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Biomedical subjects

Kazuo Hara

Publications and source records attributed to Kazuo Hara.

At least 55 records · Page 3Linked to original sources
PubMed2003

Endoscopic diagnosis and staging of mucinous cystic neoplasms and intraductal papillary-mucinous tumors.

BACKGROUND/PURPOSE: The number of patients with cystic neoplasms of the pancreas as detected using various types of imaging techniques has been steadily increasing. Among the cystic neoplasms, mucinous cystic neoplasms (MCNs) and intraductal papillary-mucinous tumors (IPMTs) were comparatively more frequently encountered. We used imaging techniques to focus on the differential diagnosis of MCNs and IPMTs, and tumor staging. METHODS: Fifteen patients with MCNs with ovarian-like stroma and 109 patients with IPMTs were experienced. We examined the image findings for the differential diagnosis and stage diagnosis of these two types of cystic neoplasms. RESULTS: Endoscopic ultrasonography could reveal detailed images of internal structure and was effective for the diagnosis of MCNs. Other endoscopic imaging modalities could not give specific findings for MCNs. Endoscopic retrograde cholangiopancreatography (ERCP; including duodenoscopic findings and pancreatogram) and pancreatoscopy showed the characteristic and specific findings of IPMTs. Also, endoscopic ultrasonography and intraductal ultrasonography were found to have high sensitivity and diagnostic accuracy for their differential diagnosis of neoplastic/nonneoplastic and invasive/noninvasive lesions in IPMTs. CONCLUSIONS: Endoscopic imaging techniques are capable of revealing the detailed structure of pancreatic cystic lesions. They are effective for differential diagnosis, for assessing the degree of malignancy, and for deciding upon an appropriate treatment in patients with IPMTs.

Adult↗
PubMed2003

Effect of a tyrosine kinase inhibitor STI571 in a patient with hepatic metastases from a duodenal gastrointestinal stromal tumor.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors. The molecular etiology is the result of mutations in the c-Kit gene. The mutant c-Kit proteins, which are activated without a stem cell factor, contribute to the tumor development. STI571 selectively inhibits c-Kit, BCR-ABL, and PDGFR tyrosine kinases. Based on this potential to inhibit critical c-Kit function in GISTs, case studies have reported effective outcomes following treatment with STI571. This case report describes a highly effective use of STI571 in a 54-year-old woman with multiple liver metastases from a GIST originating in the duodenum.

Antineoplastic Agents↗
PubMed2003

A two-step method for marking polypectomy sites in the colon and rectum.

BACKGROUND: Intraoperative localization of polypectomy sites is critical for laparoscopic and open surgery, but conventional methods of marking the colorectum are sometimes unreliable. A new two-step method for marking polypectomy sites for identification during laparoscopic and open operations is described. METHODS: Eighteen patients with postpolypectomy lesions necessitating preoperative marking were enrolled in this study. A physiologic saline solution was endoscopically injected into the submucosa to produce an artificial submucosal elevation (pseudopolyp). A small volume of India ink was then injected into the submucosal elevation (pseudopolyp) with a separate needle. RESULTS: The two-step method was easily applied for all lesions without complication. At surgery, all lesions were immediately visualized. CONCLUSION: The two-step tattooing method proved to be easy, safe, and accurate for marking polypectomy sites.

Aged↗
PubMed2003

Efficacy of peroral pancreatoscopy in the diagnosis of pancreatic diseases.

BACKGROUND: The aim of this study was to evaluate the usefulness of peroral pancreatoscopy in the diagnosis of pancreatic diseases. METHODS: Both 3.7-mm (thin) and 0.8-mm (ultra-thin) diameter fiberoptic pancreatoscopes were used in 115 cases (pancreatic cancer, 35; benign ductal stenosis, 20; intraductal papillary-mucinous tumor, 60). RESULTS: Observation rates for pancreatic cancer, benign ductal stenosis, and intraductal papillary-mucinous tumor were, respectively, 63%, 80%, and 95%. Tumor vessels and papillary tumor were observed when pancreatic cancer was smaller than 2 cm but not when the tumor was larger than 2 cm. Stenosis without significant mucosal changes was observed in 62% of cases of benign ductal stenosis. Coarse mucosa and friability were observed more frequently in association with pancreatic cancer than benign ductal stenosis. Granular mucosa or papillary tumor could be observed in 74% of cases of intraductal papillary-mucinous tumor. Papillary tumor was observed with increasing frequency in cases of intraductal papillary-mucinous tumor as the degree of malignancy increased. CONCLUSIONS: Peroral pancreatoscopy with an ultra-thin fiberscope is useful in the diagnosis of minute pancreatic lesions. Peroral pancreatoscopy with a thin fiberscope can provide a definitive diagnosis of intraductal papillary-mucinous tumor including the degree of malignancy.

Adult↗
PubMed2003

Molecular mechanism of insulin resistance and obesity.

Obesity and insulin resistance have been recognized as leading causes of major health issues. We have endeavored to depict the molecular mechanism of insulin resistance, focusing on the function of adipocyte. We have investigated a role of PPARgamma on the pathogenesis of Type II diabetes. Heterozygous PPARgamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet. Moreover, a Pro12Ala polymorphism in the human PPARgamma2 gene was associated with decreased risk of Type II diabetes in Japanese. Taken together with these results, PPARgamma is proved to be a thrifty gene mediating Type II diabetes. Pharmacological inhibitors of PPARgamma/RXR ameliorate high-fat diet-induced insulin resistance in animal models of Type II diabetes. We have performed a genome-wide scan of Japanese Type 2 diabetic families using affected sib pair analysis. Our genome scan reveals at least 9 chromosomal regions potentially harbor susceptibility genes of Type II diabetes in Japanese. Among these regions, 3q26-q28 appeared to be very attractive one, because of the gene encoding adiponectin, the expression of which we had found enhanced in insulin-sensitive PPARgamma-deficient mice. Indeed, the subjects with the G/G genotype of SNP276 in the adiponectin gene were at increased risk for Type II diabetes compared with those having the T/T genotype. The plasma adiponectin levels were lower in the subjects with the G allele, suggesting that genetically inherited decrease in adiponectin levels predispose subjects to insulin resistance and Type II diabetes. Our work also confirmed that replenishment of adiponectin represents a novel treatment strategy for insulin resistance and Type II diabetes using animal models. Further investigation will be needed to clarify how adiponectin exerts its effect and to discover the molecular target of therapies.

Adipocytes↗
PubMed2003

[The role of PPARgamma in the onset of type 2 diabetes].

We have investigated the role of PPARgamma and its related genes on the pathogenesis of type 2 diabetes. Heterozygous PPARgamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet, whose phenotypes were abrogated by PPARgamma agonist treatment. Moreover, a Pro12Ala polymorphism in the human PPARgamma 2 gene, which has been reported to cause a reduction in the PPARgamma activity, was associated with decreased risk of type 2 diabetes in Japanese. The protective effect of this polymorphism against type 2 diabetes has been confirmed by meta-analysis using reports in various ethnic groups. Taken together with these results, PPARgamma is a thrifty gene mediating type 2 diabetes both in mice and humans. Indeed, pharmacological inhibitors of PPARgamma/RXR ameliorates high-fat diet-induced insulin resistance in animal models of type 2 diabetes.

Animals↗
PubMed2003

Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic adipokine.

Genome-wide scanning is a powerful tool to identify susceptible chromosome loci, however, individual chromosomal regions still have many candidate genes. Although cDNA microarray analysis provides valuable information for identifying genes involved in pathogenesis, expression levels of many genes are changed. A novel approach for identification of therapeutic targets is the combination of genome-wide scanning and the use of DNA chips, as shown in Fig. (1). Using DNA chips, we screened for secreted molecules, the expressions of which were changed in adipose tissues from mice rendered insulin resistance. Decreased expression of one of these molecules, adiponectin/Acrp30, correlates strongly with insulin resistance. Interestingly, recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where adiponectin gene is located. Decreasing serum adiponectin levels are associated with increased risk for type 2 diabetes. Interestingly, adiponectin was decreased in insulin resistant rodent models both of obesity and lipoatrophy, and replenishment of adiponectin ameliorated their insulin resistance. Moreover, adiponectin transgenic mice ameliorated insulin resistance and diabetes Adiponectin knockout mice showed insulin resistance and glucose intolerance. In muscle and liver, adiponectin activated AMP kinase and PPARalpha pathways thereby increasing beta-oxidation of lipids, leading to decreased TG content, which ameliorated insulin resistance under a high-fat diet. Despite similar plasma glucose and lipid levels on an apoE deficient background, adiponectin transgenic apoE deficient mice showed amelioration of atherosclerosis, which was associated with decreased expressions of class A scavenger receptor and tumor necrosis factor alpha. Finally, cDNA encoding adiponectin receptors (AdipoR1 and R2) have been identified by expression cloning, which facilitates the understanding of molecular mechanisms of adiponectin actions and obesity-linked diseases such as diabetes and atherosclerosis and the designing of novel antidiabetic and anti-atherogenic drugs with AdipoR1 and R2 as molecular targets.

Adiponectin↗
PubMed2003

[Pulmonary actinomycosis diagnosed through transbronchial lung biopsy (TBLB)].

Pulmonary actinomycosis is a rather rare chronic pulmonary infection. Its diagnosis may be difficult without biopsy, because its culture from sputum or bronchial secretion is rarely successful. We report a case of pulmonary actinomycosis diagnosed by means of TBLB. A 57-year-old man was admitted to our hospital because of hemosputum. The chest radiograph at the first visit revealed a nodular lesion in the right middle lobe. The biopsy examination showed sulfur granules of which PAS-positive mycelium was arranged in a radiating pattern. On the basis of these findings, we diagnosed pulmonary actinomycosis. So far, there have been only 4 reported cases of pulmonary actinomycosis diagnosed by TBLB in Japan. TBLB is worth trying in the diagnosis of pulmonary actinomycosis, because it can avoid surgical procedures, if successful.

Actinomycosis↗
PubMed2002

Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians.

Adiponectin (ACRP30), an adipocyte-secreted protein encoded by the APM1 gene, is known to modulate insulin sensitivity and glucose homeostasis, those effects protecting obese mice from diabetes. Plasma adiponectin levels correlate well with insulin sensitivity in humans, and are decreased in both type 2 diabetes (T2D) and obesity. We screened for single-nucleotide polymorphisms (SNPs) the APM1 gene coding and 5' sequences in 40 French Caucasians: 12 SNPs and 4 rare non-synonymous mutations of exon 3 were detected. The 10 most frequent SNPs were genotyped in 1373 T2D and obese French Caucasian subjects and in all subjects available from 148 T2D multiplex families. The screening for rare mutations of exon 3 was extended to 1246 T2D and obese French subjects and to the members of the 148 T2D multiplex families. A haplotype including SNPs -11391 and -11377, both located in the 5' sequences, was associated with adiponectin levels (P<0.0001) and with T2D (P=0.004). The presence of at least one non-synonymous mutation in exon 3 showed evidence of association with adiponectin levels (P=0.0009) and with T2D (P=0.005). We failed to detect an association with insulin resistance indexes. Although family-based association analysis with T2D did not reach significance, our results suggest that an at-risk haplotype of common variants located in the promoter and rare mutations in exon 3 contribute to the variation of the adipocyte-secreted adiponectin hormone level, and may be part of the genetic determinants for T2D in the French Caucasian population.

Adipocytes↗
PubMed2002

Extraskeletal myxoid chondrosarcoma arising in the finger.

Extraskeletal myxoid chondrosarcoma (EMCS) is a rare soft tissue sarcoma and usually occurs in deep soft tissues, especially of the proximal extremities and limb girdles. We present an unusual case of the tumor arising in the finger. The diagnosis was confirmed by molecular detection of a characteristic EWS-CHN/TEC fusion gene transcript. Molecular detection of the tumor specific fusion gene could be a valuable aid for the final diagnosis of EMCS, particularly in cases with unusual clinicopathological features.

Artificial Gene Fusion↗
PubMed2002

Visceral larva migrans due to Ascaris suum which presented with eosinophilic pneumonia and multiple intra-hepatic lesions with severe eosinophil infiltration--outbreak in a Japanese area other than Kyushu.

A 32-year-old man presented with the chief complaint of severe cough. Examination of peripheral blood showed a marked increase in eosinophils. Chest CT demonstrated multiple ground glass opacities in both lungs. Bronchoalveolar lavage showed abundant eosinophils. Abdominal CT demonstrated multiple low attenuation areas in the liver. Liver biopsy with ultrasonography revealed severe eosinophil infiltrations around the portal veins. Serologically, a multi-dot enzyme linked immunosorbent assay (DOT-ELISA) and ELISA inhibition test using microtiter plates were positive for Ascaris suum. Thus, visceral larva migrans due to Ascaris suum was diagnosed. Outbreaks of this disease in Japan have previously been confined to the Kyushu area. The present case which occurred outside that area, illustrates the importance of constant attention to the epidemiology of this disease.

Adult↗
PubMed2002

Maturity-onset diabetes of the young resulting from a novel mutation in the HNF-4alpha gene.

A 52-year-old woman with early-onset diabetes mellitus, severe diabetic retinopathy, and a family history of a dominant inheritance pattern was referred to our hospital. Direct sequencing revealed a novel mutation in the HNF-4alpha gene (R244Q). The position of the mutation in the amino-acid sequence of the gene is well conserved among species and transcriptional activity of the mutant gene was significantly reduced. Therefore, a diagnosis of maturity-onset diabetes of the young (MODY)-1 was made. Genetic testing enabled early diagnosis of diabetes in the patient's 20-year-old daughter, which we consider to be important for the prevention of diabetic complications.

Adult↗
PubMed2002

Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population.

An adipocyte-derived peptide, adiponectin (also known as GBP28), is decreased in subjects with type 2 diabetes. Recent genome-wide scans have mapped a diabetes susceptibility locus to chromosome 3q27, where the adiponectin gene (APM1) is located. Herein, we present evidence of an association between frequent single nucleotide polymorphisms at positions 45 and 276 in the adiponectin gene and type 2 diabetes (P = 0.003 and P = 0.002, respectively). Subjects with the G/G genotype at position 45 or the G/G genotype at position 276 had a significantly increased risk of type 2 diabetes (odds ratio 1.70 [95% CI 1.09-2.65] and 2.16 [1.22-3.95], respectively) compared with those having the T/T genotype at positions 45 and 276, respectively. In addition, the subjects with the G/G genotype at position 276 had a higher insulin resistance index than those with the T/T genotype (1.61 +/- 0.05 vs. 1.19 +/- 0.12, P = 0.001). The G allele at position 276 was linearly associated with lower plasma adiponectin levels (G/G: 10.4 +/- 0.85 microg/ml, G/T: 13.7 +/- 0.87 microg/ml, T/T: 16.6 +/- 2.24 microg/ml, P = 0.01) in subjects with higher BMIs. Based on these findings together with the observation that adiponectin improves insulin sensitivity in animal models, we conclude that the adiponectin gene may be a susceptibility gene for type 2 diabetes.

Adiponectin↗
PubMed2002

Genome-wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate Loci on 7p and 11p.

The genetic background that predisposes the Japanese population to type 2 diabetes is largely unknown. Therefore, we conducted a 10-cM genome-wide scan for type 2 diabetes traits in the 359 affected individuals from 159 families, yielding 224 affected sib-pairs of Japanese origin. Nonparametric multipoint linkage analyses performed in the whole population showed one suggestive linked region on 11p13-p12 (maximum logarithm of odds score [MLS] 3.08, near Pax6) and seven potentially linked regions (MLS >1.17) at 1p36-p32, 2q34, 3q26-q28, 6p23, 7p22-p21, 15q13-q21, and 20q12-q13 (near the gene for hepatocyte nuclear factor-4alpha [HNF-4alpha]). Subset analyses according to maximal BMI and early age at diagnosis added suggestive evidence of linkage with type 2 diabetes at 7p22-p21 (MLS 3.51), 15q13-q21 (MLS 3.91), and 20q12-q13 (MLS 2.32). These results support previous indication for linkage found on chromosome 3q, 15q, and 20q in other populations and identifies two new potential loci on 7p and 11p that may confer genetic risk for type 2 diabetes in the Japanese population.

Adult↗