Kōbe-shi, Japan
Kōbe-shi, Japan

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Hattori N.,Ritsumeikan University | Ishihara T.,Kobe City General Hospital | Matsuoka N.,Kobe City General Hospital | Saito T.,Kansai Medical University | Shimatsu A.,National Hospital Organization
Thyroid | Year: 2017

Background: Macro-thyrotropin (TSH) is a high-molecular-weight form of TSH. Most cases of macro-TSH are TSH complexed with immunoglobulin G. This study was undertaken to characterize macro-TSH. Methods: Blood samples taken from patients with subclinical hypothyroidism were screened for the presence of macro-TSH with the polyethylene glycol method and confirmed with gel filtration chromatography. TSH receptor antibody was quantified with an electrochemiluminescence immunoassay. Binding studies were performed using 125I-human TSH, and the specificity of anti-TSH autoantibodies was tested by displacement experiments using excess amounts of the unlabeled related peptides. Macro-TSH and serum TSH levels were evaluated twice over a one- to four-year interval. Results: Sixteen patients (11 females and 5 males; aged 8-82 years) were diagnosed as having macro-TSH. None of the patients with macro-TSH tested positive for TSH receptor antibody. Judging from the affinity and the binding capacity of anti-TSH autoantibodies, two classes of binding sites were identified. Regarding specificity, there were anti-human TSH-β autoantibodies that were partially cross-reactive to bovine and/or rat TSH-β. There were also autoantibodies against human glycoprotein α, a common subunit among human TSH, luteinizing hormone, and follicle stimulating hormone. Macro-TSH persisted in 11/13 patients who could be reevaluated over a one- to four-year interval after the first evaluation. Serum TSH levels returned to normal in the remaining two patients whose macro-TSH disappeared. Conclusions: It is concluded that anti-human TSH autoantibodies are a major cause of macro-TSH and that macro-TSH may persist for a long time. © Copyright 2017, Mary Ann Liebert, Inc.


Sakamoto Y.,Japan National Cardiovascular Center Research Institute | Koga M.,Japan National Cardiovascular Center Research Institute | Yamagami H.,St. Marianna University School of Medicine | Okuda S.,National Hospital Organization Nagoya Medical Center | And 14 more authors.
Stroke | Year: 2013

BACKGROUND AND PURPOSE - : Blood pressure (BP) lowering is often conducted as part of general acute management in patients with acute intracerebral hemorrhage. However, the relationship between BP after antihypertensive therapy and clinical outcomes is not fully known. METHODS - : Hyperacute (<3 hours from onset) intracerebral hemorrhage patients with initial systolic BP (SBP) >180 mm Hg were included. All patients received intravenous antihypertensive treatment, based on predefined protocol to lower and maintain SBP between 120 and 160 mm Hg. BPs were measured every 15 minutes during the initial 2 hours and every 60 minutes in the next 22 hours (a total of 30 measurements). The mean achieved SBP was defined as the mean of 30 SBPs, and associations between the mean achieved SBP and neurological deterioration (≥2 points' decrease in Glasgow Coma Score or ≥4 points' increase in National Institutes of Health Stroke Scale score), hematoma expansion (>33% increase), and unfavorable outcome (modified Rankin Scale score 4-6 at 3 months) were assessed with multivariate logistic regression analyses. RESULTS - : Of the 211 patients (81 women, median age 65 [interquartile range, 58-74] years, and median initial National Institutes of Health Stroke Scale score 13 [8-17]) enrolled, 17 (8%) showed neurological deterioration, 36 (17%) showed hematoma expansion, and 87 (41%) had an unfavorable outcome. On multivariate regression analyses, mean achieved SBP was independently associated with neurological deterioration (odds ratio, 4.45; 95% confidence interval, 2.03-9.74 per 10 mm Hg increment), hematoma expansion (1.86; 1.09-3.16), and unfavorable outcome (2.03; 1.24-3.33) after adjusting for known predictive factors. CONCLUSIONS - : High achieved SBP after standardized antihypertensive therapy in hyperacute intracerebral hemorrhage was independently associated with poor clinical outcomes. Aggressive antihypertensive treatment may ameliorate clinical outcomes. © 2013 American Heart Association, Inc.


Hattori N.,Ritsumeikan University | Adachi T.,Kansai Medical University | Ishihara T.,Kobe City General Hospital | Shimatsu A.,National Hospital Organization
European Journal of Endocrinology | Year: 2012

Objective: Macroprolactinaemia is a condition in which serum prolactin (PRL) consists mainly of large molecular weight PRL (macroPRL). The aim of this study was to examine the natural history of macroprolactinaemia. Design and participants: Six hundred and fifty-four hospital workers participated in this study, including 27 subjects with macroprolactinaemia and 627 controls. MacroPRL and serum PRL concentrations were evaluated over a 4-year period. The ratio of macroPRL was examined by the polyethylene glycol (PEG) method and gel filtration chromatography. IgG-bound PRL and anti-PRL autoantibodies were examined by protein G and 125I-PRL binding studies respectively. Results: Over the 4 years of the study, all 27 macroprolactinaemic subjects had persistent macroprolactinaemia without the development of raised free PRL, while none of the 627 controls developed macroprolactinaemia. The ratios of PEG-precipitable PRL and IgG-bound PRL did not significantly change, but 125I-PRL binding ratios significantly increased. As a whole, total and free serum PRL concentrations did not significantly change in subjects with macroprolactinaemia over the 4-year period. However, hyperprolactinaemia developed in five of the 18 macroprolactinaemic subjects who were initially normoprolactinaemic along with an increase in anti-PRL autoantibody titres. One of the remaining nine macroprolactinaemic subjects who were initially hyperprolactinaemic showed a decrease in serum PRL concentrations, which occurred concomitantly with a decrease in the anti-PRL autoantibody titre. Conclusions: Macroprolactinaemia may develop before middle age and is likely a chronic condition leading to hyperprolactinaemia. © 2012 European Society of Endocrinology.


Horie T.,Kyoto University | Ono K.,Kyoto University | Horiguchi M.,Kyoto University | Nishi H.,Kyoto University | And 10 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Sterol regulatory element-binding protein 2 (SREBP-2) transcription factor has been identified as a key protein in cholesterol metabolism through the transactivation of the LDL receptor and cholesterol biosynthesis genes. Here, we generated mice lacking microRNA (miR)-33, encoded by an intron of the Srebp2, and showed that miR-33 repressed the expression of ATP-binding cassette transporter A1 (ABCA1) protein, a key regulator of HDL synthesis by mediating cholesterol efflux from cells to apolipoprotein A (apoA)-I. In fact, peritoneal macrophages derived from miR-33-deficient mice showed a marked increase in ABCA1 levels and higher apoA-I-dependent cholesterol efflux than those from WT mice. ABCA1 protein levels in liver were also higher in miR-33-deficient mice than in WT mice. Moreover, miR-33-deficient mice had significantly higher serum HDL cholesterol levels than WT mice. These data establish a critical role for miR-33 in the regulation of ABCA1 expression and HDL biogenesis in vivo.


Hattori N.,Ritsumeikan University | Ishihara T.,Kobe City General Hospital | Saiki Y.,Kobe City General Hospital | Shimatsu A.,National Hospital Organization Kyoto Medical Center
Clinical Endocrinology | Year: 2010

Objective: Macroprolactin, which comprises immunoglobulin G (IgG) or anti-prolactin (PRL) autoantibody-bound PRL, is one of the causes of hyperprolactinaemia. This study evaluated the composition and stability of macroprolactin and determined whether the condition was long lasting. We also investigated whether we could predict the composition of macroprolactin based on the ratio of polyethylene glycol (PEG)-precipitable PRL. Patients: Two hundred and ninety-two patients with hyperprolactinaemia (252 women and 40 men). Design: We used PEG precipitation to screen for macroprolactinaemia in 625 serum samples from 292 patients with hyperprolactinaemia visiting a city hospital over the last 5·5 years. Macroprolactinaemia was defined by PEG-precipitable PRL ratio greater than 60%. IgG-bound PRL and anti-PRL autoantibodies were measured by protein G and 125I-hPRL binding studies, respectively. We also examined the autoantibody specificity and binding characteristics. Results: In 39 patients with macroprolactinaemia, IgG-bound PRL was present in 87% and anti-PRL autoantibodies in 67%. A non-IgG-bound form of macroprolactin was found mainly in sera with marginally elevated PEG-precipitable PRL. The higher the PEG-precipitable PRL ratio, the greater the likelihood that autoantibodies were involved in the composition of macroprolactin. The autoantibodies were IgG type and specific to human PRL and had a low affinity and high capacity. Long-term follow-up (2-17 years) revealed that the ratios of PEG-precipitable PRL, IgG-bound PRL and anti-PRL autoantibody-bound PRL were relatively stable. Conclusions: This study showed that higher PEG-precipitable PRL ratio in macroprolactinaemic sera might preferentially indicate the presence of anti-PRL autoantibodies and that macroprolactinaemia might be a long-lasting condition. © 2010 Blackwell Publishing Ltd.


PubMed | Red Cross, Nakamura Memorial Hospital, Hirosaki Stroke and Rehabilitation Center, Niigata University and 3 more.
Type: Journal Article | Journal: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association | Year: 2016

Patients with penetrating artery territory infarction occasionally show progressive motor deficits during the acute stage with poor prognosis. Predictive indices or medical therapies for suppressing the symptomatic progression (SP) of penetrating artery infarction have not been established. In this study, we investigated SP-related clinical factors and functional outcomes, specifically improvement 3 months post ictus in patients with penetrating artery infarction.We retrospectively examined acute stroke patients with penetrating artery infarction admitted at 7 collaborative hospitals. SP was defined as an increase by 1 point or higher in the National Institutes of Health Stroke Scale score. Functional improvement was assessed based on the modified Rankin Scale at 3 months. The influence of factors, such as patient characteristics, clinical data, medical treatment during the acute stage and on SP, and functional improvement was statistically analyzed.Four hundred eighty-eight patients (310 men; mean age, 70 years) were examined. Sixty-eight patients (14%) exhibited SP. Multivariate logistic regression analysis revealed that higher hemoglobin A1c (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.10-1.55), body mass index (BMI; OR, .85; 95% CI, .77-.94), and systolic blood pressure on admission (OR, 1.63; 95% CI, 1.19-2.25) were independent predictors of SP in penetrating artery infarction. Dual antiplatelet therapy (DAPT; OR, 3.48; 95% CI, 1.52-8.38) independently influenced functional improvement.Initial high blood pressure, diabetes, and low BMI on admission were associated with early progression of penetrating artery infarction. DAPT during the acute stage may contribute to functional improvement.


Kamakura T.,Kyoto University | Makiyama T.,Kyoto University | Sasaki K.,Kyoto University | Yoshida Y.,Kyoto University | And 8 more authors.
Circulation Journal | Year: 2013

Background: In the short- to mid-term, cardiomyocytes generated from human-induced pluripotent stem cells (hiPSC-CMs) have been reported to be less mature than those of adult hearts. However, the maturation process in a long-term culture remains unknown. Methods and Results: A hiPSC clone generated from a healthy control was differentiated into CMs through embryoid body (EB) formation. The ultrastructural characteristics and gene expressions of spontaneously contracting EBs were analyzed through 1-year of culture after cardiac differentiation was initiated. The 14-day-old EBs contained a low number of myofibrils, which lacked alignment, and immature high-density Z-bands lacking A-, H-, I-, and Mbands. Through the long-term culture up to 180 days, the myofibrils became more tightly packed and formed parallel arrays accompanied by the appearance of mature Z-, A-, H-, and I-bands, but not M-bands. Notably, M-bands were finally detected in 360-day-old EBs. The expression levels of the M-band-specific genes in hiPSC-CMs remained lower in comparison with those in the adult heart. Immunocytochemistry indicated increasing number of MLC2v-positive/MLC2a-negative cells with decreasing number of MLC2v/MLC2a double-positive cells, indicating maturing of ventricular-type CMs. Conclusions: The structural maturation process of hiPSC-CMs through 1-year of culture revealed ultrastructural sarcomeric changes accompanied by delayed formation of M-bands. Our study provides new insight into the maturation process of hiPSC-CMs.


Sekiguchi K.,Kobe University | Kanda F.,Kobe University | Mitsui S.,Kobe University | Kohara N.,Kobe City General Hospital | Chihara K.,Kobe University
Clinical Neurophysiology | Year: 2012

Objective: The molecular mechanisms underlying fibrillation potentials are still unclear. We hypothesised that expression of the cardiac-type voltage-gated sodium channel isoform Nav1.5 in denervated rat skeletal muscle is associated with the generation of such potentials. Methods: Muscle samples were extracted and analysed biologically from surgically denervated rat extensor digitorum longus muscle after concentric needle electromyographic recording at various time points after denervation (4. h to 6. days). Results: Both nav1.5 messenger RNA (mRNA) signal on northern blotting and Nav1.5 protein expression on immunohistochemistry appeared on the second day after denervation, exactly when fibrillation potentials appeared. Administration of lidocaine, which has much stronger affinity for sodium channels in cardiac muscle than for those in skeletal muscle, dramatically decreased fibrillation potentials, but had no effect on contralateral compound muscle action potentials. Conclusions: Expression of Nav1.5 participates in the generation of fibrillation potentials in denervated rat skeletal muscle. Significance: We proposed an altered expression of voltage-gated sodium channel isoforms as a novel mechanism to explain the occurrence of fibrillation potentials following skeletal muscle denervation. © 2012 International Federation of Clinical Neurophysiology.


Sakai N.,Kobe City General Hospital | Sakai C.,Kobe City General Hospital
Nippon Geka Gakkai zasshi | Year: 2010

Carotid disease is one of important cause of stroke, may cause 10-20% of all ischemic strokes. In symptomatic patients, carotid revascularization is indicated in the presence of a stenosis 50% or more. In asymptomatic patients, the indication for revascularization is 60% or more stenosis, based on randomized trials at US and Europe. In clinical practice however, asymptomatic stenoses are usually treated only if luminal narrowing exceeds 70-80%. The choice of the revascularization strategy (endarterectomy versus stenting) should be based on the surgical risk profile of the patient and institutional expertise. Carotid artery stenting is particularly beneficial in patients at high risk for surgery: surgically inaccessible lesions; radiation-induced carotid stenosis prior ipsilateral radical neck dissection prior carotid endarterectomy and severely modical comorbid matients. Results of medical treatment become now improving. There still need more experience to establish treatment strategy for severe carotid diseases.


McDonald A.G.,Massachusetts General Hospital | Cin P.D.,Brigham and Women's Hospital | Ganguly A.,Massachusetts General Hospital | Campbell S.,Massachusetts General Hospital | And 3 more authors.
American Journal of Surgical Pathology | Year: 2011

Background: Primary sarcomas of the uterus are uncommon, leiomyosarcoma being the most frequent. Most uterine sarcomas arise de novo, with malignant transformation of a benign mesenchymal tumor being a very rare event, and is reported only in leiomyomata. DESIGN: The clinicopathologic features of 3 uterine liposarcomas arising in association with a lipoleiomyoma were studied. Immunohistochemistry for desmin, h-caldesmon, S100, and MDM2, and fluorescence in situ hybridization for the t(12;16) (q13;p11) were performed in all cases. Result: Patients ranged in age from 49 to 70 (mean, 59) years. The tumors were centered in the myometrium, ranged in size from 10 to 18.5 cm, and showed a gelatinous cut surface with foci of necrosis. On microscopic examination, the tumors had well-circumscribed pushing margins. One neoplasm was uniformly hypocellular with a prominent myxoid background, and a striking delicate vascular network. Another neoplasm showed alternating hypocellular (myxoid) and hypercellular areas, whereas the third tumor was uniformly hypercellular with a hyalinized background. In the myxoid areas, the cells were small and spindle with oval nuclei and inconspicuous nucleoli. In the hypercellular areas, the cells were pleomorphic with large, hyperchromatic nuclei. Mitotic activity ranged from <3 to 7/10 high-power fields. Lipoblasts were present in all tumors but were more common in the hypercellular areas. Two tumors merged imperceptibly with a lipoleiomyoma (1 typical and 1 with bizarre nuclei), whereas the third tumor showed an infarcted area composed of ghost mature adipocytes admixed with hyalinized smooth muscle most consistent with an infarcted lipoleiomyoma. Tumors were classified as myxoid, mixed myxoid and pleomorphic, and pleomorphic liposarcoma, respectively. The benign and malignant adipose components were positive for S100, whereas the benign smooth muscle component stained for desmin and h-caldesmon. MDM2 immunostain was positive in the 2 cases with a pleomorphic liposarcoma component. Fluorescence in situ hybridization analysis was successfully completed in only 1 of 3 tumors (pure pleomorphic liposarcoma), which failed to show the t(12;16) and HMAG2 amplification. The patients are alive and well 1, 2, and 20 years after initial surgery with no adjuvant therapy. Conclusions: Primary liposarcomas of the uterus are extremely rare and are most likely to arise from malignant transformation of a lipoleiomyoma. These tumors should be added to the differential diagnosis of benign lipomatous tumors, myxoid mesenchymal tumors, and malignant mixed Müllerian tumors (if pleomorphic) of the uterus. Copyright © 2011 by Lippincott Williams & Wilkins.

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