Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer.

BACKGROUND: Although some retrospective studies have suggested the value of adjuvant therapy, no recommended standard exists in bile duct cancer. The aim of this study was to test the hypothesis that adjuvant gemcitabine chemotherapy would improve survival probability in resected bile duct cancer. METHODS: This was a randomized phase III trial. Patients with resected bile duct cancer were assigned randomly to gemcitabine and observation groups, which were balanced with respect to lymph node status, residual tumour status and tumour location. Gemcitabine was given intravenously at a dose of 1000 mg/m2 , administered on days 1, 8 and 15 every 4 weeks for six cycles. The primary endpoint was overall survival, and secondary endpoints were relapse-free survival, subgroup analysis and toxicity. RESULTS: Some 225 patients were included (117 gemcitabine, 108 observation). Baseline characteristics were well balanced between the gemcitabine and observation groups. There were no significant differences in overall survival (median 62·3 versus 63·8 months respectively; hazard ratio 1·01, 95 per cent c.i. 0·70 to 1·45; P = 0·964) and relapse-free survival (median 36·0 versus 39·9 months; hazard ratio 0·93, 0·66 to 1·32; P = 0·693). There were no survival differences between the two groups in subsets stratified by lymph node status and margin status. Although haematological toxicity occurred frequently in the gemcitabine group, most toxicities were transient, and grade 3/4 non-haematological toxicity was rare. CONCLUSION: The survival probability in patients with resected bile duct cancer was not significantly different between the gemcitabine adjuvant chemotherapy group and the observation group. Registration number: UMIN 000000820 (http://www.umin.ac.jp/).

Wearing Compression Garment after Endurance Exercise Promotes Recovery of Exercise Performance.

The present study examined the effects of wearing a lower-body compression garment (CG) after endurance exercise on recovery of physiological function. 18 males were divided into 2 experiments, the downhill running (n=10, DHR) experiments and the level running (n=8, LR) experiments. Subjects performed 30 min of DHR (gradient: - 10%) or LR (gradient: 0%) at 70% of ˙VO2max with either wearing a CG (CG trial) or normal garment (CON trial) for 24 h after running. Changes in jump performance (counter movement jump; CMJ, rebound jump; RJ, drop jump; DJ), subjective feelings, circumferences of leg, and blood variables (creatine kinase, myoglobin, interleukin-6, high-sensitivity C-reactive protein) were evaluated before exercise, immediately after exercise, 1, 3 and 24 h following exercise. Running economy was evaluated at 24 h following exercise. CMJ height and RJ index were significantly higher in the CG trial than in the CON trial 24 h after running (P<0.05). Although changes in muscle soreness and blood variables were significantly greater in the DHR experiment than in the LR experiment, there was no significant difference between the trials in either experiment. Wearing a CG following endurance exercise facilitated recovery of jump performance under situations with severe exercise-induced muscle damage.

Factors associated with mothers not vaccinating their children against mumps in Japan.

OBJECTIVES: In Japan, mumps immunization is not mandatory, and the prevalence of mumps immunization among eligible children is only about 30%, raising concerns about increased risk of meningitis, encephalitis and deafness caused by mumps. In 2011, to understand why families are not voluntarily immunizing their children against mumps, we surveyed mothers who were university graduates to examine the factors and barriers influencing mumps vaccination in Japan. STUDY DESIGN: A cross sectional design. METHODS: We sent questionnaires including questions on demographic data and vaccination status, barriers and factors for immunizations to university alumnae to recruit participants. Data were analysed by Student's t-test for continuous variables and by univariate and multivariate analysis to obtain the odds ratio and adjusted odds ratio. RESULTS: Two hundred and twenty-six mothers with children responded with an average (range) age of 44.7 years (SD = 5.02; 30-55 years). Adjusted odds ratios (aOR) from logistic regression analysis identified fear of harmful side-effects (aOR, 2.55; 95% CI, 1.10 to 5.89), the vaccination not being mandatory (aOR, 3.30; 95% CI, 1.41 to 7.72), perceived non-efficacy (aOR, 6.21; 95% CI, 1.85 to 20.91) and being busy (aOR, 3.30; 95% CI, 1.21 to 9.01) were significantly and inversely associated with mumps vaccination. Recommendations from family doctors (aOR, 0.35; 95% CI, 0.17 to 0.71), living abroad when their children would be vaccinated (aOR, 0.10; 95% CI, 0.02 to 0.68) and the maternal age (aOR, 0.91; 95% CI, 0.85 to 0.96) were significant and positively associated with vaccination. CONCLUSIONS: In the absence of mandatory vaccinations, a public education campaign about mumps, their potential consequences and the nature and value of vaccination could improve the prevalence of mumps vaccination among children and prevent the consequences of this disease.

Randomised phase II trial of S-1 plus oxaliplatin vs S-1 in patients with gemcitabine-refractory pancreatic cancer.

BACKGROUND: This randomised, open-label, multicenter phase II study compared progression-free survival (PFS) of S-1 plus oxaliplatin (SOX) with that of S-1 alone in patients with gemcitabine-refractory pancreatic cancer. METHODS: Patients with confirmed progressive disease following the first-line treatment with a gemcitabine-based regimen were randomised to receive either S-1 (80/100/120 mg day(-1) based on body surface area (BSA), orally, days 1-28, every 6 weeks) or SOX (S-1 80/100/120 mg day(-1) based on BSA, orally, days 1-14, plus oxaliplatin 100 mg m(-2), intravenously, day 1, every 3 weeks). The primary end point was PFS. RESULTS: Between January 2009 and July 2010, 271 patients were randomly allocated to either S-1 (n=135) or SOX (n=136). Median PFS for S-1 and SOX were 2.8 and 3.0 months, respectively (hazard ratio (HR)=0.84; 95% confidence interval (CI), 0.65-1.08; stratified log-rank test P=0.18). Median overall survival (OS) was 6.9 vs 7.4 months (HR=1.03; 95% CI, 0.79-1.34; stratified log-rank test P=0.82). The response rate (RR) was 11.5% vs 20.9% (P=0.04). The major grade 3/4 toxicities (S-1 and SOX) were neutropenia (11.4% and 8.1%), thrombocytopenia (4.5% and 10.3%) and anorexia (12.9% and 14.7%). CONCLUSIONS: Although SOX showed an advantage in RR, it provided no significant improvement in PFS or OS compared with S-1 alone.

Identification of chemoresistant factors by protein expression analysis with iTRAQ for head and neck carcinoma.

BACKGROUND: Cisplatin and other anticancer drugs are important in the treatment of head and neck squamous cell carcinoma; however, some tumours develop drug resistance. If chemoresistance could be determined before treatment, unnecessary drug administration would be avoided. Here, we investigated chemoresistance factors by comprehensive analyses at the protein level. METHODS: Four human carcinoma cell lines were used: cisplatin-sensitive UM-SCC-23, UM-SCC-23-CDDPR with acquired cisplatin resistance, naturally cisplatin-resistant UM-SCC-81B, and UM-SCC-23/WR with acquired 5-fluorouracil resistance. Extracted proteins were labelled with iTRAQ and analysed by tandem mass spectrometry to identify resistance. Protein expression was confirmed by western blotting and functional analysis was carried out using siRNA. RESULTS: Thirteen multiple-drug resistance proteins were identified, as well as seven proteins with specific resistance to cisplatin, including α-enolase. Differential expression of these proteins in cisplatin-resistant and -sensitive cell lines was confirmed by western blotting. Functional analysis for α-enolase by siRNA showed that cisplatin sensitivity significantly was increased in UM-SCC-81B and slightly in UM-SCC-23-CDDPR but not in UM-SCC-23/WR cells. CONCLUSIONS: We identified proteins thought to mediate anticancer drug resistance using recent proteome technology and identified α-enolase as a true cisplatin chemoresistance factor. Such proteins could be used as biomarkers for anticancer agent resistance and as targets of cancer therapy.

High force eccentric exercise enhances serum tartrate-resistant acid phosphatase-5b and osteocalcin.

We investigated the effects of eccentric contractions (ECs) on bone metabolism markers and the relationship between bone metabolism and skeletal muscle related protein. Seventeen young untrained men were divided into two groups and performed either 60 or 30 maximal ECs. We measured serum levels of osteocalcin (OC), bone alkaline phosphatase, cross-linked N-telopeptide of type I collagen (NTx), and tartrate-resistant acid phosphatase 5b (TRACP-5b), growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Blood samples were collected for up to five days after ECs. OC with 60 ECs were significantly higher than with 30 ECs (2 hours; p<0.05, day 1 and day 5; p<0.01). TRACP-5b with 60 ECs were significantly higher than with 30 ECs (day 3 and day 5; p<0.001). IGF-1 and OC were significantly positively correlated with 60 ECs (2 hours, day 1, and day 5; p<0.05). There were also significant positive correlations between IGF-1 and NTx with 60 ECs (2 hours, p<0.01; day 1, p<0.05). We found that one bout of severe ECs caused increases in OC and TRACP-5b, which promote increased bone metabolism. Our results suggest that contraction-induced IGF-1 may activate OC and NTx in acute response.

Effect of eccentric contractions of elbow flexor on bone formation and resorption markers.

AIM: This study aimed to investigate the effects of eccentric contractions (ECs) of the biceps brachii muscle on bone metabolism markers. METHODS: Eight untrained subjects (20.0±0.5 years) performed 5 sets of 6 maximal ECs of the elbow flexors with a 2-min rest interval between each set. Blood samples were collected at 6 time points: before (Pre) ECs, immediately after (Post) ECs, and two hours (2 hours), 1 (day 1), 3 (days 3), and 5 days (days 5) after ECs. We measured the levels of the bone formation marker osteocalcin (OC) and the resorption marker tartrate-resistant acid phosphatase 5b (TRACP-5b). In addition, we measured the isometric tetanic torque and the levels of myoglobin (Mb), creatine kinase (CK), blood lactate, and insulin-like growth factor-1 (IGF-1). RESULTS: The results showed 1) CK and Mb levels increased significantly by days 3 and 5 (P<0.05); 2) OC levels significantly decreased in Post and 2 hours (P<0.01) and TRACP-5b levels significantly increased in Post (P<0.01); 3) OC positively correlated with the total work output in Post, 2 hours, and days 5 (Post: r=0.79, P<0.05; 2 hours: r=0.82, P<0.01; days 5: r=0.79, P<0.05); and 4) TRACP-5b levels positively correlated with IGF-1 levels (r=0.69, P<0.01). CONCLUSION: We conclude that a single bout of ECs of the biceps has a negative effect on bone metabolism in the acute phase.

Analysis of the nucleotide sequence of chromosome VI from Saccharomyces cerevisiae.

The complete nucleotide sequence of Saccharomyces cerevisiae chromosome VI (270 kb) has revealed that it contains 129 predicted or known genes (300 bp or longer). Thirty-seven (28%) of which have been identified previously. Among the 92 novel genes, 39 are highly homologous to previously identified genes. Local sequence motifs were compared to active ARS regions and inactive loci with perfect ARS core sequences to examine the relationship between these motifs and ARS activity. Additional ARS sequences were predominantly observed in 3' flanking sequences of active ARS loci.

Petrous internal carotid artery aneurysm rupture induced by Eustachian tube catheterisation: case report.

BACKGROUND: Petrous internal carotid artery aneurysms are very rare vascular lesions, which may present with otalgia and life-threatening massive otorrhoea. CASE REPORT: An 84-year-old woman presented at a local otolaryngology clinic with progressive otalgia due to an acute exacerbation of chronic otitis media. She was referred with left-sided massive otorrhoea following Eustachian tube catheterisation. She suffered another massive otorrhoea with epistaxis during left-sided ear cleaning at a clinic visit. Contrast-enhanced computed tomography and computed tomography angiography revealed a left-sided aneurysm and adjacent stenosis at the left internal carotid artery. Coil embolisation of the petrous internal carotid artery aneurysm was performed with percutaneous transluminal angioplasty followed by dilatation of the stenosis. CONCLUSION: Computed tomography angiography should be performed immediately when a patient reports massive otorrhoea. Endovascular occlusion is a treatment option as it avoids complications of open surgical ligation procedures.

Genetic differences and phenotypic plasticity in body size between high- and low-altitude populations of the ground beetle Carabus tosanus.

The body size of a univoltine carabid beetle Carabus tosanus on Shikoku Island, Japan, was clearly smaller in higher-altitude populations (subspecies), which possibly represents incipient speciation. To explore the determinants of altitudinal differences in body size in this species, we studied the degree of phenotypic plasticity by conducting rearing experiments at two constant temperatures and examined genetic differences through interpopulation crosses. At 15 °C, C. tosanus had a longer developmental period and a shorter adult body than at 20 °C. Nevertheless, variation in body size due to temperature effects (phenotypic plasticity) was small compared to the interpopulation differences, which suggests substantial genetic differences between populations (subspecies) at different altitudes. In F(1) offspring from crosses between a low-altitude (subspecies tosanus) and a high-altitude population (subspecies ishizuchianus), adult body length was affected by the genotypes of both parents, with an interaction effect of parental genotype and offspring sex. Further analyses revealed that adult body length was affected by sex-linked factors in addition to autosomal factors. These genetic differences in body size may have resulted from adaptations to different altitudes and may be important for the process of incipient speciation because body size differences could contribute to premating reproductive isolation.

Lung diseases directly associated with rheumatoid arthritis and their relationship to outcome.

The outcome and cause of death of each lung disease directly associated with rheumatoid arthritis (RA-LD) have been poorly investigated. A retrospective study was conducted of 144 patients with RA-LD, in whom the median follow-up period after the initial visit for a respiratory examination was 4.5 yrs. A total of 57 patients were identified with usual interstitial pneumonia (UIP), 31 with bronchiectasis, 16 with nonspecific interstitial pneumonia (NSIP), 11 with bronchiolitis, five with organising pneumonia (OP), five with diffuse alveolar damage (DAD) and 19 with combined disease. The 5-yr survival rates were 36.6% in the UIP group, 87.1% in the bronchiectasis group, 93.8% in the NSIP group, 88.9% in the bronchiolitis group, 60.0% in the OP group and 20.0% in the DAD group. Survival of patients with DAD was worse than that of patients with UIP. Overall, survival of patients with UIP was worse than that of patients with bronchiectasis, NSIP or bronchiolitis. Of the 144 patients, 71 (49.3%) died, of whom 58 (81.7%) died due to respiratory lesions. Of patients with RA-LD, patients with DAD experienced the highest mortality, and the survival of patients with UIP was worse than that of patients with NSIP.

C-reactive protein predicts incident fracture in community-dwelling elderly Japanese women: the Muramatsu study.

SUMMARY: In a 6-year cohort study of 751 community-dwelling elderly Japanese women, we found that C-reactive protein (CRP) is a significant predictor of osteoporotic fracture in elderly Asian women, who have significantly lower CRP levels than Caucasians. Mechanisms explaining such an association should be further studied. INTRODUCTION: While CRP, a systemic inflammation marker, is thought to be associated with osteoporosis, evidence supporting this claim has been limited. We aimed to assess the association between CRP levels and incident osteoporotic fracture in elderly women. METHODS: We conducted a cohort study with a follow-up period of 6 years. The study included 751 Japanese women aged 69 years or older. We measured serum high-sensitivity CRP (hs-CRP) levels as a major predictor. Covariates included age, body mass index, forearm bone mineral density, calcium intake, serum 25-hydroxyvitamin D, postural sway, osteoporosis medication, and physical activity. The primary outcome was incident limb and vertebral fractures. The Cox proportional hazards model was used to calculate the hazard ratio (HR) of fracture. RESULTS: Median hs-CRP values in study participants were 0.16 mg/L in the lowest tertile, 0.36 mg/L in the medium tertile, and 1.14 mg/L in the highest tertile. The hs-CRP values in these women were substantially lower than in their Caucasian counterparts. Limb or vertebral fractures occurred in 50 subjects during 4,250 person-years. Low CRP levels were associated with low incidence of limb or vertebral fractures (P for trend = 0.035). The adjusted HRs of fracture for the medium and highest quartiles of hs-CRP levels, compared to the lowest quartile, were 2.22 (95% CI, 1.02-4.84) and 2.40 (95% CI, 1.10-5.24), respectively. CONCLUSIONS: CRP is a significant predictor of osteoporotic fracture in elderly Asian women who have substantially lower CRP levels than Caucasians. Mechanisms explaining such an association should be further studied.

Vitamin D sufficiency is associated with low incidence of limb and vertebral fractures in community-dwelling elderly Japanese women: the Muramatsu Study.

UNLABELLED: Data on the association between vitamin D status and osteoporotic fracture in Asians are sparse. We conducted a 6-year cohort study of 773 community-dwelling elderly Japanese women and found that serum 25-hydroxyvitamin D (25(OH)D) ≥ 71 nmol/L was associated with a reduced risk of osteoporotic limb and vertebral fractures. INTRODUCTION: Data on the association between vitamin D status and osteoporotic fracture in Asians are sparse. This study aimed to clarify the association between vitamin D and other markers of nutritional status with the incidence of fracture in elderly Japanese women. METHODS: We conducted a cohort study with a 6-year follow-up of 773 community-dwelling women aged 69 years and older. The 6-year follow-up ended in 2009. We assessed serum 25-hydroxyvitamin D, undercarboxylated osteocalcin (an index of vitamin K status), and calcium intake. The primary outcome was incident limb and vertebral fractures. Covariates were forearm bone mineral density (BMD), age, body mass index, osteoporosis treatment, and physical activity. RESULTS: The mean serum 25(OH)D concentration was 60.0 nmol/L. Thirty-seven limb fractures and 14 vertebral fractures occurred in 4,392 person-years. Lower forearm BMD was significantly associated with increased incident fracture (P = 0.0242). The adjusted hazard ratios (HR) of fracture for the first quartile (<47.7 nmol/L) and the third quartile (59.2-70.9 nmol/L) of serum 25(OH)D, compared to the fourth quartile (≥71.0 nmol/L), were 2.82 (95% confidence interval (CI), 1.09-7.34) and 2.82 (95%CI, 1.09-7.27), respectively. The pooled adjusted HR was 0.42 (95%CI, 0.18-0.99) when the incidence in the fourth quartile (≥71.0 nmol/L) was compared to the other three quartiles combined (<71.0 nmol/L). Vitamin K status and calcium intake were not associated with incident fracture. CONCLUSIONS: Sufficient vitamin D status, i.e., serum 25(OH)D ≥ 71 nmol/L, is associated with low limb and vertebral fracture risk in community-dwelling elderly women.

A case of familial lecithin-cholesterol acyltransferase deficiency on hemodialysis for over 20 years.

We trace the 34-year history of a member of the first Japanese family in which lecithin-cholesterol acyltransferase (LCAT) deficiency was diagnosed. Marriage between cousins with low LCAT activity was responsible for familial LCAT deficiency (FLD). In 1976, a 27-year-old Japanese man was noted to have FLD based on proteinuria, hematuria, grayish corneal opacity and low LCAT activity (9.83%). Genetic analysis showed insertion of G-G-C coding glycine at codon 141. Total cholesterol (C) was low at 108 mg/dl and the ratio of C-ester to total C was very low (12%), while the lecithin (phosphatidylcholine) level was very high (97.3%). When his serum creatinine reached 2.6 mg/dl at the age of 41 years (in 1991), renal biopsy was performed. This showed expansion of the mesangial matrix and irregularly thickened capillary walls with a bubble-like appearance because of lipid deposits consisting of two components (partly lucent vacuolated areas and partly deeply osmiophilic areas). Magnification of the latter deposits showed curvilinear and serpiginous striated membranous structure. Hemodialysis was started in 1990 and has been continued for over 20 years until August 2010. Clinical problems have included AV shunt failure requiring 4 operations and 13 percutaneous transcatheter angioplasty procedures, as well as episodes of hemolytic anemia that subsided after infusion of fresh frozen plasma. Cardiovascular events have not yet occurred, although severe calcification of abdominal aorta has been detected by computed tomography.

Prior nonhip limb fracture predicts subsequent hip fracture in institutionalized elderly people.

SUMMARY: This 1-year cohort study of nursing home residents revealed that historical fractures of upper limbs or nonhip lower limbs were associated with hip fracture (hazard ratio = 2.14), independent of activities of daily living (ADL), mobility, dementia, weight, and type of nursing home. Prior nonhip fractures are useful for predicting of hip fracture in institutional settings. INTRODUCTION: The aim of this study was to evaluate the utility of fracture history for the prediction of hip fracture in nursing home residents. METHODS: This was a cohort study with a 1-year follow-up. Subjects were 8,905 residents of nursing homes in Niigata, Japan (mean age, 84.3 years). Fracture histories were obtained from nursing home medical records. ADL levels were assessed by caregivers. Hip fracture diagnosis was based on hospital medical records. RESULTS: Subjects had fracture histories of upper limbs (5.0%), hip (14.0%), and nonhip lower limbs (4.6%). Among historical single fractures, only prior nonhip lower limbs significantly predicted subsequent fracture (adjusted hazard ratio, 2.43; 95% confidence interval (CI), 1.30-4.57). The stepwise method selected the best model, in which a combined historical fracture at upper limbs or nonhip lower limbs (adjusted hazard ratio, 2.14; 95% CI, 1.30-3.52), dependence, ADL levels, mobility, dementia, weight, and type of nursing home independently predicted subsequent hip fracture. CONCLUSIONS: A fracture history at upper or nonhip lower limbs, in combination with other known risk factors, is useful for the prediction of future hip fracture in institutional settings.

Fracture incidence in nursing homes in Japan.

UNLABELLED: We conducted the first study to determine fracture incidence in institutionalized elderly people in East Asia. Fracture incidence was generally higher than in the general population but was not for all fracture types. Specific fracture prevention strategies for institutionalized people are needed. Ethnic differences in fracture incidence are also discussed. INTRODUCTION: The aim of this study was to determine the incidence of fractures in nursing homes in Japan, where fracture is becoming an increasingly problematic health issue. METHODS: We conducted a cohort study with a 1-year follow-up. Subjects were 8,905 residents (average age, 84.3 years) in nursing homes. Caregivers assessed activities of daily living levels using Barthel's index, and we collected demographic data of each resident. Fracture diagnosis was based on medical records from the hospitals where patients were admitted. RESULTS: Incidence of hip fracture was 14.9 per 1,000 person-years for women and 9.7 for men. Incidence of forearm and upper-arm fractures was 1.9 and 5.1 for women and 0.5 and 2.1 for men, respectively. Hip and upper-arm fracture rates were higher than in the general population, but forearm fracture rates were lower. Hazard ratio of fracture incidence in totally dependent to partially dependent or independent subjects was 0.14 (95%CI 0.05-0.33) for hip fracture and 0.34 (95%CI 0.23-0.50) for all fractures. CONCLUSIONS: Fracture incidence in institutionalized elderly people is generally higher but is not higher for all types of fractures than the general population. In addition, totally dependent persons had a much lower risk of hip fracture.

Proliferation, migration and apoptosis of periodontal ligament cells after tooth replantation.

OBJECTIVE: The aim of this study was to investigate the proliferation, migration and death of periodontal ligament (PDL) cells after tooth replantation. MATERIALS AND METHODS: Maxillary first molars were extracted from 4-week-old male (n = 28) Sprague-Dawley rats and immediately replanted, after which, proliferation, migration and death of PDL cells were investigated. RESULTS: At 3 days after tooth replantation, many proliferative cell nuclear antigen (PCNA)-positive PDL cells were observed on the alveolar bone side, but fewer on the root side. However, while a gradual decrease was observed in number of PCNA-positive PDL cells on the alveolar bone side until 7 days, an increase was seen on the root side. At 3 weeks, cells labeled with PKH26 (fluorescent dye into plasma membrane) were located in the middle of the PDL space. However, these PKH26-labeled cells did not spread to the surface of the cementum or the alveolar bone. TUNEL-positive cells were observed on both the bone and root sides at 3 days. Number of apoptotic cells increased until 7 days on the bone sides, but decreased on root sides. CONCLUSION: These results suggest that both cell proliferation and apoptosis occur in different patterns and at different times to maintain regular spacing of the PDL after tooth replantation.

Peculiar temperature dependence of dynamical sound speed in liquid Se50Te50 by inelastic x-ray scattering.

Inelastic x-ray scattering (IXS) measurements were carried out on liquid Se50Te50 at temperatures up to 1323 K to investigate how the atomic dynamics changes with temperature through the semiconductor-metal transition. The acoustic mode was clearly observed in the dynamic structure factor and its energy was determined using a damped harmonic oscillator model. The dynamical sound speed obtained by IXS for [Formula: see text] nm-1 was found to behave similarly to the temperature dependence of ultrasonic sound velocity with a minimum near the semiconductor metal transition. The results can be explained by taking liquid Se50Te50 to be an inhomogeneous liquid consisting of metallic and semiconducting domains whose size is approximately 3 nm. The relaxation time obtained from frequency dependence of the dynamical sound speed was on a picosecond time scale.

Effect of the dental adhesive, 4-META/MMA-TBB resin, on adhesion and keratinization of regenerating oral epithelium.

BACKGROUND AND OBJECTIVE: The 4-META/MMA-TBB [4-(2-methacryloxyethyl)trimellitic anhydride/methyl methacrylate-tributylborane] resin is widely used as a dental adhesive. It has also been applied in the dressing of gingival wound surfaces following periodontal surgery. However, its effect on the regeneration and/or cell attachment of the oral epithelium remains to be clarified. To evaluate the effect of the resin applied as a wound dressing, we investigated expression of laminin 5, integrin beta(4) and cytokeratin 14 in regenerating oral epithelium treated with this resin following gingivectomy from the viewpoint of cell attachment and differentiation. MATERIAL AND METHODS: The resin was applied to the entire wound surface in rats after gingival surgery, and regenerating epithelium was examined immediately and at 1, 3, 5, 7 and 14 days later. The resin was removed 2 weeks after application in some animals and tissue further examined at 1, 3, 5 and 7 days later. RESULTS: Regenerating epithelium under the resin was not keratinized, but became keratinized immediately after removal of the resin. Laminin 5 and integrin beta(4) were immunolocalized in the basal lamina, the internal basal lamina, in marginal cells of the regenerating epithelium and at the resin-regenerating epithelium interface. Cytokeratin 14 localized in the regenerating epithelium underneath the resin, as well as in healthy and regenerated junctional epithelial cells. CONCLUSION: These results suggest that this resin covers the wound surface and that the regenerating epithelium biologically adheres to the resin during the initial process of its regeneration.

Drug-induced oral lichenoid reaction during nivolumab therapy.

Oral lichenoid reaction, an immune-related adverse event of immunotherapy, has been reported in very few patients receiving anti-programmed cell death receptor-1 (anti-PD-1) therapy. Here, we describe a case of severe stomatitis (grade ≥3 by the Common Terminology Criteria for Adverse Events, version 4.0) accompanied by pharyngolaryngitis that was observed in a patient receiving nivolumab therapy. The stomatitis was diagnosed as drug-induced lichenoid reaction. Nivolumab therapy was discontinued, and the patient was administered systemic prednisolone (1mg/kg). Most of the patient's mucosal changes in the oral cavity and pharyngolarynx resolved within approximately 3 weeks after starting the prednisolone. Clinicians should be aware that severe oral lichenoid reactions can occur in patients receiving anti-PD-1 therapy.