Analysis of 605 tuberculosis outbreaks in Japan, 1993-2015: time, place and transmission site.

Since 1993, reports on tuberculosis (TB) outbreaks have been collected in Japan; however, there has never been an overall analysis of these TB outbreaks. We aim to provide one here. The TB outbreak data were obtained from the Ministry of Health, Labour and Welfare and are described in terms of time, place and transmission site. The average number of TB cases and latent tuberculosis infection (LTBI) were compared by the transmission site. Some 605 TB outbreaks with 3491 TB cases were reported in 1993-2015 with an increasing trend (r = 0.45), during which time 728 777 TB cases were reported nationwide. On an average, TB outbreaks occurred more often in April to May (5.5 outbreaks per 2 months) than in December to January (3.4). The most common transmission sites were workplaces (n = 255), followed by health facilities (n = 144), schools (n = 60) and welfare facilities (n = 48). Psychiatric hospitals and nursing homes had the highest average number of TB cases per outbreak (8.5 each), whereas schools and prisons had the highest numbers of LTBI cases (29.1 and 38.9, respectively). Countries, particularly those that have resources to investigate TB outbreaks, should collect and analyse findings of TB outbreaks, as it informs surveillance systems and eventually strengthens general health systems.

Long-term follow-up of the randomized trial of mesorectal excision with or without lateral lymph node dissection in rectal cancer (JCOG0212).

BACKGROUND: Japan Clinical Oncology Group (JCOG) 0212 (ClinicalTrials.gov NCT00190541) was a non-inferiority phase III trial of patients with clinical stage II-III rectal cancer without lateral pelvic lymph node enlargement. The trial compared mesorectal excision (ME) with ME and lateral lymph node dissection (LLND), with a primary endpoint of recurrence-free survival (RFS). The planned primary analysis at 5 years failed to confirm the non-inferiority of ME alone compared with ME and LLND. The present study aimed to compare ME alone and ME with LLND using long-term follow-up data from JCOG0212. METHODS: Patients with clinical stage II-III rectal cancer below the peritoneal reflection and no lateral pelvic lymph node enlargement were included in this study. After surgeons confirmed R0 resection by ME, patients were randomized to receive ME alone or ME with LLND. The primary endpoint was RFS. RESULTS: A total of 701 patients from 33 institutions were assigned to ME with LLND (351) or ME alone (350) between June 2003 and August 2010. The 7-year RFS rate was 71.1 per cent for ME with LLND and 70·7 per cent for ME alone (hazard ratio (HR) 1·09, 95 per cent c.i. 0·84 to 1·42; non-inferiority P = 0·064). Subgroup analysis showed improved RFS among patients with clinical stage III disease who underwent ME with LLND compared with ME alone (HR 1·49, 1·02 to 2·17). CONCLUSION: Long-term follow-up data did not support the non-inferiority of ME alone compared with ME and LLND. ME with LLND is recommended for patients with clinical stage III disease, whereas LLND could be omitted in those with clinical stage II tumours.

ANTECEDENTES: El JCOG0212 (ClinicalTrials.gov: NCT00190541) fue un ensayo fase III de no inferioridad en pacientes con cáncer de recto en estadio clínico II/III sin ganglios linfáticos aumentados de tamaño en la pared pélvica lateral. El ensayo comparó la escisión del mesorrecto (mesorectal excision, ME) con la ME con disección de los ganglios linfáticos laterales (lateral lymph node dissection, LLND), siendo el criterio de valoración principal la supervivencia libre de recidiva (recurrence free survival, RFS). El análisis primario planificado a los 5 años de seguimiento no pudo confirmar la no inferioridad de la ME frente a la ME con LLND. Este estudio tuvo como objetivo comparar la ME como procedimiento único y la ME con LLND utilizando datos de seguimiento a largo plazo del ensayo JCOG0212. MÉTODOS: En este estudio se incluyeron pacientes con cáncer de recto en estadio clínico II/III por debajo de la reflexión peritoneal sin ganglios linfáticos aumentados de tamaño en la pared pélvica lateral. Después de que los cirujanos confirmaran la resección R0 mediante la ME, los pacientes fueron asignados al azar al brazo de ME sola o al brazo de ME con LLND. El criterio de valoración principal fue la supervivencia libre de recidiva (RFS). RESULTADOS: Un total de 701 pacientes de 33 instituciones fueron asignados al azar para ser tratados mediante una ME con LLND (n = 351) o EM sola (n = 350) entre junio de 2003 y agosto de 2010. Las tasas de RFS a 7 años fueron del 71,1% para ME con LLND y 70,7 % para ME sola (cociente de riesgos instantáneos, hazard ratio, HR: 1,09 (i.c. del 95% 0,84-1,42), no inferioridad P = 0,064)). El análisis de subgrupos mostró una mejor RFS entre los pacientes en estadio clínico III que se sometieron a ME con LLND en comparación con ME sola (HR: 1,49 (i.c. del 95%: 1,02-2,17)). CONCLUSIÓN: Los datos de seguimiento a largo plazo no justificaron la no inferioridad de la ME en comparación con la ME con LLND. Se recomienda la ME con LLND para pacientes en estadio clínico III, mientras que LLND podría omitirse para pacientes en estadio clínico II.

A tuberculosis outbreak in a psychiatric hospital: Kanagawa, Japan, 2012.

In January 2012, an inpatient in a ward of a psychiatric hospital with nearly 300 beds in Kanagawa, Japan, was diagnosed with sputum smear-positive pulmonary tuberculosis (TB). Here we characterise the TB outbreak cases and identify the population at risk. TB was diagnosed when a person tested bacteriologically positive for TB or was determined to have TB by a physician. A latent TB infection (LTBI) case was defined as a person tested positive by interferon-gamma release assay (IGRA). A total of 125 contacts were screened via IGRA and chest X-ray. In all, 15 TB and 15 LTBI cases were found by the end of October 2012, and thereafter no additional TB case was found. Of the 15 TB cases, eight were culture-positive and all the isolates had identical variable number tandem repeat patterns. Twenty-four of the 56 (42.9%, 95% confidence interval (CI) 29.7-56.8) inpatients in the ward had either TB or LTBI with a relative risk of 8.6 (95% CI 1.2-59.3), compared to the staff members who did not work full-time in the ward (one of 20 (5.0%, 95% CI 0.0-24.9)). We recommend that psychiatric hospitals conduct periodic screening of staff members and inpatients for TB to prevent nosocomial TB outbreaks.

Preparation and evaluation of orally disintegrating tablets containing taste masked microparticles of acetaminophen.

In the present work, taste masked particles of acetaminophen (AAP), a highly soluble bitter tasting drug, were developed and ODT containing the taste masked particles were prepared. Taste masked particles of AAP were prepared using different amounts of tetraglycerol polyricinoleate (TGPR) and Eudragit ®E100. Although the drug content ratio and drug recovery decreased with increasing TGPR, drug release from AAP-CR100 particles containing a large amount of TGPR was mostly suppressed for 2 min. Hence, AAP-CR100 was incorporated into ODT as taste masked particles for AAP. Three major disintegrants were used for ODT, and it was confirmed that the tensile strength of all formulations showed applicable hardness for handling. The AAP-CR100-CP(40) formulation containing crospovidone showed the shortest disintegration time and the drug release from AAP-CR100-CP(40) into pH 6.8 test solution was suppressed compared with commercial AAP tablets. Because the drug release from AAP-CR100-CP(40) into the pH 1.2 test solution was rapid, it was suggested that drug release from AAP-CR100-CP(40) is suppressed in the oral cavity, and the drug is released promptly in the stomach. Thus AAP-CR100-CP(40) may be useful as an ODT in which the dissolution of AAP in the oral cavity is suppressed.

A tuberculosis outbreak at an insecure, temporary housing facility, manga café, Tokyo, Japan, 2016-2017.

In November 2016, a woman in her 30s who stayed at an insecure, temporary housing facility, a manga café in Tokyo, Japan, for a year was diagnosed with sputum smear-positive tuberculosis (TB). Since the café had 31 staff members and provided with accommodation to many people, the local health office initiated a contact investigation. This study aims to characterise the cases found in the outbreak. A TB case was defined as a person tested bacteriologically positive for TB, or was determined to have TB by a physician. A latent TB infection case was defined as a person tested positive by interferon-γ release assay. From January 2016 through November 2017, there were 31 staff members at the manga café, of which, six developed TB disease (one smear-negative, culture-positive and five smear- and culture-negative) in addition to seven LTBI. Another long-term customer was found having sputum smear-positive TB. Variable numbers tandem repeat (VNTR) test revealed that the index patient and the long-term customer had the identical type of VNTR; however, one staff member had a different VNTR. Local health authorities should intensify screening long-term customers of such facilities for TB regularly as well as once a TB outbreak occurs.

Difficulty of confining recalcitrant tuberculosis patients in isolation wards in Japan, 2013-2014.

OBJECTIVES: In Japan, approximately 7000 smear-positive tuberculosis (TB) cases were reported in 2014. According to the law, such patients must be isolated in a TB ward until they become at least sputum smear-negative. However, there are some recalcitrant patients who are difficult to isolate because of problematic behaviors. This study was conducted to characterize recalcitrant TB patients and determine why they left the hospitals and how they were followed up after they left. STUDY DESIGN: Cross-sectional study. METHODS: We sent a self-administered questionnaire to the hospitals in Japan with over 11 TB isolation beds, asking about recalcitrant TB inpatients from April 2013 through March 2014, in terms of demographic information, the reasons why they left, and how they were followed up. RESULTS: A total of 38 recalcitrant patients were reported, of whom 15 (39.5%) self-discharged, eight (21.0%) were discharged, and 15 (39.5%) were transferred. Thirty-three (86.8%) were males. The main reason (52.6%) why the patients were considered recalcitrant was related to psychiatric problems. However, nine (23.6%) patients physically assaulted or insulted the staff members. Thirty-six (94.7%) were able to continue anti-TB treatment after they left the original hospital. CONCLUSION: Although the number of recalcitrant TB patients who were abusive was small, there should be TB facilities with law enforcement officials readily available to enforce isolation.

Efficacy and safety of osteoporosis medications in a rat model of late-stage chronic kidney disease accompanied by secondary hyperparathyroidism and hyperphosphatemia.

This study showed that bisphosphonate was safe and effective for the treatment of bone disorders in stage 4 chronic kidney disease (CKD) rats. Intermittent teriparatide therapy showed an anabolic action on bone even under secondary hyperparathyroidism conditions without having an adverse effect on mineral metabolism in late-stage CKD. INTRODUCTION: Patients with late-stage CKD are at high risk for fragility fractures. However, there are no consensus on the efficacy and safety of osteoporosis medications for patients with late-stage CKD. In the present study, we aimed to examine the efficacy and safety of alendronate (ALN) and teriparatide (TPD) for treating bone disorder in late-stage CKD with pre-existing secondary hyperparathyroidism using a rat model of CKD. METHODS: Male 10-week-old Sprague-Dawley rats were subjected to a 5/6 nephrectomy or sham surgery and randomized into the following four groups: sham, vehicle (saline subcutaneous (sc) daily), ALN (50 µg/kg sc daily), and TPD (40 µg/kg sc daily). Medications commenced at 24 weeks of age and continued for 4 weeks. Micro-computed tomography, histological analysis, infrared spectroscopic imaging, and serum assays were performed. RESULTS: Nephrectomized rats developed hyperphosphatemia, secondary hyperparathyroidism (SHPT), and high creatinine, equivalent to CKD stage 4 in humans. ALN suppressed the bone turnover and increased the degree of mineralization in cortical bone, resulting in an improvement in the mechanical properties. TPD further increased the bone turnover and significantly increased the degree of mineralization, micro-geometry, and bone volume, resulting in a significant improvement in the mechanical properties. Both ALN and TPD had no adverse effect on renal function and mineral metabolism. CONCLUSIONS: BP is safe and effective for the treatment of bone disorders in stage 4 CKD rats. Intermittent TPD therapy showed an anabolic action on bone even under SHPT conditions without having an adverse effect on mineral metabolism in late-stage CKD.

Autoimmune arthritis deteriorates bone quantity and quality of periarticular bone in a mouse model of rheumatoid arthritis.

This study showed that autoimmune arthritis induces especially severe osteoporosis in the periarticular region adjacent to inflamed joints, suggesting that arthritis increases the fragility fracture risk near inflamed joints, which is frequently observed in patients with RA. INTRODUCTION: Periarticular osteoporosis near inflamed joints is a hallmark of early rheumatoid arthritis (RA). Here we show that rheumatic inflammation deteriorates the bone quality and bone quantity of periarticular bone, thereby decreasing bone strength and toughness in a mouse model of RA. METHODS: Female BALB/c mice and SKG mice, a mutant mouse model of autoimmune arthritis on the BALB/c background, were used. At 12 weeks of age, BALB/c mice underwent either Sham surgery or bilateral ovariectomy (OVX), and SKG mice underwent intraperitoneal injection of mannan to induce arthritis. Eight weeks later, the mice were killed and the femurs and tibias were subjected to micro-computed tomography, Fourier transform infrared (FTIR) spectroscopic imaging, X-ray diffraction, histology, and mechanical testing. RESULTS: SKG mice developed significant trabecular bone loss in both the distal metaphysis of the femur and the lumbar vertebral body, but the extent of the bone loss was more severe in the distal metaphysis. Neither SKG nor OVX mice exhibited changes in the geometry and matrix properties of the diaphysis of the femur, whereas SKG mice, but not OVX mice, did exhibit changes in these properties in the distal metaphysis of the femur. Bone strength and fracture toughness of the distal metaphysis of the tibia adjacent to the inflamed ankle joint were significantly decreased in SKG mice. CONCLUSIONS: Autoimmune arthritis induces periarticular osteoporosis, characterized by deterioration of cortical bone geometry and quality as well as by trabecular bone loss, leading to severe bone fragility in periarticular bone adjacent to inflamed joints.

Randomized clinical trial of single-incision versus multiport laparoscopic colectomy.

BACKGROUND: The efficacy and safety of single-incision laparoscopic colectomy (SILC) for colonic cancer remain unclear. The aim of this study was to determine the outcomes of SILC compared with multiport laparoscopic colectomy (MPLC) for colonic cancer. METHODS: Patients with histologically proven colonic carcinoma located in the caecum, ascending, sigmoid or rectosigmoid colon, clinically diagnosed as stage 0-III by CT, were eligible for this study. Patients were randomized before surgery and underwent tumour dissection with complete mesocolic excision. Safety analyses were conducted according to randomization groups. RESULTS: A total of 200 patients were enrolled and randomized to the MPLC (100 patients) or SILC (100 patients) arm. Surgical outcomes were similar between the MPLC and SILC arms, including duration of operation (mean 162 versus 156 min respectively; P = 0·273), blood loss (mean 8·8 versus 21·4 ml; P = 0·102), conversion to open laparotomy (2·0 versus 1·0 per cent; P = 0·561), reoperation (3·0 versus 3·0 per cent; P = 1·000), time to first flatus (both median 1 day; P = 0·155) and postoperative hospital stay (both median 6; P = 0·372). The total skin incision length was significantly shorter in the SILC arm (mean 4·4 cm versus 6·8 cm in the MPLC arm; P < 0·001). The median duration of analgesia use was 5 days in the MPLC and 4 days in the SILC arm (P = 0·485). Overall complication rates were equivalent (15·0 versus 12·0 per cent respecitvely; P = 0·680). CONCLUSION: SILC is not superior to MPLC. REGISTRATION NUMBER: UMIN000007220 (http://www.umin.ac.jp/ctr/index.htm).

Evaluation of the Glasgow Prognostic Score in patients receiving chemoradiotherapy for stage III and IV esophageal cancer.

High Glasgow Prognostic scores (GPSs) have been associated with poor outcomes in various tumors, but the values of GPS and modified GPS (mGPS) in patients with advanced esophageal cancer receiving chemoradiotherapy (CRT) has not yet been reported. We have evaluated these with respect to predicting responsiveness to CRT and long-term survival. Between January 2002 and December 2011, tumor responses in 142 esophageal cancer patients (131 men and 11 women) with stage III (A, B and C) and IV receiving CRT were assessed. We assessed the value of the GPS as a predictor of a response to definitive CRT and also as a prognostic indicator in patients with esophageal cancer receiving CRT. We found that independent predictors of CRT responsiveness were Eastern Cooperative Oncology Group (ECOG) performance status, GPS and cTNM stage. Independent prognostic factors were ECOG performance status and GPS for progression-free survival and ECOG performance status, GPS and cTNM stage IV for disease-specific survival. GPS may be a novel predictor of CRT responsiveness and a prognostic indicator for progression-free and disease-specific survival in patients with advanced esophageal cancer. However, a multicenter study as same regime with large number of patients will be needed to confirm these outcomes.

Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment.

The epidemiology of Mycobacterium tuberculosis (Mtb) and M. africanum (Maf) suggests differences in their virulence, but the host immune profile to better understand the pathogenesis of tuberculosis (TB) have not been studied. We compared the transcriptomic and metabolic profiles between Mtb- and Maf-infected TB cases to identify host biomarkers associated with lineages-specific pathogenesis and response to anti-TB chemotherapy. Venous blood samples from Mtb- and Maf-infected patients obtained before and after anti-TB treatment were analyzed for cell composition, gene expression and metabolic profiles. Prior to treatment, similar transcriptomic profiles were seen in Maf- and Mtb-infected patients. In contrast, post treatment, over 1600 genes related to immune responses and metabolic diseases were differentially expressed between the groups. Notably, the upstream regulator hepatocyte nuclear factor 4-alpha (HNF4α), which regulated 15% of these genes, was markedly enriched. Serum metabolic profiles were similar in both group pre-treatment, but the decline in pro-inflammatory metabolites post treatment were most pronounced in Mtb-infected patients. Together, the differences in both peripheral blood transcriptomic and serum metabolic profiles between Maf- and Mtb-infected patients observed over the treatment period, might be indicative of intrinsic host factors related to susceptibility to TB and/or differential efficacy of the standard anti-TB treatment on the two lineages.

Dielectric-loaded surface plasmon polariton crossing waveguides using multimode interference.

A low-loss low-crosstalk multimode interference (MMI) crossing design for dielectric-loaded surface plasmon polariton waveguides (DLSPPWs), which are SiO2 stripes on Au films, is demonstrated numerically and experimentally. DLSPPWs are compatible with strong surface plasmon polariton (SPP) field confinement and maintain relatively low propagation losses. Unlike simpler crossings without MMI structures, low insertion loss of 0.65 dB and low crosstalk of -20.27 dB is confirmed numerically at a crossing angle of 10° when using tilted mirror-imaged MMI crossings. Similar insertion losses were also confirmed experimentally. The proposed structure will be beneficial for plasmonic device miniaturization and flexible patterning of optical interconnections.

Increased protein and mRNA expression of resistin after dexamethasone administration.

Synthetic glucocorticoids such as dexamethasone are widely used to treat a variety of inflammatory and autoimmune conditions, but they may induce adverse events including hyperglycemia. To shed light on the effect and action mechanism of dexamethasone, we examined the alterations of gene expression levels caused by dexamethasone.Microarray analysis was performed on whole blood collected from 24 physically healthy subjects at baseline and after dexamethasone administration. The expression levels of resistin mRNA were found to be significantly increased after the dexamethasone administration. In a separate sample of 12 subjects, we examined plasma resistin protein levels and found that they were increased after dexamethasone administration. Furthermore, the plasma mRNA and protein levels of resistin were significantly higher in individuals who carried the A allele of RETN single nucleotide polymorphism rs3219175 than in those who did not carry the allele. There was no significant interaction between the genotype and dexamethasone administration. No significant correlation was found between plasma levels of cortisol and resistin. Consistent with previous studies, the genotype of RETN rs3219175 was a strong determinant of resistin levels. The present study showed that oral administration of dexamethasone increases the protein and mRNA levels of resistin irrespective of the rs3219175 genotype.

Optimizing the selection of patients with low rectal cancer for intersphincteric resection by evaluating vertical invasion to the levator and external sphincter.

AIM: The indications for intersphincteric (ISR) anterior resection are not clearly defined. The aim of this study was to evaluate vertical extension of T2 or T3 low rectal cancer treated by rectal amputation to optimize patient selection for ISR. METHOD: The abdominoperineal excision specimens of T2 or T3 low rectal cancer from 53 patients treated between 1992 and 2004 were retrospectively reviewed. Vertical invasion was quantified by measuring the shortest distance between the tumour and the striated muscle (T-SM), assuming that this represented the surgical margin that would have be achieved had an ISR been performed. RESULTS: Involvement of the dentate line (DL) and intramural distal spread were independent risk factors for T-SM ≤ 2 mm. The T-SM was less when the inferior border of the tumour was on the distal side of the DL (r = 0.572, P < 0.001). The probability of involvement of the DL, intramural distal spread or either one of these being associated with T-SM ≤ 2 mm was 43, 46 and 43%, respectively. All patients without both intramural distal spread and involvement of the DL had T-SM > 2. CONCLUSION: We recommend that ISR should only be performed for patients with T2 or T3 low rectal cancer in whom the lowest edge of the tumour is above the DL and there is no intramural distal spread. Such patients are relatively unlikely to have a T-SM ≤ 2 mm.

Nutritional management of anastomotic leakage after colorectal cancer surgery using elemental diet jelly.

BACKGROUND/AIMS: Anastomotic leakage is major complication of colorectal surgery. Total parenteral nutrition (TPN) and fasting are conservative treatments for leakage in the absence of peritonitis in Japan. Elemental diet (ED) jelly is a completely digested formula and is easily absorbed without secretion of digestive juices. The purpose of this study was to assess the safety of ED jelly in management of anastomotic leakage. METHODOLOGY: Six hundred and two patients who underwent elective surgery for left side colorectal cancer from January 2008 to December 2011 were included in the study. Pelvic drainage was performed for all patients. Sixty-three (10.5%) patients were diagnosed with an anastomotic leakage, and of these, 31 (5.2%) without diverting stoma were enrolled in this study. RESULTS: Sixteen patients received TPN (TPN group) and 15 patients received ED jelly (ED group). The duration of intravenous infusion was significantly shorter in the ED group than in the TPN group (15 days versus 25 days, P= 0.008). In the TPN group, catheter infection was occurred in 2 patients who required re-insertion of the catheter. CONCLUSION: Conservative management of anastomotic leakage after colorectal surgery with ED jelly appears to be a safe and useful approach.

Prognostic significance of CD44 variant 2 upregulation in colorectal cancer.

BACKGROUND: CD133 and CD44 are putative cancer stem cell (CSC) markers in colorectal cancer (CRC). However, their clinical significance is currently unclear. Here, we evaluated primary CRC cell isolates to determine the significance of several CSC markers, including CD133 and CD44, as predictors of tumourigenesis and prognosis. METHODS: CD133- and CD44-positive cells from fresh clinical samples of 77 CRCs were selected by flow cytometric sorting and evaluated for tumourigenicity following subcutaneous transplantation into NOD/SCID mice. Cancer stem cell marker expression was examined in both xenografts and a complementary DNA library compiled from 167 CRC patient samples. RESULTS: CD44(+), CD133(+) and CD133(+)CD44(+) sub-populations were significantly more tumourigenic than the total cell population. The clinical samples expressed several transcript variants of CD44. Variant 2 was specifically overexpressed in both primary tumours and xenografts in comparison with the normal mucosa. A prognostic assay using qRT-PCR showed that the CD44v2(high) group (n=84, 5-year survival rate (5-OS): 0.74) had a significantly worse prognosis (P=0.041) than the CD44v2(low) group (n=83, 5-OS: 0.88). CONCLUSIONS: CD44 is an important CSC marker in CRC patients. Furthermore, CRC patients with high expression of CD44v2 have a poorer prognosis than patients with other CD44 variants.

HLA-DRB1, -DRB3, -DRB4 and -DRB5 genotyping at a super-high resolution level by long range PCR and high-throughput sequencing.

Super high-resolution single molecule sequence-based typing (SS-SBT) is a human leukocyte antigen (HLA) DNA typing method to the field 4 level of allelic resolution (formerly known as eight-digit typing) to efficiently detect new and null alleles without phase ambiguity by combination of long ranged polymerase chain reaction (PCR) amplification and next-generation sequencing (NGS) technologies. We previously reported the development and application of the SS-SBT method for the eight classical HLA loci, A, B, C, DRB1, DQA1, DQB1, DPA1 and DPB1. In this article, we describe the development of the SS-SBT method for three DRB1 linked loci, DRB3, DRB4 and DRB5 (DRB3/4/5) and characterization of DRB1-DRB3/4/5 haplotype structures to the field 4 level. Locus specific PCR primers for DRB3/4/5 were designed to amplify the gene regions from intron 1 to exon 6 [3' untranslated region (3'UTR)]. In total 20 DRB1 and 13 DRB3/4/5 allele sequences were determined by the SS-SBT to the field 4 level without phase ambiguity using 19 DR51, DR52 and DR53 positive genomic DNA samples obtained from Japanese. Moreover, 18 DRB1-DRB3/4/5 haplotypes were estimated to the field 4 level by the SS-SBT method in contrast to 10 haplotypes estimated by conventional methods to the field 1 level (formerly known as two digit typing). Therefore, DRB1-DRB3/4/5 haplotyping by SS-SBT is expected to provide informative data for improved HLA matching in medical research, transplantation procedures, HLA-related disease studies and human population diversity studies.

Genetic polymorphism in IFNL4 and response to pegylated interferon-α and ribavirin in Japanese chronic hepatitis C patients.

A genetic polymorphism of the newly discovered interferon-λ 4 (IFNL4) gene was associated with hepatitis C virus (HCV) clearance in individuals of African ancestry. To assess whether a dinucleotide variant of IFNL4 (ss469415590) also affected treatment outcome of antiviral therapy in Japan, we genotyped 213 patients with chronic genotype 1 HCV infection and 176 healthy subjects. The ΔG allele was associated with treatment failure [odds ratio (OR) 4.73, P = 0.019], as was the IFL3 rs8099917 single nucleotide polymorphism (SNP) (OR 5.06, P = 0.068). The correlation between ss469415590 and rs8099917 was high (r(2) = 0.92, D' = 0.98). Multivariate analysis revealed that the rs8099917 SNP was independently associated with treatment failure (OR 5.28, P = 0.009). Therefore, ss469415590 may be another predictive marker of antiviral therapy outcome in the Japanese population.

Isolated neurosarcoidosis in the medulla oblongata involving the fourth ventricle: a case report.

We report a 61-year-old woman with definite diagnosis of isolated neurosarcoidosis in the medulla oblongata involving the fourth ventricle. We could not recognize neurosarcoidosis as one of the differential diagnoses of the lesion before biopsy because the brainstem lesion location and periventricular lesion configuration were quite unusual.