Estimation model for lower extremity strength using gait movement measured with inertial sensor considering differences of sex and environment.

In this study, we propose a method for estimating lower extremity strength from daily gait movement. Gait movement is affected by sex and gait environment. Therefore, we examined correlation coefficient between lower extremity strength and gait movement based on sex and environment and created models for estimating lower extremity strength. As a result, when only male or female data were used for model constructing, the correlation coefficient between estimates and actual measurements of lower extremity strength were approximately 0.7 and the precision had a mean absolute error of approximately 0.1 N/kg. The accuracy of the estimates was higher than that when sex was considered.

Bone Subtraction Iodine Imaging Using Area Detector CT for Evaluation of Skull Base Invasion by Nasopharyngeal Carcinoma.

BACKGROUND AND PURPOSE: Conventional CT has generally lower detectability of bone marrow invasion than MR imaging due to lower tissue contrast. The purpose of this study was to compare the diagnostic performance of conventional CT alone or in combination with bone subtraction iodine imaging using area detector CT for the evaluation of skull base invasion in patients with nasopharyngeal carcinoma. MATERIALS AND METHODS: Forty-four consecutive patients who underwent contrast-enhanced CT using 320-row area detector CT and contrast-enhanced MR imaging for nasopharyngeal carcinoma staging between April 2012 and November 2017 were enrolled in this retrospective study. Bone subtraction iodine images were generated by subtracting pre- and postcontrast volume scans using a high-resolution deformable registration algorithm. Two blinded observers evaluated skull base invasion at multiple sites (sphenoid body, clivus, bilateral base of the pterygoid process, and petrous bone) using conventional CT images alone or in combination with bone subtraction iodine images. Examination of MR and CT images by an experienced neuroradiologist was the reference standard for evaluating sensitivity, specificity, and area under the receiver operating characteristic curve. RESULTS: Twenty-six patients (59%) showed skull base invasion at 84 sites on the reference standard. Conventional CT plus bone subtraction iodine images showed higher sensitivity (92.9% versus 78.6%, P = .02) and specificity (95.6% versus 86.1%, P = .01) than conventional CT images alone for evaluating skull base invasion. The area under the receiver operating characteristic curve for conventional CT plus bone subtraction iodine (0.98) was significantly larger (P < .001) than the area under the receiver operating characteristic curve for conventional CT alone (0.90). CONCLUSIONS: Conventional CT plus bone subtraction iodine performs more closely to the accuracy of combining CT and MR imaging compared with conventional CT alone.

Curative Criteria After Endoscopic Resection for Superficial Esophageal Squamous Cell Carcinomas.

BACKGROUND: According to the Japanese Esophageal Society (JES) guidelines, risk factors for lymph node (LN) metastasis in the muscularis mucosa (MM)/submucosa to a depth of up to 200 µm (SM1) in cases of esophageal squamous cell carcinomas (ESCCs) include the presence of lymphatic invasion (ly), venous invasion (v), infiltration pattern (INF)c, and SM1. The long-term prognoses of these patients are unclear, and there are very few reports on the validation of the curative criteria for MM/SM1 ESCCs. AIMS: To examine the long-term prognoses of these patients and the risk factors for LN metastasis of MM/SM1 ESCCs after endoscopic resection (ER). METHODS: This study included patients with MM/SM1 ESCCs who underwent ER at Hiroshima University Hospital from December 1990 to November 2016. We evaluated the clinicopathological characteristics of 98 patients and overall survival, disease-specific survival, recurrence-free survival, and recurrence rates in the e-curative and non-e-curative groups. RESULTS: The mean observation period was 75 months. There was no significant difference in disease-specific survival rate between the e-curative and non-e-curative groups (100 vs. 98%). There was no significant difference in disease-specific survival rates between the groups (100 vs. 98%). In contrast, the LN recurrence-free survival rate in patients with INFa, ly(-), and v(-) was significantly higher than that in patients with INFb/c, ly(+), or v(+) (100 and 87%, P < 0.05). CONCLUSION: Contrary to the JES guidelines, our findings suggest that new criteria (MM/SM1, INFa, negative vertical margin (VM0), ly[-], and v[-]) may be associated with curative ER without additional treatment.

Diagnosis of superficial esophageal squamous cell carcinoma invasion depth before endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is a widely accepted procedure for superficial esophageal squamous cell carcinoma (SESCC) limited to the epithelium or lamina propria mucosae (EP/LPM). We aimed to compare the efficacy of endoscopic ultrasonography (EUS) and magnifying endoscopy with narrow band imaging (ME-NBI) for predicting the tumor invasion depth in patients with SESCC. Specifically, we evaluated the ability of these examinations to distinguish EP/LPM from SESCC invading the muscularis mucosae or superficial submucosa (MM/SM1) and more deeply invasive lesions before ESD.We retrospectively analyzed a database of all patients with SESCC who had undergone both EUS and ME-NBI for pretreatment staging and ESD resection at Hiroshima University Hospital between September 2007 and June 2015. The clinicopathologic characteristics of SESCCs were classified according to the Japanese Classification of Esophageal Cancer.A total of 174 lesions in 174 patients were included: 124 (71%) EP/LPMs, 35 (20%) MM/SM1s, and 15 (9%) SESCCs invading the mid submucosae (SM2). The sensitivity of EUS and of ME-NBI in distinguishing EP/LPM from MM/SM1 and more invasive lesions was 72% and 83%, respectively. The accuracy of EUS and ME-NBI in distinguishing EP/LPM from MM/SM1 and more invasive lesions was 70% and 82%, respectively. Sensitivity and accuracy of ME-NBI in distinguishing EP/LPM from MM/SM1 and more deeply invasive SESCCs is significantly higher than those of EUS (P = 0.048 and P = 0.017, respectively).ME-NBI may be more useful than EUS for the determination of SESCC invasion depth before ESD.

IL-1ß-induced matrix metalloproteinase-3 regulates cell proliferation in rat dental pulp cells.

OBJECTIVE: We previously reported that matrix metalloproteinase-3(MMP-3) accelerates wound healing following dental pulp injury. In this study, we tested the hypothesis that induction of MMP-3 activity by interleukin-1ß would promote proliferation and apoptosis of dental pulp cells. MATERIALS AND METHODS: Dental pulp cells were isolated from rat incisors and subjected to interleukin-1ß. Matrix metalloproteinase-3 mRNA and protein expression were assessed using reverse transcription-polymerase chain reaction and Western blotting, respectively. Matrix metalloproteinase-3 activity was measured using fluorescence. Dental pulp cell proliferation and apoptosis were determined using enzyme-linked immunosorbent assays (ELISA) for BrdU and DNA fragmentation, respectively. siRNA was used to reduce MMP-3 transcripts in these cells. RESULTS: Treatment with interleukin-1ß increased MMP-3 mRNA and protein levels as well as its activity in dental pulp cells. Cell proliferation was also markedly increased, with no changes in apoptosis observed. Treatment with siRNA against MMP-3 potently suppressed this interleukin-1ß-induced increase in MMP-3 expression and activity, and also suppressed cell proliferation but unexpectedly increased apoptosis in these cells (P < 0.05). This siRNA-mediated increase in apoptosis could be reversed with exogenous MMP-3 stimulation (P < 0.05). CONCLUSIONS: Interleukin-1ß induces MMP-3-regulated cell proliferation and suppresses apoptosis in dental pulp cells.

Cytokines induce MMP-3-regulated proliferation of embryonic stem cell-derived odontoblast-like cells.

OBJECTIVES: Matrix metalloproteinase (MMP)-3 expression increases after pulpectomy and accelerates angiogenesis in rat dental pulp by an uncharacterised mechanism. Odontoblasts, a major component of dental pulp, could represent a therapeutic target. We investigated whether MMP-3 activity is induced by cytokines and/or is associated with cell proliferation and apoptosis in embryonic stem cell-derived odontoblast-like cells. MATERIALS AND METHODS: We used reverse transcriptase polymerase chain reaction, western blotting, an MMP-3 activity assay, a BrdU-cell proliferation enzyme-linked immunosorbent assay and DNA fragmentation analysis to evaluate siRNA-mediated downregulation of MMP-3 expression and activity, and any changes in the proliferative and apoptotic responses associated with this reduced expression. RESULTS: Pro-inflammatory cytokines (interleukin-1ß, tumour necrosis factor-α and interferon-γ, at relatively low concentrations) induced MMP-3 mRNA and protein expression, and increased MMP-3 activity and cell proliferation, but not apoptosis. MMP-3 silencing produced a potent and significant suppression of cytokine-induced MMP-3 expression and activity, decreased cell proliferation and increased apoptosis. These effects were rescued by application of exogenous MMP-3. CONCLUSIONS: Our results suggest that pro-inflammatory cytokines induce MMP-3-regulated cell proliferation and anti-apoptosis effects in odontoblast-like cells derived from embryonic stem cells, in addition to their well-documented destructive role in inflammation.

Synchronous and subsequent lesions of serrated adenomas and tubular adenomas of the colorectum.

The characteristics of synchronous and subsequent lesions of serrated adenomas (SAs) of the colorectum are still unclear. This study aimed to clarify the characteristics of synchronous and subsequent lesions of SAs compared with tubular adenomas (TAs) of the colorectum. Patients were divided into 2 groups: SA (127 patients) and TA (158 patients). The mean follow-up durations in the SA and TA groups were 39.7 and 42.7 months, respectively. The number and clinical features of the synchronous and subsequent lesions of both groups were examined. In the SA group, 19 (15%) patients had synchronous lesions and 3 (2%) patients had subsequent lesions. In the TA group, 68 (43%) patients had synchronous lesions and 14 (9%) patients had subsequent lesions. The frequencies of patients with synchronous and subsequent lesions in the SA group were significantly lower than those in the TA group (p < 0.0001 and p = 0.02, respectively). The most frequent synchronous lesion was SA (67%) in the SA group and TA (95%) in the TA group. The most subsequent lesion was SA (62%) in the SA group and TA (100%) in the TA group. The histology of the index polyp and synchronous and subsequent lesions tended to be identical. No invasive colorectal carcinomas were observed in either group. Our data suggest that the colonic tumorigenesis potential of patients with SA may differ from that of patients with TA.

Metachronous multiple esophageal squamous cell carcinomas and Lugol-voiding lesions after endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) has been applied to the treatment of superficial esophageal squamous cell carcinoma (SCC). The incidence and characteristics of metachronous multiple esophageal SCCs and Lugol-voiding lesions (LVLs) were investigated in a retrospective study in patients who had undergone EMR for superficial esophageal SCC. PATIENTS AND METHODS: 96 patients with esophageal SCC who had been treated by EMR were followed up by endoscopy for 12 months or longer. Clinicopathologic parameters such as tumor size and location and presence of LVLs were examined. RESULTS: 10 patients (10 %) had synchronous multiple SCCs, and 12 (13 %) developed metachronous multiple SCCs. The mean annual incidence of newly diagnosed tumor was 4.4 %. The incidence of a speckled pattern of LVLs was 20/74 (27 %) in patients with solitary SCC, 5/10 (50 %) in synchronous multiple SCC, and 10/12 (83 %) in metachronous multiple SCC. The incidence of the presence of speckled pattern of LVLs was significantly higher in patients with multiple SCCs than in those with solitary SCC (68 % vs. 27 %, P = 0.0004). CONCLUSIONS: Patients who have undergone EMR for esophageal SCC, especially those with metachronous multiple LVLs in the background mucosa, should undergo follow-up with close endoscopic observation using Lugol staining.

Nuclear and mitochondrial DNA microsatellite instability in gastrointestinal stromal tumors.

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Nuclear (nMSI) and mitochondrial microsatellite instability (mtMSI) play important roles in tumorigenesis in various organs. The aim of this study was to evaluate the role of nMSI and mtMSI in GISTs. METHODS: Samples from 74 mesenchymal tumors were collected. nMSI and mtMSI were examined by microsatellite assay at BAT26 and D310 mononucleotide repeats in mtDNA, respectively. We compared nMSI, mtMSI and clinicopathologic features, including patient age and sex, tumor location, tumor size, presence of tumor ulceration and presence of distant metastasis, for 51 GISTs for which these data were available. RESULTS: nMSI and mtMSI were detected in 3 (5%) and 10 (16%) of the 62 GISTs, respectively. There was no significant relationship between nMSI, mtMSI and clinicopathologic features. CONCLUSION: These results suggest that mtMSI may play a role, but that nMSI may play little role in the development of GISTs.

Loss of heterozygosity on chromosome 10p14-p15 in colorectal carcinoma.

High frequencies of loss of heterozygosity (LOH) on chromosome 10p14-p15 have been reported in various tumors, including gliomas, pulmonary carcinoid tumors and cervical, hepatic, prostatic and esophageal carcinomas. However, LOH on chromosome 10p14-p15 in colorectal tumors has not been reported. Therefore, we examined LOH on chromosome 10p14-p15 in 60 colorectal carcinomas (21 superficial and 39 advanced types) by microsatellite assay. Three microsatellite loci, D10S191 (10p14), D10S558 and D10S249 (10p15) were examined by polymerase chain reaction [early colorectal carcinomas, LOH of markers D10S191 (36%), D10S558 (7%) and D10S249 (11%), and in advanced colorectal carcinomas, LOH of markers D10S191 (20%), D10S558 (13%) and D10S249 (33%)]. There were no significant associations between LOH on chromosome 10p14-p15 and clinicopathologic features, including patient age, sex, tumor location, depth of invasion, histologic type, lymph node metastasis and prognosis. These data suggest that a putative tumor suppressor gene associated with colorectal carcinogenesis may be located on chromosome 10p14-p15 and that alteration of this gene may be involved in the development but not progression of colorectal tumors.

Characteristics and trends of clarithromycin-resistant Helicobacter pylori isolates in Japan over a decade.

Clarithromycin has been administered to patients in Japan since 1991. Clarithromycin-resistant Helicobacter pylori strains have been on the rise in Japan. We obtained H. pylori isolates between 1989 and 2000 and examined mutations of the 23S rRNA gene, which are closely associated with clarithromycin resistance. Isolates were obtained from 356 patients with H. pylori infection treated at the Hiroshima University. Sixty-one of the patients received clarithromycin-based H. pylori eradication therapy. Mutations of the 23S rRNA gene were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by sequencing analysis. Mutant strains were found in 42 of the 356 patients (11.8%). The prevalence of mutant strains increased from 0 to 20.4% during the 12-year study period. The prevalence increased to more than 10% by 1995 and then to more 20% after 1999. The H. pylori eradication rate was significantly higher in patients with wild-type strains than in patients with mutant strains (72.0 vs. 36.4%, p = 0.024). Our data indicate that clarithromycin-resistant H. pylori strains have increased rapidly since 1995 and that the effectiveness of clarithromycin-based H. pylori eradication therapies may soon be compromised. Other new therapies may be necessary as first-line treatments in Japan.

Necessity of multiple gastric biopsies from different sites for detection of clarithromycin-resistant Helicobacter pylori strains.

BACKGROUND: It has been reported that approximately 10% of patients infected with Helicobacter pylori have both clarithromycin-susceptible and clathromycin-resistant strains. However, there have been no reports indicating whether only one gastric biopsy is sufficient to detect clarithromycin-resistant strains. METHODS: Sixty-five H. pylori-infected patients were selected for this study, and 40 of them were given clarithromycin-based eradication therapy. Four gastric biopsies, 2 from the antrum and 2 from the corpus, were obtained from each of the 65 patients. Susceptibility of H. pylori strains to clarithromycin was examined by detecting mutations of the 23S ribosomal RNA (rRNA) gene of H. pylori. RESULTS: The clarithromycin-resistant strains were detected in 16 of the 65 (25%) patients. Only 5 of the 16 (31%) patients had the resistant strains in both the antrum and corpus. When only 1 or the other biopsy from the antrum was used, the resistant strains were detected in 8 (50%) or 9 (56%) of the 16 patients. CONCLUSIONS: These data indicate that multiple gastric biopsies from both the antrum and the corpus should be used to detect clarithromycin-resistant H. pylori strains.

Human telomerase reverse transcriptase, p53 and Ki-67 expression and apoptosis in colorectal serrated adenoma.

BACKGROUND: Serrated adenoma (SA) has recently been proposed as a distinct histological lesion of the colorectum. However, no definite histopathologic criteria for SA have been established, and its histogenesis and natural history remain unclear. METHODS: We analysed 25 hyperplastic polyps (HPs), 26 low-grade SAs (LG-SAs), 32 high-grade SAs (HG-SAs), 18 low-grade tubular adenomas (LG-TAs), 16 high-grade TAs (HG-TAs) and 20 carcinoma in situ (CIS). To clarify molecular features of SA, we used in situ hybridization to examine the expression of human telomerase reverse transcriptase (hTERT), immunohistochemistry to examine the expressions of p53 and Ki-67, and in situ DNA nick end labeling to detect apoptotic cells. RESULTS: The incidence of hTERT expression was 1 (4.0%) of 25 for HP, 12 (46.2%) of 26 for LG-SA, 18 (56.3%) of 32 for HG-SA, 6 (33.3%) of 18 for LG-TA, 7 (43.8%) of 16 for HG-TA, 12 (80.0%) of 15 for CIS, respectively. The incidence of hTERT expression in SA was significantly higher than that in HP. Seventeen (29%) of the 58 SAs were regarded as positive for p53 protein, but none of the HPs showed p53 immunoreactivity. Ki-67 labeling index in SA, TA and CIS was significantly higher than that in HP. The apoptototic index was not significantly different between HP, SA, TA and CIS. In HG-SA, the incidence of hTERT expression in p53-positive lesions was significantly higher than that in p53-negative lesions. CONCLUSIONS: These results suggest that hTERT and p53 expression increase in the early stages of carcinogenesis in SA and that SA has a malignant transformation similar to that of TA. It may be useful to investigate hTERT and p53 expression for differential diagnosis of SA from HP.

Equine follicle-stimulating hormone: molecular cloning of beta subunit and biological role of the asparagine-linked oligosaccharide at asparagine(56) of alpha subunit.

Equine FSH (eFSH) and eCG are members of the glycoprotein hormone family. These proteins are heterodimeric, composed of noncovalently associated alpha and beta subunits. We have previously reported that recombinant eCG has potent LH- and FSH-like activities and that the oligosaccharide at Asn(56) of the alpha subunit plays an indispensable role in expressing LH- but not FSH-like activity. In the present study, we cloned eFSH beta subunit cDNA and expressed wild-type recombinant eFSH and a partially deglycosylated mutant FSH (eFSH alpha56/beta) to investigate the biological role of the oligosaccharide at Asn(56) in FSH activity. The wild-type eFSH and eCG stimulated estradiol production in a dose-dependent manner in the primary cultures of rat granulosa cells, indicating that these equine gonadotropins have FSH activity. Partially deglycosylated eCG (eCG alpha56/beta) also stimulated estradiol production, confirming that the FSH-like activity of eCG is resistant to the removal of the N-linked oligosaccharide. Partially deglycosylated eFSH (eFSH alpha56/beta), however, did not show any FSH activity, indicating that the oligosaccharide at Asn(56) was necessary for eFSH. Thus, FSH-like activities of two gonadotropins, eCG and eFSH, are evoked through the distinct molecular mechanisms regarding the biological role of oligosaccharide at Asn(56) of the alpha subunit.

Microsatellite instability is a genetic marker for the development of multiple gastric cancers.

Multiple gastric cancers are found in 5-15% of all patients with gastric cancer. However, no molecular markers have yet been shown to be clinically useful for predicting which patient will or will not have multiple gastric cancers. Recently, microsatellite instability (MSI) has been identified as a molecular marker for multiple colorectal cancers. To elucidate whether MSI could be used as a molecular marker for multiple gastric cancers, we examined MSI in 38 patients with a single gastric cancer, in 26 patients with synchronous multiple gastric cancers and in 14 patients with metachronous multiple gastric cancers. In the patients with synchronous multiple gastric cancers, 1 of the larger tumors was examined. In the patients with metachronous multiple gastric cancers, the first gastric cancer was examined. Five microsatellite loci, including D17S855, D18S58, D18S61, BAT25 and BAT40, were examined with microsatellite assay. MSI was divided into low frequency of MSI (MSI-L) and high frequency of MSI (MSI-H) by the number of affected loci. MSI-L was detected in 3 of the 38 (8%) patients with a single gastric cancer, in 7 of the 26 (27%) patients with synchronous multiple gastric cancers and in 6 of the 14 (43%) patients with metachronous multiple gastric cancers. MSI-H was detected only in 1 of the 38 (3%) patients with a single gastric cancer. The frequency of MSI-L was significantly higher in patients with multiple gastric cancers, both synchronous and metachronous, than in those with a single gastric cancer (p < 0.05 and p < 0.01, respectively). Patients with MSI(+) gastric cancer developed a significantly higher frequency of secondary gastric cancer, when compared with patients with MSI(-) gastric cancer (p < 0.05). These data suggest that MSI may play an important role in the development of multiple gastric cancers, and it may be used clinically as a molecular marker for the prediction of multiple gastric cancers.

Clinicopathological features of gastric mucosa-associated lymphoid tissue lymphoma: a comparison with diffuse large B-cell lymphoma without a mucosa-associated lymphoid tissue lymphoma component.

BACKGROUND AND AIMS: The aim of this study was to clinicopathologically distinguish the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma without a MALT lymphoma component (DLL). METHODS: We investigated clinicopathological features of these gastric lymphomas including age, sex ratio, tumor location and depth, macroscopic appearance, and infection with Helicobacter pylori of these gastric lymphomas and hepatitis viruses in 24 patients with gastric low-grade MALT lymphoma, 10 patients with high-grade MALT lymphoma, and 19 patients with DLL. The frequency of H. pylori infection in lymphoma patients was compared with that in age- and sex-matched control subjects. RESULTS: There was a predominance of females with MALT lymphoma (male to female ratio, 8/16 for low-grade MALT lymphomas and 1/9 for high-grade MALT lymphomas), and there was a predominance of males with DLL (male to female ratio, 13/6); the ratios differed significantly (P < 0.05). Ninety-two percent of low-grade MALT lymphomas and 80% of high-grade MALT lymphomas were confined to the mucosal and submucosal layers, but lymphoma cells invaded the muscular layer or more deeply in 74% of DLL. Helicobacter pylori infection occurred significantly more often in patients with low-grade MALT lymphoma than in age- and sex-matched controls (96 vs 67%, P < 0.01). Conversely, the frequency of H. pylori infection in DLL patients did not differ from that in controls. CONCLUSIONS: These data suggest that H. pylori infection may be associated with the development of gastric MALT lymphoma, but not DLL, and that MALT lymphoma and DLL may have a different pathogenesis.

Predominant 1,2-insertion of styrene in the Pd-catalyzed alternating copolymerization with carbon monoxide.

The regioselectivity of styrene insertion to an acyl-Pd bond was studied by NMR in (i) a stoichiomeric reaction and (ii) a copolymerization with CO. In the stoichiometric reaction of styrene with [(CH(3)CO)Pd(CH(3)CN)[(R,S)-BINAPHOS]].[B[3,5-(CF(3))(2)C(6)H(3)](4)], both 1,2- and 2,1-products were given. To mimic the real polymerization conditions, a polyketone-substituted complex [[CH(3)(CH(2)CHCH(3)CO)(n)]Pd[(R,S)-BINAPHOS]].[B(3,5-(CF(3))(2)C(6)H(3))(4)] (n approximately 14) was prepared. When this polymer-attached Pd species was treated with styrene, the 1,2-insertion product was the only detectable species. Thus, exclusive 1,2-insertion is demonstrated to be responsible for the styrene-CO copolymerization, in sharp contrast to the predominant 2,1-insertion with conventional nitrogen ligands. Chain-end analysis revealed that beta-hydride elimination took place from the 2,1-complex but not from the 1,2-complex. Thus, once 2,1-insertion occurs, rapid beta-hydride elimination proceeds to terminate the polymerization, as is common to the other phosphorus-ligand systems. The resulting Pd-H species re-initiates the copolymerization, as was proven by MALDI-TOF mass analysis of the product copolymers.