression of RAP46 in mouse thymoma S49.1 cells inhibits glucocorticoid-induced apoptosis. Conversely, glucocorticoid-induced apoptosis and transactivation were enhanced after treating S49.1 cells with the immunosuppressant rapamycin, which down-regulates cellular levels of BAG-1, the mouse homolog of RAP46. The effect of rapamycin can, however, be overcome by overexpression of RAP46. These results together identify RAP46 as a protein that controls glucocorticoid-induced apoptosis through its negative regulatory action on the transactivation property of the glucocorticoid receptor.     

ST/b and DBA/2 mice differ in brain alpha-bungarotoxin binding and alpha 7 nicotinic receptor subunit mRNA levels: a quantitative autoradiographic analysis

Inbred mouse strains vary in sensitivity to a number of behavioral and physiological effects produced by nicotine. Differences in sensitivity to nicotine are correlated with variance in the number of brain nicotinic receptors as measured in regionally dissected brain tissue. The studies reported here used quantitative autoradiography and in-situ hybridization methods to measure regional levels of alpha-bungarotoxin (alpha BTX) binding and alpha 7 mRNA levels. Two inbred mouse strains, ST/b and DBA/2, were compared because these strains differ maximally in sensitivity to nicotine-induced seizures and in alpha BTX binding measured in regional brain homogenates. The binding of alpha BTX was significantly greater in the St/b strain in 42 of 127 brain regions that were analyzed, and a trend towards increased binding was seen in many additional brain regions. The most consistent strain differences were found in hippocampal, thalamic and pontine nuclei. Strain differences in alpha 7 mRNA levels were also detected, but these were not as widespread as were the alpha BTX binding differences. The alpha 7 mRNA levels were significantly correlated with alpha BTX binding in both mouse strains which suggests that the strain differences in binding are related, in part, to the levels of alpha 7 mRNA.     

Risk factors for osteoporosis in men

Three months after the launch of the MMR programme in the United Kingdom and the Republic of Ireland, a postal questionnaire was sent to all GP scheme trainees in both Northern Ireland and the Republic of Ireland. The response rate was 81%. All trainees were enthusiastic about promoting MMR immunisation; with 27% favouring compulsory immunisation. 9% had never seen a patient with measles. This did not alter their attitude towards the beneficial effects of MMR immunisation. Of pre-practice year trainees 26% felt their level of knowledge of immunisation was inadequate, 59% claimed to have received no education on immunisation during their vocational training to date. This may reflects deficiencies in their medical curriculum to-date. 95% of third-year trainees indicated that their practice experience had been the source of at least some of their education on immunisation. Only 46% of trainees in the Republic of Ireland were aware of their Department of Health's aims in launching the MMR immunisation campaign.