Association of Gln222Arg polymorphism in the deoxyribonuclease I (DNase I) gene with myocardial infarction in Japanese patients.

AIMS: We have recently reported that serum deoxyribonuclease I (DNase I) activity, which may be involved in apoptosis, increases abruptly in the early phase of acute myocardial infarction (MI) [Kawai Y, Yoshida M, Arakawa K, Kumamoto T, Morikawa N, Masamura K, Tada H, Ito S, Hoshizaki H, Oshima S, Taniguchi K, Terasawa H, Miyamori I, Kishi K, Yasuda T. Diagnostic use of serum deoxyribonuclease I activity as a novel early-phase marker in acute myocardial infarction. Circulation 2004;109:2398-2400]. Death of vascular smooth muscle cells, in part because of apoptosis, is postulated to heighten susceptibility to disruption of vulnerable plaque, resulting in onset of MI. The present study evaluated the possibility that Gln222Arg polymorphism of the DNase I gene may be one of the factors involved in predisposition to MI. METHODS AND RESULTS: We assessed 611 Japanese patients: 311 with MI and 300 with stable angina pectoris (AP). Three common phenotypes determined by two common codominant alleles, DNASE1*1 and *2, whose corresponding gene products exhibit different properties, were found in these patient groups. The prevalence of DNASE1*2 was significantly higher in patients with MI than in those with AP (0.543 vs. 0.428, P < 0.001), being confirmed by phenotyping of the second study population. Multiple logistic regression analysis showed that the odds ratio of DNASE1*2 was 1.51 [95% confidence interval (CI) 1.04-2.18]. The association of the DNASE1*2 allele with MI was statistically significant, being independent of other conventional risk factors. CONCLUSION: Our data demonstrate that Gln222Arg polymorphism in the DNase I gene is associated with MI in the Japanese patients.     

Correlations between health status and OralChroma™-determined volatile sulfide levels in mouth air of the elderly

Dimethyl sulfide (DMS), a volatile sulfur compound (VSC) found in mouth air, is thought to be associated with systemic diseases; this in contrast to the two other VSCs found in mouth air: hydrogen sulfide and methyl mercaptan (MM). This study aimed to validate the relationship between DMS in mouth air and oral and systemic factors. The subjects were 393 elderly Japanese volunteers participating in an oral and systemic health survey. They were surveyed for the concentration of VSC components in their mouth air and for their oral and systemic health status. Using logistic regression models, the prevalence of DMS in mouth air above the organoleptic threshold level (OTL) was found to be significantly associated with high-density lipoprotein (HDL) cholesterol level, medical history of colon polyps and asthma, being female, and the presence of MM in mouth air above the OTL. Our data suggest that systemic factors, such as a high serum HDL cholesterol level and a medical history of asthma and colon polyps, might be more prominent in subjects with elevated DMS. The differences, although statistically significant, are quite small. They also indicate that an oral factor, such as a high MM mouth-air level also influences the DMS mouth-air level in addition to systemic factors.     

Results from pelvic exenteration for locally advanced colorectal cancer with lymph node metastases

PURPOSE: We examined the survival benefit of pelvic exenteration for locally advanced colorectal cancer with lymph node metastases, because this issue remains controversial. METHODS: Medical records of 50 patients who underwent curative pelvic exenteration for colorectal cancer were reviewed retrospectively. Nodal metastases were examined by the clearing method in 29 patients and by the conventional manual method in 21 patients. RESULTS: Invasion to contiguous pelvic organs was present in 40 patients (80 percent) and absent in 10 patients (20 percent). Node metastases were present in 33 patients (66 percent). Operative morbidity and mortality rates were 22 percent (11 patients) and 6 percent (3 patients), respectively. Respective five-year survival rates were 60 and 80 percent in the groups with and without organ invasion (no significant difference). Five-year survival rates in patients with nodal metastases was 54.6 percent but was significantly higher, 82.4 percent, in patients without nodal metastases. Five-year survival in 28 patients with both organ invasion and nodal metastases was 53.6 percent. CONCLUSIONS: Long-term survival was afforded by pelvic exenteration for locally advanced colorectal cancer with nodal metastases.     

A comparative study of once-a-day morning and once-a-day bedtime administration of 40 mg famotidine in treating duodenal ulcers

A randomized controlled study comparing once-a-day morning and once-a-day bedtime administration of 40 mg famotidine in treating duodenal ulcers was carried out in 99 Japanese patients. Endoscopic examinations were performed at the baseline and repeated at 3-week intervals until healing was confirmed. Eighty-two patients fulfilled the evaluation criteria (38 in the morning group and 44 in the bedtime group). In 13 of these patients the antisecretory effects of these regimens were also assessed by 24 h intragastric pH monitoring. The healing rates were 66% after 3 weeks and 95% after 6 weeks in the morning group, and 57% after 3 weeks and 80% after 6 weeks in the bedtime group. The differences were insignificant between the two groups, but there was a higher healing rate tendency after 6 weeks in the morning group (0.05<P<0.10). Regarding pain subsidence, there were no significant differences between the two groups. Both treatments were significantly superior to the controlgroup in increasing 24 h intragastric pH. The morning regimen was significantly superior to the bedtime regimen in suppression of daytime acidity. On the contrary, the bedtime regimen was significantly superior to the morning regimen in suppression of nocturnal acidity. These findings suggest that suppression of nocturnal acidity is important but not essential to promote duodenal ulcer healing and suppression of daytime acidity is equally important. Thus, once-a-day morning administration of 40 mg famotidine seems to be at least as effective as once-a-day bedtime administration of 40 mg famotidine in treating duodenal ulcers.     

Development of fluorescence-linked immunosorbent assay for high throughput screening of interferon-gamma.

BACKGROUND: Human interferon-gamma (hIFN-gamma) is produced by lymphocytes and has a variety of biological properties. Measurement of hIFN-gamma is widely used for various immunological responses for allergic or autoimmune diseases. Enzyme-linked immunosorbent assay (ELISA) is an established immunoassay used to quantify cellular metabolites or cytokines. ELISA requires many incubation and wash steps and is not practically suitable for screening large numbers of samples. METHODS: We have developed a fluorescence-linked immunosorbent assay (FLISA) method for the detection of hIFN-gamma. We measured the 50% inhibitory concentration (IC50) value of the hIFN-gamma production by interleukin (IL)-18 binding protein and anti-IL-18 monoclonal antibody. The IC50 described by FLISA was compared with that by ELISA. RESULTS: We developed a new system for measuring hIFN-gamma using Allophycocyanine (APC) fluorescent protein and compared it with the previous method using Cy5.5. The proposed FLISA had a smaller coefficient of variation than ELISA, and the means of coefficient of variation using the same samples measured by ELISA and FLISA were, respectively, 11.1% and 3.8%, suggesting that the edge effect often giving non-specific results may be smaller in FLISA than in ELISA. CONCLUSIONS: The improved FLISA system proposed is ideally suited for efficient measurements of hIFN-gamma. This homogeneous and multiplex method will be a powerful tool for high throughput screening for drug discovery research.