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Biomedical subjects

K Inui

Publications and source records attributed to K Inui.

552 records · Page 31Linked to original sources
PubMedDate not supplied

Gene therapy in Duchenne muscular dystrophy.

Experiments in dystrophin gene transgenic mice have supported the concept of treating Duchenne muscular dystrophy (DMD) by demonstrating that regional expression of recombinant dystrophin in dystrophic muscle leads to regional restoration of normal muscle morphology and that dystrophin mini-genes driven by muscle specific regulatory elements are probably more effective than the full-length dystrophin gene. As a gene therapy trial for DMD, dystrophin cDNAs were introduced into skeletal muscle fibers of dystrophin-deficient mice (mdx) through direct DNA injection into plasmid expression vectors, and by replication-defective recombinant retrovirus or adenovirus vectors. With direct injection of dystrophin cDNA into a plasmid expression vector or retrovirus vectors, less than 10% of adult mdx fibers of the injected muscle expressed dystrophin. On the other hand, greater efficiency has been reported for recombinant adenovirus injection into young mdx muscle. However, it is necessary to develop vectors, viral or plasmid DNA, which can be injected intravenously and directed to muscle tissues. This will involve designing vectors possessing appropriate cell-type specific tropism and/or gene transcriptional activity for DMD treatment. This is anticipated to be a vital component in the second stage of experiments aimed at DMD treatment.

Animals↗
PubMedDate not supplied

Endoscopic ultrasonography in diagnosis of the extent of gallbladder carcinoma.

Endoscopic ultrasonography (EUS) was performed preoperatively in 39 patients with gallbladder carcinoma. Diagnosis of the anatomical extent of gallbladder carcinoma was compared with histologic analysis, and staging accuracy was evaluated according to the TNM classification. Carcinoma considered to be at an early stage with no lymph node metastasis was correctly diagnosed in 87.5%. Differential diagnosis between early and advanced staged tumors was possible in 79.5%. Overall accuracy for depth of tumor invasion (T) was 76.9%. Limitations were due to many stones in the gallbladder and microinfiltration of carcinoma. Assessment of regional lymph node metastasis (N) was at a sensitivity of 81.8% and specificity of 92.9%, for an overall accuracy of 89.7%. We believe endoscopic ultrasonography is useful in the clinical staging of gallbladder carcinoma.

Adult↗
PubMedDate not supplied

Bentall operation for a child with Marfan syndrome: a case report.

Children with Marfan syndrome rarely undergo surgery for annuloaortic ectasia and aortic regurgitation in the first decade. A 7-year-old girl presented with congestive heart failure due to severe aortic regurgitation associated with annuloaortic ectasia (6 cm). She also had funnel chest. She underwent a Bentall operation and sternal turn-over with a satisfactory result. Since the aortic valve cusps had rolled edges, the aortic valve was not spared. Histology of the aortic valve cusps showed myxoid degeneration and fragmentation of elastic fibers.

Aorta↗
PubMedDate not supplied

Intraabdominal lymphangiosarcoma in a Fischer-344 rat.

A Sarcoma arising in the abdominal cavity in an aged Fischer-344 rat was studied by immunohistochemistry and electron microscopy. The white-yellow soft mass was located on the lumbosacral vertebrae, compressing adjacent parenchymal organs. The tumor was made up of spindle shaped cells situated in a background of myxoid substance and a small amount of reticulin and collagen fibers. The tumor cells grew in a loose storiform pattern and often adhered to each other by their cell processes to form ovoid or slitlike spaces. Immunohistochemically, the tumor cells were strongly positive for vimentin but negative for keratin, macrophage ED1 antigen, alpha-smooth muscle actin, Factor VIII-related antigen, and S100 protein. Electron microscopy demonstrated the endothelial differentiation of the tumor cells, such as occasional luminal spaces, a small number of micropinocytotic vesicles, and interdigitating junctions with desmosomes between cell processes of adjacent cells. Furthermore, its endothelial origin was suggested by the presence of electron-dense rods resembling Weibel-Palade bodies. Instead of a definitive basement lamina surrounding the tumor cells, there were extracellular thin "anchoring filaments" that were attached to the cell surface at areas of increased electron density. These findings indicate that the tumor is of lymphatic vessel type rather than blood vessel type.

Abdominal Neoplasms↗
PubMedDate not supplied

Total body and hepatic clearance in rats of recombinant tissue-type plasminogen activator expressed in mouse C127 and Chinese hamster ovary cells.

The total body and hepatic clearance of two recombinant human tissue-type plasminogen activators (t-PA) produced in mouse C127 cells [t-PA(C127)] and in Chinese hamster ovary cells [t-PA(CHO)] were determined in rats. Recombinant t-PA was administered as a constant iv or intraportal venous infusion for 60 min. The plasma t-PA level over 120 min was measured by an ELISA. Whole-body pharmacokinetics were characterized in terms of the total body clearance (CLt), total volume of distribution, and mean residence time in the body. Hepatic disposition was described by the hepatic clearance (CL(hep)) and the mean hepatoportal transit time. Whereas a marked hepatic extraction was observed with both t-PAs, the estimated CL(hep) accounted for only one-half the Clt. No elimination took place in the lung, because no difference was observed between iv and intraarterial administration. Extrahepatic elimination, such as that in circulating blood, appeared to play a significant role in the disposition of t-PA in vivo. t-PA(C127) is known to possess the Gal alpha 1-3Gal epitope in its complex-type carbohydrate chains, whereas this structure is not involved in t-PA(CHO). In the presence of Bandeiraea simplicifolia lectin I isolectin B4, which is specific to the Gal alpha 1-3Gal, the Clt of t-PA(C127) was significantly decreased, whereas that of t-PA(CHO) was unchanged. These results imply that the formation of a high molecular weight complex by this carbohydrate epitope effectively reduces the rate of catabolism of t-PA in vivo.

Animals↗
PubMedDate not supplied

Combined therapy with FK-506 and cyclosporine for canine lung allotransplantation: immunosuppressive effects and blood trough levels.

The therapeutic and adverse effects of FK-506 and cyclosporine used in combination were examined in 35 adult mongrel dogs with allotransplantation of the left lung. The experimental animals were allocated to six groups: group A, optimal dose of FK-506 (n = 5, FK-506 0.1 mg/kg/day, intramuscularly); group B, optimal dose of cyclosporine, (n = 5, cyclosporine 20 mg/kg/day, by mouth); group C (n = 5, FK-506 0.03 mg/kg/day, intramuscularly); group D (n = 5, cyclosporine 6 mg/kg/day, by mouth); group E (n = 5, FK-506 0.03 mg/kg/day+cyclosporine 6 mg/kg/day); and group F (n = 10, FK-506 0.05 mg/kg/day+cyclosporine 10 mg/kg/day). The animals were killed on postoperative day 28 or when extreme deterioration had developed. In groups C and D, the grafts underwent moderate to severe rejection. The treatment in group E resulted in insufficient immunosuppression, although additional effect was noted. The rejection was suppressed at least as strongly in group F as in groups A and B. One death occurred in each of groups A and F from hematemesis. The blood concentrations of FK-506 and cyclosporine in group E were not higher than in groups C and D. The whole blood concentrations of FK-506 deviated less, and they were superior to the serum concentrations as a monitor. The combination of FK-506 and cyclosporine at one half of their optimal doses suppressed the rejection almost completely and did not increase the adverse effects.

Animals↗
PubMedDate not supplied

Effects of intravenous perilla oil emulsion on nutritional status, polyunsaturated fatty acid composition of tissue phospholipids, and thromboxane A2 production in streptozotocin-induced diabetic rats.

The effects of a perilla oil (PO) emulsion rich in alpha-linolenic acid, administered by intravenous infusion, on nutritional status, fatty acid composition, and thromboxane A2 production were compared with those of a soybean oil (SO) emulsion in streptozotocin-induced diabetic rats given a fat-free diet for 7 days. The PO emulsion improved body weight gain and nitrogen balance compared with the SO emulsion and reduced thromboxane A2 production by platelets. The PO emulsion also increased the proportion of eicosapentaenoic acid, but decreased that of arachidonic acid, in liver and serum phospholipids. Plasma insulin concentrations and blood biochemical indices were similar in the two groups. An intravenously infused PO emulsion effectively reduces thromboxane A2 production through changes in the fatty acid composition of liver and serum phospholipids, as with oral administration, and improves the nutritional status of diabetic rats.

Animals↗
PubMedDate not supplied

Prospective study of the detection of anomalous connections of pancreatobiliary ducts during routine medical examinations.

BACKGROUND/AIMS: It is important to achieve detection of of anomalous connections of the pancreatobiliary ducts (ACPBD), because this condition often leads to pancreatobiliary disease. The present prospective investigation focused on revealing the incidence of ACPBD in asymptomatic individuals undergoing medical checkups. MATERIAL AND METHODS: Extracorporeal ultrasonography (US) was performed on all asymptomatic individuals undergoing medical checkups. Identification by abdominal ultrasonography of 3 mm or more gallbladder wall thickening, or 10 mm or more dilatation of the bile duct were considered indicative of ACPBD and endoscopic ultrasonography (EUS) was carried out in selected cases. Endoscopic retrograde cholangiopancreatography (ERCP) was then performed to confirm the existence of ACPBD. RESULTS: The overall incidence of ACPBD was 0.03% (9/27,076 subjects). ACPBD was found in 23% of cases with bile duct dilatation, and in 2.9% with gallbladder wall thickening. CONCLUSION: ACPBD was not as rare a disease as expected. For early detection of ACPBD, identification by abdominal ultrasonography of gallbladder wall thickening or dilatation of the bile duct are indicative. Patients who are suspected of having this abnormality should then undergo EUS. The final diagnosis should then be made by ERCP.

Adult↗
PubMedDate not supplied

Ras gene point mutations in gallbladder lesions associated with anomalous connection of pancreatobiliary ducts.

BACKGROUND/AIMS: The present study was undertaken to investigate possible changes in the K-ras oncogene in patients with gallbladder lesions (carcinoma, adenoma or hyperplasia) in relation to the presence or absence of an anomalous connection of pancreatobiliary ducts (ACPBD). METHODOLOGY: Gallbladder specimens were obtained from 44 patients with lesions that were either with or without ACPBD, and DNA samples were analyzed using PCR-SSCP. Point mutations in codons 12, 13 and 61 were analyzed by direct sequencing methods with oligonucleotide primers. RESULTS: The K-ras codon 12 was detected in 83.3% (5/6) of carcinomas the one adenoma tested and in 35.7% (5/14) of hyperplastic lesions with ACPBD, as opposed to only 36.4% (4/11) of carcinomas without ACPBD. The one case of gallbladder adenoma and 11 cases of normal gallbladder without ACPBD studied demonstrated no point mutations in the K-ras oncogene. CONCLUSIONS: Alteration of the K-ras oncogene appears to be involved in the early stages of gallbladder carcinogenesis when in association with ACPBD. The results further suggest that hyperplasia in cases with ACPBD may be a significant pre-cancerous lesion.

Adenocarcinoma↗
PubMedDate not supplied

Mucin-producing tumor of the pancreas--intraluminal ultrasonography.

BACKGROUND/AIMS: Many patients with mucin-producing pancreatic tumor, characterized by dilatation of the pancreatic duct, are diagnosed by conventional ultrasonography in a mass ultrasonographic survey in Japan. It is a necessary and reliable method for making a precise diagnosis and for deciding on the treatment approach. Endoscopic ultrasonography (EUS) is appreciated as a useful method for precise diagnosis of pancreatic tumors. Intraductal ultrasonography (IDUS) is expected to be a new modality for the more detailed diagnosis of pancreatic tumors. METHODOLOGY: Endoscopic ultrasonography and intraductal ultrasonography were performed in 23 patients with mucin-producing pancreatic tumor. The differences in ultrasonographic findings between benign and malignant tumors were studied. RESULTS: Ultrasonographic findings of mucin-producing pancreatic tumor revealed by EUS and IDUS were: cystic lesion, mural nodule in the cystic lesion, wall thickness of the cyst, mucus echoes, and solid tumor with a mixed echo pattern. Seven out of 11 patients with mural nodule were diagnosed as carcinomas and another 4 patients had adenoma. Seven of 8 patients with mucus echoes were diagnosed as carcinoma. Three of 4 patients with solid tumor were diagnosed as invasive carcinoma. The ultrasonographic findings suggesting malignancy were: mural nodule, irregular wall thickness, mucus echoes, and solid tumor with a mixed pattern. Solid tumor indicated invasive carcinoma exclusively. CONCLUSIONS: Intraluminal ultrasonography, EUS and IDUS are very useful in making a differential diagnosis between benign and malignant tumors in mucin-producing pancreatic tumors.

Adenocarcinoma, Mucinous↗