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Vascular smooth muscle RhoA counteracts abdominal aortic aneurysm formation by modulating MAP4K4 activity
Get PDFapplication/pdfapplication/xlsxWhether a small GTPase RhoA plays a role in the pathology of abdominal aortic aneurysm (AAA) has not been determined. We show here that RhoA expression is reduced in human AAA lesions, compared with normal areas. Furthermore, incidence of AAA formation is increased in vascular smooth muscle cell (VSMC)-specific RhoA conditional knockout (cKO) mice. The contractility of the aortic rings and VSMCs from RhoA cKO mice is reduced, and expression of genes related to the VSMC contractility is attenuated by loss of RhoA. RhoA depletion activates the mitogen-activated protein (MAP) kinase signaling, including MAP4K4, in the aorta and VSMCs. Inhibition of MAP4K4 activity by DMX-5804 decreases AAA formation. Set, a binding protein to active RhoA, functions as an activator of MAP4K4 by sequestering PP2A, an inhibitor of MAP4K4, in the absence of RhoA. In conclusion, RhoA counteracts AAA formation through inhibition of MAP4K4 in cooperation with Set.Journal Articlejournal articl
Therapeutic Potential of Valproic Acid for Postviral Olfactory Dysfunction: A Single-Arm Pilot Study.
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Although some patients with postviral olfactory dysfunction (PVOD) recover spontaneously, many others are left with the degree of smell loss and there are no established drugs for the treatment of patients with PVOD. Valproic acid (VPA) has been widely used for the treatment of epilepsy. Its potential neuroregenerative effects have been shown via animal studies. This is the first study to treat PVOD patients with VPA. This open-label, single-arm, phase II study was conducted to investigate the effects of VPA in patients with PVOD.Methods:
The patients received oral tablets of VPA 200 mg twice a day for 24 weeks. In total, 11 patients with PVOD were recruited. Oder scores of recognition and detection threshold (measured with a T&T olfactometer), and visual analog scale were examined during the treatment.Results:
All odor scores significantly improved over time. Although the mean duration of olfactory dysfunction in this study was 11.5 months, both odor recognition threshold and odor detection threshold scores significantly improved 4 weeks after treatment initiation compared to the pre-treatment threshold scores. The olfactory recovery rates in patients treated with VPA were clearly better than those we previously reported in PVOD patients who received Toki-shakuyaku-san, the traditional treatment in Japan. The olfactory recovery rates of patients with PVOD at 12 weeks and 24 weeks of VPA treatment were both 77.8%, and the olfactory cure rates at 12 weeks and 24 weeks of VPA treatment were 33.3% and 44.4%, respectively. No serious adverse events were observed.Conclusions:
VPA seems to be a safe treatment option in patients with PVOD. The effects of VPA treatment for PVOD patients should be studied with a controlled study design in the future.Journal Articlejournal articl
Effect of diabetes and prediabetes on the development of disability and mortality among middle-aged Japanese adults : A 22-year follow up of NIPPON DATA90.
Get PDFpdfAims/introduction:
To examine the association between diabetes and prediabetes at baseline, and disability, mortality over a 22-year period among middle-aged Japanese adults.Materials and methods:
Participants consisted of 1,788 adults aged 45-64 years at baseline from the cohort study National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged 1990 (NIPPON DATA90). Disability, defined as having a decline in activities of daily living (ADL), was assessed by a modified Katz questionnaire at four time points. Disability and death without disability for 22-year follow up were used as outcomes to test the association with a diagnosis of diabetes or prediabetes at baseline, using multinomial logistic regression. Adjusted odds ratios (ORs) were obtained from four models that contained appropriate adjustment factors, such as age, sex, smoking status, drinking status, body mass index and cardiovascular risk factors (hypertension, hypercholesterolemia, triglycerides, low serum high-density lipoprotein), at baseline.Results:
In the present study, 334 participants (18.7%) reported at least one disability, and 350 (19.6%) were reported dead without observation of disability during follow up. Adjusting sex and other risk factors, participants with diabetes and prediabetes had a higher risk for disability (OR 1.43, 95% confidence interval [CI] 1.07-1.91 and OR 1.66, 95% CI 1.10-2.50, respectively) and for mortality (OR 1.56, 95% CI 1.16-2.08 and OR 1.77, 95% CI 1.18-2.65, respectively) than individuals with normal glucose tolerance.Conclusions:
In middle-aged Japanese adults, individuals with diabetes and prediabetes were more likely to be associated with disability and mortality. Our findings suggest that prediabetes and diabetes in middle-aged adults should be paid more attention, and requires more intervention to prevent disability and mortality in later life.Journal Articlejournal articl
Vascular smooth muscle RhoA counteracts abdominal aortic aneurysm formation by modulating MAP4K4 activity.（最新研究の紹介）
Get PDFapplication/pdfOthersCommunications Biology. 2022 Oct 7;5(1):1071.
DOI: 10.1038/s42003-022-04042-zothe
Correction to: Relationship between retinal fluid and visual acuity in patients with exudative age-related macular degeneration treated with intravitreal aflibercept using a treat-and-extend regimen: subgroup and post-hoc analyses from the ALTAIR study.
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Atypical fetal junctional ectopic tachycardia: a case report and literature review
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Junctional ectopic tachycardia (JET) is caused by ectopic rhythms, originating in the atrioventricular node, typically with heart rate between 200 and 250 bpm. Herein, we present a case of fetal JET with normal fetal heart rate and a review of nine cases.Case presentation:
A 32-year-old, gravida 2, para 1, woman in whom fetal JET could not be diagnosed prenatally because the fetal heart rate was within the normal range. The fetus was diagnosed with premature restriction of the foramen ovale, and a cesarean section was performed, owing to the right heart overload that was characterized by fetal ascites and abnormal fetal Doppler velocity. Postnatally, the female neonate was diagnosed with JET on a 12-lead electrocardiogram, which revealed a neonatal heart rate of 158 bpm with narrow QRS and atrioventricular dissociation. After failure to respond to amiodarone therapy, she was treated with flecainide, which controlled the JET rate from 120 to 150 bpm. Fetal tachycardia with ventriculo-atrial (VA) dissociation or 1:1 VA conduction with a shorter VA interval than that of atrioventricular reentrant tachycardia confirmed the diagnosis of fetal JET.Conclusions:
JET should be suspected even in the absence of tachycardia in patients with ductus venosus and pulmonary vein retrograde flow or tricuspid and mitral regurgitation without a cardiac anomaly, as tachycardia might sometimes be intermittent in cases of JET.Journal Articlejournal articl
Large Questionnaire Survey on Sleep Duration and Insomnia Using the TV Hybridcast System by Japan Broadcasting Corporation (NHK)
Get PDF滋賀医科大学博士（医学）pdfThesis or DissertationInternational journal of environmental research and public health. 2021 Mar 7;18(5):2691.令和3年度thesi
Inactivated whole influenza virus particle vaccines induce neutralizing antibodies with an increase in immunoglobulin gene subclones of B-lymphocytes in cynomolgus macaques.
Get PDFpdfThe All-Japan Influenza Vaccine Study Group has been developing a more effective vaccine than the current split vaccines for seasonal influenza virus infection. In the present study, the efficacy of formalin- and/or β-propiolactone-inactivated whole virus particle vaccines for seasonal influenza was compared to that of the current ether-treated split vaccines in a nonhuman primate model. The monovalent whole virus particle vaccines or split vaccines of influenza A virus (H1N1) and influenza B virus (Victoria lineage) were injected subcutaneously into naïve cynomolgus macaques twice. The whole virus particle vaccines induced higher titers of neutralizing antibodies against H1N1 influenza A virus and influenza B virus in the plasma of macaques than did the split vaccines. At challenge with H1N1 influenza A virus or influenza B virus, the virus titers in nasal swabs and the increases in body temperatures were lower in the macaques immunized with the whole virus particle vaccine than in those immunized with the split vaccine. Repertoire analyses of immunoglobulin heavy chain genes demonstrated that the number of B-lymphocyte subclones was increased in macaques after the 1st vaccination with the whole virus particle vaccine, but not with the split vaccine, indicating that the whole virus particle vaccine induced the activation of vaccine antigen-specific B-lymphocytes more vigorously than did the split vaccine at priming. Thus, the present findings suggest that the superior antibody induction ability of the whole virus particle vaccine as compared to the split vaccine is attributable to its stimulatory properties on the subclonal differentiation of antigen-specific B-lymphocytes.Journal Articlejournal articl