Trimerization and cyclization of reactive P-functionalities confined within OCO pincers

In order to stabilize a 10–P–3 species with C_2v symmetry and two lone pairs on the central phosphorus atom, a specialized ligand is required. Using an NCN pincer, previous efforts to enforce this planarized geometry at P resulted in the formation of a C_s-symmetric, 10π-electron benzazaphosphole that existed as a dynamic “bell-clapper” in solution. Here, OCO pincers 1 and 2 were synthesized, operating under the hypothesis that the more electron-withdrawing oxygen donors would better stabilize the 3-center, 4-electron O–P–O bond of the 10–P–3 target and the sp³-hybridized benzylic carbon atoms would prevent the formation of aromatic P-heterocycles. However, subjecting 1 to a metalation/phosphination/reduction sequence afforded cyclotriphosphane 3, resulting from trimerization of the P(i) center unbound by its oxygen donors. Pincer 2 featuring four benzylic CF₃ groups was expected to strengthen the O–P–O bond of the target, but after metal–halogen exchange and quenching with PCl₃, unexpected cyclization with loss of CH₃Cl was observed to give monochlorinated 5. Treatment of 5 with (p-CH₃)C₆H₄MgBr generated crystalline P-(p-Tol) derivative 6, which was characterized by NMR spectroscopy, elemental analysis, and X-ray crystallography. The complex ¹⁹F NMR spectra of 5 and 6 observed experimentally, were reproduced by simulations with MestreNova.

Attempted synthesis of OCO-supported 10–P–3 species led to trimerization or cyclization.     

Apoptosis and microglial activation in influenza encephalopathy

During influenza epidemics in Japan, the number of children with acute encephalopathies and encephalitis has recently increased. Although the pathophysiologies remain unclear, there is usually brain edema with evidence of damage to the blood-brain-barrier (BBB). We investigated the glial reaction and apoptosis in brains of eight such cases comprising two of acute necrotizing encephalopathy and six of influenza encephalopathy, and compared the results with those in five control brains. Apoptosis, evidenced by chromatin condensation and fragmentation in hematoxylin sections, in situ end labeling of fragmented DNA (TUNEL) and DNA laddering, was observed in neurons and glial cells in four brains with influenza encephalopathy. In the TUNEL-positive brains, the increase in microglia was greater than in the TUNEL-negative brains. Immunoreactivity for active-caspase 3, demonstrated by immunohistochemistry, and the overexpression of a caspase-cleaved fragment of poly(ADP-ribose) polymerase, demonstrated by Western blotting, indicated that activation of caspase 3 is involved in the apoptotic pathway in the brains of influenza encephalopathy cases. Apoptosis or specific pathological processes that cause apoptosis may give rise to aggravated encephalopathy.     

Intravenous anesthetic,propofol inhibits invasion of cancer cells

Intravenous anesthetic, propofol (2,6-diisopropylphenol), is extensively used for general anesthesia without knowing the effects on cancer. We found here that clinically relevant concentrations of propofol (1-5 microg/ml) decreased the invasion ability of human cancer cells (HeLa, HT1080, HOS and RPMI-7951). In the HeLa cells treated with propofol, formation of actin stress fibers as well as focal adhesion were inhibited, and propofol had little effect on the invasion ability of the HeLa cells with active Rho A (Val(14)-Rho A). In addition, continuous infusion of propofol inhibited pulmonary metastasis of murine osteosarcoma (LM 8) cells in mice. These results suggest that propofol inhibits the invasion ability of cancer cells by modulating Rho A and this agent might be an ideal anesthetic for cancer surgery.     

Pancreatic pseudocyst extending into the liver via the hepatoduodenal ligament: a case report

A case of pancreatic pseudocyst extending into the liver via the hepatoduodenal ligament is reported. This is the first report clearly demonstrating that the hepatoduodenal ligament is another route of hepatic extension of pancreatic pseudocysts as well as the hepatogastric ligament, which is the most common. The importance of the topological anatomy of the peritoneum is emphasized in understanding the extrapancreatic extension of pancreatic pseudocysts.     

Comparative Studies of the Detection Rates of Leishmania Parasites from Formalin,Ethanol-fixed,Frozen Human Skin Specimens by Polymerase Chain Reaction and Southern Blotting

In this study, detection rates of Leishmania parasites from human skin were compared among three different types of specimens, formalin-fixed, ethanol-fixed, and frozen, by polymerase chain reaction (PCR) and Southern blotting. For this purpose, we used biopsy specimens collected from 19 leishmaniasis patients and performed PCR and Southern hybridization with the probe specific for Leishmania (Viannia) braziliensis complex. Among these 19, 16 specimens were from cutaneous leishmaniasis (CL), one, diffuse cutaneous leishmaniasis (DCL) and 2, mucocutaneous leishmaniasis (MCL) and were formalin-fixed and paraffin-embedded. The causative agents for one case of CL and one case of DCL were already identified as L. (Leishmania) complex. Six specimens of CL were preserved in 100% ethanol. Two specimens of MCL were frozen tissues. PCR using the formalin-fixed and paraffin-embedded specimens revealed positive bands at 70bp in 9 (47.4%) out of 19 specimens of CL, MCL and DCL. Southern blotting detected the signals in 12 (63.2%) out of the 19. PCR using the 100% ethanol-fixed specimens revealed positive bands in 4 (66.7%) out of 6, and Southern blotting also detected the signals in 4 (66.7%) out of the 6. PCR and Southern blotting using 2 frozen specimens of MCL were always positive (100%). Although we failed to detect significant differences by Chi-square test between the results from the formalin-fixed, paraffin-embedded specimens and those from 100% ethanol-fixed ones, we concluded that ethanol-fixed specimens, convenient for transportation and storage, would be more useful for diagnosis of leishmaniasis by PCR in a developing country.     

Prevalence of trachoma in preschool and schoolchildren in the city of São Paulo

OBJECTIVE: To assess the prevalence of trachoma among preschool and school children of public schools to give new focus to control programs. METHODS: An epidemiological survey was carried out in S?o Paulo City in 1999. Children between four and 14 years old were selected by a cluster sampling where school shift was the sampling unit. External eye examination was conducted to detect trachoma. RESULTS: A total of 27,091 children were examined and 597 cases of trachoma were found (2.2%; 95% CI: 1.86-2.55). The prevalence ranged from 0.4% to 4.2% in 10 city areas. The trachoma detection rate in the household contacts examined was 8.7%. Follicular trachoma was found in 99% of the cases and intense trachoma in 1.0%. It was observed that 21.8% of the cases were asymptomatic. CONCLUSIONS: Though the trachoma prevalence was low, the occurrence of severe cases points out to the likelihood of cicatricial trachoma cases in the future if they are not adequately treated and controlled. The great difference in the prevalences in different city areas indicates the need for strengthening epidemiological surveillance activities.     

Pulmonary tumor thrombotic microangiopathy caused by a gastric carcinoma expressing vascular endothelial growth factor and tissue factor

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare clinicopathological entity causing severe pulmonary hypertension. Its histological features include widespread tumor emboli along with fibrocellular intimal proliferation and thrombus formation in the small arteries and arterioles of the lungs. The result is occlusion or stenosis of the pulmonary vasculature, but the detailed pathogenesis has yet to be clarified in spite of the serious clinical manifestations. Herein is described the case of a 62-year-old man with a gastric adenocarcinoma who died of sudden cardiopulmonary arrest. The autopsy revealed advanced cancer disease as well as findings of PTTM, which seemed to be the cause of his unexpected death. The carcinoma cells were immunohistochemically positive for vascular endothelial growth factor (VEGF) and also for tissue factor (TF). There is another report suggesting that TF might play an important role in the pathogenesis of PTTM. Also, VEGF has been reported to be involved in a variety of forms of pulmonary hypertension and to be upregulated by TF. These findings suggest that VEGF and TF may be involved in the pathogenesis of PTTM. The present PTTM case, in which the tumor cells demonstrate the coexpression of VEGF and TF, is important in facilitating understanding of the lethal disorder in the future.     

Changes of body temperature and thermoregulatory responses of freely moving rats during GABAergic pharmacological stimulation to the preoptic area and anterior hypothalamus in several ambient temperatures

Action of gamma-aminobutyric acid (GABA) in the preoptic area and anterior hypothalamus (PO/AH) has been implicated to regulate body temperature (T(b)). However, its precise role in thermoregulation remains unclear. Moreover, little is known about its release pattern in the PO/AH during active thermoregulation. Using microdialysis and telemetry techniques, we measured several parameters related to thermoregulation of freely moving rats during pharmacological stimulation of GABA in normal (23 degrees C), cold (5 degrees C), and hot (35 degrees C) ambient temperatures. We also measured extracellular GABA levels in the PO/AH during cold (5 degrees C) and heat (35 degrees C) exposure combined with microdialysis and high performance liquid chromatography (HPLC). Perfusion of GABA(A) agonist muscimol into the PO/AH increased T(b), which is associated with increased heart rate (HR), as an index of heat production in all ambient temperatures. Although tail skin temperature (T(tail)) as an index of heat loss increased only under normal ambient temperatures, its response was relatively delayed in comparison with HR and T(b), suggesting that the increase in T(tail) was a secondary response to increased HR and T(b). Locomotor activity also increased in all ambient temperatures, but its response was not extraordinary. Interestingly, thermoregulatory responses were different after perfusion of GABA(A) antagonist bicuculline at each ambient temperature. In normal ambient temperature conditions, perfusion of bicuculline had no effect on any parameter. However, under cold ambient temperature, the procedure induced significant hypothermia concomitant with a decrease in HR in spite of hyperactivity and increase of T(tail). It induced hyperthermia with the increase of HR but no additional change of T(tail) in hot ambient temperature conditions. Furthermore, the extracellular GABA level increased significantly during cold exposure. Its release was lower during heat exposure than in a normal environment. These results indicate that GABA in the PO/AH is an important neurotransmitter for disinhibition of heat production and inhibition of heat loss under cold ambient temperature. It is a neurotransmitter for inhibition of heat production under hot ambient temperature.