Tsuji S.,Kansai Medical University |
Yamashita M.,Saiseikai Noe Hospital |
Unishi G.,Unishi Clinic |
Takewa R.,Kansai Medical University |
And 5 more authors.
BMC Nephrology | Year: 2013
Background: Pseudohypoaldosteronism type II (PHA II), also referred to as Gordon syndrome, is a rare renal tubular disease that is inherited in an autosomal manner. Though mutations in WNK1 and WNK4 partially account for this disorder, in 2012, 2 research groups showed that KLHL3 and CUL3 were the causative genes for PHA II. Here, we firstly report on the Japanese child of PHA II caused by a mutation of CUL 3. Case presentation. The patient was a 3-year-old Japanese girl having healthy unrelated parents. She was initially observed to have hyperkalemia, hyperchloremia, metabolic acidosis, and hypertension. A close investigation led to the diagnosis of PHA II, upon which abnormal findings of laboratory examinations and hypertension were immediately normalized by administering thiazides. Genetic analysis of WNK1 and WNK4 revealed no mutations. However, analysis of the CUL3 gene of the patient showed abnormal splicing caused by the modification of exon 9. The patient is currently 17 years old and does not exhibit hypertension or any abnormal findings on laboratory examination. Conclusions: In this patient, CUL3 was found to play a fundamental role in the regulation of blood pressure, potassium levels, and acid-base balance. © 2013 Tsuji et al.; licensee BioMed Central Ltd.
Nanba K.,National Hospital Organization Kyoto Medical Center |
Tsuiki M.,National Hospital Organization Kyoto Medical Center |
Sawai K.,National Hospital Organization Kyoto Medical Center |
Mukai K.,Keio University |
And 11 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013
Context: Although primary aldosteronism (PA) is the most common cause of endocrine hypertension, histopathological methods to reveal the presence and sites of aldosterone overproduction remain to be established. Objective: The objective of the study was to investigate the significance of immunohistochemical staining to detect CYP11B2 and CYP11B1 in adrenal tissue of patients with PA. Design and Patients: Thirty-two patients with PA who underwent unilateral adrenalectomy were studied. Immunohistochemical staining was performed using anti-CYP11B2 and anti-CYP11B1 antibodies on paraffin-embedded sections. We analyzed the expression of each enzyme semiquan-titatively by scoring staining intensity and correlating it with clinical findings. Results: Twenty-two patients showed positive CYP11B2 immunostaining in their tumors (aldosterone producing adenoma, APA). Four patients with CYP11B2-negative unilateral adenomas and 4 patients without tumors on computed tomography showed aldosterone-producing cell clusters (APCCs) with CYP11B2 immunostaining in the zona glomerulosa (multiple APCCs). The remaining 2 patients had unilateral multiple adrenocortical micronodules and diffuse adrenocortical hyperplasia, respectively. In APA, CYP11B2 score adjusted for tumor volume was positively correlated with plasma aldosterone and negatively correlated with serum potassium. The APA group was divided into 3 subgroups based on relative CYP11B2 and CYP11B1 immunostaining levels. The CYP11B2/CYP11B1-equivalent and CYP11B1-dominant APA groups showed significantly higher serum cortisol after 1 mg dexamethasone and larger tumor size than the CYP11B2-dominant APA group. Conclusions: The present study clearly demonstrates that CYP11B2 immunostaining is a powerful tool for histopathological diagnosis of aldosterone overproduction in PA and for subtype classification of APA, multiple APCCs, unilateral multiple adrenocortical micronodules, and diffuse hyperplasia. Copyright © 2013 by The Endocrine Society.
Ikenaga M.,Sohma Hospital |
Mukaida M.,Kyoto Medical Center |
Nagahara R.,Kyoto City Hospital |
Yasunaga T.,Saiseikai Noe Hospital |
And 2 more authors.
Spine | Year: 2012
Study Design: Case report. Objective: To describe a new method of anterior cervical reconstruction with pedicle screws. Summary of Background Data: Anterior reconstruction after multilevel corpectomy is a challenging technique, and there are many reports on its complications. Graft dislodgement is one of the major complications after long cervical fusion. The main cause of failure seems to be a lack of stability in the conventional reconstruction technique. However, pedicle screws for posterior cervical reconstruction show remarkable stability. We describe a new technique of anterior cervical reconstruction with pedicle screws and fibular strut grafting. Methods: Seven patients with multilevel cervical myelopathy were treated with this new reconstruction technique after a 4-level corpectomy. We describe this new technique and review the patients' clinical history, results of radiographical imaging, and outcomes. Clinical outcomes were assessed preoperatively and at 3 months postoperatively. Postoperative radiographs were assessed 3 months and 6 months postoperatively. Results: The mean operative time was 182 minutes and the mean blood loss was 271 mL. The average Japanese Orthopaedic Association score for cervical myelopathy improved from 11.5 points preoperatively to 14.5 points 3 months postoperatively. No patients experienced major complications, such as neurological deterioration, infection, or massive blood loss. There was no case of reconstruction failure, graft dislodgement, migration, or screw displacement. Conclusion: To our knowledge, this is the first description of an anterior cervical reconstruction approach, using pedicle screws and fibular strut grafting after a 4-level corpectomy. It is likely that this technique will result in better clinical outcomes with fewer complications in the treatment of patients with multilevel cervical myelopathy. Copyright © 2012 Lippincott Williams & Wilkins.
Matsunaga T.,Kyoto University |
Shoji A.,Kyoto University |
Gu N.,Harbin Institute of Technology |
Joo E.,Kyoto University |
And 6 more authors.
Molecular Medicine Reports | Year: 2012
Tocotrienols, members of the vitamin E family, have been shown to possess anti-inflammatory properties and display activity against a variety of chronic diseases, such as cancer, cardiovascular and neurological diseases. However, whether tocotrienols contribute to the prevention of inflammatory responses in adipose tissue remains to be elucidated. In this study, we examined the effects of γ-tocotrienol, the most common tocotrienol isomer, on tumor necrosis factor-α (TNF-α)-induced inflammatory responses by measuring the expression of the adipokines, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and adiponectin in 3T3-L1 adipocytes. Exposure to TNF-α (10 ng/ml) for 24 h increased MCP-1 and IL-6 secretion, and decreased adiponectin secretion and peroxisome proliferator-activated receptor-γ (PPARγ) mRNA expression. γ-tocotrienol effectively improved the TNF-α-induced adverse changes in MCP-1, IL-6 and adiponectin secretion, and in MCP-1, IL-6, adiponectin and PPARγ mRNA expression. Furthermore, TNF-α-mediated IκB-α phosphorylation and nuclear factor-κB (NF-κB) activation were significantly suppressed by the γ-tocotrienol treatment. Our results suggest that γ-tocotrienol may improve obesity-related functional abnormalities in adipocytes by attenuating NF-κB activation and the expression of inflammatory adipokines.
Tanaka D.,Kyoto University |
Nagashima K.,Kyoto University |
Sasaki M.,Kyoto University |
Funakoshi S.,Kyoto University |
And 4 more authors.
Molecular Genetics and Metabolism | Year: 2013
The aim of this study was to investigate the genetic background of familial clustering of diabetes using genome-wide linkage analysis combined with exome sequencing. We recruited a Japanese family with a 3-generation history of diabetes. The family comprised 16 members, 13 having been diagnosed with diabetes. Nine members had been diagnosed before the age of 40. Linkage analysis was performed assuming an autosomal dominant model. Linkage regions were observed on chromosomes 4q34, 5q11-q13, and 12p11-q22 and the logarithm of odds (LOD) scores were 1.80. To identify the susceptibility variants, we performed exome sequencing of an affected family member. We predicted that the familial clustering of diabetes is caused by a rare non-synonymous variant, and focused our analysis on non-synonymous variants absent in dbSNP131. Exome sequencing identified 10 such variants in the linkage regions, 7 of which were concordant with the affection status in the family. One hundred five normal subjects and 67 lean diabetes subjects were genotyped for the 7 variants; the only variant found to be significantly more frequent in the diabetes subjects than in the normal subjects was the N1072K variant of the early endosome antigen 1 (EEA1) gene (0 in normal subjects and 4 in diabetes subjects, p = 0.022). We therefore propose that the N1072K variant of the EEA1 gene is a candidate mutation for susceptibility to diabetes in the Japanese population. © 2013 Elsevier Inc.