Different origin of leiomyoblastoma by immunohistochemical study.

Leiomyoblastoma has been regarded as a neoplasm of smooth muscle origin. With recent progress in immunohistostaining techniques, many clinicopathological discrepancies have been pointed out about the origin of leiomyoblastoma. It has been claimed that gastrointestinal non-epithelial tumors should be regarded as stromal tumors in order to study their origin. In the present study, we performed various forms of immunohistostaining in seven cases of leiomyoblastoma to determine their origin. One case expressed desmine and muscle specific actin and was considered to be derived from smooth muscle. Four neoplasms expressed X-100 protein (two cases were also NSE positive) and were thought to be derived from the nerve. Two cases were of unknown derivation. These results suggest that the cells of leiomyoblastoma may arise from a primitive to totipotential cell of neural lineages that may anomalously express smooth muscle filaments.     

Whole genome association study of rheumatoid arthritis using 27 039 microsatellites

A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.     

Effect of thromboxane A2 synthetase inhibitor on immediate-type hypersensitivity reactions

The effect of the thromboxane (TX) A2 synthetase inhibitor, OKY-046, on human leukocyte histamine release and bronchial hypersensitivity in asthmatic subjects was evaluated. It was found that OKY-046 inhibited IgE- and Ca2+ ionophore A23187-mediated leukocyte histamine release in a dose-dependent fashion (IC50: 1.0 and 3.0 X 10(-3) M, respectively) and that OKY-046 could diminish bronchial hypersensitivity, determined by leukotriene D4 inhalation, following a 2-week oral medication. These data suggest that the TXA2 synthetase inhibitor can produce favorable effects upon the course of immediate-type hypersensitivity reactions.     

Direct in vivo protein transduction into a specific restricted brain area in rats

Attempts at protein transduction into specific restricted brain areas have remained unsuccessful. We attempted targeted, direct in vivo protein transduction by microinjecting beta-galactosidase (beta-gal) with hemagglutinating virus of Japan envelope (HVJ-E) vector into the rat nucleus tractus solitarius (NTS). The medulla oblongata including the NTS was removed 6h post-injection and cryostat sections were histochemically stained to detect beta-gal enzymatic activity. beta-gal-positive cells were present in these sections as was beta-gal activity determined by colorimetric analysis. beta-gal-positive cells were not present in the rats microinjected only beta-gal protein without HVJ-E vector. Our findings suggest that direct in vivo protein transduction into specific restricted brain areas is possible. The type of targeted delivery system we present may have wide applications in the administration of therapeutic proteins to the central nervous system.     

Density heterogeneity of eosinophil leucocytes: induction of hypodense eosinophils by platelet-activating factor.

We have examined the induction of hypodense eosinophils by platelet-activating factor (PAF), a mediator which may be involved in eosinophil activation in allergic diseases. Guinea-pig eosinophils were incubated with buffer or PAF and applied to continuous Percoll density gradients. Cellular density ranged from 1.0142 to 1.1369 g/ml. Peak eosinophil density in control was 1.0887 +/- 0.0008 g/ml (mean +/- SEM), and 91.1 +/- 1.4% of eosinophils were distributed between 1.0810 and 1.1000 g/ml. Preincubation of eosinophils with PAF(10(-7) M) resulted in a time-dependent and non-cytolytic increase of the number of hypodense eosinophils, with peak densities after incubation for 1 hr and 2 hr of 1.0834 +/- 0.0014 (n = 4, P less than 0.05) and 1.0755 +/- 0.0007 g/ml (n = 6, P less than 0.01), respectively. After incubation for 2 hr, 82.0 +/- 4.9% (n = 6) eosinophils showed a density lower than 1.080 g/ml. Lyso-PAF, the inactive precursor and metabolite of PAF, at a concentration of 10(-7) M had no effect on cell density. The specific PAF receptor antagonist WEB 2086 (10(-6) M) inhibited the PAF-induced density shift by 87.0 +/- 5.3%. Our results demonstrate that a single mediator is able to induce the formation of hypodense eosinophils. We conclude that the appearance of hypodense eosinophils in allergic diseases such as asthma may occur, at least in part, in response to inflammatory mediators which activate these cells.     

Involvement of platelet activating factor (PAF) in ovalbumin antigen-induced late asthmatic response and increase of airway hyperresponsiveness in a guinea pig experimental model of asthma

Platelet activating factor, a potent chemical mediator, has been implicated in the pathogenesis of asthma in terms of inflammatory cell recruitment and activation. We have recently demonstrated that repeated antigen (ovalbumin; OA) exposure by inhalation to guinea pigs results in a development of late asthmatic response (LAR) in more than 50% of the animals and significant increase in airway hyperresponsiveness (AH). We have studied the effect of WEB 2086, a specific PAF receptor-antagonist, on this model. Respiratoly resistance (Res) of guinea pigs was measured by a oscillation technique and AH was evaluated by the provocative concentration of aerosols of histamine causing 200% increase of Rrs over the baseline Rrs (PC200 Hist). Four out of 5 actively sensitized and diphenhydramine-pretreated animals developed LAR 3 to 9 hr after allergen (20 mg/ml OA, 10 min inhalation)-induced immediate bronchoconstriction (LAR). Treatment with WEB 2086 (3 mg/kg intravenously) 30 min before and 3 hr after the exposure suppressed LAR clearly without affecting the IAR. Significant increase in AH from 2.80 +/- 0.03 to 2.51 +/- 0.01 and 2.60 +/- 0.08 (p less than 0.05, n = 8) of PC200 Hist (mg/ml, log) was observed 24 hr and 5 day after the OA exposure, respectively. The WEB 2086 treatment also prevented the increase of AH after the OA exposure (PC200 Hist; 2.82 +/- 0.09 before the challenge 2.80 +/- 0.07 and 2.75 +/- 0.09 24 hr and 5 days after, respectively. n = 8). Administration of WEB 2086 did not affect baseline Rrs and PC200 Hist in normal guinea pigs without any antigen challenge. We conclude that WEB 2086 is capable of preventing the development of LAR and increase in AH, and thus PAF may play an important causal role in LAR and increased AH observed in asthma.     

The effects of media violence on aggression: focus on the role of anger evoked by provocation

This study investigated the effects of anger evoked by earlier provocation on cognition, emotion, and aggressive behavior after being exposed to media violence. Sixty male undergraduates participated in the experiment. Before viewing one of three videos (either highly violent, violent with high entertainment, or nonviolent), half of the subjects were provoked by a confederate posing as another subject. Subjects' heart rates and eyeblink rates were recorded while viewing the video. After viewing the video, subjects described their thoughts that occurred while watching the video and rated their affective reactions toward the video. Finally, subjects' aggressive behavior toward the confederate was measured. Results of covariance structure analysis suggested that (a) anger evoked by provocation and high level of violence in videos additively elicited negative cognition and affect, which further facilitated aggressive behavior, and (b) high level of entertainment in videos elicited positive cognition and affect, which alleviated negative cognition and affect.