We conducted phylogenetic analyses and an estimation of coalescence times for East Asian strains of HTLV-1. Phylogenetic analyses showed that the following three lineages exist in Japan: “JPN”, primarily comprising Japanese isolates; “EAS”, comprising Japanese and two Chinese isolates, of which one originated from Chengdu and the other from Fujian; and “GLB1”, comprising isolates from various locations worldwide, including a few Japanese isolates. It was estimated that the JPN and EAS lineages originated as independent lineages approximately 3,900 and 6,000 years ago, respectively. Based on archaeological findings, the “Out of Sunda” hypothesis was recently proposed to clarify the source of the Jomon (early neolithic) cultures of Japan. According to this hypothesis, it is suggested that the arrival of neolithic people in Japan began approximately 10,000 years ago, with a second wave of immigrants arriving between 6,000 and 4,000 years ago, peaking at around 4,000 years ago. Estimated coalescence times of the EAS and JPN lineages place the origins of these lineages within this 6,000–4,000 year period, suggesting that HTLV-1 was introduced to Japan by neolithic immigrants, not Paleo-Mongoloids. Moreover, our data suggest that the other minor lineage, GLB1, may have been introduced to Japan by Africans accompanying European traders several centuries ago, during or after “The Age of Discovery.” Thus, the results of this study greatly increase our understanding of the origins and current distribution of HTLV-1 lineages in Japan and provide further insights into the ethno-epidemiology of HTLV-1.

Endemic areas of human T-lymphotropic virus type 1 (HTLV-1) have been reported in Japan as well as tropical Africa, Central and South America and Melanesia. The existence of two subgroups, i.e., the transcontinental and Japanese subgroups, was reported in Japan. In the present study, we provide data on the ratio of the two subgroups in each endemic area and infection foci and examine the distribution of HTLV-1 in Japan and neighboring areas. A 657 bp fragment of env region of HTLV-1 proviral genome was successfully amplified for 183 HTLV-1 positive DNA samples. The subgroup determination was done by RFLP reactions using endonucleases HpaI and HinfI. The northern part of mainland Kyushu, represented by Hirado and Kumamoto, was monopolized by the Japanese subgroup, while the transcontinental subgroup ranged from 20 to 35% in the Pacific coast areas of Shikoku (Kochi), the Ryukyu Archipelago (Kakeroma and Okinawa) and Taiwan. An interesting finding in the present study is the presence of the transcontinental subgroup in Kochi, suggesting the endemicity of the transcontinental subgroup along the Kuroshio Current.

Background/Aims: Intestinal fibrosis is a major complication of Crohn’s disease (CD). The profibrotic protein transforming growth factor-β (TGF-β) has been considered to be critical for the induction of the fibrotic program. TGF-β has the ability to induce not only the expression of extracellular matrix (ECM) including collagen, but also the production of plasminogen activator inhibitor-1 (PAI-1) that prevents enzymatic degradation of the ECM during the onset of fibrotic diseases. However, the significance of PAI-1 in the developing intestinal fibrosis has not been fully understood. In the present study, we examined the actual expression of PAI-1 in fibrotic legion of intestinal inflammation and its correlation with the abnormal ECM deposition. Methods: Chronic intestinal inflammation was induced in BALB/c mice using 8 repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). TM5275, a PAI-1 inhibitor, was orally administered as a carboxymethyl cellulose suspension each day for 2 weeks after the sixth TNBS injection. Results: Using a publicly available dataset (accession number, GSE75214) and TNBS-treated mice, we observed increases in PAI-1 transcripts at active fibrotic lesions in both patients with CD and mice with chronic intestinal inflammation. Oral administration of TM5275 immediately after the onset of intestinal fibrosis upregulated MMP-9 (matrix metalloproteinase 9) and decreased collagen accumulation, resulting in attenuation of the fibrogenesis in TNBS-treated mice. Conclusions PAI-1-mediated fibrinolytic system facilitates collagen degradation suppression. Hence, PAI-1 inhibitor could be applied as an anti-fibrotic drug in CD treatment.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease causing dyspnea on exertion, exercise intolerance, decline in quality of life, and physical inactivity. The patient is a 78-year-old male. He complained of quadriplegia and was diagnosed with a C7/Th1 cervical epidural abscess. After treatment with antibiotics, he was transferred to our hospital. He had tetraplegia, which corresponded to the ASIA impairment scale D, and his Functional Independence Measure (FIM) motor score was 35 points. In addition, he had severe COPD; the Medical Research Council (MRC) dyspnea scale was grade 5, and the COPD assessment test (CAT) score was 26 points. He complained of dyspnea on exertion with low intensity movements. Despite rehabilitation, improvement in ADL and physical function was poor, his FIM motor score was 43 points and the Berg balance scale (BBS) score was 21 points at the 30th day. Therefore, we started assist use of a short-acting β2 agonist (SABA) before rehabilitation on the 33rd day, and his dyspnea on exertion, physical activity, and respiratory dysfunction improved. On the 83rd day, the improvement was as follows: the MRC dyspnea scale was grade 4, the CAT score was 18 points, his 6-minute walk distance was 110 m, and his BBS score was 40 points. He was weaned from continuous oxygen therapy and discharged on day 112, at which time his FIM motor score was 69 points. We considered that the assist use of SABA before rehabilitation improved his respiratory status and physical activity without worsening his respiratory function or limb muscle weakness due to dyspnea and quadriplegia.