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Kazuo Hara

Publications and source records attributed to Kazuo Hara.

At least 37 records · Page 2Linked to original sources
PubMed2005

Adiponectin: an adipokine linking adipocytes and type 2 diabetes in humans.

Adipocyte-derived adiponectin is an insulin-sensitizing and antiatherosclerotic hormone, and replenishment of adiponectin in animal models ameliorated insulin resistance and atherosclerosis. In humans, recent studies have demonstrated that adiponectin level is a good predictor of developing type 2 diabetes and coronary artery disease. Decreasing level of adiponectin is caused by the interaction between genetic factors, such as single nucleotide polymorphisms in the adiponectin gene, and environmental factors, such as high-fat diet. Agents that increase blood level of adiponectin or enhance the actions of adiponectin can be an ideal medicine for ameliorating insulin resistance and type 2 diabetes.

Adipocytes↗
PubMed2005

Signet-ring cell ependymoma with intratumoral hemorrhage in the medulla oblongata.

We report a case of signet-ring cell ependymoma of the medulla oblongata. The patient presented with acute paralysis of the soft palate and absent gag reflex resulting in respiratory distress after accidental inhalation of water. MRI revealed a large intra-axial mass with foci of intratumoral hemorrhage in the medulla oblongata. A subtotal resection was performed as histopathological findings on the frozen section were consistent with metastatic carcinoma. However, the final paraffin section showed an ependymoma with signet-ring cells. A total removal was then performed with preservation of the lower cranial nerves. Postoperatively, the patient made a slow but steady recovery, and was able to swallow both water and food within 3 months. Signet-ring cell ependymoma must be included in the differential diagnosis of metastatic carcinoma to the central nervous system.

Adult↗
PubMed2005

Immunohistochemical study of chromogranin A in Stage D2 prostate cancer.

OBJECTIVES: To study the clinical and pathologic factors that affect the time to recurrence after hormonal therapy in patients with Stage D2 prostate cancer and to determine whether cells positive for chromogranin A (CgA) in tissue biopsied at diagnosis is a useful marker for predicting the duration to recurrence after hormonal therapy. METHODS: A total of 50 patients diagnosed with Stage D2 prostate cancer at our institution from January 1998 to December 2001 were studied. The needle prostate biopsy specimens obtained at diagnosis were stained by immunohistochemistry using the labeled streptavidin biotin method, and the results were considered positive if CgA-positive cells constituted 10% or more of the tumor area. RESULTS: No significant differences were found between patients on the basis of the time to recurrence of less than 2 years versus 2 years or more with respect to prostate-specific antigen level, patient age, Gleason score, or extent-of-disease grade. Of the 50 patients, 11 (22.0%) had positive cell staining for CgA. No significant differences were found between the CgA-positive group and the CgA-negative group in age, prostate-specific antigen level, Gleason score, extent-of-disease grade, T stage, or N stage. The rate of freedom from recurrence after 2 years as analyzed by the Kaplan-Meier method was 18.2% for the CgA-positive group and 47.4% for the CgA-negative group, and the CgA-positive group had a significantly shorter time to recurrence (P < 0.0122). CONCLUSIONS: The results of our study have shown that patients with overexpression of CgA-positive cells in the prostate have a significantly shorter time to recurrence after hormonal therapy than patients with CgA-negative cells; thus, CgA expression may be a useful marker predictive of the time to recurrence.

Aged↗
PubMed2005

A case of epidermotropic metastatic malignant melanoma with multiple nodular lesions of the scalp.

Epidermotropic metastatic malignant melanoma (EMMM) is a form of metastatic malignant melanoma that has dermal cell nests with epidermotropism and specific histopathological features. We report a patient with eight nodular lesions of the scalp with histopathological findings compatible with EMMM. The tumors developed one year before consultation and increased in size simultaneously. The histopathological findings of all eight tumors were very similar. The tumor cells were located mainly in the dermis and partly in the basal layer of the epidermis. They contained melanin pigments and were positive for anti-HMB45 antibody. The tumors did not respond to combination chemotherapy with dacarbazine, nimustine, vincristine, and interferon-beta. Therefore, all the tumors were surgically removed. No local relapse, distant metastasis or re-elevation of plasma 5-S-cysteinyldopa was identified during nine months of follow-up. Histopathologically, all eight tumors lacked apparent vascular invasion, which may be related to a slow clinical course of the present case.

Aged↗
PubMed2005

Single-nucleotide polymorphisms in the 17beta-hydroxysteroid dehydrogenase genes might predict the risk of side-effects of estramustine phosphate sodium in prostate cancer patients.

BACKGROUND: Estramustine phosphate sodium (EMP) frequently causes side-effects such as gastrointestinal discomfort, nausea, and edema in extremities. We analyzed single nucleotide polymorphisms (SNP) in the 17beta-hydroxysteroid dehydrogenase (HSD17B) genes, which are involved in the metabolism of EMP, to predict the risk of EMP side-effects in prostate cancer patients. METHODS: We performed genotyping of SNP in the HSD17B genes of 44 Japanese patients with newly diagnosed prostate cancer. The association of SNP and individual EMP side-effects was evaluated. RESULTS: Peripheral edema occurred more frequently in patients with C/C genotype of IMS-JST123219 than in those with C/G genotype (OR: 5.47, 95% CI: 1.27-23.64). Haplotype analysis showed that appetite loss was associated with the G allele of IMS-JST123219 and the T allele of IMS-JST123218 (OR: 9.13, 95% CI: 1.15-72.76). CONCLUSIONS: These preliminary data demonstrated that analyses of SNP in the HSD17B genes might predict the occurrence of side-effects from EMP.

17-Hydroxysteroid Dehydrogenases↗
PubMed2005

Usefulness of contrast-enhanced transabdominal ultrasonography in the diagnosis of intraductal papillary mucinous tumors of the pancreas.

BACKGROUND: The differentiation of benign from malignant intraductal papillary mucinous tumors (IPMT) is often difficult even by various examination methods. We evaluated the qualitative and quantitative diagnostic ability of contrast-enhanced transabdominal ultrasonography (CE-US), mainly in differentiating benign from malignant tumors in patients with IPMT. PATIENTS AND METHODS: There were 21 patients with IPMT who underwent CE-US and endoscopic ultrasonography (EUS). Surgery was performed in all 21 patients. Pathological findings were 4 with carcinoma and 17 with adenoma. CE-US was performed using a contrast agent (Levovist; Tanabe, Osaka, Japan) consisting of galactose microbubbles and a small (0.1%) admixture of palmitic acid, and the following items were evaluated by the following procedure. (1) Two reviewers with experienced sonographic and endosonographic ability evaluated CE-US images before and after contrast enhancement and classified the enhancement effects into three grades. In addition, the presence or absence of enhancement effects by CE-US was compared with that of mural nodules visualized by EUS. (2) In all 21 patients, changes in intensity after contrast enhancement were quantitatively measured using an HDI Lab. HDI Lab was provided by ATL (Philips; Bothell, WA) and these software tools rapidly quantify image characteristics within multiple ROI (regions of interest) and make comparisons between several areas or images. In both the early and late phases, the post-enhancement intensity, difference between pre- and post-enhancement intensity, and the percentage change ((post-enhancement value-pre-enhancement value)/pre-enhancement value) were compared between malignant and benign lesions, and the ability of CE-US to differentiate between benign and malignant lesions was evaluated in comparison with the ability of EUS to diagnose the degree of malignancy. RESULTS: (1) In both the early and the late phases, both reviewers observed enhancement effects in all 21 patients. And both reviewers observed mural nodules by EUS in all 21 patients. (2) In all 21 patients who underwent resection of IPMT, the intensity increased in both the early and late phases. When the patients with carcinoma were compared with those with adenoma, the post-enhancement intensity was significantly higher, and the difference between pre- and post-enhancement intensity and the percentage change in the early phase and the late phase was significantly more marked in the carcinoma group (p= 0.019, p= 0.002, p= 0.015, p= 0.012, and p= 0.039, respectively). CONCLUSIONS: CE-US was useful for qualitatively diagnosing tumor lesions in patients with IPMT. Moreover, quantitative changes in intensity can be a parameter for the differential diagnosis of benign and malignant tumors.

Abdomen↗
PubMed2005

Angioimmunoblastic T cell lymphoma with an unusual proliferation of Epstein-Barr virus-associated large B cells arising in a patient with progressive systemic sclerosis.

We report an unusual case of angioimmunoblastic T cell lymphoma arising in the setting of 5 years of immunosuppressive treatment for progressive systemic sclerosis. The lymph node lesion was accompanied by large blastic B cells with an association of Epstein-Barr virus. Southern blot study demonstrated the clonal rearrangement of T cell receptor beta-chain gene, but not of immunoglobulin heavy chain gene. Phenotypical examination of the lymph node also revealed the predominance of CD4+ T cells in addition to the proliferation of follicular dendritic cells, but no light chain restriction in large B cell components. In the clinical and laboratory aspects, neutrophilia (15.8 x 10(9)/l) and plasmacytosis (40%) in bone marrow were noted, which were considered to be closely related to elevated serum granulocyte colony-stimulating factor, interleukin (IL)-4 and IL-6. Based on the combined data described here, our preferred diagnosis was angioimmunoblastic T cell lymphoma with Epstein-Barr virus-associated B cell lymphoproliferative disorder, the pathogenesis of which was suggested to be closely associated with immunosuppressive treatment for progressive systemic sclerosis.

Aged↗
PubMed2004

Expression of DGAT2 in white adipose tissue is regulated by central leptin action.

Acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes catalyze the final step in mammalian triglyceride synthesis, and their functions are considered to be involved in the mechanisms of obesity, insulin resistance, and leptin resistance. Insulin receptor substrate-2 (IRS-2)-deficient mice exhibit obesity-associated with hypertrophic adipocytes and leptin resistance. Screening for transcripts of genes involved in fatty acid and triglyceride synthesis to investigate the mechanism of the hypertrophic change in the adipocytes showed that expression of DGAT2 mRNA was up-regulated in the white adipose tissue (WAT) of Irs2-/- mice, whereas that of DGAT1 was down-regulated. This reciprocal expression of DGAT1 and DGAT2 was also observed in WAT of leptin-deficient ob/ob mice. A high fat diet also resulted in increased DGAT2 and reduced DGAT1 in the WAT of C57BL/6 mice. Induction of adipocyte hypertrophy in vitro up-regulated both DGAT1 and DGAT2 expression in 3T3-L1 cells, suggesting that adipocyte non-autonomous mechanism in vivo is required for the reciprocal changes in expression of DGAT1 and DGAT2. In fact, intracerebroventricular infusion of leptin reduced DGAT2 expression in WAT of Irs2-/- mice and ob/ob mice, independently of DGAT1 expression. We propose the hypothesis that leptin regulates adipocyte size by altering expression patterns of DGAT via central nervous system to determine the levels of triglyceride synthesis.

3T3-L1 Cells↗
PubMed2004

Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity.

Adiponectin/Acrp30 is a hormone secreted by adipocytes, which acts as an antidiabetic and antiatherogenic adipokine. We reported previously that AdipoR1 and -R2 serve as receptors for adiponectin and mediate increased fatty acid oxidation and glucose uptake by adiponectin. In the present study, we examined the expression levels and roles of AdipoR1/R2 in several physiological and pathophysiological states such as fasting/refeeding, obesity, and insulin resistance. Here we show that the expression of AdipoR1/R2 in insulin target organs, such as skeletal muscle and liver, is significantly increased in fasted mice and decreased in refed mice. Insulin deficiency induced by streptozotocin increased and insulin replenishment reduced the expression of AdipoR1/R2 in vivo. Thus, the expression of AdipoR1/R2 appears to be inversely correlated with plasma insulin levels in vivo. Interestingly, the incubation of hepatocytes or myocytes with insulin reduced the expression of AdipoR1/R2 via the phosphoinositide 3-kinase/Foxo1-dependent pathway in vitro. Moreover, the expressions of AdipoR1/R2 in ob/ob mice were significantly decreased in skeletal muscle and adipose tissue, which was correlated with decreased adiponectin binding to membrane fractions of skeletal muscle and decreased AMP kinase activation by adiponectin. This adiponectin resistance in turn may play a role in worsening insulin resistance in ob/ob mice. In conclusion, the expression of AdipoR1/R2 appears to be inversely regulated by insulin in physiological and pathophysiological states such as fasting/refeeding, insulin deficiency, and hyper-insulinemia models via the insulin/phosphoinositide 3-kinase/Foxo1 pathway and is correlated with adiponectin sensitivity.

Adenoviridae↗
PubMed2004

A pilot study of imatinib mesylate (STI571) on gastrointestinal stromal tumors in Japanese patients.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common type of nonepithelial tumor in the gastrointestinal tract. The gastrointestinal stromal tumor is defined immunohistologically as a c-Kit-positive tumor. For those GISTs that are malignant, the only effective treatment modality has been surgical. Early clinical reports have shown that imatinib mesylate (STI571) produces substantial anticancer activity in patients with metastatic or unresectable GIST. METHODS: Nine Japanese patients who were found clinically and immunohistochemically to have inoperable GISTs were entered into this study. These patients were given 400 mg STI571 orally once daily. We then evaluated the tumor response and the safety of the drug. RESULTS: Five of the nine patients achieved partial responses, two had stable disease, and two had progressive disease. The main side effects were skin rash, edema, periorbital edema, diarrhea, nausea, and vomiting. Mild anemia, leukocytopenia, and neutropenia were also noted. No patients required dose reduction or cessation because of adverse events. CONCLUSIONS: This study demonstrates that STI571 might be an active agent against malignant GIST in Japanese patients with manageable toxicities. Gastrointestinal stromal tumor (GIST) is the most common type of nonepithelial tumor in the gastrointestinal tract. The gastrointestinal stromal tumor is defined immunohistologically as a c-Kit-positive tumor. For those GISTs that are malignant, the only effective treatment modality has been surgical. Early clinical reports have shown that imatinib mesylate (STI571) produces substantial anticancer activity in patients with metastatic or unresectable GIST.

Adult↗
PubMed2004

Risk factors for vitamin D deficiency in patients with Crohn's disease.

BACKGROUND: Although the pathogenesis of osteopenia in Crohn's disease is not established, vitamin D deficiency is thought to be an important risk factor. However, little is known about the prevalence of vitamin D deficiency in patients with Crohn's disease in Japan. This study aimed to clarify the prevalence of vitamin D deficiency in patients with Crohn's disease in Japan and to examine the possible causes of the deficiency. METHODS: We investigated serum 25-hydroxyvitamin D (25-OHD) levels, various laboratory parameters, and patient histories in 33 outpatients (25 men, 8 women; median age, 37 years; range, 26-57 years) and 15 age- and sex-matched healthy controls (8 men, 7 women; median age, 37 years; range, 24-57 years) and assessed risk factors for vitamin D deficiency. RESULTS: Although patients with Crohn's disease did not have significantly lower serum concentrations of 25-OHD than controls, 9 of 33 patients (27.3%) were considered vitamin D deficient (serum 25-OHD level </=10 ng/ml) compared with only 1 of 15 (6.7%) controls. Serum 25-OHD levels were significantly related to disease duration ( r = 0.46, P = 0.003), Crohn's Disease Activity Index (CDAI) score ( r = 0.44, P = 0.005), International Organization for the Study of Inflammatory Bowel Disease score ( r = 0.30, P < 0.05), and serum values of ferritin ( r = 0.34, P = 0.03), C-reactive protein ( r = 0.34, P = 0.03), total cholesterol ( r = 0.31, P = 0.04), and intact parathyroid hormone ( r = 0.23, P < 0.05). A logistic regression analysis was performed to investigate the ability of variables to predict low or normal 25-OHD values. Results showed that disease duration ( P = 0.03) and CDAI score ( P = 0.04) could predict the occurrence of vitamin D deficiency ( r(2) = 0.472, P = 0.0004). CONCLUSIONS: Vitamin D deficiency exists in patients with Crohn's disease in Japan. 25-OHD levels should be assessed in patients who have had Crohn's disease for a long time (>15 years) and who have been in the active stage of the disease for long periods.

Adult↗
PubMed2004

Endoscopic ultrasound-guided fine-needle aspiration biopsy for the diagnosis of gastrointestinal stromal tumors in the stomach.

BACKGROUND: For the diagnosis of gastric submucosal tumors (SMTs), endoscopic ultrasound (EUS) alone does not reveal the complete pathology, such as the degree of malignancy, and EUS-guided fine-needle aspiration biopsy (EUS-FNAB) has been reported to be more useful. Recently, most cases initially diagnosed as leiomyosarcomas have received further study with immunohistochemical staining and have been given the new diagnosis of gastrointestinal stromal tumors (GISTs). The degree of malignancy of GISTs differs widely in clinical aspects. In this study, we examined whether EUS-FNAB was useful in diagnosing GISTs and differentiating their degrees of malignancy. METHODS: From January 1997 to March 2002, 21 cases of gastric GISTs were diagnosed from the immunohistochemical staining of specimens resected at Aichi Cancer Center Hospital. Of these 21 patients, 14 (5 with high-grade malignancy and 9 with low-grade malignancy) underwent EUS-FNAB preoperatively, and were examined further: their EUS-FNAB specimens were submitted for additional immunohistochemical testing. RESULTS: The EUS-FNAB specimens from all patients were positive for c-kit and CD34 immunohistochemical testing, coinciding with the staining results of the resected specimens. The MIB-1 labeling indices in specimens of high-grade malignancy were significantly higher than those of low-grade malignancy. If we assumed that a tumor with an MIB-1 labeling index of more than 5% was a high-grade malignancy, the diagnostic accuracy was 85.7%. CONCLUSIONS: The EUS-FNAB procedure is a useful tool for diagnosing GISTs of the stomach with immunohistochemical staining. When used with MIB-1 staining, the procedure may indicate GIST prognosis and influence decisions regarding therapeutic strategies.

Adult↗
PubMed2004

Aberrant nuclear/cytoplasmic localization and gene mutation of beta-catenin in classic pulmonary blastoma: beta-catenin immunostaining is useful for distinguishing between classic pulmonary blastoma and a blastomatoid variant of carcinosarcoma.

It is now known that gene mutation of beta-catenin with subsequent nuclear/cytoplasmic (N/C) overaccumulation of the protein plays an important role in tumorigenesis of various organs. We recently demonstrated that low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA), the epithelial prototype of classic pulmonary blastoma (CPB), shows N/C localization of beta-catenin with genetic mutation. This prompted us to further investigate the state of beta-catenin abnormality in CPB and related neoplasms. We studied 9 lung tumors previously diagnosed as biphasic pulmonary blastoma (PB). Histologically, 4 cases (median age 34 years) were CPB with l-FLAC/WDFA as the epithelial component, whereas 5 cases (median age 65 years) were a variant of carcinosarcoma with high-grade FLAC/clear cell adenocarcinoma with fetal lung features as the epithelial component, which we term the blastomatoid variant of carcinosarcoma (BCS). Immunohistochemically, all 4 CPBs showed aberrant N/C localization of beta-catenin both in the epithelial and mesenchymal components, with especially high staining intensity in the budding glands and morules. In contrast, all 5 BCSs showed preserved or diminished membranous expression and no significant N/C expression of beta-catenin in the epithelial component, and absent or focal N/C expression of beta-catenin in the mesenchymal component. Mutational analysis of exon 3 of the beta-catenin gene revealed that 3 CPBs harbored missense mutations (S29F, S37F, and S37F), whereas none of the 5 BCSs had this mutation. This study suggests that beta-catenin gene mutations may play a role in the tumorigenesis of CPB. Although CPB and BCS have often been grouped together as biphasic PB, they are different entities based on immunohistochemical and molecular analysis of beta-catenin. Immunostaining for beta-catenin is useful for the discrimination.

Adult↗
PubMed2003

Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin.

Adiponectin is an adipocyte-derived hormone, which has been shown to play important roles in the regulation of glucose and lipid metabolism. Eight mutations in human adiponectin have been reported, some of which were significantly related to diabetes and hypoadiponectinemia, but the molecular mechanisms of decreased plasma levels and impaired action of adiponectin mutants were not clarified. Adiponectin structurally belongs to the complement 1q family and is known to form a characteristic homomultimer. Herein, we demonstrated that simple SDS-PAGE under non-reducing and non-heat-denaturing conditions clearly separates multimer species of adiponectin. Adiponectin in human or mouse serum and adiponectin expressed in NIH-3T3 or Escherichia coli formed a wide range of multimers from trimers to high molecular weight (HMW) multimers. A disulfide bond through an amino-terminal cysteine was required for the formation of multimers larger than a trimer. An amino-terminal Cys-Ser mutation, which could not form multimers larger than a trimer, abrogated the effect of adiponectin on the AMP-activated protein kinase pathway in hepatocytes. Among human adiponectin mutations, G84R and G90S mutants, which are associated with diabetes and hypoadiponectinemia, did not form HMW multimers. R112C and I164T mutants, which are associated with hypoadiponectinemia, did not assemble into trimers, resulting in impaired secretion from the cell. These data suggested impaired multimerization and/or the consequent impaired secretion to be among the causes of a diabetic phenotype or hypoadiponectinemia in subjects having these mutations. In conclusion, not only total concentrations, but also multimer distribution should always be considered in the interpretation of plasma adiponectin levels in health as well as various disease states.

3T3 Cells↗
PubMed2003

Cloning of adiponectin receptors that mediate antidiabetic metabolic effects.

Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30) is a hormone secreted by adipocytes that acts as an antidiabetic and anti-atherogenic adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice. Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes. This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase and PPAR-alpha. Here we report the cloning of complementary DNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning. AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver. These two adiponectin receptors are predicted to contain seven transmembrane domains, but to be structurally and functionally distinct from G-protein-coupled receptors. Expression of AdipoR1/R2 or suppression of AdipoR1/R2 expression by small-interfering RNA supports our conclusion that they serve as receptors for globular and full-length adiponectin, and that they mediate increased AMP kinase and PPAR-alpha ligand activities, as well as fatty-acid oxidation and glucose uptake by adiponectin.

Adiponectin↗
PubMed2003

Establishment of a method of anonymization of DNA samples in genetic research.

As the number of the genetic studies has rapidly increased in recent years, there has been growing concern that the privacy of the participants in such studies can be invaded unless effective measures are adopted to protect confidentiality. It is crucial for the scientific community to establish a method to anonymize DNA samples so that the public will trust genetic researchers. Here, we present a reliable and practical method of making DNA samples used in the genetic research anonymous. It assures complete anonymity by coding samples and personal information twice. Since it does not require equipment, such as bar-code readers or a software package, its cost is nominal compared with the laboratory costs. All institutions engaged in genetic research may wish to take measures such as the one described here to ensure the privacy and confidentiality of the participants in their genetic studies.

Anonymous Testing↗