Utility of human epidermal growth factor 2 heterogeneity as a prognostic factor in triple-negative breast cancer.

In some cases of human epidermal growth factor 2 (HER2)-negative breast cancer, including triple-negative breast cancer, HER2 expression is sporadically and strongly upregulated, a condition known as HER2 heterogeneity. We investigated the clinicopathological features of patients with HER2 heterogeneity in triple-negative breast cancers treated with neoadjuvant chemotherapy. Thirty-nine patients with triple-negative breast cancer who had undergone preoperative chemotherapy participated in this study. To assess for HER2 heterogeneity, we used dual in situ hybridization slides. We evaluated the association between HER2 heterogeneity and clinicopathological factors such as rates of pathologic complete response (pCR) and of recurrence-free survival. Of the 39 patients, 15 (38.5%) had cancers with HER2 heterogeneity. The pCR rates were 13.3% among patients with HER2 heterogeneity and 20.8% among those with HER2 nonheterogeneity, but the difference was not significant. The recurrence-free survival rate was significantly lower in patients with HER2 heterogeneity than in those without (P = 0.025). HER2 heterogeneity is a significant predictor of poor prognosis in patients with triple-negative breast cancer treated with neoadjuvant chemotherapy.

Development of a New Two-Arm Transurethral Surgical System for En Bloc Resection of Bladder Tumor: A Preclinical Study.

Backgrounds and Objectives: To overcome the piecemeal nature of bladder tumor resection, en bloc resection of bladder tumor (ERBT) has been introduced. ERBT is difficult for surgeons to perform using the currently available system because it has only one arm. Herein, we aimed to develop a new transurethral surgical system to facilitate two-arm ERBT and to report the results of preclinical experiments using tumor phantoms. Methods: Initially, we aimed to develop a brand-new surgical system for ERBT but, after trial and error, we redirected our development to the creation of three elements: the left arm to grasp the tumor; the right arm to cut the tumor; and the system to operate the arms that can be attached to the existing surgical system (UES-40 SurgMaster® [Olympus Co. Ltd., Tokyo, Japan]). The current system was evaluated by performing simulated ERBTs using tumor phantoms made from konjac jelly. Results: Following the assembly of developed arms into the UES-40 SurgMaster, we conducted preliminary ERBTs. After performing several resections, we adopted a basket-shaped forceps as the left arm instead of grasping forceps and an arched electrode as the right arm. The two arms and single endoscope were placed in an equilateral triangle. We performed ERBT for the tumor phantoms that ranged from 0.5 to 2.0 cm without major redo. Conclusion: Herein, we introduced our development for two-arm ERBT. The current concept of "two-hand transurethral surgery" has the potential to be developed in future in vivo and clinical trials.

A case of conversion hepatectomy for huge hepatocellular carcinoma with adrenal metastasis and vascular invasion after atezolizumab-bevacizumab treatment.

We herein report a case of huge hepatocellular carcinoma (HCC) with adrenal metastasis and vascular invasion successfully treated by conversion hepatectomy after atezolizumab-bevacizumab treatment. A 77-year-old male patient with chest pain was admitted. He had a history of HCC treatment; however, the patient stopped receiving follow-up treatment based on his own decision. This time, he visited the emergency department of our hospital for the first time in 5 years. The tumor at the right lobe had grown into a lump with adrenal metastases and was 15 cm in diameter. It had invaded the inferior vena cava. Atezolizumab-bevacizumab treatment was selected for HCC treatment. Before starting treatment, his liver function was preserved (Child-Pugh A5). His alpha fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels were 759.0 ng/mL and 5,681 mAU/mL, respectively. Atezolizumab-bevacizumab treatment resulted in a marked decrease in tumor marker levels and tumor staining. After nine courses of atezolizumab-bevacizumab treatment, it became difficult to continue the administration of bevacizumab because of proteinuria. Because the tumor had decreased in size and the tumor markers were in the normal range, we decided to perform conversion hepatectomy. The tumor was completely removed by combined resection of the diaphragm, and pathological analyses showed a complete response to atezolizumab-bevacizumab treatment. No viable tumor cells remained on histological analyses. The patient is doing well without any signs of recurrence at 3 months after conversion surgery.

[A Case of Hepatocellular Carcinoma Complicated by Liver Metastasis of Colon Cancer during the Course of Treatment].

A 72‒year‒old man with hepatocellular carcinoma(HCC)was treated with transarterial chemoembolization(TACE)and radiofrequency ablation(RFA). Six months after RFA, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd‒ EOB‒DTPA)‒enhanced magnetic resonance imaging(MRI)revealed multiple metastatic recurrences in the liver. TACE was performed for the recurrent HCC. However, the treatment response on the Gd‒EOB‒DTPA‒enhanced MRI showed that the lesions had advanced and that the liver metastatic nodules had ring‒shaped contrast effects. We suspected metastatic liver cancer based on the MRI findings and performed colonoscopy. Finally, we diagnosed the patient with multiple hepatic metastases of sigmoid colon cancer based on the results of the endoscopic colon biopsy and percutaneous liver tumor biopsy. In conclusion, we had a teachable case of the treatment of HCC.

Microsatellite Instability-high Intrahepatic Cholangiocarcinoma with Portal Vein Tumor Thrombosis Successfully Treated with Pembrolizumab.

A 60-year-old man presented with postoperative recurrence of intrahepatic cholangiocarcinoma with right portal vein tumor thrombosis (PVTT). After failure of standard chemotherapy, a liver biopsy showed that his microsatellite instability (MSI) status was high. Treatment with the immune checkpoint inhibitor (ICI) pembrolizumab was commenced, which resulted in a partial response and resolution of the PVTT. There were no significant immune-related adverse events. According to recently published reports, the frequency of MSI-high biliary tract cancer (BTC) is about 0-2.1%, which is extremely rare. However, ICIs may be effective in patients with MSI-high BTC, such as the present patient.

Effects of the long octyl chain on complex formation of nickel(ii) with dimethyl sulfoxide, methanol, and acetonitrile in ionic liquid of [C8mim][TFSA].

In the room-temperature ionic liquid (IL) of 1-methyl-3-octylimidazolium bis(trifluoromethylsulfonyl)amide ([C8mim][TFSA]), the complex formation of Ni2+ with molecular liquids (MLs), dimethyl sulfoxide (DMSO), methanol (MeOH), and acetonitrile (AN), has been examined using ultraviolet (UV)-visible spectroscopy. The overall stability constants log ßn, enthalpies , and entropies of the equilibria have been determined to elucidate the mechanism of complex formation. From a comparison of such thermodynamic parameters of the present [C8mim][TFSA] systems with those of the previous systems of 1-ethyl-3-methylimidazolium-based IL, [C2mim][TFSA], the effects of the octyl chain of the imidazolium cation, [C8mim]+, on the complex formation of Ni2+ with MLs have been demonstrated. In [C8mim][TFSA]-ML systems, more stable complexes are formed with MLs in the sequence of AN > DMSO ≫ MeOH. This sequence differs from that of DMSO ≫ AN > MeOH in [C2mim][TFSA]. For the AN systems, the stabilities of [Ni(an)n] in [C8mim][TFSA] are higher as compared to those in [C2mim][TFSA]. In contrast, for the DMSO systems, [Ni(dmso)n] is less stable in the IL with the longer alkyl chain than that in the IL with the shorter chain. The dependence of the alkyl chain length on the stabilities of [Ni(meoh)n] is the least significant among the three MLs. These varieties of the stabilities of Ni2+ complexes with the MLs have been interpreted from the thermodynamic parameters, together with the static interactions in the [C8mim][TFSA]-ML and [C2mim][TFSA]-ML solvents observed by means of 1H and 13C NMR, small-angle neutron scattering (SANS), and infrared (IR) with an ATR diamond prism.

Changes in pulmonary function of residents in Sanriku Seacoast following the tsunami disaster from the Great East Japan Earthquake.

BACKGROUND: Residents in the district struck by the Great East Japan Earthquake Tsunami (GEJET) suffered from adverse living conditions and various pulmonary diseases. OBJECTIVES: To evaluate the influence of GEJET, we performed serial assessment of pulmonary function of approximately 10,000 residents in the district struck by GEJET. METHODS: Using a spirometer, we assessed the pulmonary function of approximately 10,000 residents older than 18 years in the Sanriku seacoast, which was struck by the tsunami. Measurements were performed in 2011 and 2012. RESULTS: We compared FVC (forced vital capacity) % pred. and FEV1 (forced expiratory volume in 1second) % pred. of subjects between 2011 and 2012, by serial spirometry. Of the 7053 subjects studied, including 2611 men and 4442 women, FVC% pred. and FEV1% pred. were significantly higher in 2012 than in 2011. Physical indices including height, body weight and the body mass index (BMI) did not change significantly during this period. Smoking prevalence changed significantly between 2010, 2011, and 2012. Both FVC% pred. and FEV1% pred. of subjects who had quit smoking increased significantly on spirometry carried out in 2012, compared with those in 2011. CONCLUSIONS: The pulmonary function expressed as FVC% pred. and FEV1% pred. were significantly higher in 2012 than in 2011 among the subjects studied. The changes in the smoking status may be one of the reasons for the increase in values observed. However, other undetermined factors during recovery from a disaster might have resulted in improved pulmonary function.

Combined associations of physical activity and dietary intake with health status among survivors of the Great East Japan Earthquake.

BACKGROUND AND OBJECTIVES: Each of the effects of physical activity and dietary intake on health is well known, but combined associations of physical activity and dietary intake on health has not been reported yet. Physical activity and dietary intake are key factors for maintaining health of survivors of the Great East Japan Earthquake in 2011. This study aimed to examine combined associations of physical activity and dietary intake with survivors' health status. METHODS AND STUDY DESIGN: We used data from 6668 participants of a cross-sectional survey taken 3 years (2013) after the disaster. To evaluate combined associations of physical activity and dietary intake, answers to questions regarding these two variables were categorized into four groups: poor physical activity and poor dietary intake (Group 1), poor physical activity and good dietary intake (Group 2), good physical activity and poor dietary intake (Group 3), and good physical activity and good dietary intake (Group 4). Multiple logistic regression analyses were performed by sex, with good self-rated health and good mental health as dependent variables, and age, place of residence, living conditions and physical activity/dietary intake group (with Group 1 as the reference category) as independent variables. RESULTS: Good self-rated health was associated with age in both sexes, and Groups 3 (male: odds ratios (ORs) 1.84 (95% confidence intervals (95% CIs) 1.32-2.57), female: OR 1.82 (95% CI 1.32-2.51)) and 4 (male: OR 1.96 (95% CI 1.39-2.76), female: OR 1.94 (95% CI 1.42-2.64)). Good mental health was associated with Groups 3 (OR 1.48 (95% CI 1.10-1.97)) and 4 (OR 1.86 (95% CI 1.37-1.97)) for male respondents; and living place (other than temporary housing) (OR 1.45 (95% CI 1.26-1.68)) was associated with Group 4 (OR 1.42 (95% CI 1.09-1.85)) for female respondents. CONCLUSIONS: Good physical activity alone or combined with good dietary intake was associated with good self-rated health and good mental health. Further interventions regarding physical activity and dietary intake are needed to improve the health status of survivors.

Predicting neurological deficit severity due to subarachnoid haemorrhage: soluble CD40 ligand and platelet-derived growth factor-BB.

BACKGROUND: Several biological markers can predict outcomes in patients with subarachnoid haemorrhage (SAH), but markers to predict neurological deficit severity in patients with SAH and poor neurological condition have not yet been established. Soluble CD40 ligand (sCD40L) and platelet-derived growth factor (PDGF) are related to the systemic inflammatory response. OBJECTIVE: In a prospective study, to investigate the relationship between clinical outcomes and blood test results in patients with SAH and severe neurological deficits. METHODS: We studied 17 patients with Hunt and Hess Grade IV and Fisher Class III neurological deficits who had undergone aneurysmal clipping within 48 hours of onset of SAH. We measured their levels of sCD40L, PDGF-AA, PDGF-AB, PDGF-BB and C-reactive protein (CRP), their white blood cell (WBC) and platelet counts and their body temperature. Blood tests were performed at an early time point (Day 0, the day of the SAH before craniotomy) and at a late time point (Day 10). The modified Rankin Scale (mRS) score of the patients was assessed at Day 60. RESULTS: Seven patients (41%) were classified as mRS 0-2 (good outcome) and 10 (59%) as mRS 3-5 (poor outcome). The blood levels of sCD40L (P = 0.05), PDGF-BB (P = 0.02) and CRP (P = 0.02), WBC count (P = 0.005) and body temperature (P = 0.01) at the late time point were significantly higher in patients with poor outcomes than in patients with good outcomes. CONCLUSION: Our data suggest that sCD40L, PDGF-BB, WBC count, CRP and body temperature can predict the neurological outcome in patients with SAH and poor neurological condition.

Weight Gain in Survivors Living in Temporary Housing in the Tsunami-Stricken Area during the Recovery Phase following the Great East Japan Earthquake and Tsunami.

INTRODUCTION: Survivors who lost their homes in the Great East Japan Earthquake and Tsunami were forced to live in difficult conditions in temporary housing several months after the disaster. Body weights of survivors living in temporary housing for a long period might increase due to changes in their life style and psychosocial state during the medium-term and long-term recovery phases. The aim of this study was to determine whether there were differences between body weight changes of people living in temporary housing and those not living in temporary housing in a tsunami-stricken area during the medium-term and long-term recovery phases. MATERIALS AND METHODS: Health check-ups were performed about 7 months after the disaster (in 2011) and about 18 months after the disaster (in 2012) for people living in a tsunami-stricken area (n = 6,601, mean age = 62.3 y). We compared the changes in body weight in people living in temporary housing (TH group, n = 2,002) and those not living in temporary housing (NTH group, n = 4,599) using a multiple linear regression model. RESULTS: While there was no significant difference between body weights in the TH and NTH groups in the 2011 survey, there was a significant difference between the mean changes in body weight in both sexes. We found that the changes in body weight were significantly greater in the TH group than in the NTH group in both sexes. The partial regression coefficients of mean change in body weight were +0.52 kg (P-value < 0.001) in males in the TH group and +0.56 kg (P-value < 0.001) in females in the TH group (reference: NTH group). CONCLUSION: Analysis after adjustment for life style, psychosocial factors and cardiovascular risk factors found that people living in temporary housing in the tsunami- stricken area had a significant increase in body weight.

[A Case of Rectal Neuroendocrine Carcinoma with Metachronous Liver Metastasis Treated with Multimodality Therapy].

A 6 2-year-old woman visited our hospital with a complaint of anal bleeding and was diagnosed with rectal cancer. She underwent low anterior resection and D3 lymphadenectomy. The pathological diagnosis was shown as follows: Ra, Circ, type 2, por1, pSS, ly3, v1, pN2, pStage III b, and KRAS wild type. UFT/UZEL with polysaccharide K(PSK)was initiated as adjuvant chemotherapy after the operation. However, multiple liver metastases were found on CT after 3 courses of UFT/UZEL with PSK, and pathological reexamination revealed that the primary tumor was a neuroendocrine carcinoma. She underwent chemotherapy with CBDCA combined with CPT-11, but bone marrow suppression was observed after 4 courses of the treatment. As second-line chemotherapy, FOLFOX4 plus panitumumab(Pmab)was administered. Although the disease remained stable through 10 courses of FOLFOX4 plus Pmab, Grade 3 peripheral neuropathy was observed. Hence, FOLFIRI plus bevacizumab(Bmab)was administered as third-line chemotherapy. Twenty-eight courses of FOLFIRI plus Bmab were administered, and transcatheter arterial chemoembolization(TACE)was performed during chemotherapy. However, her general condition worsened after the therapies, and she died 2 years 3 months after the initial chemotherapy.

A case of idiopathic portal hypertension associated with nodular regenerative hyperplasia-like nodule of the liver and mixed connective tissue disease.

A 51-year-old woman was diagnosed with mixed connective tissue disease (MCTD) in 2011. She underwent treatment with prednisolone. Her hepatobiliary enzyme level increased, and multiple nodules were found in both liver lobes in abdominal imaging studies. Ultrasonography revealed large and small hyperechoic lesions with indistinct or well-defined borders. No findings of classic hepatocellular carcinoma or liver cirrhosis were observed on contrast-enhanced computed tomography, but some nodules showed an enhanced effect of the central lesion that was characteristic of focal nodular hyperplasia (FNH) in an arterial phase. On gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging, slightly high-intensity nodules, 10-40mm in size, were observed on T1- and T2-weighted images. The nodules showed highest intensities in the hepatocyte phase and were enhanced with the uptake of Gd-EOB-DTPA as compared with the background liver. FNH was suspected based on the imaging findings, but we performed a liver tumor biopsy for differential diagnosis of the malignant lesion. Based on the immunohistopathological examination results, the final diagnosis was idiopathic portal hypertension associated with nodular regenerative hyperplasia (NRH)-like nodule of the liver. Benign nodular hepatocellular lesions are caused by abnormal hepatic circulation and were previously known as anomalous portal tract syndrome. Our case of atypical NRH with large nodules may be included in this disease entity. Here, we report a rare case of MCTD with NRH-like nodules and idiopathic portal hypertension with a review of literature.

Post-carotid endarterectomy changes in cerebral glucose metabolism on (18)F-fluorodeoxyglucose positron emission tomography associated with postoperative improvement or impairment in cognitive function.

OBJECT: Cognitive function is often improved or impaired after carotid endarterectomy (CEA) for patients with cerebral hemodynamic impairment. Cerebral glucose metabolism measured using positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) correlates with cognitive function in patients with neurodegenerative diseases. The present study aimed to determine whether postoperative changes in cerebral glucose metabolism are associated with cognitive changes after CEA. METHODS: In patients who were scheduled to undergo CEA for ipsilateral internal carotid artery (ICA) stenosis (≥ 70% narrowing), cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to acetazolamide were assessed preoperatively using brain perfusion single-photon emission computed tomography (SPECT). CBF measurement using SPECT was also performed immediately after CEA. For patients with reduced preoperative CVR to acetazolamide in the cerebral hemisphere ipsilateral to surgery, cerebral glucose metabolism was assessed using FDG-PET before surgery and 3 months after surgery and was analyzed using 3D stereotactic surface projection. Neuropsychological testing was also performed preoperatively and 3 months postoperatively. RESULTS: Twenty-two patients with reduced preoperative CVR to acetazolamide successfully underwent FDG-PET studies and neuropsychological testing before and after CEA. Seven, 9, and 6 patients were defined as showing improved, unchanged, and impaired postoperative cognition, respectively, based on the neuropsychological assessments. The cortical area with increased postoperative glucose metabolism was greater in patients with improved postoperative cognition than in those with unchanged (p < 0.001) or impaired (p < 0.001) postoperative cognition. The cortical area with decreased postoperative glucose metabolism was greater in patients with impaired postoperative cognition than in those with improved (p < 0.001) or unchanged (p < 0.001) postoperative cognition. All 7 patients with improved cognition exhibited postoperative hemispheric increases in glucose metabolism, while 5 of the 6 patients with impaired cognition exhibited postoperative hemispheric decreases in glucose metabolism. Brain perfusion SPECT revealed that the latter 6 patients experienced postoperative cerebral hyperperfusion, and 2 of the 6 patients exhibited cerebral hyperperfusion syndrome. The cortical area with decreased postoperative glucose metabolism in these 2 patients was greater than that in other patients. CONCLUSIONS: Postoperative changes in cerebral glucose metabolism, as measured using FDG-PET, are associated with cognitive improvement and impairment after CEA.

Results of Prospective Cohort Study on Symptomatic Cerebrovascular Occlusive Disease Showing Mild Hemodynamic Compromise [Japanese Extracranial-Intracranial Bypass Trial (JET)-2 Study].

The purpose of this study is to determine the true threshold of cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) for subsequent ischemic stroke without extracranial-intracranial (EC-IC) bypass surgery in patients with hemodynamic ischemia due to symptomatic major cerebral arterial occlusive diseases. Patients were categorized based on rest CBF and CVR into four subgroups as follows: Group A, 80% < CBF < 90% and CVR < 10%; Group B, CBF < 80% and 10% < CVR < 20%; Group C, 80% < CBF < 90% and 10% < CVR < 20%; and Group D, CBF < 90% and 20% < CVR < 30%. Patients were followed up for 2 years under best medical treatment by the stroke neurologists. Primary and secondary end points were defined as all adverse events and ipsilateral stroke recurrence respectively. A total of 132 patients were enrolled. All adverse events were observed in 9 patients (3.5%/year) and ipsilateral stroke recurrence was observed only in 2 patients (0.8%/year). There was no significant difference among the four subgroups in terms of the rate of both primary and secondary end points. Compared with the medical arm of the Japanese EC-IC bypass trial (JET) study including patients with CBF < 80% and CVR < 10% as a historical control, the incidence of ipsilateral stroke recurrence was significantly lower in the present study. Patients with symptomatic major cerebral arterial occlusive diseases and mild hemodynamic compromise have a good prognosis under medical treatment. EC-IC bypass surgery is unlikely to benefit patients with CBF > 80% or CVR > 10%.

High-flow bypass and wrap-clipping for ruptured blood blister-like aneurysm of the internal carotid artery using intraoperative monitoring of cerebral hemodynamics.

Aneurysms at non-branching sites in the supraclinoid internal carotid artery (ICA) can be classified as "blood blister-like aneurysms" (BBAs), which have blood blister-like configurations and fragile walls. While surgical treatment for the BBA in the acute stage is recommended, the optimal surgical procedure remains controversial. In the study reported here, we describe the case of a 37-year-old woman with a ruptured BBA in the ophthalmic segment of the right ICA who underwent wrap-clipping with external carotid artery-internal carotid artery bypass by intraoperative estimation of the measurement of cortical cerebral blood flow (CoBF) using a thermal diffusion flow probe. Trapping of the ICA in the acute stage of subarachnoid hemorrhage may result in ischemic complications secondary to hemodynamic hypoperfusion or occlusion of the perforating artery, and/or delayed vasospasm, even with concomitant bypass surgery. We believe that it is important to perform scheduled external carotid artery-internal carotid artery bypass before trapping of the ICA in patients with a ruptured BBA in the acute stage of subarachnoid hemorrhage and to perform wrap-clipping rather than trapping. This would provide much more CoBF if a reduction of CoBF occurs after trapping occlusion of the ICA including a ruptured BBA according to intraoperative CoBF monitoring. As far as we are aware, the case reported here is the first report on high-flow bypass and wrap-clipping for a ruptured BBA of the ICA using intraoperative monitoring of cerebral hemodynamics.

Relative and absolute risks of all-cause and cause-specific deaths attributable to atrial fibrillation in middle-aged and elderly community dwellers.

BACKGROUND: The relative and absolute risks of outcomes other than all-cause death (ACD) attributable to atrial fibrillation (AF) stratified age have not been sufficiently investigated. METHODS: A prospective study of 23,634 community dwellers aged 40 years or older without organic cardiovascular disease (AF=335, non-AF=23,299) was conducted. Multivariate-adjusted rates, rate ratios (RRs) and excess deaths (EDs) for ACD, cardiovascular death (CVD) and non-cardiovascular death (non-CVD), and sex- and age-adjusted RR and ED in middle-aged (40 to 69) and elderly (70 years or older) for ACD, CVD, non-CVD, sudden cardiac death (SCD), stroke-related death (Str-D), neoplasm-related death (NPD), and infection-related death (IFD) attributable to AF were estimated using Poisson regression. RESULTS: Multivariate-adjusted analysis revealed that AF significantly increased the risk of ACD (RR [95% confidence interval]:1.70 [1.23-2.95]) and CVD (3.86 [2.38-6.27]), but not non-CVD. Age-stratified analysis revealed that AF increased the risk of Str-D in middle-aged (14.5 [4.77-44.3]) and elderly individuals (4.92 [1.91-12.7]), SCD in elderly individuals (3.21 [1.37-7.51]), and might increase the risk of IFD in elderly individuals (2.02 [0.80-4.65], p=0.098). The RR of CVD was higher in middle-aged versus elderly individuals (RRs, 6.19 vs. 3.57) but the absolute risk difference was larger in elderly individuals (EDs: 7.6 vs. 3.0 per 1000 person-years). CONCLUSIONS: Larger absolute risk differences for ACD and CVD attributable to AF among elderly people indicate that the absolute burden of AF is higher in elderly versus middle-aged people despite the relatively small RR.

Enzyme kinetics of an alternative splicing isoform of mitochondrial 8-oxoguanine DNA glycosylase, ogg1-1b, and compared with the nuclear ogg1-1a.

Eight alternatively spliced isoforms of human 8-oxoguanine DNA glycosylase (OGG1) (OGG1-1a to -1c and -2a to -2e) are registered in the National Center for Biotechnology Information. OGG1(s) in mitochondria have not yet been fully characterized biochemically. In this study, we purified mitochondrial recombinant OGG1-1b protein and compared its activity with nuclear OGG1-1a protein. The reaction rate constant (kg ) of the 7,8-dihydro-8-oxoguanine (8-oxoG) glycosylase activity of OGG1-1b was 8-oxoG:C >> 8-oxoG:T >> 8-oxoG:G > 8-oxoG:A (7.96, 0.805, 0.070, and 0.015 min(-1) , respectively) and that of the N-glycosylase/DNA lyase activity (kgl ) of OGG1-1b was 8-oxoG:C > 8-oxoG:T ≃8-oxoG:G >> 8-oxoG:A (0.286, 0.079, 0.040, and negligible min(-1) , respectively). These reaction rate constants were similar to those of OGG1-1a except for kgl against 8-oxoG:A. APEX nuclease 1 was required to promote DNA strand breakage by OGG1-1b. These results suggest that OGG1-1b is associated with 8-oxoG cleavage in human mitochondria and that the mechanism of this repair is similar to that of nuclear OGG1-1a.

Associations of number of teeth with risks for all-cause mortality and cause-specific mortality in middle-aged and elderly men in the northern part of Japan: the Iwate-KENCO study.

OBJECTIVES: The objective of this study was to determine the associations of number of teeth with all-cause mortality and cause-specific mortality among middle-aged and elderly Japanese men. METHODS: A total of 7779 men aged 40-79 years who were free from cardiovascular disease (CVD) were followed up prospectively for 5.6 years. Participants were categorized into four groups (no teeth, 1-9 teeth, 10-19 teeth, and ≥20 teeth) by a self-administered questionnaire. Using Cox's proportional hazard model, multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality from all causes, CVD, cancer, and noncancer, non-CVD according to number of teeth were estimated with adjustments for age, body mass index, systolic blood pressure, total- and HDL-cholesterol, HbA1c, current smoking, current alcohol drinking, and low level of education. RESULTS: The numbers (proportions) of participants with no teeth, 1-9 teeth, 10-19 teeth, and ≥20 teeth were 1613 (20.7%), 1650 (21.2%), 1721 (22.1%), and 2795 (35.9%), respectively. During follow-up, a total of 455 deaths (including 175 deaths from cancer, 98 deaths from CVD, and 130 deaths from noncancer, non-CVD) were recorded. In total participants, an inverse relationship between number of teeth and all-cause mortality was found (P for trend = 0.049). Among men aged 40-64 years, inverse relationships were also found in risks for mortality from all causes, CVD, and cancer: multivariate-adjusted HRs (95% CI) for all-cause mortality in men with no teeth, 1-9 teeth, and 10-19 teeth relative to men with ≥20 teeth were 2.75 (1.37-5.49), 1.89 (0.99-3.63), and 1.94 (1.09-3.43), respectively. However, there were no associations of number of teeth with all-cause mortality and cause-specific mortality among men aged 65-79 years. CONCLUSIONS: The number of teeth is an important predictive factor for mortality among middle-aged Japanese men.

Intratumoral heterogeneity of genomic imbalance in a case of epithelioid glioblastoma with BRAF V600E mutation.

Epithelioid glioblastoma is among the rarest variants of glioblastoma and is not formally recognized in the World Health Organization classification; it is composed of monotonous, discohesive sheets of small, round cells with eccentric nuclei and eosinophilic cytoplasm devoid of cytoplasmic stellate processes, showing the retention of nuclear staining of INI-1 protein. Here, we report a case involving a 22-year-old man with a right occipital lobe tumor, which comprised mainly epithelioid tumor cells with a small area of diffusely infiltrating less atypical astrocytoma cells showing a lower cell density. Array comparative genomic hybridization separately performed for each histologically distinct component demonstrated eight shared copy number alterations (CNAs) and three CNAs observed only in epithelioid cells; one of the latter was a homozygous deletion of a tumor suppressor gene, LSAMP, at 3q13.31. BRAF V600E mutation was observed both in epithelioid tumor cells and in diffusely infiltrating less atypical astrocytoma cells. Our findings suggest that the regional loss of LSAMP led to the aggressive nature of epithelioid cells in the present case of epithelioid glioblastoma.