Complete nucleotide sequences of hepatitis B virus genomes associated with epidemic fulminant hepatitis

Pre-core/core mutants are frequently observed in patients with fulminant hepatitis. To investigate the extent of molecular characteristics of hepatitis B virus (HBV) genomes implicated in the development of fulminant hepatitis, full-length HBV genomes were sequenced directly from sera of two patients with epidemic fatal fulminant hepatitis, after amplification by the polymerase chain reaction. These two genomes, of 3215 nucleotides, were 99.6% identical, indicating that a common source of HBV potentially caused fulminant hepatitis. Thirty unique nucleotide mutations were commonly found in the two entire HBV genomes. Three were located in the stem-loop structure, changing this element to a more stable structure. Twenty-five unique amino acid substitutions were found in each open reading frame, except for the X and pre-surface 2 genes. One was located in the pre-surface 1 gene; two were in the surface gene; three were in the pre-core gene, including codons 28 (tryptophan to stop codon) and 29 (glycine to aspartic acid); eight were in the core gene; and 11 were in the polymerase gene. The pre-core mutations at codons 28 and 29 were common to the two HBV strains reported previously in patients with epidemic fulminant hepatitis. Thus, HBV genomes associated with epidemic fatal fulminant hepatitis have numerous unique mutations, located mainly in the polymerase gene, as well as the pre-core/core gene, including mutations in the stem-loop structure of the pregenome encapsidation signal sequence. These mutations may be associated with the development of fulminant hepatitis. © 1996 Wiley-Liss, Inc.     

Low prevalence of anti-hepatitis C virus antibodies in female hemodialysis patients without blood transfusion: A multicenter analysis

To investigate whether nosocomial infection with hepatitis C virus (HCV) in chronic hemodialysis patients is related primarily to hemodialysis procedures, a multicenter analysis was carried out on 2,132 chronic hemodialysis patients (male: 1,274, female: 858) from 23 dialysis units using a second-generation anti-HCV antibody assay. The prevalence of anti-HCV antibodies in patients with blood transfusion (29.9%) was significantly higher (P < .0001) than in those without blood transfusion (7.6%). Although the prevalence of anti-HCV antibodies increased with the length of hemodialysis in males without blood transfusion, it did not increase even after long-term hemodialysis (more than 5 years) in females without blood transfusion, who exhibited a rate (1.9%) similar to that of healthy blood donors in Japan. There was a significant correlation between the presence of anti-HCV antibodies and anti-HBs antibody in males without blood transfusion. In anti-HBs antibody-negative male patients without blood transfusion, the prevalence of anti-HCV antibodies was significantly lower compared with anti-HBs antibody-positive male patients without blood transfusion. There was marked difference in the prevalence rate in patients without blood transfusion among dialysis units, and there was no correlation between the prevalence and the mean period of dialysis of each dialysis unit. Although nosocomial infection with HCV appears to be related to the hemodialysis environment, the low prevalence of anti-HCV antibodies in females suggests that dialysis procedures per se may not present the risk of hepatitis C virus infection. © 1996 Wiley-Liss, Inc.     

Associations of Serum Folate and Holotranscobalamin with Cardiometabolic Risk Factors in Rural and Urban Cameroon

A low intake of fruit and vegetables and a high intake of meat are associated with higher cardiometabolic disease risk; however much prior research has relied on subjective methods for dietary assessment and focused on Western populations. We aimed to investigate the association of blood folate as an objective marker of fruit and vegetable intake and holotranscobalamin (holoTC) as a marker of animal-sourced food intake with cardiometabolic risk factors. We conducted a population-based cross-sectional study on 578 adults (mean ± SD age = 38.2 ± 8.6 years; 64% women). The primary outcome was a continuous metabolic syndrome score. The median serum folate was 12.9 (IQR: 8.6–20.5) nmol/L and the mean holoTC was 75 (SD: 34.3) pmol/L. Rural residents demonstrated higher serum folate concentrations (15.9 (9.8–25.9) nmol/L) than urban residents (11.3 (7.9–15.8) nmol/L), but lower holoTC concentrations (rural: 69.8 (32.9) pmol/L; urban: 79.8 (34.9)) pmol/L, p < 0.001 for both comparisons. There was an inverse association between serum folate and metabolic syndrome score by −0.20 in the z-score (95% CI, −0.38 to −0.02) per 10.8 (1 SD) of folate) in a model adjusted for socio-demographic factors, smoking status, alcohol intake, BMI, and physical activity. HoloTC was positively associated with the metabolic syndrome score in unadjusted analysis (0.33 (95% CI, 0.10 to 0.56)) but became non-significant (0.17 (−0.05 to 0.39)) after adjusting for socio-demographic and behavioural characteristics. In conclusion, serum folate and holoTC were associated with the metabolic syndrome score in opposite directions. The positive association between serum holoTC and the metabolic syndrome score was partly dependent on sociodemographic characteristics. These findings suggest that, based on these biomarkers reflecting dietary intakes, public health approaches promoting a higher intake of fruit and vegetables may lower cardiometabolic risk factors in this population.     

Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012‐2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2‐3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type‐specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type‐specific RCs between CIN1 and CIN2‐3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type‐specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2‐3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2‐3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01‐4.98), followed by HPV31 (2.51, 1.54‐5.24), HPV18 (2.43, 1.59‐4.32), HPV35 (1.56, 0.43‐8.36), HPV33 (1.01, 0.49‐3.31), HPV52 (0.99, 0.76‐1.33), and HPV58 (0.97, 0.75‐1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71‐2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14‐0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9‐valent vaccine contributed to 89.7% (95% CI, 88.7‐90.7) of CIN2‐3/AIS and 93.8% (95% CI, 92.4‐95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9‐valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.     

Effects of mobility/immobility of surface modification by 2-methacryloyloxyethyl phosphorylcholine polymer on the durability of polyethylene for artificial joints

Surface modification is important for the improvement in medical device materials. 2-Methacryloyloxyethyl phosphorylcholine (MPC) polymers have attracted considerable attention as surface modifiable polymers for several medical devices. In this study, we hypothesize that the structure of the surface modification layers might affect the long-term stability, hydration kinetics, wear resistance, and so forth, of medical devices such as artificial joints, and the poly(MPC) (PMPC) grafted surface might assure the long-term performance of such devices. Therefore, we investigate the surface properties of various surface modifications by using dip coatings of MPC-co-n-butyl methacrylate (PMB30) and MPC-co-3-methacryloxypropyl trimethoxysilane (PMSi90) polymers, or photoinduced radical grafting of PMPC and also the effects of the surface properties on the durability of cross-linked polyethylene (CLPE) for artificial joints. The PMPC-grafted CLPE has an extremely low and stable coefficient of dynamic friction and volumetric wear as compared to the untreated CLPE, PMB30-coated CLPE, and PMSi90-coated CLPE. It is concluded that the photoinduced radical graft polymerization of MPC is the best method to retain the benefits of the MPC polymer used in artificial joints under variable and multidirectional loads for long periods with strong bonding between the MPC polymer and the CLPE surface, and also to retain the high mobility of the MPC polymer.     

MicroRNA-10b is a Prognostic Indicator in Colorectal Cancer and Confers Resistance to the Chemotherapeutic Agent 5-Fluorouracil in Colorectal Cancer Cells

Purpose

Recent evidence has shown that altered patterns of microRNA (miRNA) expression correlate with various human cancers. We investigated the clinical significance of miR-10b and its involvement in chemotherapeutic resistance to 5-fluorouracil (5-FU), which is a key component of common chemotherapy regimens in colorectal cancer.

Methods

Quantitative RT-PCR was used to evaluate the clinicopathologic significance of miR-10b expression in 88 colorectal cancer cases. We also investigated the chemotherapeutic sensitivity to 5-FU in miR-10b-overexpressing colorectal cancer cells. To explore the mechanism of chemoresistance in miR-10b transfected cells, we examined whether miR-10b inhibits the pro-apoptotic BH3-only Bcl-2 family member BIM(BCL2L11), a key mediator of chemotherapy-induced cell death.

Results

High level miR-10b expression was found to be significantly associated with high incidence of lymphatic invasion (P?=?0.0257) and poor prognosis (P?=?0.0057). Multivariate analysis indicated that high miR-10b expression is an independent prognostic factor for survival. In vitro studies revealed that miR-10b directly inhibits pro-apoptotic BIM, and the overexpression of miR-10b confers chemoresistance in colorectal cancer cells to 5-FU.

Conclusions

MiR-10b is a novel prognostic marker in colorectal cancer. Moreover, the expression of miR-10b is a potential indicator of chemosensitivity to the common 5-FU-based chemotherapy regimen.     

Possibility of "distraction arthrogenesis": first report in rabbit model

We investigated the possibility of articular cartil-age distraction for use in reconstructing joint structure and for increasing the donor site of osteochondral grafts. Intraarticular osteotomy was performed at the femoral condyle in 12 Japanese white rabbits. The bone segment was fixed with a specially designed external fixator. After a 3-week waiting period, distraction was performed intermittently for 3 weeks (0.7 mm × 3 times per week) in the distraction group (n = 7) and, in the remaining animals (gap group; n = 5), a gap of 6.3 mm in length was made at surgery. All rabbits received etidronate injections (20 mg/kg ×2 times per week) for 5 weeks, to slow mineralization. The femoral condyle was harvested 9 weeks postoperatively and decalcified sagittal sections were stained and evaluated, using a histological grading scale. In the distraction group, distraction of 4.2 ± 1.4 mm was achieved, and the distracted cartilage area was filled with regenerated cartilage, without any gap between the regenerated and the adjacent articular cartilage. This regenerated cartilage showed metachromasia with toluidine blue. In the gap group, newly formed cartilage tissue was folded from the edge of the osteotomy site and fibrous tissue was interposed in the gap. The histological grading score was significantly lower in the distraction group (P < 0.02). Our preliminary results demonstrated the possibility of cartilage distraction; however, long-term observation will be necessary to confirm the characteristics of the distracted cartilage. We may call the process "distraction arthrogenesis", because the entire articular entity, which consists of cartilage, subchondral bone, and bone, could be distracted at once. Received: April 5, 2001 / Accepted: July 15, 2001