Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

Comparative promoting activities of phosphate salts on rat two-stage bladder carcinogenesis under conditions of equivalent urinary Na+ or K+ levels.

Promoting effects of Na or K phosphate salts on rat two-stage bladder carcinogenesis were compared. Animals were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks and thereafter received 1.4% Na3PO4, 2.0% NaH2PO4, 1.0% K3PO4, or 2.5% KH2PO4, these dietary concentrations being selected because they result in approximately equal levels of Na+ and K+ in the urine, equivalent to moderate natriuresis or kaluresis in comparison with our previous data. Treatment with Na3PO4 or K3PO4 induced significant increase in urinary pH compared with control values, whereas urinary pH in the NaH2PO4 and KH2PO4 groups was comparable to control values. With regard to preneoplastic lesion development, both incidences and multiplicity were significantly increased in the groups given Na3PO4 or K3PO4 compared with both controls and NaH2PO4 or KH2PO4 groups, respectively. Furthermore, treatment with Na3PO4 significantly increased multiplicity of papillomas, accompanied by a tendency to increased incidence. No statistically significant difference in promoting potential between Na3PO4 and K3PO4 groups was evident. The present results thus suggest that tumor promotion under conditions of moderate natriuresis or kaluresis depends primarily on high urinary pH.     

New analogues of rosaramicin isolated from a Micromonospora strain. I. Taxonomy, fermentation, isolation and physico-chemical and biological properties

Antibiotics 6108 A1, B, C and D, a new series of analogues of rosaramicin, were found together with rosaramicin, juvenimicin A4 and M-4365 A1 from the cultured broth of strain BA06108 which was assigned to be a new species of Micromonospora. 6108 A1 and C showed inhibitory activity against Gram-positive and some Gram-negative bacteria as potent as rosaramicin and exhibited low acute toxicity in mice. However, 6108 B showed less potent antimicrobial activity and 6108 D showed higher toxicity than those two antibiotics.     

Intracytoplasmic Lumina in Human Oviduct Epithelium

Intracytoplasmic lumina (ICL) in human oviduct epithelium were investigated with transmission electron microscopy. ICL were found in 43 out of 60 cases examined. They were ultra-structurally characterized by microvilli lining the lumina, periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining-positive finely granular material in the lumina, and secretory vesicles in the cytoplasm surrounding the lumina. Although ICL were observed at various heights within the epithelium, they were mainly seen in basally located cells that did not face the oviduct lumen. Various stages of formation and development of ICL were observed in the basally located epithelial cells with secretory activities. Primary ICL were originated in the cytoplasm where the secretory granules were aggregated with smooth-surfaced tubular vesicles. Electron microscopic observations after PA-TCH-SP staining revealed that ICL were formed by fusion of the secretory granules with the tubular vesicles. ICL were enlarged into round profiles by further fusion of secretory granules and tubular vesicles, and subsequently opened to the oviduct lumen, or fused to each other to develop into large extracellular cysts within the epithelium.     

Antibody dependent cell mediated cytotoxicity on human cervical carcinoma cell line, ME-180, with human monoclonal antibody.

A human monoclonal antibody (MCA), CLN-IgG, showed cytotoxic effect in vitro against the cervical carcinoma cell line, ME-180, by antibody dependent cell-mediated cytotoxicity (ADCC). To determine which fractions of cells in peripheral blood lymphocyte (PBL) mediate ADCC, PBL were separated with nylon wool column and sheep red blood cells (SRBC). Both adherent cells (monocyte) and non-T, non-B cells showed cytotoxicity by ADCC. Human non-T, non-B cells showed higher cytotoxic activity against ME-180 cells than monocytes. Furthermore murine effector cells were less effective in ADCC than human effector cells with human MCA.     

FR 113680: a novel tripeptide substance P antagonist with NK1 receptor selectivity.

1. We have discovered a novel tripeptide substance P (SP) antagonist, FR 113680 [N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N'-formyl-D- tryptophyl]-N-methyl-N-phenylmethyl-L-phenylalaninamide]. In binding experiments, FR 113680 inhibited [3H]-SP binding to guinea-pig lung membranes (NK1) in a competitive manner but had not effect on [3H]-SP binding to rat cerebral cortical membranes (NK1), [3H]-neurokinin A ([3H]-NKA) binding to rat duodenum smooth muscle membranes (NK2) and [3H]-eledoisin (Ele) binding to rat cerebral cortical membranes (NK3). 2. In bioassay experiments, FR 113680 dose-dependently inhibited SP-induced guinea-pig ileum contraction (NK1), but did not inhibit either NKA-induced rat vas deferens contraction (NK2) or neurokinin B (NKB)-induced contraction of rat portal vein (NK3). According to Schild plot analysis, the inhibitory effect of FR 113680 on SP-induced guinea-pig ileum contraction is competitive and the pA2 value is 7.53. 3. The inactivity of FR 113680 on NK1 receptors in rat compared to guinea-pig may represent species-specific forms of the NK1 receptor. 4. These findings suggest that FR 113680 interacts selectively with the NK1 neurokinin receptor.     

Characterization of certain hepatocyte-proliferating and/or protective factors induced by the sensitization of freezing-thawing hepatic tissue

Although tumor cryosurgery would be expected to produce beneficial immunological effects from the enhancement of anti-tumor activity, under certain conditions the tumor may become enlarged and metastases promoted due to increased immunosuppressive activity and a high zone tolerance. In the present study, we examined whether hepatocyteproliferating factors were produced by the inoculation of freezing-thawing hepatic tissue (FTHT). Serum obtained from rats inoculated with FTHT increased DNA synthesis, according to measurement by [³H]thymidine incorporation in primary cultured rat hepatocytes. This increase was dependent on the serum concentration, with serum obtained on day 14 after the inoculation being the most potent for hepatocyte proliferation. The sensitized serum promoted DNA synthesis nearly as much as serum obtained from a 70% hepatectomized rat, but slightly less than 10ng/ml hepatocyte growth factor. The sensitized serum also protected hepatocytes from carbon tetrachloride (CCI₄)-induced hepatotoxicity. Optical density measured by the 3-(4,5-dimethyl-thiazole-2-yl)-2,5-diphenyl tetrozolium bromide (MTT) cytotoxicity assay was increased, and the release of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in medium was decreased by treating hepatocytes damaged by CCI₄ with the sensitized serum. These results suggest that certain hepatocyte-proliferating and protective factors are induced in serum by the inoculation of freezing-thawing hepatic tissue, and that the sensitized serum may be useful in the treatment of liver failure.     

Present status and tasks for future of point of care testing

This paper introduces Point-Of-Care Testing(POCT) developed by Bayer, mainly focusing on urine dipstick and tests for Diabetes Mellitus. Urinalysis using a dipstick has been widely carried out as a screening test for various kinds of diseases. Ten-pad urine dipstick is commercially available at the present time, and the desktop instruments have been developed for automatic optical reading, such as the Clinitek 50/100/500 systems. More recently, Bayer developed a new urine dipstick intended for reliable detection of the early stage of kidney disease without the influence of urine condensation or dilution. The dipstick adds 2 pads to conventional urine dipsticks: one for the measurement of small amounts of protein(albumin), and the other for creatinine. A semi-quantitative urine protein-to-creatinine ratio is based on these results. There have been significant advances made in blood glucose meters for POCT in terms of reliability, simplicity of operation, sample volume, etc. And not only healthcare professionals but also patients with diabetes have used POCT meters. Dexter-ZII is available as one of these meters. DCA2000 is a portable analyzer for measuring HbA1c in 6 min. Patients could be treated and instructed on the basis of HbA1c measured by DCA2000. As one of the tasks for the future, it is preferable that some POCT systems be available as OTC for ordinary people to manage their own health. Also, I emphasize that it is important to review the usability of conventional urine dipsticks like a check for drug side effects, as well as for developing new urine analyses.     

Anionic polymerization of fluorine-containing vinyl monomers, 12. Anionic polymerization mechanism of hexafluoro-1,3-butadiene

Initiation and propagation reaction mechanisms of the anionic polymerization of hexafluoro-1,3-butadiene (HEBD) were investigated. The initiation reaction with caesium tert-butoxide was found to be completed within 5 min although the reactions were carried out at a much lower temperature than that of the polymerization reaction. The initiation reaction was, therefore, inferred to take place in an anionic fashion by adding the tert-butoxide anion to HFBD. In order to clarify the propagation reaction mechanism of HFBD which yielded a polymer with a polyvinylene structure, the polymerization reactivity of HFBD and hexafluoro-2-butyne (HFBY), the isomerization of HFBD to HFBY, and the structural difference between poly(HFBD) and poly(HFBY) were discussed. In spite of the low yield of HFBY by the isomerization reaction under polymerization conditions, higher yields of poly(HFBD) were obtained. Judging from the X-ray analysis which showed that poly(HFBD) was highly crystalline and poly(HFBY) was amorphous, poly(HFBD) might not be produced by polymerization of HFBY. An addition reaction of the propagating anion to the carbon-2 of the HFBD monomer followed by isomerization at the propagating living end to yield poly[1,2-bis(trifluoromethyl)vinylene] is proposed.