Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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BACKGROUND: Although guideline-directed medical therapy (GDMT), including β-blockers, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs), improves survival and quality of life, most patients with heart failure with reduced (HFrEF) and mildly reduced (HFmrEF) ejection fraction are treated with inadequate medications. We investigated the prescription patterns of GDMT in elderly patients with HFrEF and HFmrEF and their characteristics, including the certification of long-term care insurance (LTCI), which represents frailty and disability.Methods and Results: This retrospective cross-sectional study analyzed 1,296 elderly patients with symptomatic HFrEF and HFmrEF with diuretic use (median age 78 years; 63.8% male; median left ventricular ejection fraction 40%). Prescription rates of GDMT were inadequate (ACEi, ARBs, β-blockers, and MRAs: 27.0%, 30.1%, 54.1%, and 41.9%, respectively). LTCI certification was independently associated with reduced prescription of all medications (ACEi/ARB: odds ratio [OR] 0.591, 95% confidence interval [CI] 0.449-0.778, P=0.001; β-blockers: OR 0.698, 95% CI 0.529-0.920, P<0.001; MRAs: OR 0.743, 95% CI 0.560-0.985, P=0.052). Patients with LTCI certification also had a high prevalence of polypharmacy and prescription of diuretics. CONCLUSIONS: Vulnerable patients with LTCI may be an explanation for the challenges in implementing GDMT, and communicating is required for favorable heart failure care in this population.

DOI： 10.1253/circj.CJ-22-0830

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/eip.13390

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/eip.13390

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BACKGROUND: A previous clinical trial for autoimmune pulmonary alveolar proteinosis (APAP) demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation reduced the mean density of the lung field on computed tomography (CT) across 18 axial slice planes at a two-dimensional level. In contrast, in this study, we challenged three-dimensional analysis for changes in CT density distribution using the same datasets. METHODS: As a sub-study of the trial, CT data of 31 and 27 patients who received GM-CSF and placebo, respectively, were analyzed. To overcome the difference between various shooting conditions, a newly developed automatic lung field segmentation algorithm was applied to CT data to extract the whole lung volume, and the accuracy of the segmentation was evaluated by five pulmonary physicians independently. For normalization, the percent pixel (PP) in a certain density range was calculated as a percentage of the total number of pixels from -1,000 to 0 HU. RESULTS: The automatically segmented images revealed that the lung field was accurately extracted except for 7 patients with minor deletion or addition. Using the change in PP from baseline to week 25 (ΔPP) as the vertical axis, we created a histogram with 143 HU bins set for each patient. The most significant difference in ΔPP between GM-CSF and placebo groups was observed in two ranges: from -1,000 to -857 and -143 to 0 HU. CONCLUSION: Whole lung extraction followed by density histogram analysis of ΔPP may be an appropriate evaluation method for assessing CT improvement in APAP.

DOI： 10.1159/000528038

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AIMS: Megalin, a proximal tubular endocytosis receptor, is excreted in urine in two forms: ectodomain (A-megalin) and full-length (C-megalin). We explored whether urinary megalin levels can be used as independent prognostic biomarkers in the progression of diabetic kidney disease (DKD). METHODS: The associations between baseline urinary A-megalin/creatinine (Cr) and/or C-megalin/Cr levels and the subsequent estimated glomerular filtration rate (eGFR) slope were analyzed using a generalized estimating equation. Patients were categorized into higher or lower groups based on the optimal cutoff values, obtained from a receiver operating characteristic curve, of the two forms of urinary megalin. RESULTS: We retrospectively analyzed 188 patients with type 2 diabetes. The eGFR slopes of the higher A-megalin/Cr and higher C-megalin/Cr groups were - 0.904 and -0.749 ml/min/1.73 m2/year steeper than those of the lower groups, respectively. Moreover, the eGFR slope was -1.888 ml/min/1.73 m2/year steeper in the group with both higher A- and higher C-megalin/Cr than in the other group. These results remained significant when adjusted for known urinary biomarkers (albumin, α1-microglobulin, β2-microglobulin, and N-acetyl-β-d-glucosaminidase). CONCLUSIONS: Urinary A- and C-megalin/Cr levels are likely to be prognostic biomarkers in the progression of DKD independent of other urinary biomarkers.

DOI： 10.1016/j.jdiacomp.2022.108312

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ctro.2022.09.005

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DOI： 10.1002/osi2.1122

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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BACKGROUND: Heart failure in elderly people causes physical and cognitive dysfunction and often requires long-term care insurance (LTCI); however, among patients with left ventricular (LV) systolic dysfunction, the incidence and risk factors of future LTCI requirements need to be elucidated.Methods and Results:The study included 1,852 patients aged ≥65 years with an echocardiographic LV ejection fraction (LVEF) ≤50%; we referred to their LTCI data and those of 113,038 community-dwelling elderly people. During a mean 1.7-year period, 332 patients newly required LTCI (incidence 10.7 per 100 person-years); the incidence was significantly higher than that for the community-dwelling people (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.32-1.64). On multivariate analysis, the risk factors at the time of echocardiography leading to future LTCI requirement were atrial fibrillation (HR, 1.588; 95% CI, 1.279-1.971), history of stroke (HR, 2.02; 95% CI, 1.583-2.576), osteoporosis (HR, 1.738; 95% CI, 1.253-2.41), dementia (HR, 2.804; 95% CI, 2.075-3.789), hypnotics (HR, 1.461; 95% CI, 1.148-1.859), and diuretics (HR, 1.417; 95% CI, 1.132-1.773); however, the LVEF was not a risk factor (HR, 0.997; 95% CI, 0.983-1.011). CONCLUSIONS: In elderly patients with LV systolic dysfunction, the incidence of LTCI requirement was more common than that for community-dwelling people; its risk factors did not include LVEF, but included many other non-cardiac comorbidities and therapies, suggesting the need for interdisciplinary cooperation to prevent disabilities.

DOI： 10.1253/circj.CJ-21-0580

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BACKGROUND: Low-dose droperidol has been reported to suppress the amplitude of transcranial electrical motor-evoked potentials (TCE-MEPs), but no randomized controlled trials have been conducted to assess this. This randomized, double-blinded, placebo-controlled trial aimed to test the hypothesis that low-dose droperidol reduced TCE-MEP amplitudes. METHODS: Twenty female patients with adolescent idiopathic scoliosis, aged between 12 and 20 years, and scheduled to undergo corrective surgery were randomly allocated to receive droperidol (20 µg/kg) or 0.9% saline. After recording baseline TCE-MEPs, the test drug was administered, following which TCE-MEP recordings were carried out every 2 minutes for up to 10 minutes. The primary outcome was the minimum relative TCE-MEP amplitude (peak-to-peak amplitude, percentage of baseline value) recorded in the left tibialis anterior muscle. Secondary outcomes included minimum relative MEP amplitudes recorded from all other muscle groups monitored in the study. Data are expressed as medians (interquartile range). RESULTS: The TCE-MEP amplitude of the left tibialis anterior muscle was significantly reduced following droperidol administration compared with saline (37% [30% to 55%] vs. 76% [58% to 93%], respectively, P<0.01). In the other muscles, the amplitudes were reduced in the droperidol group, except for the bilateral abductor pollicis brevis and the left quadriceps femoris muscles. The relative amplitude of the bilateral F waves recorded from the gastrocnemius was decreased in the droperidol group. CONCLUSIONS: Low-dose droperidol (20 µg/kg) reduced TCE-MEP amplitudes. Anesthesiologists should pay attention to the timing of droperidol administration during intraoperative TCE-MEP recordings, even if used in a low dose.

DOI： 10.1097/ANA.0000000000000784

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：English   Publisher：(一社)日本循環器学会  

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Language：English   Publisher：(一社)日本循環器学会  

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INTRODUCTION: The precise blood glucose (BG) profile of hemodialysis patients is unclear, as is the effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors in hemodialysis patients with type 2 diabetes. Here, we used continuous glucose monitoring (CGM) to evaluate BG variability in these patients and to assess the efficacy of DPP-4 inhibitors, particularly during hemodialysis sessions and at nighttime (UMIN000012638). METHODS: We examined BG profiles using CGM in 31 maintenance hemodialysis patients with type 2 diabetes. Differences between patients with and without DPP-4 inhibitors (n = 15 and 16, respectively) were analyzed using a linear mixed-effects model to assess changes in glucose levels in 5-min intervals. RESULTS: The model revealed that DPP-4 inhibitor use was significantly associated with suppression of a rapid drop in glucose levels, both with and without adjustment for BG levels at the start of hemodialysis. Moreover, the model revealed that the two groups differed significantly in the pattern of changes in BG levels from 0:00 to 6:55 am. DPP-4 inhibitors suppressed the tendency for subsequent nocturnal hypoglycemia. CONCLUSIONS: This prospective observational exploratory study showed that DPP-4 inhibitors could suppress BG variability during hemodialysis sessions as well as subsequent nocturnal changes in patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, UMIN000012638.

DOI： 10.1007/s13300-020-00928-5

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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BACKGROUND: Parechovirus-A3 (PeV-A3) and the enteroviruses (EVs) are the most common viral pathogens responsible for sepsis and meningoencephalitis in neonates and young infants; however, differences in the clinical presentations of two infections are not well described. OBJECTIVES: To describe the clinical presentations of PeV-A3- and EVs-related diseases and develop a novel scoring system to differentiate two diseases. STUDY DESIGN: This prospective study used real-time PCR and genetic sequencing to evaluate viral etiologies of febrile neonates and infants <4 months with suspected sepsis or meningoencephalitis in Niigata area, Japan, in 2014-2016. The clinical manifestations of PeV-A3- and EVs-infected patients were compared, and a novel scoring system was developed after identifying the most distinguishable clinical findings, followed by the external cohort validation. RESULTS: In 210 patients evaluated, we identified 56 PeV-A3-infected (27%) and 43 EVs-infected (20%) patients. The following clinical manifestations were significant in PeV-A3-infected patients, as compared with EVs-infected patients; a higher body temperature (38.9°C vs. 38.5°C, P < .01) and heart rate (181/min vs. 168/min, P = .01), cold extremities (72% vs. 34%, P < .01) and skin mottling (65% vs. 23%, P < .01), lower white blood cell count (5,200/μL vs. 8,900/μL, P < .01) and incidence of cerebrospinal fluid (CSF) pleocytosis (2% vs. 63%, P < .01). Using some of these significant findings, the scoring system successfully distinguished the diseases (accuracy: 86% and 83% for the derivative and external validation cohorts, respectively). CONCLUSIONS: We found significant clinical manifestations in PeV-A3-infected patients compared to EVs-infected patients. The scoring system may be helpful to distinguish two infections, especially at onset of outbreak.

DOI： 10.1016/j.jcv.2019.104256

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Very recently, a modest but significant efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation therapy for the treatment of mild to moderate autoimmune pulmonary alveolar proteinosis (aPAP) has been reported. As the ability to measure the level of GM-CSF autoantibody (GMAb) in the serum is required to decide the indication for this therapy, we developed a high-performance GMAb testing kit for clinical use. As the kit succeeded in reducing nonspecific IgG binding to the ELISA plate, the predictive performance shown in the training study to discriminate aPAP patients from healthy subjects was perfect, providing a cut-off value of 1.65 U·mL-1 in 78 patients with aPAP and 90 healthy subjects in an operator-blinded manner using logistic regression analysis. As in the validation study, serum samples from another 213 patients with aPAP were also blinded and evaluated in an operator-blinded manner against external 207 samples from patients with other types of PAP and patients exhibiting various ground-glass opacities on chest high-resolution computed tomography that require discrimination from PAP. The logistic regression analysis of these validation data sets revealed values of 97.6% and 100% for specificity and sensitivity, respectively. Thus, this new GMAb testing kit is reliable for the diagnosis of aPAP and differential diagnosis of other lung diseases.

DOI： 10.1183/23120541.00259-2019

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DOI： 10.1056/NEJMc1914606

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DOI： 10.3390/nu11122919

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DOI： 10.1002/rcr2.494

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MASSACHUSETTS MEDICAL SOC  

Background Pulmonary alveolar proteinosis is a disease characterized by abnormal accumulation of surfactant in the alveoli. Most cases are autoimmune and are associated with an autoantibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) that prevents clearing of pulmonary surfactant by alveolar macrophages. An open-label, phase 2 study showed some therapeutic efficacy of inhaled recombinant human GM-CSF in patients with severe pulmonary alveolar proteinosis; however, the efficacy in patients with mild-to-moderate disease remains unclear. Methods We conducted a double-blind, placebo-controlled trial of daily inhaled recombinant human GM-CSF (sargramostim), at a dose of 125 mu g twice daily for 7 days, every other week for 24 weeks, or placebo in 64 patients with autoimmune pulmonary alveolar proteinosis who had a partial pressure of arterial oxygen (Pao(2)) while breathing ambient air of less than 70 mm Hg (or <75 mm Hg in symptomatic patients). Patients with severe pulmonary alveolar proteinosis (Pao(2) <50 mm Hg) were excluded to avoid possible exacerbation of the disease in patients who were assigned to receive placebo. The primary end point was the change in the alveolar-arterial oxygen gradient between baseline and week 25. Results The change in the mean (+/- SD) alveolar-arterial oxygen gradient was significantly better in the GM-CSF group (33 patients) than in the placebo group (30 patients) (mean change from baseline, -4.50 +/- 9.03 mm Hg vs. 0.17 +/- 10.50 mm Hg; P=0.02). The change between baseline and week 25 in the density of the lung field on computed tomography was also better in the GM-CSF group (between-group difference, -36.08 Hounsfield units; 95% confidence interval, -61.58 to -6.99, calculated with the use of the Mann-Whitney U test and the Hodges-Lehmann estimate of confidence intervals for pseudo-medians). Serious adverse events developed in 6 patients in the GM-CSF group and in 3 patients in the placebo group. Conclusions In this randomized, controlled trial, inhaled recombinant human GM-CSF was associated with a modest salutary effect on the laboratory outcome of arterial oxygen tension, and no clinical benefits were noted.

DOI： 10.1056/NEJMoa1816216

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DOI： 10.1016/j.imlet.2019.05.013

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：EUROPEAN RESPIRATORY SOC JOURNALS LTD  

The incidence and prevalence of autoimmune pulmonary alveolar proteinosis in Japan were previously estimated to be 0.49 and 6.2 per million, respectively. Thereafter, an increase in serological diagnosis forced a re-estimation of the incidence based on more contemporaneous data using more robust methods.Sera of 702 patients were positive for granulocyte-macrophage colony-stimulating factor autoantibody during the 2006-2016 period (group A). Of these patients, 43 were actively surveyed in Niigata prefecture (group B) for estimation of the incidence. To estimate the survival period, 103 patients (group C) were investigated retrospectively for the 1999-2017 period using restricted mean survival time.In group A, the number of patients diagnosed in each prefecture was closely correlated with the corresponding population, indicating no regional integration of onset. In group B, a total of 43 patients were diagnosed, the annual number followed a Poisson distribution and the incidence was thus estimated to be 1.65 per million. In group C, the retrospective cohort study revealed the mean survival period to be 16.1 years. Taken together, the prevalence was estimated to be 26.6 per million, indicating that the previous data for incidence and prevalence was an underestimation.

DOI： 10.1183/23120541.00190-2018

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During a clinical trial of a Saccharomyces cerviciae-derived recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), sargramostim, in patients with autoimmune pulmonary alveolar proteinosis (aPAP), we conducted a pharmacokinetic study of single-dose sargramostim inhalation. Several problems were encountered whereby sargramostim formed an immune-complex with GM-CSF autoantibodies (GMAbs) immediately after entering the body; thus, we could not measure the concentration of sargramostim using a commercial high sensitivity enzyme-linked immunosorbent assay (ELISA). Moreover, the ELISA could not discriminate inhaled sargramostim from intrinsic GM-CSF. To solve these problems, we developed a novel ELISA system with a capture antibody that is specific for sargramostim and a detection antibody capable of binding with GM-CSF. This system quantified the serum sargramostim concentration, but not E. coli-, CHO-, or HEK293T-derived human recombinant GM-CSF. Using this system, serum pharmacokinetics were estimated in five patients after inhalation of 250 μg sargramostim, with a mean Cmax of 9.7 ± 2.85 pg/ml at a Tmax of 2 ± 1.22 h.

DOI： 10.1016/j.jim.2018.05.012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

PurposeLymphangioleiomyomatosis is a rare lung disease caused by proliferation of abnormal smooth muscle-like cells and typically occurs in premenopausal women. Sirolimus is now the first-line drug for the treatment of lymphangioleiomyomatosis. Sirolimus-induced stomatitis is the most frequent adverse event experienced during treatment. To identify risk factors, we investigated the association of stomatitis incidence with patient background data and treatment parameters, using data from the multicenter long-term sirolimus trial.
MethodsSubjects received sirolimus for 2years at doses adjusted to maintain a trough blood level of 5 to 15ng/mL. The incidence of stomatitis was correlated with baseline demographics, clinical characteristics, and changes in the longitudinal data. Risk factors at baseline were assessed by using univariate and multivariate analyses.
ResultsThe most frequent adverse event was stomatitis, with the cumulative rate reaching 88.9% by 9months, higher than that reported in postrenal transplant patients. The repetition, the duration, and the severity of stomatitis events were variable among patients. We found that patients with low hemoglobin (Hb) (&lt;14.5g/dL) showed significantly higher incidence than those with high Hb (14.5g/dL, P&lt;.01). The cumulative rate for stomatitis incidence was significantly associated with a decrease in the mean corpuscular volume, while the Hb level was constant; thus, red blood cell count in patients increased during the study.
ConclusionsBaseline Hb levels and a decrease in mean corpuscular volume during treatment were correlated with the incidence of stomatitis.

DOI： 10.1002/pds.4259

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Persistent endoleaks may lead to adverse events after endovascular aortic repair. We prospectively examined the relationship between intraoperative residual spontaneous echocardiographic contrast (SEC) within the aneurysmal sac and the incidence of postoperative endoleaks in 60 patients undergoing thoracic endovascular aortic repair. Patients with SEC had a higher incidence of postoperative endoleaks than did patients without SEC within a few days postoperatively (60.0% vs 12.5%, respectively; P &lt; .001) and at 6 months postoperatively (40.0% vs 2.5%, respectively; P &lt; .001). Intraoperative confirmation of the absence of SEC may identify patients at low risk for persistent endoleaks after thoracic endovascular aortic repair.

DOI： 10.1213/ANE.0000000000002207

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: The oral hygiene of patients with a mental illness is an important concern in psychiatric care, and it is necessary to increase the level of self-care among these patients. In this study, we administered an oral care questionnaire to people with mental illness in Japan and compared their answers before (baseline) and at 1 week and 1, 3 and 6 months after they participated in an educational program.
Methods: The questionnaire was distributed to 390 patients. It included questions about age, education, income, between-meal snacks, number of teeth, frequency of tooth brushing, and other items. The educational program was developed for the purposes of improving self-care.
Results: Before the program, the proportion of male patients who had had a mental illness for &gt;= 10 years was significantly higher among those patients who did not brush their teeth before bed. In addition, such patients did not have primary care dentists, and a significantly higher proportion of male patients, compared with female patients, did not undergo routine dental checkups more than once per year. The educational program resulted in an improvement in the use of fluoride toothpaste from baseline to 6 months after the intervention (p = 0.001). The daily use of interdental brushes or floss was significantly different 6 months after the intervention.
Conclusions: Male and long-term inpatients need oral hygiene instructions. Our educational program showed the effects of using oral hygiene tools. Future studies should include a control group to measure the impact of the educational program.

DOI： 10.1186/s12903-017-0372-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Thoracic Society  

Rationale: Sirolimus has been shown in a randomized, controlled clinical trial to stabilize lung function in patients with lymphangioleiomyomatosis (LAM) treated for a 12-month time period
however the pretreatment decline in lung function after the drug was discontinued indicated that continued exposure is required to suppress disease progression. Objectives: To elucidate the durability and tolerability of long-term sirolimus treatment in Asian patients with LAM. Methods: We conducted a single-arm, open-label, investigatorinitiated safety and efficacy study of sirolimus in 63 women with LAM at 9 sites in Japan. Subjects received sirolimus for 2 years at doses adjusted to maintain a trough blood level of 5-15 ng/ml. Measurements and Main Results: Fifty-two subjects (82.5%) completed the trial with mean drug compliance of more than 80% overall during the study. The number of adverse events was greatest during the initial 6 months of therapy, but they continued to occur with declining frequency throughout the 2-year study period. Of the 1,549 adverse events, 27 were classified as serious, including reversible sirolimus pneumonitis in 3 patients. New hypercholesterolemia occurred in 30 patients (48%)
microcytosis in 10 patients
loss of body weight in 33 patients
and increase in blood pressure that required treatment in 5 patients. FEV1, FVC, and quality-of-life parameters were stable in the overall study cohort during the study period, but baseline to 2-year improvements in lung function occurred in the subset of patients with a prior history of chylothorax. Conclusions: Although long-term sirolimus treatment of Asian patients with LAM was associated with a large number of adverse events, including three episodes of pneumonitis, most patients completed the 2-year course of medication with good drug compliance and stable quality of life and lung function.

DOI： 10.1513/AnnalsATS.201605-335OC

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DOI： 10.1513/AnnalsATS.201605-335OC

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Publishing type：Research paper (scientific journal)   Publisher：AMER THORACIC SOC  

Rationale: Sirolimus has been shown in a randomized, controlled clinical trial to stabilize lung function in patients with lymphangioleiomyomatosis (LAM) treated for a 12-month time period; however the pretreatment decline in lung function after the drug was discontinued indicated that continued exposure is required to suppress disease progression. Objectives: To elucidate the durability and tolerability of long-term sirolimus treatment in Asian patients with LAM. Methods: We conducted a single-arm, open-label, investigator-initiated safety and efficacy study of sirolimus in 63 women with LAM at 9 sites in Japan. Subjects received sirolimus for 2 years at doses adjusted to maintain a trough blood level of 5-15 ng/ml. Measurements and Main Results: Fifty-two subjects (82.5%) completed the trial with mean drug compliance of more than 80% overall during the study. The number of adverse events was greatest during the initial 6 months of therapy, but they continued to occur with declining frequency throughout the 2-year study period. Of the 1,549 adverse events, 27 were classified as serious, including reversible sirolimus pneumonitis in 3 patients. New hypercholesterolemia occurred in

DOI： 10.1513/AnnalsATS.201605-335OC

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC NEPHROLOGY  

Obesity, an important risk factor for metabolic syndrome (MetS) and cardiovascular disease, is often complicated by CKD, which further increases cardiovascular risk and causes ESRD. To elucidate the mechanism underlying this relationship, we investigated the role of the endocytic receptor megalin in proximal tubule epithelial cells (PTECs). We studied a high-fat diet (HFD)-induced obesity/MetS model using kidney-specific mosaic megalin knockout (KO) mice. Compared with control littermates fed a normal-fat diet, control litter mates fed an HFD for 12 weeks showed autolysosomal dysfunction with autophagy impairment and increased expression of hypertrophy, lipid peroxidation, and senescence markers in PTECs of the S2 segment, peritubular capillary rarefaction with localized interstitial fibrosis, and glomerular hypertrophy with mesangial expansion. These were ameliorated in HFD-fed megalin KO mice, even though these mice had the same levels of obesity, dyslipidemia, and hyperglycemia as HFD-fed control mice. Intravital renal imaging of HFD-fed wild-type mice also demonstrated the accumulation of autofluorescent lipofuscin-like substances in PTECs of the S2 segment, accompanied by focal narrowing of tubular lumens and peritubular capillaries. In cultured PTECs, fatty acid-rich albumin induced the increased expression of genes encoding PDGF-B and monocyte chemoattractant protein-1 via megalin, with large (auto)lysosome formation, compared with fatty acid-depleted albumin. Collectively, the megalin-mediated endocytic handling of glomerular-filtered (lipo)toxic substances appears to be involved primarily in hypertrophic and senescent PTEC injury with autophagy impairment, causing peritubular capillary damage and retrograde glomerular alterations in HFD-induced kidney disease. Megalin could be a therapeutic target for obesity/MetS-related CKD, independently of weight, dyslipidemia, and hyperglycemia modification.

DOI： 10.1681/ASN.2015020190

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMC  

Background: Although no report has demonstrated the efficacy of corticosteroid therapy for autoimmune pulmonary alveolar proteinosis (aPAP), we sometimes encounter patients who have received this therapy for various reasons. However, as corticosteroids can suppress alveolar macrophage function, corticosteroid therapy might worsen disease severity and increase the risk of infections.
Methods: For this retrospective cohort study, we sent a screening form to 165 institutions asking for information on aPAP patients treated with corticosteroids. Of the resulting 45 patients screened, 31 were enrolled in this study. We collected demographic data and information about corticosteroid treatment period, dose, disease severity score (DSS) over the treatment period, and complications.
Results: DSS deteriorated during corticosteroid therapy in 23 cases (74.1 %) and the estimated overall cumulative worsening rate was 80.8 % for the total observation period. The worsening rate was significantly higher in patients treated with high-dose prednisolone (&gt; 18.9 mg/day, n = 16) than treated with low-dose prednisolone (&lt;= 18.9 mg/day, n = 15) divided by median daily dose (p &lt; 0.02). Of patients with worsening, one died of disseminated aspergillosis and another of respiratory failure. Infections newly emerged in 6 cases during corticosteroid therapy (p &lt; 0.05). Median serum granulocyte/macrophage colony-stimulating factor (GM-CSF) autoantibody levels were similar to previously reported data in a large cohort study.
Conclusion: The results demonstrate that corticosteroid therapy may worsen DSS of aPAP, increasing the risk for infections.

DOI： 10.1186/s12890-015-0085-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMC  

Background: Cytogenomic mutations and chromosomal abnormality are implicated in the neuropathology of several brain diseases. Cell heterogeneity of brain tissues makes their detection and validation difficult, however. In the present study, we analyzed gene dosage alterations in brain DNA of schizophrenia patients and compared those with the copy number variations (CNVs) identified in schizophrenia patients as well as with those in Asian lymphocyte DNA and attempted to obtain hints at the pathological contribution of cytogenomic instability to schizophrenia.Results: Brain DNA was extracted from postmortem striatum of schizophrenia patients and control subjects (n = 48 each) and subjected to the direct two color microarray analysis that limits technical data variations. Disease-associated biases of relative DNA doses were statistically analyzed with Bonferroni's compensation on the premise of brain cell mosaicism. We found that the relative gene dosage of 85 regions significantly varied among a million of probe sites. In the candidate CNV regions, 26 regions had no overlaps with the common CNVs found in Asian populations and included the genes (i.e., ANTXRL, CHST9, DNM3, NDST3, SDK1, STRC, SKY) that are associated with schizophrenia and/or other psychiatric diseases. The majority of these candidate CNVs exhibited high statistical probabilities but their signal differences in gene dosage were less than 1.5-fold. For test evaluation, we rather selected the 10 candidate CNV regions that exhibited higher aberration scores or larger global effects and were thus confirmable by PCR. Quantitative PCR verified the loss of gene dosage at two loci (1p36.21 and 1p13.3) and confirmed the global variation of the copy number distributions at two loci (11p15.4 and 13q21.1), both indicating the utility of the present strategy. These test loci, however, exhibited the same somatic CNV patterns in the other brain region.Conclusions: The present study lists the candidate regions potentially representing cytogenomic CNVs in the brain of schizophrenia patients, although the significant but modest alterations in their brain genome doses largely remain to be characterized further.

DOI： 10.1186/s13039-015-0144-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER PHYSIOLOGICAL SOC  

Whole-lung lavage (WLL) remains the standard therapy for pulmonary alveolar proteinosis (PAP), a process in which accumulated surfactants are washed out of the lung with 0.5-2.0 l of saline aliquots for 10 -30 wash cycles. The method has been established empirically. In contrast, the kinetics of protein transfer into the lavage fluid has not been fully evaluated either theoretically or practically. Seventeen lungs from patients with autoimmune PAP underwent WLL. We made accurate timetables for each stage of WLL, namely, instilling, retaining, draining, and preparing. Subsequently, we measured the volumes of both instilled saline and drained lavage fluid, as well as the concentrations of proteins in the drained lavage fluid. We also proposed a mathematical model of protein transfer into the lavage fluid in which time is a single variable as the protein moves in response to the simple diffusion. The measured concentrations of IgG, transferrin, albumin, and beta(2)-microglobulin closely matched the corresponding theoretical values calculated through differential equations. Coefficients for transfer of beta(2)-microglobulin from the blood to the lavage fluid were two orders of magnitude higher than those of IgG, transferrin, and albumin. Simulations using the mathematical model showed that the cumulative amount of eliminated protein was not affected by the duration of each cycle but dependent mostly on the total time of lavage and partially on the volume instilled. Although physicians have paid little attention to the transfer of substances from the lung to lavage fluid, WLL seems to be a procedure that follows a diffusion-based mathematical model.

DOI： 10.1152/ajplung.00239.2014

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DOI： 10.4172/2157-7420.1000180

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

To date, the biological activity of granulocyte macrophage-colony stimulating factor (GM-CSF) has been investigated by using mostly Escherichia coli- or yeast cell-derived recombinant human GM-CSF (erhGM-CSF and yrhGM-CSF, respectively). However, Chinese hamster ovary cell-derived recombinant human GM-CSF (crhGM-CSF), as well as natural human GM-CSF, is a distinct molecule that includes modifications by complicated oligosaccharide moieties. In the present study, we reevaluated the bioactivity of crhGM-CSF by comparing it with those of erhGM-CSF and yrhGM-CSF. The effect of short-term stimulation (0.5 h) on the activation of neutrophils/monocytes or peripheral blood mononuclear cells (PBMCs) by crhGM-CSF was lower than those with erhGM-CSF or yrhGM-CSF at low concentrations (under 60 pM). Intermediate-term stimulation (24 h) among the different rhGM-CSFs with respect to its effect on the activation of TF-1 cells, a GM-CSF-dependent cell line, or PBMCs was not significantly different. In contrast, the proliferation/survival of TF-1 cells or PBMCs after long-term stimulation (72-168 h) was higher at low concentrations of crhGM-CSF (15-30 pM) than that of cells treated with other GM-CSFs. The proportion of apoptotic TF-1 cells after incubation with crhGM-CSF for 72 h was lower than that of cells incubated with other rhGM-CSFs. These effects were attenuated by desialylation of crhGM-CSF. Clearance of crhGM-CSF but not desialylated-crhGM-CSF by both TF-1 cells and PBMCs was delayed compared with that of erhGM-CSF or yrhGM-CSF. These results suggest that sialylation of oligosaccharide moieties delayed the clearance of GM-CSF, thus eliciting increased long-term bioactivity in vitro. (C) 2014 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.cyto.2014.03.009

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

The spreading of neurofibrillary tangles (NFTs), intraneuronal aggregates of highly phosphorylated microtubule-associated protein tau, across the human brain is correlated with the cognitive severity of Alzheimer's disease (AD). To identify genes relevant to NFT expansion defined by the Braak stage, we conducted whole-genome exon array analysis with an exploratory sample set consisting of 213 human post-mortem brain tissue specimens from the entorinal, temporal and frontal cortices of 71 brain-donor subjects: Braak NFT stages 0 (N = 13), I-II (N = 20), III-IV (N = 19) and V-VI (N = 19). We identified eight genes, RELN, PTGS2, MYO5C, TRIL, DCHS2, GRB14, NPAS4 and PHYHD1, associated with the Braak stage. The expression levels of three genes, PHYHD1, MYO5C and GRB14, exhibited reproducible association on real-time quantitative PCR analysis. In another sample set, including control subjects (N = 30), and in patients with late-onset AD (N = 37), dementia with Lewy bodies (N = 17) and Parkinson disease (N = 36), the expression levels of two genes, PHYHD1 and MYO5C, were obviously associated with late-onset AD. Protein-protein interaction network analysis with a public database revealed that PHYHD1 interacts with MYO5C via POT1, and PHYHD1 directly interacts with amyloid beta-peptide 42. It is thus likely that functional failure of PHYHD1 and MYO5C could lead to AD development.

DOI： 10.1038/tp.2014.35

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Objective: To quantify negative aesthetic ratings in primary unrepaired cleft lip infants by further refining our previously reported paired comparison method. Design: The Thurstone paired comparison method was used to quantify negative aesthetic ratings of plaster facial models selected and ordered according to a table of paired random numbers. Patients, Participants: A total of 30 facial models of unrepaired incomplete unilateral cleft lip infants were used in this study. Raters comprised 20 oral surgeons and anesthesiologists. Results: Quantification of aesthetic ratings for the 30 face models of unrepaired incomplete unilateral cleft lip infants was obtained. The ratings ranged from 0 to 5.08. Conclusion: Quantification of the aesthetic ratings for the 30 face models will be used as objective variables in a multivariate analysis in the third stage of this ongoing study. © Copyright 2014 American Cleft Palate-Craniofacial Association.

DOI： 10.1597/11-124

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Rare non-synonymous variants of TREM2 have recently been shown to be associated with Alzheimer's disease (AD) in Caucasians. We here conducted a replication study using a well-characterized Japanese sample set, comprising 2,190 late-onset AD (LOAD) cases and 2,498 controls. We genotyped 10 non-synonymous variants (Q33X, Y38C, R47H, T66M, N68K, D87N, T96K, R98W, H157Y, and L211P) of TREM2 reported by Guerreiro et al. (2013) by means of the TaqMan and dideoxy sequencing methods. Only three variants, R47H, H157Y, and L211P, were polymorphic (range of minor allele frequency [MAF], 0.0002-0.0059); however, no significant association with LOAD was observed in these variants. Considering low MAF of variants examined and our study sample size, further genetic analysis with a larger sample set is needed to firmly evaluate whether or not TREM2 is associated with LOAD in Japanese.

DOI： 10.3233/JAD-140225

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Previous studies demonstrated that antigranulocyte colony-stimulating factor autoantibody (GMAb) was consistently present in patients with autoimmune pulmonary alveolar proteinosis (aPAP), and, thus, represented candidature as a reliable diagnostic marker. However, our large cohort study suggested that the concentration of this antibody was not correlated with disease severity in patients. We found that the kappa/lambda ratio of GMAb was significantly correlated with the degree of hypoxemia. The proportion of lambda-type GMAb per total lambda-type IgG was significantly higher in severely affected patients than those in mildly affected patients, but the proportion of kappa-type was unchanged. The kappa/lambda ratio was significantly correlated with both KL-6 and SP-D, which have been previously reported as disease severity markers. Thus, the light chain isotype usage of GMAb may not only be associated with the severity of aPAP, but may also represent a useful disease severity marker. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.clim.2013.10.002

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Background: Molecular biomarkers are essential for monitoring treatment effects, predicting prognosis, and improving survival rate in oral squamous cell carcinoma. This study sought to verify the effectiveness of two integrin gene expression ratios as biomarkers.Methods: Gene expression analyses of integrin α3 (ITGA3), integrin β4 (ITGB4), CD9 antigen (CD9), and plakoglobin (JUP) by quantitative real-time PCR were conducted on total RNA from 270 OSCC cases. The logrank test, Cox proportional hazards model, and Kaplan-Meier estimates were performed on the gene expression ratios of ITGA3/CD9 and ITGB4/JUP and on the clinicopathological parameters for major clinical events.Results: A high rate (around 80%) of lymph node metastasis was found in cases with a high ITGA3/CD9 ratio (high-ITGA3/CD9) and invasive histopathology (YK4). Primary site recurrence (PSR) was associated with high-ITGA3/CD9, T3-4 (TNM class), and positive margin, indicating that PSR is synergistically influenced by treatment failure and biological malignancy. A high ITGB4/JUP ratio (high-ITGB4/JUP) was revealed to be a primary contributor to distant metastasis without the involvement of clinicopathological factors, suggesting intervention of a critical step dependent on the function of the integrin β4 subunit. Kaplan-Meier curves revealed positive margin as a lethal treatment consequence in high-ITGA3/CD9 and YK4 double-positive cases.Conclusion: Two types of metastatic trait were found in OSCC: locoregional dissemination, which was reflected by high-ITGA3/CD9, and distant metastasis through hematogenous dissemination, uniquely distinguished by high-ITGB4/JUP. The clinical significance of the integrin biomarkers implies that biological mechanisms such as cancer cell motility and anchorage-independent survival are vital for OSCC recurrence and metastasis. © 2013 Nagata et al.
licensee BioMed Central Ltd.

DOI： 10.1186/1471-2407-13-410

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IOS PRESS  

SORL1 was shown to be genetically associated with late-onset Alzheimer's disease (LOAD) in a large-scale genome-wide association study (GWAS) involving clinically verified subjects. Here, we attempted to replicate the association of SORL1 in Japanese neuropathologically characterized brain donor subjects (LOAD, 213; control, 370) through a single-nucleotide polymorphism (SNP)-based genetic study involving 19 SNPs: 11 SNPs were selected from the initial study reported by Rogaeva et al. (2007), and the other eight were from our GWAS. Among these SNPs, five exhibited a significant association with LOAD after multiple test correction (p &lt; 2.63E-03 [=0.05/19]), which was supported by means of multiple logistic regression analysis with adjustment for age, gender, and carrier status of the APOE epsilon 4 allele. Three of these SNPs (rs985421, rs12364988 [Rogaeva's SNP 7], and rs4598682) were encompassed by a 5' linkage disequilibrium (LD) region, and the remaining two (rs3781834 and rs3781836) by a 3' LD region. Strong LD among SNPs was observed within each LD region, implying that there are two genomic regions showing association with LOAD in SORL1. Case-control haplotype analysis demonstrated that some haplotypes are associated with LOAD in both LD regions. Our replication study strongly supports the preceding evidence that SORL1 is likely one of the genes associated with LOAD.

DOI： 10.3233/JAD-122395

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Objectives. The aim of the present study was to evaluate the factors affecting the prognosis of the autotransplantation of teeth with complete root formation.
Study Design. A total of 259 transplanted teeth were studied. The significance of each of the prognostic factors was examined in 2 ways, first in a univariate analysis and then in a multivariate analysis. The comprehensive risk combining these factors that remained after multivariate analysis was calculated.
Results. Among 259 transplanted teeth, 27 (10.4%) were judged as unsuccessful cases. In the multivariate analysis, history of root canal treatment of donor tooth, multirooted, maxillary tooth as a donor, and duration of tooth absence at recipient site remained significantly associated with unsuccessful transplantation. Multifarious combination of the significant prognostic factors can decrease the comprehensive risk.
Conclusions. Minimizing the comprehensive risk by combining significant prognostic factors improved the prognosis of autotransplantation of teeth with complete root formation. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114(suppl 5):S216-S228)

DOI： 10.1016/j.oooo.2011.09.037

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC CANCER RESEARCH  

Purpose: High-grade serous ovarian cancers are heterogeneous not only in terms of clinical outcome but also at the molecular level. Our aim was to establish a novel risk classification system based on a gene expression signature for predicting overall survival, leading to suggesting novel therapeutic strategies for high-risk patients.
Experimental Design: In this large-scale cross-platform study of six microarray data sets consisting of 1,054 ovarian cancer patients, we developed a gene expression signature for predicting overall survival by applying elastic net and 10-fold cross-validation to a Japanese data set A (n = 260) and evaluated the signature in five other data sets. Subsequently, we investigated differences in the biological characteristics between high-and low-risk ovarian cancer groups.
Results: An elastic net analysis identified a 126-gene expression signature for predicting overall survival in patients with ovarian cancer using the Japanese data set A (multivariate analysis, P = 4 x 10(-20)). We validated its predictive ability with five other data sets using multivariate analysis (Tothill's data set, P = 1 x 10(-5); Bonome's data set, P = 0.0033; Dressman's data set, P = 0.0016; TCGA data set, P = 0.0027; Japanese data set B, P = 0.021). Through gene ontology and pathway analyses, we identified a significant reduction in expression of immune-response-related genes, especially on the antigen presentation pathway, in high-risk ovarian cancer patients.
Conclusions: This risk classification based on the 126-gene expression signature is an accurate predictor of clinical outcome in patients with advanced stage high-grade serous ovarian cancer and has the potential to develop new therapeutic strategies for high-grade serous ovarian cancer patients. Clin Cancer Res; 18(5); 1374-85. (C)2012 AACR.

DOI： 10.1158/1078-0432.CCR-11-2725

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE  

Autotransplantation is often performed to replace a missing tooth, but tooth autotransplantation has been reported in fewer teeth with complete root formation than those with incomplete root formation. The aim of this prospective study was to evaluate the factors that affect the prognosis of autotransplantation of teeth with complete root formation. 109 patients with 117 transplants were studied. Of the 117 transplants investigated, 14(12%) failed during the observation period. The overall 1-year survival rate was 96%; the 5-year survival rate was 84%. The major causes of failure were unsuccessful initial healing and replacement root resorption with periodontal inflammation. Factors significantly associated with unsuccessful transplantation, in single factor analysis, were age 40 years or more, molar tooth as donor, probing pocket depth to 4 mm or more, history of root canal treatment, multi-rooted teeth and fixation with sutures. Pocket depth of 4 mm or more and history of root canal treatment appeared to increase the risk of unsuccessful transplantation in multivariate analysis. It is suggested that the pocket depth of the donor tooth and history of root canal treatment are related to the healing of paratransplantal tissue and root resorption.

DOI： 10.1016/j.ijom.2010.06.018

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-LISS  

Accurate assessment of malignancy in oral squamous cell carcinoma is essential to optimize treatment planning. To detect a biomarker related to malignant propensity in gingival squamous cell carcinoma (GSCC), quantitative gene expression analysis of tetraspanin family genes was conducted. In 73 cases of GSCC, total RNA was extracted from carcinoma tissues, and gene expression was analyzed by quantitative real time-PCR. Six tetraspanin family genes (CD9, CD63, CD81, CD82, CD151, NAG-2) were investigated. Housekeeping genes (ACTB and GAPDH), anchor protein genes (JUP and PXN) and an integrin gene (ITGA3) were used as reference genes. Forty-five gene expression ratios were calculated from these It gene expression levels and were analyzed with clinical parameters using multivariate statistical methods. According to the results of the logistic regression analysis subjecting cervical lymph node metastasis as a target variable, CD9/ACTB (p = 0.0.13) or CD9/CD82 (p = 0.013) in addition to tumor size (p = 0.028) were detected as significant factors. In Cox proportional hazards regression analysis, delayed cervical lymph node metastasis (p = 0.039) and tumor cell positive surgical margin (p = 0.032) in addition to CD151/GAPDH (p = 0.024) were detected as significant factors for death outcome. A Kaplan-Meier survival curve presented a significantly lower survival rate of the group with a CD151/GAPDH value of 10 or more (log rank and generalized Wilcoxon tests: p = 0.0003). Results of this study present the usefulness of CD9 and CD151 expression levels as biomarkers for assessment of malignancy in GSCC. They also indicate that detection of residual tumor cells at the surgical margin and the biological malignancy of a tumor interdependently affects prognosis. (C) 2009 UICC

DOI： 10.1002/ijc.24297

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY-ELSEVIER  

Objective. The objective of this study was to assess the influence of factors of obesity and craniofacial morphology on the degree of obstructive sleep apnea syndrome (OSAS) in Japanese individuals.
Study design. The subjects were 138 adult male patients who visited the Clinic for Snoring & Obstructive Sleep Apnea at Niigata University Medical and Dental Hospital with chief complaints of snoring and apnea. Standardized lateral cephalograms were taken at the first visit, and overnight polysomnography was carried out for evaluation of each subject before treatment.
Results. Univariate and multivariate analyses were performed to investigate factors affecting the severity of OSAS. These analyses showed that obesity, skeletal conditions such as short mandibular body and mandibular retreat, size of the tongue and position of the hyoid bone, and shape of the airway were associated with the severity of OSAS.
Conclusion. In Japanese male OSAS patients, skeletal abnormalities are thought to be the factors that most greatly affect severity of OSAS. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:343-349)

DOI： 10.1016/j.tripleo.2008.08.021

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Motivation: A two-stage association study is the most commonly used method among multistage designs to efficiently identify disease susceptibility genes. Recently, some SNP studies have utilized more than two stages to detect disease genes. However, there are few available programs for calculating statistical powers and positive predictive values (PPVs) of arbitrary n-stage designs.
Results: We developed programs for a multistage case-control association study using R language. In our programs, input parameters include numbers of samples and candidate loci, genome-wide false positive rate and proportions of samples and loci to be selected at the k-th stage (k = 1,..., n). The programs output statistical powers, PPVs and numbers of typings in arbitrary n-stage designs. The programs can contribute to prior simulations under various conditions in planning a genome-wide association study.

DOI： 10.1093/bioinformatics/btn616

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

A two-stage association study is the most commonly used method to efficiently identify disease susceptibility genes. However, some recent single nucleotide polymorphism (SNP) studies recently utilized three-stage designs. The purpose of this study was to investigate the practical properties of statistical powers and positive predictive values (PPVs) of replication-based analysis (RBA) and the joint analysis (JA) in multistage designs. For this purpose, a program for multistage designs was developed to calculate these performance indicators under various conditions of the number of samples, alleles of candidates, alleles remaining in the final stage, and genotypings. The results showed that the powers and PPVs of RBA and JA in three-stage designs were higher than those in two-stage designs in the range of a smaller proportion of sample size than 0.5 at the first stage. This tendency was more remarkable in JA. In conclusion, researchers who perform SNP studies for identifying disease susceptibility genes need to take account of three-stage case-control association studies, corresponding to study conditions such as the total numbers of samples, alleles, and genotypings. Furthermore, the program developed in this study is useful for estimating powers and PPVs in planning multistage association studies.

DOI： 10.1007/s10038-008-0258-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE  

The aim of this study was to determine the effects of mandibular setback surgery on craniofacial and pharyngeal morphology and on respiratory function during sleep. The subjects were 17 patients in whom skeletal class III malocclusions were corrected by bilateral sagittal split ramus osteotomy. Arterial oxygen saturation (SPO2) during sleep was measured by pulse oximetry, and morphological changes were studied using cephalograms. The mean posterior movement of the mandible at surgery was 8.6 mm at the pogonion, and many morphological and functional changes occurred with mandibular setback. Although there was no significant change at the oropharyngeal airway, significant protrusive head position and inferior displacement of the hyoid bone were seen postoperatively. Decreased SPO2 during sleep was found just after surgery, but had improved I month after surgery. It seems that almost all of the subjects adapted to the new environment in respiratory function during sleep, but patients with obesity, potential sleep-disordered breathing and a large amount of setback may suffer from obstructive sleep apnea (OSA) in the future. Careful postoperative follow up is needed for patients who have undergone mandibular setback surgery, and a strategy to prevent obstructive sleep apnea after mandibular setback surgery is needed.

DOI： 10.1016/j.ijom.2007.12.005

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Language：Japanese   Publisher：(株)ジェフコーポレーション  

著者らが所属する病棟看護師361名を対象に、低栄養患者の栄養管理に関する意識とその介入行動を問うアンケート調査を行い、回答の得られた301名(83%)の調査結果を分析した。1)低栄養患者に対する看護師の意識については、看護介入の必要性に対する意識の違い(高低)および知識不足に対する意識の違い(高低)は実際の介護行動に影響することが示唆された。2)多重ロジステック回帰分析では、介入行動に有意に影響を与える因子として、看護介入の必要性について意識が高いこと、栄養管理について医師と十分に連携が取れているという意識が高いことが挙げられた。

DOI： 10.11244/jjspen.23.51

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2008&ichushi_jid=J03242&link_issn=&doc_id=20080411150008&doc_link_id=10.11244%2Fjjspen.23.51&url=https%3A%2F%2Fdoi.org%2F10.11244%2Fjjspen.23.51&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JOHN WILEY & SONS INC  

BACKGROUND. The objective of the current study was to identify biomarkers that reflect the clinical course of squamous cell carcinoma of the tongue (TSCC).
METHODS. TSCC tissue samples from 66 patients were subjected to gene expression analysis by real-time polymerase chain reaction. Eleven integrin family genes and 14 genes used for normalization, including housekeeping genes and genes that encode desmosomal, cytoskeletal, and extracellular matrix molecules, were considered. Multivariate statistical analysis was performed on 154 expression ratios of integrin genes with clinical parameters.
RESULTS. in principal-component analysis, the first principal component was related to the outcome of death, and the second principal component mainly reflected the tendency for cervical lymph node (LN) metastasis. The former axis consisted of the variance of the integrin beta 4 gene (ITGB4) and ITGB5 expression levels, and the latter axis agreed with the expression level of the integrin alpha 3 gene (ITGA3). Multivariate logistic regression analysis with cervical LN metastasis as the response variable concordantly identified ITGA3/junction plakoglobin gene (JUP) expression (P =.02) and ITGB5/paxillin gene (PXN) expression (P = .04) as significant factors. Only ITGB4/JUP expression was identified as a significant factor in terms of the outcome of death (P &lt;.00049) by a Cox proportional hazards model. The group with high ITGB4/JUP levels exhibited a significantly high death rate on a Kaplan-Meier curve (P &lt;.0001; Wilcoxon and log-rank tests).
CONCLUSIONS. The expression levels of ITGA3, ITGB4, and ITGB5 with functional normalization by desmosomal or cytoskeletal molecule genes were selected as candidate biomarkers for cervical LN metastasis or for the outcome of death in TSCC.

DOI： 10.1002/cncr23295

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JOHN WILEY & SONS INC  

BACKGROUND. The objective of the current study was to identify biomarkers that reflect the clinical course of squamous cell carcinoma of the tongue (TSCC).
METHODS. TSCC tissue samples from 66 patients were subjected to gene expression analysis by real-time polymerase chain reaction. Eleven integrin family genes and 14 genes used for normalization, including housekeeping genes and genes that encode desmosomal, cytoskeletal, and extracellular matrix molecules, were considered. Multivariate statistical analysis was performed on 154 expression ratios of integrin genes with clinical parameters.
RESULTS. in principal-component analysis, the first principal component was related to the outcome of death, and the second principal component mainly reflected the tendency for cervical lymph node (LN) metastasis. The former axis consisted of the variance of the integrin beta 4 gene (ITGB4) and ITGB5 expression levels, and the latter axis agreed with the expression level of the integrin alpha 3 gene (ITGA3). Multivariate logistic regression analysis with cervical LN metastasis as the response variable concordantly identified ITGA3/junction plakoglobin gene (JUP) expression (P =.02) and ITGB5/paxillin gene (PXN) expression (P = .04) as significant factors. Only ITGB4/JUP expression was identified as a significant factor in terms of the outcome of death (P &lt;.00049) by a Cox proportional hazards model. The group with high ITGB4/JUP levels exhibited a significantly high death rate on a Kaplan-Meier curve (P &lt;.0001; Wilcoxon and log-rank tests).
CONCLUSIONS. The expression levels of ITGA3, ITGB4, and ITGB5 with functional normalization by desmosomal or cytoskeletal molecule genes were selected as candidate biomarkers for cervical LN metastasis or for the outcome of death in TSCC.

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DOI： 10.11259/jsg1987.23.97

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DOI： 10.11259/jsg1987.23.90

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN  

Objectives: Simultaneous dealing of hundreds of thousands of single nucleotide polymorphisms (SNPs) in genome-wide association studies is laborious. The aim of our study is to develop a method to decrease the number of candidate SNPs prior to the genotyping of study subjects.
Methods. We created virtual genotype data on case and control subjects from data of the International HapMap Project by using haplotype-based simulation method. We repeated virtual case-control association studies and selected candidate SNPs. We applied the selected SNPs to previously published genetic case-control studies. Sensitivity to detect association with causative genes using our method was compared to the original studies and results using tag SNPs.
Results. We found a discrete distribution pattern of SNPs, which was able to produce significant results in case-control association studies. The number of candidate SNPs that we selected was 24.7% of the number of the original set of SNPs, We applied this method to previously published genetic case-control studies and found that the use of candidate SNPs improved the sensitivity for detecting significant alleles, both compared to the original studies and to the use of tag SNPs. The results were not affected by the difference of the diseases and genes involved.
Conclusions. Our simulation-based approach has advantages of reducing costs and improving performance to detect significant alleles. This method can be used without considering the specific disease and genes involved.

DOI： 10.3414/ME9129

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Matrix metalloproteinase (MMP) is known to be involved in the initial and progressive stages of cancer development, and in the aggressive phenotypes of cancer. This study examines the association of single nucleotide polymorphisms in promoter regions of MMP-1 and MMP-3 with susceptibility to oral squamous cell carcinoma (OSCC).
Methods: We compared 170 Japanese OSCC cases and 164 healthy controls for genotypes of MMP-1 and MMP-3.
Results: The frequency of the MMP-1 2G allele was higher and that of the 1G homozygote was lower in the OSCC cases ( p = 0.034). A multivariate logistic regression analysis revealed that subjects who were 45 years old or older had a significantly increased (2.47-fold) risk of OSCC (95% CI 1.47-4.14, p = 0.0006), and those carrying the MMP-1 2G allele had a 2.30-fold risk (95% CI 1.15-4.58, p = 0.018), indicating independent involvement of these factors in OSCC. One of the key discoveries of this research is the apparent reduction of the MMP-1 1G/1G and 1G/2G genotype distributions among the early onset OSCC cases under the ages of 45 years. It should be noted that the tongue was the primary site in 86.2% of these early onset cases. This could suggest the specific carcinogenic mechanisms, i.e. specific carcinogenic stimulations and/or genetic factors in the tongue.
Conclusion: Since the 2G allele is a majority of the MMP-1 genotype in the general population, it seems to act as a genetic pre-condition in OSCC development. However this report suggests a crucial impact of the MMP-1 2G allele in the early onset OSCC.

DOI： 10.1186/1471-2407-7-187

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Angiogenesis is induced by various angiogenic factors including vascular endothelial growth factors (VEGFs), such as VEGF-A, -B, -C and -D, and is involved in tumor progression and metastasis. In an effort to define the expression pattern of VEGFs in oral squamous cell carcinoma (OSCC) and its correlation with clinicopathological factors, we determined the expression levels of VEGFs in OSCC cell lines (HSC-2, HSC-3, HSC-4 and OSC-19) by quantitative RT-PCR and examined their relationship with regional lymph node (LN) and distant metastasis, intratumoral microvessel density (MVD) in tumor transplanted nude mice. We found that HSC-2 and OSC-19 expressed significantly higher levels of VEGF-A and VEGF-C, and caused frequent regional LN metastasis and higher MVD than did the other cell lines. Since VEGF-C is a lymphangiogenic factor, these results suggest that expression of VEGF-C is a useful predictor for LN metastasis.

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Angiogenesis and lymphangiogenesis are essential requirements for tumor growth, invasion and metastasis. The vascular endothelial growth factor (VEGF) family, VEGF-A, VEGF-B, VEGF-C and VEGF-D, are thought to be specific potent angio- and lymphangiogenetic stimulators that may play an important role in tumor invasion and metastasis. Although it has been reported that the VEGF family is expressed in a variety of human tumors in different ways, their precise role in oral squamous cell carcinoma (OSCC) is not well understood. To obtain some clues as to this role, we evaluated the expression levels of the VEGF family in OSCC cell lines (HSC-2, HSC-3, HSC-4 and OSC-19) by using quantitative real-time PCR analysis and investigated the relationship with lymph node metastasis, distant metastasis and intratumoral micro vessel density (MVD) in tumor transplanted nude mice. All of the VEGF family were expressed at different levels in four OSCC cell lines. There were significant correlations between VEGF-A, VEGF-C expression and the incidence of lymph node metastasis and the ratio of MVD. These results suggest that VEGF-A and VEGF-C expression may be useful predictors for lymph node metastasis and implicated to treat patients with head and neck SCC for further aggressive therapy. © 2005, Japan Society for Head and Neck Cancer. All rights reserved.

DOI： 10.5981/jjhnc.31.84

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We performed fresh autogenous bone grafting from the symphysis mandible (chin bone grafting: CBG) in 47 patients, and obtained favorable results.<BR>Since CBG involves grafting of particulate cancellous bone and marrow, bone formed rapidly. Because the grafted bone was taken from the oral cavity, CBG was less stressful than iliac bone grafting to patients. However, as only a small quantity of bone can be taken, this method cannot be used when there is substantial bone loss. Some patients showed disturbances of the mental nerve and felt a slight upward extrusion of the mandibular anterior teeth after surgery, but these symptoms disappeared within several days or weeks.

DOI： 10.5794/jjoms.41.537

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Analyzed were the articulatory movements during production of [Ka] in 5 cleft palate patients before and after superior based pharyngeal flap operation by using Videofluorography and 3-D computer graphic system.<BR>The results were as follows:<BR>1. This system allows viewing of the dynamic changes l of articulatory movement during a single consonant sound in one picture.<BR>2. Before pharyngeal f lap operation, various abnormalities of tongue, soft palate and posterior pharyngeal wall were observed during articulatory movement.<BR>3. After operation, the findings that the exte nt of the upward movement of tongue at production of preceding consonant plosive sound was larger than before operation, the tongue dorsum touched the velum and flap, and how similar they were to the controls were obtained.<BR>4. The findings obtained from the images with computer graphics wer e related to the listener judgenents of speech production of [Ka].<BR>5. This system is useful becau se the mechanism of cleft palate speech can be elucidated.

DOI： 10.11224/cleftpalate1976.18.3_272

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Individual displaced teeth are generally treated orthodontically or prosthetically. But in cases of ankylosed teeth, the orthodontic approach, even when used with corticotomies, do not work at all. In cases of rotated teeth, it has a greater propensity for relapse. On the other hand, the prosthetic approach sacrifices the healthy tooth structure and may produce a somewhat compromised esthetic result. Single-tooth dento-osseous osteotomy is one of the orthognatic surgeries only for correction of individual tooth-bone segment alone. By attempting to use single-tooth dento-osseous osteotomies for ankylosed teeth and rotated teeth, we obtained satisfactory results. The advantages are: it is rapid and will move, a slight propensity for relapse and a good esthetic result. In order to successfully use this method, be especially careful to maintain the blood supply to the tooth-bone segment and when cutting Lbetween adjacent teeth so as not to injury to them.

DOI： 10.5794/jjoms.38.649

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DOI： 10.5794/jjoms.38.805

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It is very important to reposition and to keep the occlusal plane in harmonious relation to TMJ and the skull in two jaw surgery. In addition, the surgery should be performed as accurately as the presurgical planning.<BR>However, it is not always easy to satisfy the above-mentioned items in deformities indicating sagittal, transverse and vertical dysplasia or discrepancy of maxilla and mandible. For this reason, we have performed the method of intra-operative repositioning of the Le Fort I osteotomized maxilla according to the pre-operative planning by using the semi-adjustable articulator SAM or Whip-Mix facebow. We use routinely the simultaneous jaw movement by Le Fort I and sagittal splitting osteotomy for two jaw surgery.<BR>The maxillary position determined by preplanning of the cephalometric prediction tracing and model operation is recorded with the facebow. After the recording, the facebow with the bitefork is removed from the articulator, and is sterilized with gas to be ready for the intraoperative transfer.<BR>The maxilla is adequately mobilized as usual, the vertical dimensions of maxilla are reduced to the same extent as the model operation. The osteotomized maxilla is inserted into the bite fork. Then, the facebow is adjusted to the external auditory canal.<BR>In addition, intermaxillary wiring is performed after the mandible is also inserted into the bitefork. Once the facebow is fixed by the nasion locator, the facebow system is kept rigid and free from distortion.<BR>The characteristics or advantages and the indication of this facebow transfer system are as follows:<BR>1. This system using the Whip-mix or the SAM facebow guarantees precise transfer from the articulator to the patient.<BR>2. It has the possibility of obtaining intra-operatively accurate reproduction of the position of osteotomized maxilla in relation to the skull, the mandibular teeth arch, and the TMJ as preplanned.<BR>3. It has the possibility of keeping the transferred position and stabilizing maxilla with the mini-plates without freehanding.<BR>4. As this system is a "step by step" technical procedure, the laboratory workup is very important.<BR>5. The model operation in this system is for the oral surgeon operation training.<BR>6. The indication of this system seems to be facial asymmetry or long face with mandibular protrusion.<BR>We have performed this facebow transfer system on 14 patients and obtained good results. All patients currently have acceptable results.

DOI： 10.5794/jjoms.37.982

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DOI： 10.11224/cleftpalate1976.16.3_130

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Generally limited to a period of 4 or 5 years, histiocytosis X may last 10 or 15 years. However, there may be no long-term follow up report whose signs were observed primarily in oral region.<BR>We experienced case of eosinophilic granuloma of mandible in a 3 year-old girl. We performed surgical therapy, irradiation and chemotherapy. Two times recurrence was observed in 11 years follow-up. However we judged this case cured, because 5 years passed after intraosseous lesion disappearance.

DOI： 10.5794/jjoms.35.693

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DOI： 10.11224/cleftpalate1976.13.2_133

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DOI： 10.11477/mf.1404205860

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DOI： 10.11477/mf.1404205860

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DOI： 10.11258/jjghp.25.268

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&lt;p&gt;Oral hygiene of patients with mental disorders is an issue that needs to be addressed in the fields of mental health and preventive dental care for the disabled, as poor oral hygiene can adversely affect their health. In order to promote oral hygiene support for patients with schizophrenia, the aims of this study were two-fold: (1) to investigate research trends in the study of oral hygiene of patients with schizophrenia by reviewing the domestic and international literature, and (2) to highlight effective support systems and issues that need to be addressed in Japan regarding the oral hygiene of such patients in Japan. It was found that domestic research tends to focus on case reports and results of oral hygiene surveys, while international studies provide results of oral hygiene surveys and outlines of problems particular to schizophrenics. The results of the literature review suggest the need to enhance epidemiologic research about oral hygiene instructions to patients, improve organizational support systems to implement and manage oral hygiene instructions, and examine effective support systems based on Japanese mental health care and welfare systems.&lt;/p&gt;

DOI： 10.11258/jjghp.25.268

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ヒト口腔扁平上皮癌細胞株（HSC-2，HSC-3，HSC-4，OSC-19）においてVEGF-A mRNA 発現量が高い細胞株（HSC-2，OSC-19）ではVEGF-C mRNA 発現量も高いとされている。そこで本研究は，ヒト口腔扁平上皮癌細胞株における癌細胞が発現するVEGF-A，VEGF-C， およびVEGF 受容体（VEGFR（VEGFR-1，VEGFR-2，VEGFR-3））の相互作用を調べることを目的として行った。 Reverse transcription polymerase chain reaction（RT-PCR）法を用い，ヒト口腔扁平上皮癌細胞株（HSC-2，HSC-3，HSC-4，OSC-19）におけるVEGFR 発現の有無を確認した。さらに４種全てのヒト口腔扁平上皮癌細胞株に外部刺激としてヒトrecombinant VEGF-A およびVEGF-C 添加することによるVEGF-A，VEGF-C， およびVEGFR mRNA 発現量の増加をreal-time RT-PCR 法で定量した。 その結果VEGFR は４種全てのヒト口腔扁平上皮癌細胞株においてVEGFR-1 のみ発現しており，またヒトrecombinant VEGF-A およびVEGF-C 添加によるVEGF-A，VEGF-C，およびVEGFR mRNA の発現量に明らかな相互作用はみられなかった。 このことからヒト口腔扁平上皮癌細胞株においてはVEGF-A，VEGF-C，およびVEGFR mRNA 発現量に相互作用はないものと考えられた。 今後はヒトにおける口腔扁平上皮癌が発現するVEGF-A，VEGF-C，およびVEGFR の相互作用を明らかにするために，更なる研究が必要である。Among in human oral squamous cell carcinoma (OSCC) cell lines HSC2, HSC-3, HSC-4, and OSC-19, HSC-2 and OSC-19 cell lines that were highly expressed VEGF-A mRNA showed high of VEGF-C mRNA expression. The purpose of the present study was to clarify that interaction of VEGF-A, VEGF-C, and VEGF receptors (VEGFR(VEGFR-1, VEGFR-2, and VEGFR-3)) in human OSCC cell lines. We investigated the expression of VEGFR in human OSCC cell lines (HSC-2, HSC-3, HSC-4, and OSC-19) by reverse transcription polymerase chain reaction (RT-PCR). Furthermore, whether the expression levels of VEGF-A, VEGF-C, and VEGFR mRNA may be changed adding the human recombinant VEGF-A and VEGF-C, we examined the expression levels of VEGF-A, VEGF-C, and VEGFR mRNA by real-time RT-PCR in cultured human OSCC cell lines. In each cell line expression of VEGFR-1 mRNA was detected, however, that of VEGFR-2 and VEGFR-3 mRNA were not detected. Expression levels of VEGF-A, VEGF-C, and VEGFR-1 mRNA when added to human recombinant VEGF-A and VEGF-C did not have statistically significant differences. In OSCC cell lines, the expression levels of VEGF-A, VEGF-C, an VEGFR did not have any correlations in each other. Further studies were required to clarify the correlation of VEGF-A, VEGF-C, and VEGFR in human OSCC.

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DOI： 10.11259/jsg1987.23.97

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DOI： 10.11259/jsg1987.23.90

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A multistage case-control association study is one of the study designs to efficiently identify disease susceptibility genes. The purpose of this study was to clarify the properties of multistage case - control association studies. For this purpose, new programs for n-stage designs (n being an arbitrary integer larger than 1) were developed to calculate statistical powers, positive predictive values (PPVs) and numbers of genotypings of replication - based analysis (RBA) and joint analysis (JA) . Assuming that the numbers of alleles remaining at the final stage or the numbers of genotypings were fixed, the powers and PPVs of RBA and JA in three - stage designs were higher than those indicators in two - stage designs when a proportion of the sample size at the 1st stage (π_<s,1>) was smaller than 0.5. On the other hand, when π_<s,1> j was larger than 0.5, the indicators in the two - stage designs were higher than those in the three - stage designs. This tendency was more remarkable the closer the proportions of sample sizes of the 2nd and 3rd stages were and was more remarkable in JA than in RBA. It may be useful to conduct a prior simulation under various conditions by our programs for multistage designs at the planning stage of a genome - wide association study.

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DOI： 10.11244/jjspen.23.51

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Language：Japanese   Publisher：一般社団法人 日本老年歯科医学会  

Introduction: The moisture content in the oral mucosa is affected by foods and beverages. However, there have only been a few reports of these effects. Therefore, we studied the moisture content in the oral mucosa periodically for elderly residents of nursing facilities and examined the relationship between items that are associated with xerostomia and the moisture content in the oral mucosa.&lt;BR&gt;Subjects and methods: 41 subjects (21 males, 20 females) with an average age of 79&amp;plusmn;8.5 years, who resided in the Tokyo Metropolitan Itabashi Nursing Home, took part inthe study. They had no history of diseases associated with xerostomia, and showed no symptoms such as fever during the study period. As for methodology, the moisture on the dorsal surface of the tongue and the buccal mucosa wasmeasured using an oral moisture checking device (Moisture checking device &amp;ldquo;Mucus&amp;rdquo;: hereinafter referred to as &amp;ldquo;improved type&amp;rdquo;). At one site, it was measured three times, and the mean was set as the measured value. It was measured three times a day; immediately after waking up in the morning, before having breakfast, after having lunch, and after having dinner. Furthermore, the relationshipwas examined between the moisture content in the oral mucosa and each of the following items: gender, whether or not any internal medicine was being taken, the presence orabsence of xerostomia and a history of smoking.&lt;BR&gt;Results: It is suggested that the moisture content inthe oral mucosa is affected by foods and beverages. Significant differences were observed in the moisture on the dorsal surface of the tongue according to gender: in lower values were observed in females. No relationship was observedbetween the moisture content in the oral mucosa and the patient&#039;s smoking history, internal medicines or history of xerostomia.

DOI： 10.11259/jsg1987.23.97

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A moisture checker of the skin is one type of device that is used to measure the moisture content in the stratum corneum of the skin. Applying the principles of such equipment, an oral moisture checking device was developed in order to measure the moisture content in the oral mucosa. There have been no previous reports of the relationship between the measured values of the oral moisture checking device and the actual moisture content in the oral mucosa. We therefore devised a method in which solid agar processed with varying moisture contents was used as measurement samples, and examined the accuracy of the oral moisture meters via the measurement of these samples.&lt;BR&gt;Materials and methods: Solid agar was produced using powdered agar (standard quantity of moisture content 250 ml per 2g of powder). Maintaining the quantity of 2g of powder and increasing/decreasing the moisture content in 25-ml increments, a total of twelve types of liquid agar were thus prepared with a moisture content varying from 25 to 300 ml. These were then poured into round petri dishes so as to reach a certain volume and solidify at room temperature. Two types of oral moisture checking devices were used for the measurements: Moisture Checker for Mucus (&amp;ldquo;old type&amp;rdquo;) and Oral Moisture Checking Device Mucus (&amp;ldquo;improved type&amp;rdquo;). A specific sensor cover was attached to each device, and the moisture content of each sample of solid agar was measured three times each.&lt;BR&gt;Results: The measured values showed increases as the contained moisture content increased under 75 ml with both types of the oral moisture checking devices. Furthermore, a close correlation was observed between the moisture content and the measured values, with a significant level 0.1% or less according to the Friedman rank test. In comparisons between the two types of oral moisture checking devices, the improved type showed higher measured values than the old one. The sensitivity was 75% in both types. The specificity was 95% in the old type and 100% in the improved one. The positive predictive value was 75% in the old type and 100% in the improved type. The negative predictive value was 95% in both. Therefore, both oral moisture checking devices were considered to have excellent precision as measuring instruments. However, the ability to accurately predict mouth dryness under clinical conditions was higher for the improved type than for the old type.

DOI： 10.11259/jsg1987.23.90

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Angiogenesis and lymphangiogenesis are essential requirements for tumor growth, invasion and metastasis. The vascular endothelial growth factor (VEGF) family, VEGF-A, VEGF-B, VEGF-C and VEGF-D, are thought to be specific potent angio- and lymphangiogenetic stimulators that may play an important role in tumor invasion and metastasis. Although it has been reported that the VEGF family is expressed in a variety of human tumors in different ways, their precise role in oral squamous cell carcinoma (OSCC) is not well understood. To obtain some clues as to this role, we evaluated the expression levels of the VEGF family in OSCC cell lines (HSC-2, HSC-3, HSC-4 and OSC-19) by using quantitative real-time PCR analysis and investigated the relationship with lymph node metastasis, distant metastasis and intratumoral micro vessel density (MVD) in tumor transplanted nude mice. All of the VEGF family were expressed at different levels in four OSCC cell lines. There were significant correlations between VEGF-A, VEGF-C expression and the incidence of lymph node metastasis and the ratio of MVD. These results suggest that VEGF-A and VEGF-C expression may be useful predictors for lymph node metastasis and implicated to treat patients with head and neck SCC for further aggressive therapy. © 2005, Japan Society for Head and Neck Cancer. All rights reserved.

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Angiogenesis and lymphangiogenesis are essential requirements for tumor growth, invasion and metastasis. The vascular endothelial growth factor (VEGF) family, VEGF-A, VEGF-B, VEGF-C and VEGF-D, are thought to be specific potent angio- and lymphangiogenetic stimulators that may play an important role in tumor invasion and metastasis. Although it has been reported that the VEGF family is expressed in a variety of human tumors in different ways, their precise role in oral squamous cell carcinoma (OSCC) is not well understood. To obtain some clues as to this role, we evaluated the expression levels of the VEGF family in OSCC cell lines (HSC-2, HSC-3, HSC-4 and OSC-19) by using quantitative real-time PCR analysis and investigated the relationship with lymph node metastasis, distant metastasis and intratumoral micro vessel density (MVD) in tumor transplanted nude mice. All of the VEGF family were expressed at different levels in four OSCC cell lines. There were significant correlations between VEGF-A, VEGF-C expression and the incidence of lymph node metastasis and the ratio of MVD. These results suggest that VEGF-A and VEGF-C expression may be useful predictors for lymph node metastasis and implicated to treat patients with head and neck SCC for further aggressive therapy. © 2005, Japan Society for Head and Neck Cancer. All rights reserved.

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Angiogenesis and lymphangiogenesis are essential requirements for tumor growth, invasion and metastasis. The vascular endothelial growth factor (VEGF) family, VEGF-A, VEGF-B, VEGF-C and VEGF-D, are thought to be specific potent angio- and lymphangiogenetic stimulators that may play an important role in tumor invasion and metastasis. Although it has been reported that the VEGF family is expressed in a variety of human tumors in different ways, their precise role in oral squamous cell carcinoma (OSCC) is not well understood. To obtain some clues as to this role, we evaluated the expression levels of the VEGF family in OSCC cell lines (HSC-2, HSC-3, HSC-4 and OSC-19) by using quantitative real-time PCR analysis and investigated the relationship with lymph node metastasis, distant metastasis and intratumoral micro vessel density (MVD) in tumor transplanted nude mice. All of the VEGF family were expressed at different levels in four OSCC cell lines. There were significant correlations between VEGF-A, VEGF-C expression and the incidence of lymph node metastasis and the ratio of MVD. These results suggest that VEGF-A and VEGF-C expression may be useful predictors for lymph node metastasis and implicated to treat patients with head and neck SCC for further aggressive therapy. © 2005, Japan Society for Head and Neck Cancer. All rights reserved.

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DOI： 10.11224/cleftpalate1976.23.1_13

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Secondary bone grafting into alveolar clefts has become a very popular procedure, though ideal results are not always obtained. In 76 patients treated alveolar bone graft from 1975 to 1988, data were obtained by studying 64 alveolar clefts of 51 patients. In order to evaluate the prognostic factors of this procedure, the relationships of clinical factors and prognosis of alveolar cleft after bone grafting were evaluated by univariate and multiple logistic regression analyses.&lt;BR&gt;The results were as follows:&lt;BR&gt;1. Bone bridge formation w as found in 51 alveolar clefts (79.7% ).&lt;BR&gt;2. The factors correlated with bone bridge formation were the age at the time of bone grafting, pre-and postoperative orthodontic treatment, and kinds of bone materials for univariate analysis.&lt;BR&gt;As for multiple logistic regression analysis, the age at the time of bone grafting, kinds of bone materials and kinds of closure techniques by soft tissue flaps were found to be independent cofactors.&lt;BR&gt;3. The fac tors correlated with acceptable alveolar bone level were the age at the time of bone grafting, the eruption stage of the canine on the cleft side and the cleft width. As for multiple logistic regression analysis, only the cleft width was found to be an independent cofactor.

DOI： 10.11224/cleftpalate1976.23.1_13

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We performed fresh autogenous bone grafting from the symphysis mandible (chin bone grafting: CBG) in 47 patients, and obtained favorable results.<BR>Since CBG involves grafting of particulate cancellous bone and marrow, bone formed rapidly. Because the grafted bone was taken from the oral cavity, CBG was less stressful than iliac bone grafting to patients. However, as only a small quantity of bone can be taken, this method cannot be used when there is substantial bone loss. Some patients showed disturbances of the mental nerve and felt a slight upward extrusion of the mandibular anterior teeth after surgery, but these symptoms disappeared within several days or weeks.

DOI： 10.5794/jjoms.41.537

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：日口蓋誌  

Analyzed were the articulatory movements during production of [Ka] in 5 cleft palate patients before and after superior based pharyngeal flap operation by using Videofluorography and 3-D computer graphic system.&lt;BR&gt;The results were as follows:&lt;BR&gt;1. This system allows viewing of the dynamic changes l of articulatory movement during a single consonant sound in one picture.&lt;BR&gt;2. Before pharyngeal f lap operation, various abnormalities of tongue, soft palate and posterior pharyngeal wall were observed during articulatory movement.&lt;BR&gt;3. After operation, the findings that the exte nt of the upward movement of tongue at production of preceding consonant plosive sound was larger than before operation, the tongue dorsum touched the velum and flap, and how similar they were to the controls were obtained.&lt;BR&gt;4. The findings obtained from the images with computer graphics wer e related to the listener judgenents of speech production of [Ka].&lt;BR&gt;5. This system is useful becau se the mechanism of cleft palate speech can be elucidated.

DOI： 10.11224/cleftpalate1976.18.3_272

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Language：Japanese   Publisher：Japanese Society of Oral and Maxillofacial Surgeons  

DOI： 10.5794/jjoms.38.805

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Language：Japanese   Publisher：Japanese Society of Oral and Maxillofacial Surgeons  

Individual displaced teeth are generally treated orthodontically or prosthetically. But in cases of ankylosed teeth, the orthodontic approach, even when used with corticotomies, do not work at all. In cases of rotated teeth, it has a greater propensity for relapse. On the other hand, the prosthetic approach sacrifices the healthy tooth structure and may produce a somewhat compromised esthetic result. Single-tooth dento-osseous osteotomy is one of the orthognatic surgeries only for correction of individual tooth-bone segment alone. By attempting to use single-tooth dento-osseous osteotomies for ankylosed teeth and rotated teeth, we obtained satisfactory results. The advantages are: it is rapid and will move, a slight propensity for relapse and a good esthetic result. In order to successfully use this method, be especially careful to maintain the blood supply to the tooth-bone segment and when cutting Lbetween adjacent teeth so as not to injury to them.

DOI： 10.5794/jjoms.38.649

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Language：Japanese  

DOI： 10.11224/cleftpalate1976.16.3_130

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Language：Japanese   Publisher：Japanese Society of Oral and Maxillofacial Surgeons  

Generally limited to a period of 4 or 5 years, histiocytosis X may last 10 or 15 years. However, there may be no long-term follow up report whose signs were observed primarily in oral region.<BR>We experienced case of eosinophilic granuloma of mandible in a 3 year-old girl. We performed surgical therapy, irradiation and chemotherapy. Two times recurrence was observed in 11 years follow-up. However we judged this case cured, because 5 years passed after intraosseous lesion disappearance.

DOI： 10.5794/jjoms.35.693

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J-GLOBAL

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