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.     

Transluminal balloon angioplasty, stents, and atherectomy

Arterial bypass grafting for occlusive disease is still considered the gold standard in the treatment of arterial occlusive disease. However, less invasive methods are available for select patients. Percutaneous balloon angioplasty has been shown to be effective in focal iliac artery stenosis, with patency rates of 50% to 90% at 5 years. Patency rates for femoropopliteal lesions are generally less than 50% at 2 years. Complications seen with balloon angioplasty often can be treated with arterial stents. Stents can be categorized into balloon-expandable, which provide a rigid scaffold to support the artery, self-expanding, which exert radial force to resist external compression, and thermal expanding stents, which allow for the use of a smaller introducer sheath. Another treatment option is atherectomy, in which the offending lesion is removed instead of fracturing and dilating the lumen. Although overall initial results of atherectomy have not been favorable, short lesions with eccentric atheroma or intimal hyperplasia, such as those seen in dialysis access fistulas or vein graft stenoses, may respond well.     

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.     

Arterial oxygen saturation in Tibetan and Han infants born in Lhasa, Tibet

BACKGROUND: Reduced oxygen availability at high altitude is associated with increased neonatal and infant mortality. We hypothesized that native Tibetan infants, whose ancestors have inhabited the Himalayan Plateau for approximately 25,000 years, are better able to maintain adequate oxygenation at high altitude than Han infants, whose ancestors moved to Tibet from lowland areas of China after the Chinese military entered Tibet in 1951. METHODS: We compared arterial oxygen saturation, signs of hypoxemia, and other indexes of neonatal wellbeing at birth and during the first four months of life in 15 Tibetan infants and 15 Han infants at 3658 m above sea level in Lhasa, Tibet. The Han mothers had migrated from lowland China about two years previously. A pulse oximeter was placed on each infant's foot to provide measurements of arterial oxygen saturation distal to the ductus arteriosus. RESULTS: The two groups had similar gestational ages (about 38.9 weeks) and Apgar scores. The Han infants had lower birth weights (2773 +/- 92 g) than the Tibetan infants (3067 +/- 107 g), higher concentrations of cord-blood hemoglobin (18.6 +/- 0.8 g per deciliter, vs. 16.7 +/- 0.4 in the Tibetans), and higher hematocrit values (58.5 +/- 2.4 percent, vs. 51.4 +/- 1.2 percent in the Tibetans). In both groups, arterial oxygen saturation was highest in the first two days after birth and was lower when the infants were asleep than when they were awake. Oxygen saturation values were lower in the Han than in the Tibetan infants at all times and under all conditions during all activities. The values declined in the Han infants from 92 +/- 3 percent while they were awake and 90 +/- 5 percent during quiet sleep at birth to 85 +/- 4 percent while awake and 76 +/- 5 percent during quiet sleep at four months of age. In the Tibetan infants, oxygen saturation values averaged 94 +/- 2 percent while they were awake and 94 +/- 3 percent during quiet sleep at birth and 88 +/- 2 percent while awake and 86 +/- 5 percent during quiet sleep at four months. Han infants had clinical signs of hypoxemia--such as cyanosis during sleep and while feeding--more frequently than Tibetans. CONCLUSIONS: In Lhasa, Tibet, we found that Tibetan newborns had higher arterial oxygen saturation at birth and during the first four months of life than Han newborns. Genetic adaptations may permit adequate oxygenation and confer resistance to the syndrome of pulmonary hypertension and right-heart failure (subacute infantile mountain sickness).