Self-Organized Criticality Theory of Autoimmunity

博士（保健学）神戸大

CLINICAL PREDICTORS FOR ATHEROMA PROGRESSION DESPITE OPTIMAL GLYCEMIC CONTROL IN EARLY-STAGE DIABETIC PATIENTS: SUB-ANALYSIS FROM DIANA STUDY

Data de realització de les fotografies del Mercat aproximada (1994

Memory-related gene expression profile of the male rat hippocampus induced by teeth extraction and occlusal support recovery

Objectives: The present study aimed to identify the effect of memory-related genes on male rats tested for spatial memory with either molar teeth extraction or its restoration by occlusal support using experimental dentures. Design: Memory-related genes were detected from hippocampi of male Wistar rats (exposed to teeth extraction with or without dentures, or no extraction (control)) (7-week old) after behavioural testing (via the radial maze task) using a DNA microarray. The time course of the expression of these genes was evaluated by quantitative real-time polymerase chain reaction (PCR) (on 49-week-old rats). Results: In preliminary experiments, to determine which memory genes are affected by spatial memory training, DNA microarray analysis revealed that thyrotropin-releasing hormone (Trh) and tenascin XA (Tnxa) were up-regulated and neuronatin (Nnat) and S100a9 were down-regulated after the maze training. The expression of Tnxa, Nnat and S100a9 of 49-week-old rats (during the time course) via quantitative real-time PCR was consistent with the results of microarrays of the preliminary experiment. Expression of Trh that was evaluated by quantitative real-time PCR did not agree with the results for this gene from the microarray for all groups. Therefore, expression of Trh may have increased in only young, trained rats. The expression of S100a9 prior to the maze task was down-regulated in only the extraction group. Conclusion: These results demonstrated that Trh, Tnxa and Nnat genes were affected according to the degree of memory in male rats. This study also indicated that S100a9 is a memory-related gene, which is affected by the presence of occlusal support

〈Originals〉Relationship between clinical manifestations and CMR findings in cardiac sarcoidosis

[Abstract] Background : Different cardiac manifestations/events have been reported in patients with sarcoidosis ; however, factors related to the onsetof manifestations in cardiac sarcoidosis (CS) remain unclear. Late gadolinium-enhancement cardiac magnetic resonance (LGE-CMR) has been used to detect myocardial damage/fibrosis. Therefore, we examined the characteristics of clinical manifestations in CS patients using LGE-CMR. Methods : Thirty-three consecutive CS patients underwent CMR. According to the mural location of LGE ; mid-wall, epicardial, or transmural, the LGE pattern was classified into three groups : A : LGE existing at one location only, B: LGE at any two locations, C : LGE at all locations. CMR findings were also analyzed in relation to each clinical manifestation. Results : Myocardial damage was detected by LGE imaging in 91% of the patients and was most frequently observed in the basal septal myocardium. %LGE area was negatively correlated with LV ejection fraction (EF) (P <0.01). Significantly decreased LV EF and increased %LGE area were observed in Group B and C. In addition, all patients in group C exhibited a clinical manifestation. The patients with high-grade atrioventricular block showed the increased %LGE area (P < 0.01). Although occurrence of ventricular tachycardia was not associated with any changes in LV EF, mass, and %LGE area, hospitalization for heart failure was associated with reduced LV EF, and increased mass and %LGE area (P<0.05 for all).Conclusions : Different clinical manifestations in CS have been associated with the development of myocardial fibrosis/damage and resultant myocardial dysfunction shown by CMR. CMR may be useful for characterizing the pathophysiology of respective clinical manifestations/events

Broccoli consumption and chronic atrophic gastritis among Japanese males: an epidemiological investigation.

Previous in vitro and animal experiments have shown that sulforaphane, which is abundant in broccoli, inhibits Helicobacter pylori (H. pylori) infection and blocks gastric tumor formation. This suggests that broccoli consumption prevents chronic atrophic gastritis (CAG) introduced by H. pylori infection and, therefore, gastric cancer. For an epidemiological investigation of the relationship between the broccoli consumption and CAG, a cross-sectional study of 438 male employees, aged 39 to 60 years, of a Japanese steel company was conducted. CAG was serologically determined with serum cut-off values set at pepsinogen I &#60; or = 70 ng/ml and a ratio of serum pepsinogen I/pepsinogen II &#60; or = 3.0. Broccoli consumption (weekly frequency) and diet were monitored by using a 31-item food frequency questionnaire. The prevalence of CAG among men who ate broccoli once or more weekly was twice as high as that among men who consumed a negligible amount (P &#60; 0.05). Multiple logistic regression analysis indicated that broccoli consumption once or more weekly significantly increased the risk for CAG (odds ratio, 3.06; 95% confidence interval, 1.12-8.38; P &#60; 0.05), after controlling for age, education, cigarette smoking, and alcohol consumption. The present study failed to show an expected association between frequent broccoli consumption and a low prevalence of CAG.</p

Risk of bleeding and repeated bleeding events in prasugrel-treated patients: a review of data from the Japanese PRASFIT studies

Prasugrel is a third-generation thienopyridine that achieves potent platelet inhibition with less pharmacological variability than other thienopyridines. However, clinical experience suggests that prasugrel may be associated with a higher risk of de novo and recurrent bleeding events compared with clopidogrel in Japanese patients undergoing percutaneous coronary intervention (PCI). In this review, we evaluate the risk of bleeding in Japanese patients treated with prasugrel at the doses (loading/maintenance doses: 20/3.75 mg) adjusted for Japanese patients, evaluate the risk factors for bleeding in Japanese patients, and examine whether patients with a bleeding event are at increased risk of recurrent bleeding. This review covers published data and new analyses of the PRASFIT (PRASugrel compared with clopidogrel For Japanese patIenTs) trials of patients undergoing PCI for acute coronary syndrome or elective reasons. The bleeding risk with prasugrel was similar to that observed with the standard dose of clopidogrel (300/75 mg), including when bleeding events were re-classified using the Bleeding Academic Research Consortium criteria. The pharmacodynamics of prasugrel was not associated with the risk of bleeding events. The main risk factors for bleeding events were female sex, low body weight, advanced age, and presence of diabetes mellitus. Use of a radial puncture site was associated with a lower risk of bleeding during PCI than a femoral puncture site. Finally, the frequency and severity of recurrent bleeding events during continued treatment were similar between prasugrel and clopidogrel. In summary, this review provides important insights into the risk and types of bleeding events in prasugrel-treated patients. Trial registration numbers: JapicCTI-101339 and JapicCTI-111550

Isolation and immortalization of macrophages derived from fetal porcine small intestine and their susceptibility to porcine viral pathogen infections

Macrophages are a heterogeneous population of cells that are present in all vertebrate tissues. They play a key role in the innate immune system, and thus, in vitro cultures of macrophages provide a valuable model for exploring their tissue-specific functions and interactions with pathogens. Porcine macrophage cultures are often used for the identification and characterization of porcine viral pathogens. Recently, we have developed a simple and efficient method for isolating primary macrophages from the kidneys and livers of swine. Here, we applied this protocol to fetal porcine intestinal tissues and demonstrated that porcine intestinal macrophages (PIM) can be isolated from mixed primary cultures of porcine small intestine-derived cells. Since the proliferative capacity of primary PIM is limited, we attempted to immortalize them by transferring the SV40 large T antigen and porcine telomerase reverse transcriptase genes using lentiviral vectors. Consequently, immortalized PIM (IPIM) were successfully generated and confirmed to retain various features of primary PIM. We further revealed that IPIM are susceptible to infection by the African swine fever virus and the porcine reproductive and respiratory syndrome virus and support their replication. These findings suggest that the IPIM cell line is a useful tool for developing in vitro models that mimic the intestinal mucosal microenvironments of swine, and for studying the interactions between porcine pathogens and host immune cells