Transmission of Specific Genotype Streptomycin Resistant Strains of Mycobacterium tuberculosis in the Tokyo Metropolitan Area in Japan

<p>Abstract</p> <p>Background</p> <p>From 2003 through to 2004, an outbreak of tuberculosis was identified at a university campus in Yokohama City, located in the southern part of the Tokyo Metropolitan Area (TMA). All <it>Mycobacterium tuberculosis </it>(<it>M. tuberculosis</it>) strains detected with regards to this outbreak turned out to be Streptomycin resistant with matched patterns of 14 IS<it>6110 </it>bands of Restriction Fragment Length Polymorphism (RFLP). The <it>M. tuberculosis </it>bacilli, which had the matched IS<it>6110 </it>band patterns with resistance to Streptomycin to those of bacilli isolated in the outbreak, were also concurrently detected through either the population-based or the hospital-based DNA fingerprinting surveillance of <it>M. tuberculosis </it>either in Shinjuku City or in Kawasaki City respectively.</p> <p>The aim of the present study is to describe the spread of the specific genotype strains of <it>M. tuberculosis </it>in the TMA as observed in the above incident, and to identify the possible transmission routes of the strains among people living in urban settings in Japan.</p> <p>Methods</p> <p>We applied Variable Numbers of Tandem Repeats (VNTR) analysis to all <it>M. tuberculosis </it>isolates which were resistant to Streptomycin with a matched IS<it>6110</it>-RFLP band pattern (M-strains). They were isolated either from cases related to the tuberculosis outbreak that happened at a university, or through DNA fingerprinting surveillance of <it>M. tuberculosis </it>both in Shinjuku City and in Kawasaki City. For VNTR analysis, 12MIRU loci, 4ETR loci, seven loci by Supply, four loci by Murase (QUB15, Mtub24, VNTR2372, VNTR3336) were selected.</p> <p>Results</p> <p>Out of a total of 664 isolates collected during the study period, 46 isolates (6.9%) were identified as M-strains. There was a tendency that there was a higher proportion of those patients whose isolates belonged to M4-substrains, with four copies of tandem repeat at the ETR-C locus, to have visited some of the internet-cafés in the TMA than those whose isolates belonged to M5-substrains, with five copies at the ETR-C locus, although statistically not significant (38.1% vs. 10.0%, Exact p = 0.150).</p> <p>Conclusion</p> <p>Although firm conclusions could not be reached through the present study, it suggested that we have to take into consideration that tuberculosis can be transmitted in congregated facilities like internet cafés where tuberculosis high-risk people and general people share common spaces.</p

(−)-Epigallocatechin Gallate Induces Fas/CD95-Mediated Apoptosis through Inhibiting Constitutive and IL-6-Induced JAK/STAT3 Signaling in Head and Neck Squamous Cell Carcinoma Cells

In this study, we examined the effects of several plant-derived natural compounds on head and neck squamous cell carcinoma (HNSCC) cells. The results revealed that (−)-epigallocatechin gallate (EGCG) demonstrated the most efficient cytotoxic effects on HNSCC cells. We then investigated the underlying molecular mechanism for the potent proapoptotic effect of EGCG on HNSCC. Cell apoptosis was observed in the EGCG-treated SAS and Cal-27 cells in a time- and dose-dependent manner. In concert with the caspase-8 activation by EGCG, an enhanced expression in functional Fas/CD95 was identified. Consistent with the increased Fas/CD95 expression, a drastic decrease in the Tyr705 phosphorylation of STAT3, a known negative regulator of Fas/CD95 transcription, was shown within 15 min in the EGCG-treated cells, leading to downregulation of the target gene products of STAT3, such as bcl-2, vascular endothelial growth factor (VEGF), mcl-1, and cyclin D1. An overexpression in STAT3 led to resistance to EGCG, suggesting that STAT3 was a critical target of EGCG. Besides inhibiting constitutive expression, EGCG also abrogated the interleukin-6 (IL-6)-induced JAK/STAT3 signaling and further inhibited IL-6-induced proliferation on HNSCC cells. In comparison with apigenin, curcumin, and AG490, EGCG was a more effective inhibitor of IL-6-induced proliferation on HNSCC cells. Overall, our results strongly suggest that EGCG induces Fas/CD95-mediated apoptosis through inhibiting constitutive and IL-6-induced JAK/STAT3 signaling. This mechanism may be partially responsible for EGCG’s ability to suppress proliferation of HNSCC cells. These findings provide that EGCG may be useful in the chemoprevention and/or treatment of HNSCC