Histamine downregulates CD14 expression via H2 receptors on human monocytes

Lipopolysaccharide (LPS) binds to LPS-binding protein (LBP) in plasma and is delivered to the cell surface receptor CD14 on human monocyte. LPS is transferred to the transmembrane signaling receptor toll-like receptor (TLR) 4. In the present study, the effect of histamine on the expression of CD14 on human monocytes was investigated. Histamine concentration- and time-dependently decreased the expression of cell surface CD14, whereas histamine did not decrease mRNA for CD14 nor increase soluble CD14 (sCD14). The inhibitory effects of histamine on CD14 expression were antagonized by H2-receptor antagonist, but not by H1 and H3/H4 antagonist. The effects of selective H2-receptor agonists, 4-methylhistamine and dimaprit, on CD14 expression mimicked that of histamine indicating that histamine regulated CD14 expression through the stimulation of H2-receptors. The pretreatment with histamine partially inhibited the LPS-induced TNF-alpha production in human peripheral blood mononuclear cells (PBMC). Such inhibition might be due to the down-regulation of CD14 expression on monocytes by histamine.     

Three cases of the gastrosplenic and the hepatomesenteric trunks

Three common branches of the celiac trunk are the left gastric artery, the splenic artery and the common hepatic artery. The variation of the three branches of the celiac trunk has an importance for the arterial supply to the digestive organs of the upper abdomen. In this study, we present three cases of the gastrosplenic and the hepatomesenteric trunks in Japanese cadavers. Especially, in Case 1, the left inferior phrenic artery arose from the gastrosplenic trunk and the left hepatic artery arose from the left gastric artery. In Cases 2 and 3, the common hepatic artery penetrated the pancreatic parenchyma before reaching liver. In Case 3, the right hepatic artery arose from the hepatomesenteric trunk.     

The volume-activated chloride current in human endothelial cells depends on intracellular ATP

We have studied the effect of intracellular ATP on volume-activated Cl^–-currents in endothelial cells from human umbilical veins by means of the whole-cell patch clamp technique. The run-down of this current in ruptured patches during repetitive applications of hypotonic solutions (HTS) could be significantly reduced if the cells were internally perfused with a pipette solution that contained 4 mmol/l ATP. This run-down was much less pronounced if currents were recorded using nystatin-perforated patches. The amplitude of the current was drastically reduced and its activation became slower if the cells were superfused with a glucose-free medium with 1 mmol/l KCN. Adding 4 mmol/l ATPS, a poorly hydrolyzable ATP-analogue, to the patch pipette prevented run-down of the current during repetitive activations by HTS, even if the cells were superfused with glucose-free solution with 1 mmol/l KCN. It is concluded that activation of the mechanosensitive Cl^– conductance in human endothelial cells requires the presence of intracellular ATP, but not its hydrolysis.     

Phase stability after aging and its influence on pin-on-disk wear properties of Ce-TZP/Al2O3 nanocomposite and conventional Y-TZP

Recently zirconia/alumina composites have been examined by many researchers as the new generation of bearing materials in total joint replacements. In this study, the phase stability of a Ce-TZP/Al(2)O(3) nanocomposite and conventional Y-TZP after aging, and its influence on wear resistance, were investigated. Very slight phase transformation was observed in both types of ceramics 18 months after the implantation of Ce-TZP/Al(2)O(3) or Y-TZP samples into rabbit tibiae. However, Y-TZP showed marked phase transformation (approximately 80%) after aging in an autoclave (121 degrees C) for 190 h or in physiological saline at 62 degrees C for 18 months, whereas the new composite remained almost resistant to degradation. According to the results of self-pairing pin-on-disk wear tests using ceramic specimens with or without autoclave aging, the wear factor was almost the same between Ce-TZP/Al(2)O(3) samples with and without aging (6.74 +/- 0.36 x 10(-8) and 6.04 +/- 0.95 x 10(-8) mm(3)/Nm, respectively). In contrast, although non-aged Y-TZP had the lowest wear factor (4.88 +/- 0.51 x 10(-8) mm(3)/Nm) of all specimens tested, aged Y-TZP showed 10-fold greater wear than nonaged Y-TZP. The present study suggests that Ce-TZP/Al(2)O(3) nanocomposite has much greater phase stability than Y-TZP, and that its wear properties are not influenced by aging.     

In vitro and in vivo antifungal activities of FX0685, a novel triazole antifungal agent with potent activity against fluconazole-resistant Candida albicans.

To evaluate the therapeutic potential of FX0685, a new triazole antifungal agent, for the treatment of opportunistic fungal infections, particularly systemic candidiasis and aspergillosis, in vitro and in vivo studies were performed using fluconazole (FLC), itraconazole (ITC) and/or amphotericin B (AMB) as reference drugs. A preliminary in vitro study showed that the antifungal activity of FX0685 against FLC-susceptible Candida albicans, several non-C. albicans Candida species and Cryptococcus neoformans was superior to that of FLC and comparable or superior to those of ITC and AMB, while the anti-Aspergillus fumigatus activity of FX0685 was to varying degrees lower than that of ITC. FX0685 appeared to be comparable to FLC and ITC in the treatment of murine systemic C. albicans and pulmonary A. fumigatus infection, respectively. The biological property of FX0685 was characterized by its potent in vitro and in vivo activity against FLC-resistant C. albicans. Part of this unique property was explained by the finding that it retained potent inhibitory activity against those CYP51 molecules in which amino acid substitutions confer a phenotype of resistance to FLC and some other azole derivatives. All of these results lead to the possibility that FX0685 may be a potential antifungal drug candidate for the treatment of various clinical forms of systemic candidiasis, including those caused by FLC-resistant C. albicans, as well as for the treatment of pulmonary aspergillosis.     

A HISTOPATHOLOGICAL STUDY OF DIFFUSE HYPERPLASIA OF GASTRIC ARGYROPHIL CELLS

The present study includes a histopathological and immunohistochemical study of 4 cases of diffuse hyperplasia of gastric argyrophil cells. The mode of proliferation of these cells and the production of hormone by these cells have been documented. The distribution of microacinar nests composed of argyrophil cells was thought to be related to chronic gastritis in which there are atrophy of mucosa and intestinal metaplasia. In the case in which these nests were found only in the corpus ventriculi, there was intestinal metaplasia throughout the stomach. On the other hand, in the case in which these nests appeared only in the pyloric area, atrophy of the mucosa with mild intestinal metaplasia was observed only in the pyloric area. The microacinar nests composed of argyrophil cells were distributed in the deep mucosa at the basal portion of the glands in the area with intestinal metaplasia. Serial sections revealed a sprout composed of argyrophil cells budding from the gland with intestinal metaplastic changes. The sprout buds out from the growth zone of glands with Intestinal metaplasia and then becomes isolated and gives rise to reactive hyperplasia. The peptide hormone contained in these cells differs according to the mucosal environments. Cells containing gastrin were observed in the pyloric area, but not in the corpus ventriculi where there was marked intestinal metaplasia. The cells in this area were assumed to contain other hormones.     

Effects of sex hormones on induction of intestinal metaplasia by X-irradiation in rats.

The influence of sex hormones on induction of intestinal rnetaplasia was examined in 5 week old Crj: CD (SD) rats of both sexes. At the age of 4 weeks, the animals were gonadectornized and given testosterone or dimethyl estradiol (DES). One week after operation, they were irradiated with two 10 Gy doses of X-rays to the gastric region at a 3 day interval for a total of 20 Gy. At the termination of the experiment, 6 months after the X-irradiation, the incidence of intestinal metaplasia with alkaline phosphatase (ALP) positive foci in males was significantly higher than in females, in orchidectomized males or orchidectomized plus DES treated rats (P <0.01). On the other hand, the incidence of intestinal metaplasia with ALPpositive foci in normal females appeared lower than in ovariectomized females (P < 0.01), and was increased in rats by treatment with testosterone or decreased by DES. Numbers of foci of intestinal metaplasias with Paneth cells and total numbers appeared to increase in males treated with DES. The results suggested a promoting role for testosterone in the development of ALP positive lesions and indicated considerable heterogeneity between intestinal metaplasia subtypes.     

Circular dichroism of poly{γ-[2-(9-carbazolyl)ethyl] L-glutamate} in dilute solution and in solid state

Circular dichroism (CD) and ultraviolet absorption (UV) spectra were measured for poly{γ-[2-(9-carbazolyl)ethyl] L -glutamate} (PCLG), whose side chain chromophore has three π – π^* transitions in a wavelength region not overlapping with the n – π^* transition of the main chain peptide group. For the dilute solution in any given helicogenic solvent, the observed CD sign had a good correlation to the polarization direction of the π – π^* transitions. On the other hand, a concentrated solution with a concentration of ca. 15 wt.-% was found to form a liquid crystalline phase, which was probably nematic at room temperature. The CD spectral profiles of the cast film of the polypeptide were quite different from that of the dilute solution. Origins of the optical activity are discussed.