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1.
ESMO Open ; 6(2): 100077, 2021 04.
Article in English | MEDLINE | ID: mdl-33714860

ABSTRACT

BACKGROUND: The ACTS-CC 02 trial demonstrated that S-1 plus oxaliplatin (SOX) was not superior to tegafur-uracil and leucovorin (UFT/LV) in terms of disease-free survival (DFS) as adjuvant chemotherapy for high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). We now report the final overall survival (OS) and subgroup analysis according to the pathological stage (TNM 7th edition) for treatment efficacy. PATIENTS AND METHODS: Patients who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300 mg/m2 of UFT and 75 mg/day of LV on days 1-28, every 35 days, five cycles) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80 mg/m2/day of S-1 on days 1-14, every 21 days, eight cycles). The primary endpoint was DFS and the patients' data were updated in February 2020. RESULTS: A total of 478 patients in the UFT/LV group and 477 patients in the SOX group were included in the final analysis. With a median follow-up time of 74.3 months, the 5-year DFS rate was 55.2% in the UFT/LV group and 58.1% in the SOX group [stratified hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.76-1.11; P = 0.3973], and the 5-year OS rates were 78.3% and 79.1%, respectively (stratified HR 0.97; 95% CI 0.76-1.24; P = 0.8175). In the subgroup analysis, the 5-year OS rates in patients with T4N2b disease were 51.0% and 64.1% in the UFT/LV and SOX groups, respectively (HR 0.72; 95% CI 0.40-1.31). CONCLUSION: Our final analysis reconfirmed that SOX as adjuvant chemotherapy is not superior to UFT/LV in terms of DFS in patients with high-risk stage III colon cancer. The 5-year OS rate was similar in the UFT/LV and SOX groups.


Subject(s)
Colonic Neoplasms , Leucovorin , Oxaliplatin , Tegafur , Uracil , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Humans , Leucovorin/therapeutic use , Neoplasm Staging , Oxaliplatin/therapeutic use , Tegafur/therapeutic use , Uracil/therapeutic use
3.
Public Health ; 181: 114-118, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32006854

ABSTRACT

OBJECTIVES: With the progress of aging, fall injuries have become a global public health issue. This research was conducted to describe in detail situations of injury occurrence among the elderly by distinguishing between falls from heights and ground-level falls. We assume that different fall mechanisms occur in different situations and result in a wide range of consequences. STUDY DESIGN: This is a registry-based descriptive study. METHODS: The analysis included 55,126 patients with fall injuries, aged 65 years and more, having an Injury Severity Score (ISS) ≧9, and registered in a trauma registry in Japan between 2004 and 2015. We described patients' distribution in terms of age, severity, outcome, season, time, and injured body parts by gender and fall mechanisms. RESULTS: Falls from heights (n = 15,748) were more common among men and those younger than 75 years. Ground-level falls (n = 39,378) were more common among women and those older than 75 years. The ISS was high in men and for those who fell from heights. Falls from heights were common in autumn, whereas ground-level falls were common in winter. Both mechanisms occurred frequently during the daytime. The head and lower extremities were the most commonly injured parts for those who fell from heights and ground-level falls, respectively. Injuries to the head, chest, spine, upper extremities, and pelvis were common among those who fell from heights. Injuries to the lower extremities were common in ground-level fallers. Among those who fell from heights, women had more frequent lower extremity injuries than did men. Among ground-level fallers, men had more frequent head injuries than did women. The highest case-fatality rate was recorded for abdominal injuries among those who fell from heights and head injuries among ground-level fallers. In both mechanisms of injury, the case-fatality rate of limbs was the lowest. CONCLUSIONS: Our study showed different patterns between falls from heights and ground-level falls, whereas previous studies rarely distinguished between these two fall mechanisms.


Subject(s)
Accidental Falls/statistics & numerical data , Aging , Registries , Wounds and Injuries/mortality , Abdominal Injuries/etiology , Abdominal Injuries/mortality , Accidental Falls/mortality , Aged , Aged, 80 and over , Craniocerebral Trauma/mortality , Female , Fractures, Bone/etiology , Fractures, Bone/mortality , Geriatrics , Humans , Injury Severity Score , Japan/epidemiology , Male , Retrospective Studies , Seasons , Wounds and Injuries/etiology
4.
J Laryngol Otol ; 133(12): 1046-1049, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31679530

ABSTRACT

OBJECTIVE: There are few detailed studies about peripheral branch resection of the posterior nasal nerves in the inferior turbinate; thus, this study aimed to investigate this. METHODS: Patients who underwent submucosal turbinoplasty with or without resection of the peripheral branches of posterior nasal nerves in the inferior turbinate were included. RESULTS: The resection of the posterior nasal nerves with turbinoplasty significantly reduced detection and recognition thresholds on olfactory testing. The rhinorrhoea severity, detection threshold and recognition threshold were significantly lower after resection of the posterior nasal nerves with turbinoplasty than after turbinoplasty alone, although there were no significant differences between the two groups before surgery. CONCLUSION: This is the first study to show that the resection of the peripheral branches of the posterior nasal nerves in the inferior turbinate with turbinoplasty more effectively inhibits allergic symptoms compared with turbinoplasty alone. It also showed that the resection of the peripheral branches of the posterior nasal nerves can inhibit olfactory dysfunction.


Subject(s)
Olfaction Disorders/surgery , Turbinates/surgery , Adult , Female , Humans , Male , Middle Aged , Olfaction Disorders/diagnosis , Olfaction Disorders/etiology , Rhinitis, Allergic/complications , Rhinitis, Allergic/surgery , Smell/physiology , Treatment Outcome , Turbinates/innervation , Young Adult
5.
J Laryngol Otol ; 133(8): 674-677, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31378208

ABSTRACT

OBJECTIVE: Transnasal inferior meatal antrostomy is increasingly used for the treatment of post-Caldwell-Luc mucoceles in maxillary sinus. This study aimed to report the outcomes after inferior meatal antrostomy with a mucosal flap for recurrent mucoceles. METHOD: The records of patients who had undergone transnasal inferior meatal antrostomy with or without a mucosal flap were reviewed. RESULTS: Transnasal endoscopic inferior meatal antrostomy with or without a mucosal flap was performed in 21 and 49 patients, respectively. No complications were observed. A closing of the antrostomy was found in 9 (18.4 per cent) of the 49 patients who underwent antrostomy without a mucosal flap. No closings were observed in the 21 patients who underwent antrostomy with a mucosal flap. There was a significant difference in the rate of closing for surgery with and without the mucosal flap. CONCLUSION: Transnasal endoscopic inferior meatal antrostomy with a mucosal flap is a safe method for the treatment of post-Caldwell-Luc maxillary mucoceles that effectively prevents recurrence.


Subject(s)
Mucocele/surgery , Paranasal Sinus Diseases/surgery , Paranasal Sinuses/surgery , Surgical Flaps , Aged , Aged, 80 and over , Endoscopy , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
6.
J Laryngol Otol ; 131(8): 696-701, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28597806

ABSTRACT

OBJECTIVE: Although organised haematoma often induces bone thinning and destruction similar to malignant diseases, the aetiology of organised haematoma and the optimal treatment remain unclear. This paper presents the clinical features of individuals with organised haematoma, and describes cases in which a novel modified approach was successfully applied for resection of organised haematoma in the maxillary sinus. METHOD: Pre-operative examination data were evaluated retrospectively. Modified transnasal endoscopic medial maxillectomy was employed. RESULTS: Fourteen patients with organised haematoma were treated. Contrast-enhanced computed tomography showed heterogeneous enhancement in all patients. Eight patients underwent modified transnasal endoscopic medial maxillectomy, without complications such as facial numbness, tooth numbness, facial tingling, lacrimation and eye discharge. Dissection of the apertura piriformis and anterior maxillary wall was not necessary for any of these eight patients. No recurrence was observed. CONCLUSION: Pre-operative examinations can be helpful in determining the likelihood of organised haematoma. Modified transnasal endoscopic medial maxillectomy appears to be a safe and effective method for organised haematoma resection.


Subject(s)
Hematoma/surgery , Maxillary Sinus/surgery , Natural Orifice Endoscopic Surgery/methods , Paranasal Sinus Diseases/surgery , Adult , Aged , Aged, 80 and over , Female , Hematoma/pathology , Humans , Male , Maxillary Sinus/pathology , Middle Aged , Nose/surgery , Paranasal Sinus Diseases/pathology , Retrospective Studies , Treatment Outcome , Young Adult
7.
Allergy ; 72(7): 1043-1053, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27878831

ABSTRACT

BACKGROUND: In allergic asthma, environmental allergens including house dust mite (HDM) trigger pattern recognition receptors and activate downstream signaling pathways including NF-κB pathways not only in immune cells but also in airway epithelial cells. Recent studies have shown that NF-κB activation is regulated positively or negatively depending on the cellular context by IκBNS (encoded by the gene Nfkbid), one of atypical IκB proteins, in the nucleus. Therefore, we hypothesized that IκBNS expressed in immune cells or epithelial cells is involved in the regulation of asthmatic responses. AIM: To determine the roles of IκBNS in HDM-induced asthmatic responses. METHODS: Roles of IκBNS in HDM-induced airway inflammation and airway hyper-responsiveness (AHR) were examined by using IκBNS-deficient (Nfkbid-/- ) mice. Roles of IκBNS expressed in hematopoietic cells and nonhematopoietic cells were separately evaluated by bone marrow chimeric mice. Roles of IκBNS expressed in murine tracheal epithelial cells (mTECs) were examined by air-liquid interface culture. RESULTS: House dust mite-induced airway inflammation and AHR were exacerbated in mice lacking IκBNS in hematopoietic cells. In contrast, HDM-induced airway inflammation was exacerbated, but AHR was attenuated in mice lacking IκBNS in nonhematopoietic cells. The induction of Muc5ac, a representative mucin in asthmatic airways, was reduced in Nfkbid-/- mTEC, whereas the induction of Spdef, a master regulator of goblet cell metaplasia, was not impaired in Nfkbid-/- mTEC. Moreover, IκBNS bound to and activated the MUC5AC distal promoter in epithelial cells. CONCLUSION: IκBNS is involved in inducing Muc5ac expression in lung epithelial cells and causing AHR in HDM-induced asthma models.


Subject(s)
Gene Expression Regulation , I-kappa B Proteins/metabolism , Mucin 5AC/genetics , Respiratory Hypersensitivity/etiology , Respiratory Hypersensitivity/metabolism , Respiratory Mucosa/metabolism , Allergens/immunology , Animals , Asthma/etiology , Asthma/metabolism , Asthma/pathology , Blood Cells/metabolism , Cytokines/metabolism , Dermatophagoides pteronyssinus/immunology , Disease Models, Animal , Disease Progression , I-kappa B Proteins/genetics , Inflammation Mediators/metabolism , Mice , Mice, Knockout , Mucus/metabolism , Promoter Regions, Genetic , Protein Binding , Respiratory Hypersensitivity/pathology , Respiratory Mucosa/pathology
8.
Rev Sci Instrum ; 87(11): 11D615, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27910421

ABSTRACT

A new tracer-encapsulated solid pellet (TESPEL) injection system has been developed additionally for the LHD heliotron. This system has three-dimensionally bended guide tubes, which allows us to inject the TESPEL obliquely on a poloidal cross-section of the LHD plasma. Consequently, this system enables us to control a tracer-impurity-deposited location more precisely. Moreover, this system can make it possible for the tracer impurity to be deposited even only inside the ergodic region (outside a last closed flux surface of the LHD plasma). A stereoscopic fast camera system has been also developed for capturing a three-dimensional TESPEL trajectory.

9.
Genet Mol Res ; 15(1)2016 Feb 22.
Article in English | MEDLINE | ID: mdl-26909996

ABSTRACT

Translocation of minerals from substrate to mushrooms can change the medicinal characteristics, commercial value, and biological efficiency of mushroom. In the present study, we demonstrated that addition of iron to the substrate reduces the yield of Pleurotus ostreatus mushroom. The biological efficiency of the mushroom varied from 36.53% on the unsupplemented substrate to 2.08% for the substrate with 500 mg/kg iron added. The maximum iron concentration obtained for mushroom was 478.66 mg/kg (dry basis) and the maximum solubility in vitro was 293.70 mg/kg (dry basis). Iron translocation increased the ash and protein content, reduced antioxidant activity, and enhanced the aroma and flavor characteristics of the mushroom. However mushroom has higher amounts of iron than vegetables like collard greens, it is not feasible to use mushrooms as the only dietary source of iron. The study also indicated that because of more bioaccumulation of iron in mycelium than in the mushroom, mycelium and not mushroom, could be a better alternative as a non-animal iron source.


Subject(s)
Fruiting Bodies, Fungal/metabolism , Iron/metabolism , Mycelium/metabolism , Pleurotus/metabolism , Antioxidants/chemistry , Antioxidants/isolation & purification , Biological Availability , Biological Transport , Biphenyl Compounds/antagonists & inhibitors , Culture Media/chemistry , Culture Media/pharmacology , Food Analysis , Fruiting Bodies, Fungal/chemistry , Fruiting Bodies, Fungal/drug effects , Humans , Iron/pharmacology , Mycelium/chemistry , Mycelium/drug effects , Oxidation-Reduction , Picrates/antagonists & inhibitors , Pleurotus/chemistry , Pleurotus/drug effects
10.
Int J Occup Environ Health ; 20(2): 126-33, 2014.
Article in English | MEDLINE | ID: mdl-24999847

ABSTRACT

BACKGROUND: Thermal safety standards for the use of chemical, biological, radiological, and nuclear (CBRN) ensembles have been established for various US occupations, but not for law enforcement personnel. OBJECTIVES: We examined thermal strain levels of 30 male US law enforcement personnel who participated in CBRN field training in Arizona, Florida, and Massachusetts. METHODS: Physiological responses were examined using unobtrusive heart rate (HR) monitors and a simple thermoregulatory model to predict core temperature (Tc) using HR and environment. RESULTS: Thermal strain levels varied by environments, activity levels, and type of CBRN ensemble. Arizona and Florida volunteers working in hot-dry and hot-humid environment indicated high heat strain (predicted max Tc>38·5°C). The cool environment of Massachusetts reduced thermal strain although thermal strains were occasionally moderate. CONCLUSIONS: The non-invasive method of using physiological monitoring and thermoregulatory modeling could improve law enforcement mission to reduce the risk of heat illness or injury.


Subject(s)
Heat Stress Disorders/etiology , Inservice Training/methods , Occupational Diseases/etiology , Occupational Exposure/adverse effects , Police , Protective Devices , Adult , Body Temperature , Heart Rate , Humans , Male , Middle Aged , Occupational Health
11.
J Clin Pharm Ther ; 38(6): 456-61, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23848321

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: External experts play an important role in shaping regulatory decisions in the new drug review process in the United States, Europe and Japan. No rigorous study has been performed addressing how and to what extent external experts, in contrast to internal reviewers in the agency, influence the regulatory decisions during new drug reviews. We examined their contributions in Japanese regulatory reviews in contrast to the internal reviewers, focusing on the labelling decision on therapeutic indications. METHODS: With the data set of 219 new molecular entities (NMEs) approved in Japan from 2000 to 2009, we observed how proposed indications in labelling were modified in a stepwise manner during the review process and conducted multinomial logistic analysis to examine the possible mechanism behind. RESULTS AND DISCUSSION: We found that interim assessment of indications by the internal reviewers was modified substantially by the influence of the external experts in about 20% of the 219 NMEs. Our analysis suggested that internal reviewers provided their opinion mainly based on strict review discipline, whereas external experts added flexibility and reality to their reviews. Our analysis revealed different evaluations between internal reviewers and external experts during regulatory discussions in new drug reviews and how the external panel contributes to changing internal decisions. WHAT IS NEW AND CONCLUSION: This study provides a new and quantitative approach to better label setting by emphasizing the contributions of each stakeholder in new drug reviews, which would improve the efficiency, quality and transparency of new drug reviews to enhance public health.


Subject(s)
Drug Approval/statistics & numerical data , Drug Labeling/statistics & numerical data , Drug Therapy/standards , Humans , Japan , Logistic Models
12.
Clin Pharmacol Ther ; 90(3): 432-41, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21814198

ABSTRACT

We analyzed regulatory reviews in Japan to study the modifications made in drug labeling with respect to proposed therapeutic indications, and investigated factors associated with these changes so as to gain insight into the reasons behind the decisions. Of 220 new molecular entities (NMEs) approved in Japan from 2000 to 2009, 70 received more restricted indications and 14 received more expanded indications than those proposed by the applicants. Multinomial regression analysis suggested that the presence of competitive drugs in the market, higher estimated peak sales, and higher complexity of the proposed indication were factors that significantly increased the likelihood of the indications being restricted on review, in addition to factors related to adequacy of efficacy data. Our results give us a clue to how the approved therapeutic indications reflect the characteristics of the applicants, drugs, review areas (RAs), and clinical evidence in the submitted data package, as well as to the principle behind the decisions.


Subject(s)
Drug Approval , Drug Industry , Drug Labeling , Drugs, Investigational , Clinical Trials, Phase III as Topic , Drug Design , Drugs, Investigational/adverse effects , Drugs, Investigational/pharmacology , Humans , Japan , Risk Assessment
13.
J Dent Res ; 90(1): 35-40, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21059869

ABSTRACT

The efficacy of the local application of recombinant human fibroblast growth factor-2 (FGF-2) in periodontal regeneration has been investigated. In this study, a randomized, double-blind, placebo-controlled clinical trial was conducted in 253 adult patients with periodontitis. Modified Widman periodontal surgery was performed, during which 200 µL of the investigational formulation containing 0% (vehicle alone), 0.2%, 0.3%, or 0.4% FGF-2 was administered to 2- or 3-walled vertical bone defects. Each dose of FGF-2 showed significant superiority over vehicle alone (p < 0.01) for the percentage of bone fill at 36 wks after administration, and the percentage peaked in the 0.3% FGF-2 group. No significant differences among groups were observed in clinical attachment regained, scoring approximately 2 mm. No clinical safety problems, including an abnormal increase in alveolar bone or ankylosis, were identified. These results strongly suggest that topical application of FGF-2 can be efficacious in the regeneration of human periodontal tissue that has been destroyed by periodontitis.


Subject(s)
Fibroblast Growth Factor 2/therapeutic use , Guided Tissue Regeneration, Periodontal/methods , Periodontitis/surgery , Adult , Alveolar Bone Loss/diagnostic imaging , Alveolar Bone Loss/surgery , Alveolar Process/drug effects , Dental Plaque Index , Double-Blind Method , Female , Fibroblast Growth Factor 2/administration & dosage , Follow-Up Studies , Gingiva/pathology , Gingival Hemorrhage/classification , Gingival Recession/classification , Humans , Male , Middle Aged , Periodontal Attachment Loss/classification , Periodontal Index , Periodontal Ligament/drug effects , Periodontal Pocket/classification , Placebos , Radiography , Recombinant Proteins , Surgical Flaps , Tooth Mobility/classification , Treatment Outcome
14.
J Periodontal Res ; 45(4): 550-6, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20412415

ABSTRACT

BACKGROUND AND OBJECTIVE: Inflammatory agents, such as lipopolysaccharide (LPS), in periodontal pockets may promote atherogenesis by activating leukocytes. In our previous study, we developed a microchannel chip to observe the cell adhesion process in a fluid system. The objective of this investigation was to examine the mechanism by which periodontopathic bacterial LPS enhances plaque-like formation on a microchannel chip. MATERIAL AND METHODS: To evaluate the effect of Aggregatibacter actinomycetemcomitans LPS on the expression of adhesion molecules, e.g. intercellular adhesion molecule 1 (ICAM-1), lymphocyte function-associated antigen 1 (LFA-1) and L-selectin, on the surface of murine macrophage RAW264.7 cells, the expression of each adhesion molecule was examined by flow cytometry and western blot analysis. Moreover, a flow test on the microchannel chip involving anti-adhesion molecule antibodies was conducted to clarify which adhesion molecule is related to plaque-like formation of RAW264.7 cells. RESULTS: The expressions of ICAM-1 and LFA-1 on the surface of RAW 264.7 cells increased following 12 h culture with LPS; L-selectin expression was unaffected. An increase in ICAM-1 expression was also confirmed by western blot analysis. The flow test revealed that anti-ICAM-1 antibody inhibited plaque-like formation of LPS-stimulated macrophages on the micropillars of the microchannel chip. CONCLUSION: These findings indicate that ICAM-1 plays an important role in plaque-like formation of LPS-stimulated macrophages. Our microchannel chip is a suitable tool for the investigation of etiological factors of atherosclerosis, including periodontitis, in vitro.


Subject(s)
Aggregatibacter actinomycetemcomitans/physiology , Intercellular Adhesion Molecule-1/drug effects , L-Selectin/drug effects , Lipopolysaccharides/pharmacology , Lymphocyte Function-Associated Antigen-1/drug effects , Macrophages/drug effects , Animals , Antibodies , Atherosclerosis/pathology , Blotting, Western , Cell Adhesion/drug effects , Cell Aggregation/drug effects , Cell Culture Techniques , Cell Line , Flow Cytometry , Intercellular Adhesion Molecule-1/analysis , L-Selectin/analysis , Lab-On-A-Chip Devices , Lymphocyte Function-Associated Antigen-1/analysis , Mice
15.
Oral Dis ; 16(3): 305-9, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20374514

ABSTRACT

OBJECTIVES: Infection of murine macrophage cell line J774.1 with the periodontopathic bacterium Aggregatibacter actinomycetemcomitans induces apoptotic cell death. The infection induces cell cycle arrest in the G1 phase prior to the appearance of apoptotic cells. This study determined the involvement of various cell cycle-related signal molecules in A. actinomycetemcomitans-induced G1 cell cycle arrest. MATERIALS AND METHODS: Cell cycle in J774.1 cells infected with A. actinomycetemcomitans was analyzed with a flow cytometer. Immunoblot analysis was also employed to determine the expression levels of intracellular signal molecules. RESULTS: Flow cytometric analysis revealed that the percentage of cells in the G1 phase increased to 77.2% at 12 h after A. actinomycetemcomitans infection. Additionally, according to immunoblot analysis, expression levels of hyperphosphorylated forms of retinoblastoma protein (ppRb) declined in J774.1 cells following A. actinomycetemcomitans infection, whereas hypophosphorylated Rb (pRb) expression levels were elevated slightly. Expression levels of cyclin D1 and D2 in the cells decreased gradually postinfection; CDK2, CDK4, CDK6 and cyclin E levels were not changed. Furthermore, postinfection, p21(CIP1/WAF1) expression increased at 6 h, followed by a subsequent decrease. CONCLUSION: These findings suggest that cyclin D1 and D2 and p21(CIP1/WAF1) participate in G1 cell cycle arrest in A. actinomycetemcomitans-infected J774.1 cells.


Subject(s)
Aggregatibacter actinomycetemcomitans/physiology , Apoptosis/physiology , G1 Phase/physiology , Macrophages/microbiology , Animals , Cell Line , Cyclin D1/biosynthesis , Cyclin D2/biosynthesis , Cyclin-Dependent Kinase Inhibitor p21/biosynthesis , Macrophages/metabolism , Mice , Phosphorylation , Retinoblastoma Protein/metabolism
16.
Diabetologia ; 53(2): 234-46, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19727657

ABSTRACT

AIMS/HYPOTHESIS: Resistin is a cytokine derived from adipose tissue and is implicated in obesity-related insulin resistance and type 2 diabetes mellitus. Polymorphisms of the resistin gene (RETN) have been shown to affect the plasma resistin concentration. The aims of this study were to identify polymorphisms of RETN that influence plasma resistin concentration and to clarify the relation between plasma resistin level and metabolic disorders in an aged Japanese cohort. METHODS: The study participants comprised 3133 individuals recruited to a population-based prospective cohort study (KING study). Plasma resistin concentration, BMI, abdominal circumference, blood pressure, fasting plasma glucose and serum insulin concentrations, HbA(1c) content and serum lipid profile were measured in all participants. The HOMA index of insulin resistance (HOMA-IR) was also calculated. Eleven polymorphisms of RETN were genotyped. RESULTS: A combination of ANOVA and multiple linear regression analysis in screening and large-scale subsets of the study population revealed that plasma resistin concentration was significantly associated with rs34861192 and rs3745368 polymorphisms of RETN. Multiple linear regression analysis with adjustment for age and sex also showed that the plasma resistin level was significantly associated with serum concentrations of HDL-cholesterol, triacylglycerol and insulin, as well as with BMI. CONCLUSIONS/INTERPRETATION: Our results implicate the rs34861192 and rs3745368 polymorphisms of RETN as robust and independent determinants of plasma resistin concentration in the study population. In addition, plasma resistin level was associated with dyslipidaemia, serum insulin concentration and obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00262691.


Subject(s)
Genetic Variation , Metabolic Diseases/blood , Resistin/blood , Resistin/genetics , Aged , Analysis of Variance , Blood Glucose/metabolism , Blood Pressure , Body Mass Index , Body Size , Cohort Studies , Diabetes Mellitus, Type 2/genetics , Female , Genotype , Glycated Hemoglobin/metabolism , Humans , Japan , Lipids/blood , Male , Metabolic Diseases/genetics , Middle Aged , Regression Analysis
17.
Anim Genet ; 41(1): 81-4, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19754851

ABSTRACT

The Patagonian pejerrey Odontesthes hatcheri is an atherinopsid species presenting genotypic sex determination (GSD) at intermediate temperatures and temperature-dependent sex determination at the low and high ranges of thermal tolerance. A recent study revealed the presence of a sex-linked SNP marker in some males of this species, but a strain which inherits the marker faithfully has not been established. This research was conducted to develop such a strain, for use as a tool to study the molecular mechanisms of gonadal sex differentiation and sexual dimorphism, and to obtain basic information on the GSD mode in this species. For these purposes, we performed backcrosses and full-sibling crosses using males and females whose presumptive genotypic sex was inferred from the presence of the sex-linked SNP marker. Four backcrosses between SNP(-) daughters and their SNP(+) father generated balanced sex ratios with the phenotypic sex matching the genotypic sex in most cases (98.21%) at an intermediate, sexually neutral temperature (21 degrees C). Full-sibling crosses between these four SNP(-) females and their SNP(+) brothers produced three progenies with balanced sex ratios and one with 94.4% males. The results of this study confirm that a strain inheriting the sex-linked SNP marker was successfully developed. Moreover, the inheritance pattern of the marker and the sex ratios of the progenies provide strong evidence that the GSD mode in O. hatcheri is the XX-XY system.


Subject(s)
Sex Determination Processes , Smegmamorpha/genetics , Animals , Crosses, Genetic , Female , Male , Polymorphism, Single Nucleotide , Temperature
18.
Arch Oral Biol ; 54(4): 369-73, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19185851

ABSTRACT

OBJECTIVE: We have recently reported that flow rates of whole saliva in young healthy humans correlate positively with salivary gland sizes. The low rate of salivary secretion in xerostomia patients may be related to the small size of the salivary glands. To investigate this possibility, relationships between salivary secretions and salivary gland sizes were investigated in unknown-etiology xerostomia patients and healthy controls. DESIGN: The sizes of the three major salivary glands in seven xerostomia patients and seven age- and gender-matched healthy controls who have no previous disease history and prescription medication related to xerostomia, were measured by use of a magnetic resonance imaging technique. The salivary glands of all subjects failed to show any pathological aspects in magnetic resonance images. The flow rates of unstimulated and chewing-stimulated whole saliva were also measured. RESULTS: Flow rates of unstimulated and chewing-stimulated whole saliva and the sizes of the parotid and submandibular glands were significantly lower and smaller in xerostomia patients of unknown etiology when compared with healthy controls. In addition, salivary flow rates per size of the combined three major salivary glands were also significantly lower in the xerostomia patients of unknown etiology. CONCLUSIONS: The smaller salivary gland size in xerostomia patients of unknown etiology may be one of the causes of the reduced salivary secretion. The secretion rates as a function of gland sizes were also lower, and so it is likely that functional impairments of the salivary gland are also present in patients with xerostomia of unknown etiology.


Subject(s)
Saliva/metabolism , Salivary Glands/pathology , Salivation/physiology , Xerostomia/pathology , Aged , Female , Humans , Magnetic Resonance Imaging , Male , Mastication , Middle Aged , Salivary Glands/metabolism , Xerostomia/etiology , Xerostomia/metabolism
19.
Heart ; 94(10): 1302-6, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18198205

ABSTRACT

OBJECTIVE: To evaluate regional and global left ventricular (LV) function and LV wall thickness (LVWT) in patients with hypertrophic cardiomyopathy (HCM). DESIGN AND SETTING: Observational study at the National Cardiovascular Centre and Nagoya University Hospital in Japan. PARTICIPANTS: Thirty-six patients with HCM and 16 patients with hypertensive LV hypertrophy (LVH). MAIN OUTCOME MEASURES: Conventional echocardiography and strain rate (SR) imaging derived from tissue Doppler imaging were performed. Systolic strain (epsilon(sys)), peak systolic SR (SR(sys)), peak early diastolic SR (SR(dia)) and LVWT were obtained from eight LV segments. LV pressure was simultaneously recorded with a high-fidelity micromanometer. RESULTS: The regional epsilon(sys) and SR(sys) were correlated with LVWT in patients with HCM (r = 0.50, p<0.001 and r = 0.63, p<0.001, respectively) but not in patients with hypertensive LVH. The standard deviations of LVWT, epsilon(sys) and SR(sys) obtained from the eight LV segments of each subject were greater for patients with HCM than for patients with hypertensive LVH. The standard deviation of LVWT was correlated with those of epsilon(sys) and SR(sys) (r = 0.55, p<0.001 and r = 0.56, p<0.001, respectively). The standard deviations of LVWT, epsilon(sys) and SR(sys) were correlated with tau (r = 0.35, p<0.05; r = 0.47, p<0.001; and r = 0.39, p<0.005, respectively). CONCLUSIONS: Heterogeneity of regional LV systolic function detected by SR imaging is in part attributable to heterogeneity of LVH and may be linked to impaired global LV relaxation in HCM.


Subject(s)
Cardiomyopathy, Hypertrophic/physiopathology , Ventricular Dysfunction, Left/physiopathology , Cardiomyopathy, Hypertrophic/diagnostic imaging , Echocardiography, Doppler , Female , Humans , Male , Middle Aged , Systole , Ventricular Dysfunction, Left/diagnostic imaging
20.
Dentomaxillofac Radiol ; 36(4): 218-23, 2007 May.
Article in English | MEDLINE | ID: mdl-17536089

ABSTRACT

PURPOSE: To evaluate the functional differences between the parotid and submandibular glands using dynamic MR sialography. METHODS: In 30 volunteers, the time-dependent changes (dynamic changes) in the maximum area of the detectable parotid and submandibular gland ducts on dynamic MR sialographic images were analysed. RESULTS: Dynamic changes in the parotid gland ducts were detectable on MR sialographic images in all volunteers, but images of the submandibular gland ducts were detectable in only 23 volunteers. In addition, the dynamic changes in the submandibular gland ducts in these 23 subjects were less than those seen in the parotid gland ducts. A relationship was found between the changing ratio of parotid (Pearson r=0.448, P=0.013) or submandibular gland ducts (Pearson r=0.418, P=0.047) and the salivary flow rate during the stimulation period. CONCLUSIONS: Dynamic MR sialography allows evaluation of rest and stimulated functioning and morphological evaluation of the parotid and submandibular glands. This technique appears to have many possible applications in the dental, medical and biological fields.


Subject(s)
Magnetic Resonance Imaging/methods , Parotid Gland/metabolism , Submandibular Gland/metabolism , Adult , Citric Acid , Female , Humans , Male , Saliva/metabolism , Stimulation, Chemical
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