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Biomedical subjects

T Obara

Publications and source records attributed to T Obara.

At least 19 recordsLinked to original sources

Total cost minimization control scheme for biological wastewater treatment process and its evaluation based on the COST benchmark process.

This paper proposes a new cost minimisation control scheme for a predenitrification type of biological wastewater treatment process and evaluates the validity of the control scheme based on the benchmark process presented by Copp. The control scheme adopting a hierarchical control structure incorporates lower-level controllers that consist of a set of local dynamic controllers and a higher-level static optimiser that provides the set points of the lower-level controllers based on the total cost index of Vanrolleghem and Gillot. Prior to benchmarking, this paper derives a simplified process model used for the optimiser, which is able to approximate the benchmark process model effectively as well as is simplified sufficiently for faster set point optimisation for on-line purposes. Numerical experiments evaluate the effectiveness of the proposed control scheme from various viewpoints including process operational and optimisation viewpoints.

Benchmarking↗

[New forceps for a sutureless patch technique using sheet materials].

Intraoperative air leaks are often treated by a sutureless patch technique using a fibrin tissue-adhesive collagen fleece or synthetic materials with fibrin sealant. Intraoperatively, the technique of using these materials has been troublesome, therefore air leaks fail to close. Akicette has been applied as an easy sutureless patch technique for air leaks. Seven air leaks (5 were lung cancers, 2 were spontaneous pneumothorax) were treated with Akicette. Akicette is simple to operate with, and can easily carry sheet materials. Using Akicette, the sheet materials tightly adhered onto surrounding the pleural defect without any sliding on the wet lung surface. Akicette is feasible tool for a sutureless patch technique and is useful to easily place the sheet materials.

Biocompatible Materials↗

[Surgical management of acute empyema].

Basic principles apply to the management of all forms of acute empyema: investigation and treatment of the underlying infection, drainage of purulent collection, obliteration of the space, and treatment of the associated intercurrent medical conditions. From July 1999 to May 2001, we performed surgical treatment in 11 patients for acute empyema. There were 4 cases of the fibrinopurulent phase and 7 cases of the organizing phase. Surgical procedure was 7 open thoracotomies and 4 thoracoscopies. The mean operating time was 154.2 +/- 36.6 minutes and blood loss during surgery was 344.7 +/- 274.8 ml. There was no procedure-related morbidity. In conclusion, early aggressive surgical approach is a feasible method for treatment of acute empyema.

Acute Disease↗

Requirement of c-jun N-terminal kinase for apoptotic cell death induced by farnesyltransferase inhibitor, farnesylamine, in human pancreatic cancer cells.

Farnesyltransferase inhibitors (FTIs) represent a novel class of anticancer drugs and are now in clinical trial. We have previously shown that farnesylamine, synthetic isoprenoid-linked with "amine" which acts as a potent FTI, induces apoptosis in human pancreatic cancer cells through the ras signaling cascade. Since the effect of FTI is usually "cytostatic" rather than "cytotoxic", we speculated another apoptotic machinery of farnesylamine in addition to the effect of FTI. Farnesylamine induced sustained activation of c-jun N-terminal kinase (JNK), which was not caused by other FTI, FTI-277. Blockage of JNK activity by dominant-negative mutant abrogated the DNA laddering and significantly reduced "cytotoxic" effect of farnesylamine. Strikingly similar effect on JNK activation and apoptosis was induced by structurally related long-chain fatty amine (LFA), oleylamine, but not by farnesol, an isoprenoid analogue of farnesylamine without "amine." Taken together, apoptosis induction through JNK activation by farnesylamine based on the LFA structure rather than an effect of FTI.

Alkyl and Aryl Transferases↗

Clonality and field cancerization in intraductal papillary-mucinous tumors of the pancreas.

BACKGROUND: Multiple lesions of intraductal papillary-mucinous tumor of the pancreas (IPMT) in the same pancreas often are encountered. To elucidate field (multicentric) cancerization and clonality of IPMT, clonal analyses of IPMT and its precursor lesion of ductal hyperplasia were performed. K-ras codon 12 mutations and X-chromosome inactivation of human androgen receptor gene (HUMARA) were investigated. METHODS: Paraffin embedded tissue samples from the pancreata of 37 patients who underwent resection for IPMTs were microdissected manually or by laser capture microdissection. Multiple samples from each surgical specimen were microdissected representing each IPMT and discrete ductal hyperplasias. DNA was extracted, and K-ras codon 12 mutations were examined by two-step polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The mutations were analyzed by direct DNA sequence. The HUMARA locus was digested with or without HpaII and HhaI prior to amplification. The HUMARA assay was conducted by fluorescence-labeled PCR-RFLP and was analyzed with specialized software. RESULTS: All 37 pancreata had at least two lesions of ductal hyperplasia, and 23 of 37 pancreata (62%) had K-ras codon 12 mutations in these precursor lesions. Of 23 pancreata with mutated K-ras hyperplasia, 15 (65%) had multiple, distinct mutations in different lesions of hyperplasia in the same pancreas, suggesting a field defect. Thirty-two of 37 IPMTs (86%) had K-ras codon 12 mutations. Among these, 16 IPMTs (50%) had multiple, distinct mutations at K-ras codon 12. The HUMARA assay showed that 12 of 15 IPMTs were informative, and 9 were considered polyclonal and/or oligoclonal origin in origin. With the combined results of multiple K-ras mutation detection and the HUMARA assay, 12 of 15 IPMTs from female patients (80%) were considered polyclonal and/or oligoclonal in origin. CONCLUSIONS: The current results suggest that multiple, distinct K-ras mutations of different ductal hyperplasias in a given pancreas are due to a field (multicentric) cancerization effect in IPMTs. Thus, most of IPMTs are polyclonal and/or oligoclonal in origin, i.e., IPMTs may originate from multiple (molecularly distinct) precursor lesions.

Adenocarcinoma, Mucinous↗

Biological characteristics and chemosensitivity profile of four human anaplastic thyroid carcinoma cell lines.

Anaplastic thyroid carcinoma is a rapidly growing, aggressive neoplasm affecting the elderly which does not respond to most of the therapies. We established cultured cell lines from four untreated tumors. The cultures grew in a monolayer of spindle-shaped cells in three cell lines and of small polygonal cells in one line, having relatively long doubling times and chromosomal abnormalities. The xenotransplantation of the lines in athymic nude mice produced tumors with a histology similar to the original tumors. The immunocytochemical staining showed the expression of PCNA, HLA-class 1, cytokeratin, vimentin and FAS (fatty acid synthase) but not CEA, desmin or P-glycoprotein. The lines secreted TPA, IL-6, IL-8 and few or no thyroid-related hormones in the culture supernatant. One cell line produced G-CSF. The chemosensitivity assay revealed intrinsic drug resistance to nine out of 11 antineoplastic agents. The reverse transcriptase-polymerase chain reaction (RT-PCR) detected MRP (multidrug resistance-associated protein) mRNA but not mdr (multidrug resistance protein)-1 and mdr-3 mRNAs. This finding indicates that the multidrug resistance of these lines is mediated by a P-glycoprotein-unrelated mechanism. The RT-PCR also presented FAS mRNA in all the lines, and IL-6 and IL-8 mRNAs in some of the lines.

ATP Binding Cassette Transporter, Subfamily B↗

Prevalence and distinctive biologic features of flat colorectal adenomas in a North American population.

BACKGROUND & AIMS: To assess the prevalence of flat and depressed (F&D) colorectal adenomas in the United States, we performed a prospective study of 211 American patients. METHODS: Dye-assisted colonoscopy was performed in the presence of both an American and a Japanese investigator. RESULTS: F&D lesions were found in 22.7% of patients, and these were more likely to be adenomatous than polypoid lesions (82% vs. 67%; P = 0.03) and contained more invasive cancer (4.5% vs. 0%; P = 0.04), which also appeared to be at a disproportionately advanced stage. The average size of all F&D advanced lesions (high-grade dysplasia and cancer) was significantly smaller than comparable polypoid lesions (10.75 +/- 2.7 mm vs. 20 +/- 2.9 mm; P < 0.05). F&D adenomas showed significantly stronger fragile histidine triad (FHIT) expression and lower p53 reactivity than similarly sized polypoid adenomas, whereas proliferative and apoptotic indices were similar in both groups. CONCLUSIONS: We conclude that there is a significant prevalence of colonic F&D colorectal adenomas in this country and that these lesions have significantly different biologic features than polypoid lesions. The clinical and epidemiologic implications of these findings for American patients need to be addressed in further studies.

Acid Anhydride Hydrolases↗

Laparoscopic ultrasonography for resection of insulinomas.

BACKGROUND: There have been few reports on the use of laparoscopic ultrasonography as an aid for the resection of insulinomas. In this study, we review our experience with laparoscopic ultrasonography for the intraoperative localization and resection of insulinomas. METHODS: We attempted laparoscopic resection of insulinomas in 7 patients (median age, 50 years) during a 4-year period. Preoperative imaging showed that 1 of the insulinomas was located in the head of the pancreas, 2 were located in the body, and 4 were located in the tail. RESULTS: We identified the insulinomas in all 7 patients with laparoscopic ultrasonography. In 6 of the patients, the insulinomas were laparoscopically resectable, either by enucleation (4 patients) or by resection of the pancreatic tail (2 patients). Conversion to laparotomy was necessary for the insulinomas in the head of the pancreas because they were close to the portal vein and the major pancreatic duct. All patients showed improvement in their hypoglycemia after the operations. Minor leakage of pancreatic juice occurred in 4 patients, and this was resolved with conservative treatment. CONCLUSIONS: Laparoscopic ultrasonography is useful for the intraoperative localization of insulinomas. Laparoscopy is a safe and feasible technique for resecting insulinomas located in the body or tail of the pancreas.

Adult↗

Inactivating mutations of calcium-sensing receptor results in parathyroid lipohyperplasia.

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disease characterized by mild hypercalcemia, an inappropriately high parathyroid hormone level, and absence of hypercalciuria. Heterozygous inactivating mutations of calcium-sensing receptor (CaSR) are found in about two thirds of patients with FHH. Histologic examination of parathyroid glands in FHH is reported to show normal histology or chief cell hyperplasia. Thus, histologic features of the parathyroid glands in FHH vary, and there is no clear histologic criterion that indicates FHH. The authors have encountered three hypercalcemic patients with characteristic histologic features of enlarged parathyroid glands. Clusters of parenchymal cells were mixed with fat cells, and the area of fat cells was 33% to 49% of the total area. These features are similar to those described as parathyroid lipohyperplasia. Postoperative evaluation showed that fractional excretion of calcium was low in these patients. Direct sequencing of the polymerase chain reaction product showed that the first patient was heterozygous for an already reported inactivating mutation of CaSR (P55L). The second patient was also heterozygous for a novel inactivating mutation (R220W). The third was homozygous for an inactivating mutation (Q27R). These results indicate that histologic features of parathyroid lipohyperplasia suggest the presence of inactivating mutations of CaSR.

Adipose Tissue↗

Somatic mutations of the MEN1 gene and microsatellite instability in a case of tertiary hyperparathyroidism occurring during high phosphate therapy for acquired, hypophosphatemic osteomalacia.

Somatic mutations of the MEN type 1 (MEN1) gene were recently shown to be responsible for tumorigenesis in 13-26% of sporadic, nonfamilial primary hyperparathyroidism. However, it is unknown whether these mutations are also involved in tumorigenesis of parathyroid glands occurring during high phosphate therapy for hypophosphatemic rickets or osteomalacia. A male patient with adult-onset, hypophosphatemic osteomalacia had been treated with 1alpha-OHD3 and oral phosphate for 13 yr when tertiary hyperparathyroidism developed. After total resection of four enlarged parathyroid glands and autotransplantation of a hyperplastic gland, the patient has continued to do well for the last 2 yr. Sequence analysis of the coding exons of MEN1 gene revealed a 36-bp deletion with a 2-bp insertion (exon 2) in the right upper parathyroid gland accompanied with loss of heterozygosity at 11q13 locus and a heterozygous mutation of 2-bp deletion (AG) in exon 10 in the right lower gland, in which microsatellite instability was also found. No MEN1 gene mutation was detected in the other two hyperplastic parathyroid glands or in the peripheral blood. These findings indicate that MEN1 gene mutations contributed to tumorigenesis of the right upper parathyroid gland in this case of phosphate-induced tertiary hyperparathyroidism. Very recently a bone tumor was found in the right femoral neck, and the tumor (chondroblastoma) was resected.

Adult↗

Prognostic significance of the labeling of Adnab-9 in pancreatic intraductal papillary mucinous neoplasms.

BACKGROUND: Pancreatic intraductal papillary mucinous neoplasms (IPMN), morphologically resembling colonic adenomas, often have an indefinable malignant potential. We used a monoclonal antibody (MAb) raised against colonic adenomas, Adnab-9, to identify patients with a better prognosis. METHODS: We assessed Adnab-9-labeled sections of these neoplasms from 50 patients, 13 pancreatic adenocarcinomas, and 32 colonic adenomas using standard immunohistochemical techniques. RESULTS: 26% of the IPMNs labeled with Adnab-9 as compared to 0% of pancreatic ductal cancers or surrounding benign tissues, (p < 0.001) and 53% of adenomas (p < 0.025). Labeling in IPMNs was usually seen in the noninvasive epithelium suggesting that Adnab-9 is a premalignant marker in these lesions. Labeling of invasive IPMN's identified a group of patients with a superior overall survival (p = 0.027). CONCLUSION: Adnab-9 labeling-characteristics appear similar for both IPMNs and adenomatous polyps, suggesting that they are analogous lesions. Adnab-9 labeling may also be a useful prognostic marker for invasive intraductal papillary mucinous neoplasms.

Adenocarcinoma, Mucinous↗

Ultrasonographic features of parathyroid carcinoma.

Although several authors have reported single cases illustrative of some ultrasonographic characteristic of parathyroid carcinoma, the value of ultrasonography for diagnosing this entity remains to be determined. The purpose of our study was to investigate the ultrasonographic features of parathyroid carcinoma in a large number of cases. We assessed the shape, contour, echogenicity, and depth-width (DW) ratio of 16 parathyroid carcinomas and 61 parathyroid adenomas. Ultrasonography showed that parathyroid carcinomas tend to be large, inhomogeneous, hypoechoic masses with lobulated contours. In contrast, parathyroid adenomas were small, homogeneous, hypoechoic masses with smooth borders. The mean (range) DW ratios for parathyroid carcinomas were 1.21 (0.91-2.5) and 0.64 (0.33-1.47) for adenomas; the difference was statistically significant (p<0.0001). The DW ratio was > or =1 in 15 (94%) of the 16 cases of carcinoma, whereas only 3 (5%) of the 61 adenomas had a similar ratio. Ultrasonographic examination is useful not only for preoperative localization but also for differentiating parathyroid carcinoma from adenoma. Parathyroid tumors with irregular margins, inhomogeneous echogenicity, and a DW ratio > or =1 are likely to be malignant.

Adenoma↗

Rational, effective metyrapone treatment of ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH).

Standard therapy for ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH), a rare form of Cushing's syndrome, is bilateral adrenalectomy. Patients with AIMAH are usually elderly, with a variety of complications, and at risk for surgery. Postoperatively, they must receive lifelong corticosteroids and spend the remainder of their lives avoiding adrenal crisis. Therapy using metyrapone, a potent inhibitor of steroidogenesis, provides the advantages of avoiding the surgery. Its effectiveness is further anticipated because adrenal steroidogenic enzymes are reportedly weak in AIMAH. Treatment with metyrapone thus appears a good therapy for AIMAH, but its effectiveness has not, to our knowledge, been studied. We treated a 59-year-old man with AIMAH with metyrapone. At a low dose of metyrapone (500 to 750 mg/day), his plasma cortisol levels decreased to the normal range, and hypertension and diabetes mellitus were ameliorated. Therapy using metyrapone thus appears effective in treating AIMAH, and can be recommended for high risk AIMAH patients as an alternative therapy.

Adrenal Glands↗

Full-length nucleotide sequence of a simian TT virus isolate obtained from a chimpanzee: evidence for a new TT virus-like species.

Recently, we identified TT virus (TTV) isolates from nonhuman primates and named them simian TTV (s-TTV). To characterize the genomic structure of these isolates in more detail, the full-length nucleotide sequence of the s-TTV isolate (designated s-TTV CH65-1), recovered from a chimpanzee born in West Africa, was amplified by nested PCR with inverted primers deduced from the untranslated region of s-TTV DNA. CH65-1 was composed of 3899 nucleotides (nt) and had two open reading frames (ORF) spanning 2295 nt (ORF1) and 402 nt (ORF2). The sequence had only 52.3% similarity to the prototype TA278 human isolate. Phylogenetic analysis demonstrated that CH65-1 was distinct from the human TTV isolates. These results suggested that s-TTV may represent a new TTV-like viral species or genus.

Animals↗

Activation of peroxisome proliferator-activated receptor gamma by troglitazone inhibits cell growth through the increase of p27KiP1 in human. Pancreatic carcinoma cells.

In the present study, we examine whether human pancreatic carcinoma cells express peroxisome proliferator-activated receptor gamma (PPARgamma) and the effect of PPARgamma activation by its selective ligand on cellular growth in pancreatic cancer cells. Immunohistochemical study of resected human pancreata using a polyclonal PPARgamma antibody revealed that PPARgamma protein expression in the nuclei of carcinoma cells was observed in 9 of 10 pancreatic adenocarcinomas. In contrast, normal pancreatic duct epithelial cells in the samples expressed no PPARgamma. Reverse transcription-PCR and Northern blot analysis demonstrated that all four tested human pancreatic cancer cell lines, PK-1, PK-8, PK-9, and MIA Paca-2, expressed PPARgamma mRNA. Luciferase assay in PK-1 cells showed that troglitazone, a selective ligand for PPARgamma, transactivated the transcription of a peroxisome proliferator response element-driven promoter in a dose-dependent fashion. Troglitazone inhibited the growth of all four pancreatic carcinoma cell lines in a dose-dependent manner. Cell cycle analysis by flow cytometry demonstrated that troglitazone induced G1 arrest in PK-1 cells. To examine the role of cyclin-dependent kinase inhibitors in the G1 arrest by troglitazone, we determined p27KiP1, p21CiP1/Waf1, or p18Ink4c protein expression by Western blot analysis in troglitazone-treated PK-1 cells. Troglitazone increased p27Kip1 but not p21Cip1/Waf1 or p18Inkc protein levels in time- and dose-dependent manners. To clarify the functional importance of p27Kip1 in the cell growth inhibition by troglitazone. All these results suggest that PPARgamma could be considered as a possible target molecule for treatment in human pancreatic carcinomas.

Adenocarcinoma↗

Cloning and characterization of two promoters for the human calcium-sensing receptor (CaSR) and changes of CaSR expression in parathyroid adenomas.

Histological analyses showed that expression of the parathyroid calcium-sensing receptor (CaSR) is decreased in parathyroid adenomas. Because reduced expression of CaSR may result in insufficient suppression of parathyroid hormone secretion, the elucidation of regulatory mechanisms of CaSR expression is indispensable for understanding the pathogenesis of parathyroid adenomas. Two cDNA clones for human CaSR with different 5'-untranslated regions have been isolated. However, the structure of the promoter region of human CaSR and the mechanisms of production of multiple CaSR mRNAs are unknown. We have cloned promoter regions of human CaSR by screening a genomic library. The human CaSR gene has two promoters and two 5'-untranslated exons (exons 1A and 1B), and alternative usage of these exons leads to production of multiple CaSR mRNAs. The upstream promoter has TATA and CAAT boxes, and the downstream promoter is GC-rich. Northern blot analysis showed that expression levels of exon 1A in parathyroid adenomas are significantly less than those in normal glands. However, expression of exon 1B was not different between adenomas and normal glands. Thus, specific reduction of the transcript driven by the upstream promoter was observed in parathyroid adenomas. Further analyses of factors that modulate the activity of the upstream promoter are necessary to clarify the pathogenesis of parathyroid adenomas.

Adenoma↗

Adrenocortical carcinoma manifesting pure primary aldosteronism: a case report and analysis of steroidogenic enzymes.

Adrenocortical carcinoma manifesting pure hyperaldosteronism is extremely rare. We report here a 61-year-old woman with biochemically proven primary aldosteronism due to right adrenocortical carcinoma. Computed tomographic scan showed 4.5x5.3 cm lobulated mass with tiny calcification, while there was no significant uptake of 131I-iodomethyl norcholesterol in the tumor. Immunohistochemical analysis demonstrated expression of steroidogenic enzymes in the tumor tissue: P-450scc, P-45c21, 3beta-hydroxysteroid dehydrogenase, P450(17alpha), and P-450(11beta). In addition, we could demonstrate mRNA expression of aldosterone synthase (P-450aldo:CYP11B2) in the tumor by specific ribonuclease protection assay. This is the first report of a case of primary aldosteronism due to adrenocortical carcinoma, in which expression of all sets of steroidogenic enzymes required for aldosterone synthesis was proven.

Adrenal Cortex Neoplasms↗