Maternal and fetal nitric oxide synthesis is decreased in pregnancies with small for gestational age infants

Our purpose was to evaluate whether maternal and fetal nitric oxide synthesis in pregnancies with small for gestational age (SGA) infants are different from those in pregnancies with appropriate for gestational age (AGA) infants. Maternal and fetal circulating nitrate and nitrite concentrations were compared between 30 pregnancies with AGA and 10 pregnancies with SGA at birth. End-products of nitric oxide synthesis were measured in maternal and cord venous blood samples using a fluorometric assay. Umbilical artery blood pH and PO2 were also measured. Maternal circulating nitrite and nitrate concentrations (6.91 +/- 1.27 microM) in pregnancies with SGA were significantly lower than those (11.69 +/- 1.33 microM) in pregnancies with AGA (P = 0.015). Fetal circulating nitrite and nitrate concentrations (7.54 +/- 1.09 microM) in pregnancies with SGA were also significantly lower than those (11.24 +/- 1.08 microM) in pregnancies with AGA (P = 0.024). There were no significant differences in umbilical artery blood pH and PO2 between the two groups. These results suggest that maternal and fetal nitric oxide synthesis are decreased in pregnancies with SGA infants.      

The change of antithrombin III activity of pregnant women and women on oral contraceptives (author's transl)

Antithrombin 3 (AT 3) activity was examined in pregnant women, women using oral contraceptives (mestranol .1 mg plus norethisterone 2 mg daily or mestranol .05 mg plus norethisterone 1 mg daily), and women on the gestagens alone. AT 3 activity in serum was found to decrease significantly in the third trimester of pregnancy and postpartum period (2 or 3 days); it returned to the level of nonpregnant females 6 or 7 days postpartum. AT 3 in plasma as well as serum was found to decrease significantly after the first month administration of the oral contraceptives. It returned to normal level after the cessation of administration. The successive course of administration again caused the decrease of AT 3 activity. The degree of the decrease became less and less. Finally the decrease was not in effect after 3-5 courses of administration. Norethisterone alone did not cause any change of AT 3 level. (Author's Modified)     

Stromal-derived factor-1alpha/CXCL12-CXCR 4 axis is involved in the dissemination of NSCLC cells into pleural space

Malignant pleural effusion (PE) is one of the poor prognostic factors in non-small cell lung cancer (NSCLC), and the detailed mechanism of the malignant PE formation is not fully elucidated. Recently, CXCR4, a receptor for chemokine stromal-derived factor-1alpha (SDF-1alpha) that can induce chemotaxis of cells, was reported to be expressed on NSCLC. In this study, we hypothesized that the SDF-1alpha/CXCR4 axis may be involved in the dissemination of malignant cells into pleural space, and investigated its expression, function, and signaling pathway using NSCLC cell lines and clinical samples from 43 patients with NSCLC with malignant PE. We found functional expression of CXCR4 on NSCLC cell lines, and also found that SDF-1alpha could induce migration via phosphatidylinositol 3 (PI-3) kinase- and p44/42 mitogen-activated protein kinase-dependent manner. The SDF-1alpha levels in malignant PE were significantly higher than those in transudate PE and showed a significant positive correlation with PE volumes. The sensitivity and specificity for prediction of recurrence of malignant PE was 61.5% and 83.3%, respectively (cutoff SDF-1alpha = 2,500 ng/ml), and better than those using pH of PE. Cancer cells in malignant PE expressed CXCR4, and mesothelial cells of the pleura stained positive for SDF-1alpha. The SDF-1alpha/CXCR4 axis is involved in the dissemination of NSCLC cells into pleural space.     

Osteopontin affects the persistence of beta-glucan-induced hepatic granuloma formation and tissue injury through two distinct mechanisms

Osteopontin (OPN) plays a pivotal role in various immune responses and inflammatory diseases. OPN is expressed in various granulomatous diseases; however, the cellular and molecular role of OPN in these diseases is not well known. We analyzed the role of OPN in a beta-glucan-induced hepatic granuloma model. First, we found that neither OPN deficiency nor overexpression of OPN affected the number and the size of hepatic granulomas at day 7, indicating that OPN is not involved in the formation of hepatic granulomas at the early stages. Importantly, OPN did not influence the liver tissue damage as defined by alanine aminotransferase and aspartate aminotransferase levels at early stages. Second, OPN deficiency resulted in the reduction of IL-12 and IFN-gamma production at early stages. Third, at late stages, OPN deficiency resulted in a decrease in the number and size of hepatic granulomas, and a reduction of liver tissue injury. This was due to the reduction of the cellular recruitment including macrophages, CD4 T cells and dendritic cells into the liver, and the reduction of tumor necrosis factor (TNF)-alpha production in the liver. In contrast, overexpression of OPN resulted in the persistence of granuloma formation. These data suggest that OPN affects the persistence of hepatic granuloma formation. Our results indicate that OPN up-regulates the production of IL-12 and IFN-gamma within the granulomas at early stages, and OPN has an additional role in the regulation of cellular recruitment and TNF-alpha production at late stages that determine the severity of liver tissue injury.     

Primary carcinosarcoma of the vagina

Primary carcinosarcoma of the vagina is a very rare tumor, with only eight cases diagnosed as carcinosarcoma in the literature that we are aware of. We recently encountered a case of primary carcinosarcoma of the vagina in a 75-year-old woman. The patient had a history of hysterectomy and bilateral ovariectomy for uterine corpus cancer at 55 years of age. Recurrence of the cancer was suspected 17 years after the operation and irradiation therapy was performed, but the patient died 3 years after the recurrence. Autopsy revealed a mass lesion in the pelvic cavity that originated in the vagina. Histological examination showed that the tumor contained anaplastic carcinoma, rhabdomyosarcoma, leiomyosarcoma and chondrosarcoma components, and it was diagnosed as carcinosarcoma. The histological diagnosis of the uterine corpus cancer was well-differentiated adenocarcinoma, and there was no sarcomatous component. The carcinosarcoma occurred 17 years after the hysterectomy, and it was concluded to be a primary carcinosarcoma of the vagina. This is the first case of primary vaginal carcinosarcoma in which the epithelial and sarcomatous components were clearly identified histologically and immunohistochemically.     

Papovavirus detection by electron microscopy in the brain of an elderly patient without overt progressive multifocal leukoencephalopathy

Virions resembling papovavirus were demonstrated in glial cells in the brain of an aged patient without overt progressive multifocal leukoencephalopathy. The patient was not in a severely immunocompromised state. On histological examination, only a few tiny incomplete necrotic foci were found in the subcortical area. These foci were widely dispersed. Rare, swollen oligodendroglial cells and astrocytes in which papovavirus capsid protein (VP-1) was demonstrated immunohistochemically were present around the foci. The two typical types of virus particles i.e. 35 to 40 nm round particles and elongated particles, were observed in the nuclei of the swollen glial cells. The latter were in the minority. Distinct crystals were also found in the nuclei. The centre-to-centre distance of the particles in the crystals, about 40 nm, and the electron-opaque spots of the round-shaped virions and of the elongated particles, were indicative of structural subunits of papovavirus capsids. This case provides further evidence that papovavirus, possibly JC virus, may be reactivated in the brains of aged patients who are not in an immunocompromised state.     

Chromophobe renal cell carcinoma

Chromophobe renal cell carcinoma (RCC) is a recently established subtype of RCC, which has rarely been reported in Japan. In this communication, the authors report two Japanese cases of chromophobe RCC together with the immunohistochemical findings. The tumors were composed of sheets and cribriform glands formed by tumor cells with cloudy and reticular cytoplasm. Ultrastructurally, the cytoplasm was filled with numerous microvesicles. The tumor cells were positive for cytokeratin, epithelial membrane antigen, and Tamm-Horsfall protein. Occasionally, LeuM1-positive cells were also noted. Vimentin was negative, unlike the usual RCC. Reactivity for peanut agglutinin was more frequent than that to Lotus tetragonolobus agglutinin. The results of this study suggest that the tumor cellq possessed phenotypes similar to the distal nephron rather than to the proximal tubular cells.     

Synthesis of methyl methacrylate/styrene copolymer bearing a carbomethoxyallyl end group with limited molecular weight by addition-fragmentation reaction of methyl α-(bromomethyl)-acrylate

The synthesis of methyl methacrylate/styrene copolymer bearing overwhelmingly bromine and the 2-carbomethoxyallyl group (CH₂?C(COOCH₃)CH₂? ) at the α- and ω-termini instead of the fragment of the initiator with reduced molecular weight was investigated by using methyl α-(bromomethyl)acrylate as chain transfer agent through the addition-fragmentation mechanism. The molecular weight of the copolymer was effectively decreased with bromomethylacrylate, and the unsaturated end groups quantitatively bound to two types of the monomeric units were differentiated by means of ¹H NMR spectroscopy. Equations estimating the reactivities of methyl α-(bromomethyl)acrylate towards polystyrene and poly(methyl methacrylate) radicals were derived. Methyl α-(bromomethyl)acrylate was found to be more reactive toward the poly(methyl methacrylate) radical than the polystyrene radical by a factor of 0,62.