IL-12 p40 prevents the development of chronic enterocolitis in IL-10-deficient mice

T-helper-1 (Th1) cytokines play an important role in Crohn's disease, and interleukin-12 (IL-12), which is composed of two subunits, p40 and p35, drives Th1 differentiation. In previous reports, IL-12 p40 was shown to prevent IL-12 from binding to the receptor. We demonstrate here the effect of IL-12 p40 overexpression in intestinal epithelia on enterocolitis mediated by Th1 cells in IL-10-deficient (IL-10(-/-)) mice on a C57BL/6J background. IL-10 deficient (IL-10(-/-))/T3b-IL-12 p40+ (IL-12 p40+) mice and IL-10(-/-)/T3b-IL-12 p40- (IL-12 p40-) mice were generated by crossing T3b-IL-12 p40 transgenic mice and IL-10(-/-) mice. At 8 weeks of age, IL-12 p40+ mice did not show any clinical manifestations of colitis. The colon length of IL-12 p40- mice became shorter than that of IL-12 p40+ mice. The histological score of IL-12 p40+ mice was lower. Interferon-gamma (IFN-gamma) production was suppressed in both the mesenteric lymph node cell culture and colon tissue culture of IL-12 p40+ mice. There was no significant difference in IL-4 production and tumor necrosis factor-alpha (TNF-alpha) production between the two groups. These results show that overexpression of IL-12 p40 in intestinal epithelia prevents enterocolitis in IL-10(-/-) mice by suppressing IFN-gamma production, and suggest a potential clinical application of IL-12 p40 for Crohn's disease. Furthermore, these results also suggest that local gene transduction in the intestinal epithelium may be a potent therapeutic approach for Crohn's disease.     

Isolation of vaccine-derived type 1 polioviruses displaying similar properties to virulent wild strain Mahoney from sewage in Japan

Type 1, 2, and 3 vaccine-derived polioviruses were isolated from a sewage disposal plant located downstream of the Oyabe River in Toyama Prefecture, Japan, between October 1993 and September 1995. Neurovirulence was analyzed in 13 type 1 vaccine-derived strains, using mutant analysis by polymerase chain reaction and restriction enzyme cleavage (MAPREC). Nine strains (69%) were estimated to have marked neurovirulence. Some of the neutralizing antigenic sites, temperature sensitivity, and plaque-forming ability of two virulent vaccine-derived poliovirus strains were similar to Mahoney strain. The neutralizing activity of human sera obtained after oral poliomyelitis vaccine (OPV) administration against one of the virulent vaccine-derived polioviruses was examined. Although all human sera showed sufficient neutralizing activity for the prevention of poliomyelitis by vaccine-derived poliovirus strains, a lower titer than that against Sabin type 1 strain was observed. Vaccination against virulent vaccine-derived poliovirus will be effective. However, the environmental presence of viruses that have properties similar to those Mahoney strain is a threat. The introduction of inactivated poliovirus vaccine (IPV), and well-maintained herd immunity, together with reinforced environmental surveillance is important for the final phase of the polio eradication program by the World Health Organization (WHO).     

Pituitary Folliculo-Stellate-Like Cells Stimulate Somatotroic Pituitary Tumor Growth in Nude Mice

A new cell line (TtT/GF) established from a murine pituitary thyrotropic tumor having characteristics similar to those of pituitary folliculo-stellate cell (FS cell) was implanted into nude mice together with cells from a rat pituitary somatotrophic tumor cell line (MtT/S) to determine whether the former enhances pituitary tumor growth. For as long as 2-3 mo after implantation, MtT/S cells implanted either alone or together with fibroblasts formed either no tumors or only very small tumors in the nude mice. In contrast all of the nude mice that had received MtT/S cells implanted together with TtT/GF cells developed large tumors. Furthermore, the mice bearing the MtT/S and TtT/GF implants showed a significantly higher body weight and serum growth hormone level than those bearing only MtT/S cells or a combination of MtT/S cells and fibroblasts. The TtT/GF cell line itself had no tumorigenicity during the experimental period. Therefore, the TtT/GF cell line as a model of FS cells enhanced pituitary endocrine cell tumor formation. Additionally, immunocytochemistry showed that TtT/GF cells positive for glial fibrillary acidic protein (GFAP) or S-100 protein were present in the parenchymatous tissue elements or connective tissue surrounding the tumor nests. In the parenchymatous tissue, the TtT/GF cells exhibited a stellate appearance and surrounded neighboring tumor cells with their long cell processes. These results suggest that TtT/GF cells can serve as a model for pituitary FS cells, and are capable of stimulating pituitary tumor growth either by modifying the microenvironment or producing growth factors.     

Effects of Alkyl Alcohols and Related Chemicals on Rat Liver Structure and Function: III. Physicochemical Properties of Ethanol-, Propanol- and Butanol-treated Rat Liver Mitochondrial Membranes

The physicochemical properties of mitochondria in liver tissue obtained from rats given 32% ethanol, 32% propanol or 6.9% butanol in drinking water for up to 3 months were investigated using differential scanning calo-rimetry and fluorescence polarization measurements. The results obtained were as follows: 1) Phospholipids extracted from mitochondria showed increases in the relative amounts of phosphatidylcholine, phosphatidylinositol and phosphatidylserine, and a decrease in the relative amount of phosphatidylethanolamine. An increase in the unsatu-rated/saturated fatty acid ratio of phospholipids was also observed. 2) Elevation of the thermotropic lipid phase transition temperature with a decrease in the enthalpy value (δ H ) was revealed by differential scanning calo-rimetry. 3) The elevation of the lipid phase transition temperature was detected also by fluorescence polarization measurements using 1,6 diphenyl 1, 3, 5 hexatriene (DPH) as a probe. Elevation of mitochondrial membrane fluidity was found in some of the experimental animals, but most showed no changes in comparison with the control. A possible role of membrane fusion in the mechanism of formation of ethanol-, propanol- and butanol induced hepatic megamitochondria is discussed on the basis of these results. Acta Pathol Jpn 42: 549–557, 1992.     

Mapping nondominant voices into understanding stress-coping mechanisms

This study reports key findings from a research project, which examined the stress and coping mechanisms of several nondominant groups of individuals. The groups were based in Winnipeg, Manitoba, Canada and included (a) Aboriginal individuals with diabetes, (b) individuals with disabilities, and (c) gays and lesbians. Our analyses of personal narratives and life stories have led to develop an interpretive map of findings that depicts mechanisms of how stress and coping operate. Specifically, the interpretive map consists of personal and structural stressors, meanings of stress, and personal and structural resources, as well as of two constructs termed intersectionality and social exclusion. Not only are nondominant voices and lived experiences recognized and incorporated into an emergent interpretive map, but this map also articulates the complex ways in which multiple identities intersect (i.e., intersectionality) and the realities of being excluded socioeconomically, culturally, and politically among nondominant groups (i.e., social exclusion). © 2008 Wiley Periodicals, Inc.     

Avoidance learning under delayed shock termination in prenatally x-irradiated rats

Groups of MP1 male albino rats were exposed to x-irradiation of 200 rad on Day 17 of gestation. Irradiated and control rats were trained in a shuttlebox with either immediate or .5-sec delayed termination of both the electric shock (US) and the conditioned stimulus (CS) on escape trials. An avoidance response always produced prompt CS termination. Irradiated rats showed a higher degree of avoidance behavior than controls and, under the delay condition, tended to run rapidly in the CS-US interval.     

Lowered effectiveness of immunotherapy for cypress pollinosis by using Japanese cedar pollen extract]

BACKGROUND: Japanese cedar and cypress pollen share a common antigen. The cedar pollen season is followed by the cypress pollen season. However, both the clinical significance and involvement of cypress pollinosis in the treatment of the cedar pollinosis have not yet been clarified. METHODS: The clinical efficacy of sublingual immunotherapy with cedar pollen extract for cedar pollinosis was evaluated during the cypress pollen dispersal season in Japan. In addition, the change in cypress pollen specific IgE antibodies of the patients with cedar pollinosis was examined before and after the pollen season. RESULTS: Sublingual immunotherapy with cedar pollen extract did not improve the clinical symptoms of the cedar pollinosis patients combined with cypress pollinosis in the cypress pollen season. The cypress pollen specific IgE antibodies were found to demonstrate significant seasonal changes. CONCLUSION: The presence of cypress pollinosis should therefore be taken into consideration when planning the optimal treatment for cedar pollinosis. Sublingual immunotherapy with cedar pollen extract may not be effective for cypress pollinosis.     

Epitope-specific impairment of production of antibody against merozoite surface glycoprotein 1 of Plasmodium falciparum in symptomatic patients with malaria

We analyzed the relationships between levels of antibody specific for merozoite surface glycoprotein-1 (MSP1) of Plasmodium falciparum and clinical manifestations in humans. We prepared recombinant MSP1 proteins representing block 3 (M3), block 6 (M6), blocks 1–6 (M1/6), and block 17. When we divided the slide-positive individuals in Guadalcanal into symptomatic and asymptomatic groups, the former group showed lower IgG levels against M6 and block 17, but not against M3, than did the asymptomatic group (P < 0.01). The possibility of nonspecific suppression was unlikely, given that the levels of antibody against poliomyelitis virus observed in the two groups were almost the same. Among the IgG subclasses tested, production of cytophilic IgG₃ seemed to be dominant. When we analyzed epitopes recognized by antibodies against block 17, a peptide (SSSNFLGIS) was preferentially recognized by sera from asymptomatic individuals. These results suggest that clinical symptoms occurring during falciparum malaria seem to be associated with the development of levels of antibody against particular epitopes on MSP1, which is under the control of an immunoregulatory mechanism. Received: 1 October 1999 / Accepted: 21 October 1999     

Soluble Fas and soluble Fas L levels in patients with acute pancreatitis

The FasL-Fas system is an apoptosis induction system and plays an important role in homeostasis and biophylaxis. The present study was conducted to investigate soluble Fas (sFas), soluble Fas ligand (sFasL), and tumor necrosis factor alpha (TNF-alpha) in patients with acute pancreatitis. As acute pancreatitis became severe, the levels of sFas in the serum increased significantly, while those of sFasL decreased significantly. A significant inverse correlation was observed between the serum levels of sFas and those of sFasL. Also, a significant positive correlation was observed between the levels of TNF-alpha and sFas. A greater increase in serum sFas and decrease in serum sFasL levels was observed in patients with complicating multiple organ dysfunction syndrome (MODS) than in those without it. The results of the study suggest that the pathological aggravation of acute pancreatitis could be related to changes in the Fas-FasL system.