Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 127 records · Page 7Linked to original sources

PubMed2000

Manometric and hormonal changes after distal partial gastrectomy.

BACKGROUND: Alkaline oesophagitis attributable to duodenal mechanisms may induce oesophageal carcinogenesis in a rat reflux model. AIM: To investigate the mechanism of the regurgitation after distal partial gastrectomy. METHODS: Oesophageal manometry was used in 16 patients before and after distal partial gastrectomy with reconstruction by Bilroth methods. Serum concentrations of four gastrointestinal hormones were measured by radioimmunoassay in 10 gastrectomy patients and nine healthy volunteers before and after a standardized meal. RESULTS: The lower oesophageal sphincter pressure was reduced to 83% after surgery. The amplitude and duration of the peristaltic waves tended to be increased, and the velocity tended to be less after surgery (amplitude 120%, duration 114%, velocity 88%). Interrupted waves appeared more frequently after surgery. The manometric changes in gastrectomized patients are considered to be disadvantageous relative to regurgitation. After surgery, gastrin and pancreatic polypeptide were completely abolished postprandially, whereas cholecystokinin and neurotensin were significantly increased. CONCLUSION: The hormonal changes should have a suppressive effect on the lower oesophageal sphincter. Both the manometric and the hormonal changes may exacerbate reflux oesophagitis after distal partial gastrectomy.

Aged↗

PubMed2000

Pulmonary lipiodol embolism during transcatheter arterial chemoembolization for hepatoblastoma under general anaesthesia.

We present a case of pulmonary embolism that occurred during the injection of lipiodol during transcatheter arterial chemoembolization under general anaesthesia. A 7-year-old child suffering from a large hepatoblastoma was admitted for arterial chemoembolization and carcinostatic administration. Pulmonary embolism due to lipiodol during arterial chemoembolization was evident by a sudden fall in oxyhaemoglobin saturation from 100 to 90%. This was associated with a spread of lipiodol into both lungs, particularly the middle lung zones and detected by chest fluoroscopy. Arterial blood gases returned to normal values 1 day later but pulmonary infiltration persisted for 7 days before final clearance. Pulmonary embolism caused by lipiodol during arterial chemoembolization is infrequent, but such a complication could prove fatal. Understanding the risk of pulmonary embolism in patients receiving lipiodol, during and after arterial chemoembolization, and late onset pulmonary injury is important and a close follow-up for several days after arterial chemoembolization is advisable.

Antibiotics, Antineoplastic↗

PubMed2000

Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases is indispensable for mTOR function in vivo and in vitro.

BACKGROUND: The mammalian target of rapamycin (mTOR) belongs to the family of phosphoinositide (PI)-kinase-related kinases that includes the ataxia-telangiectasia gene product (ATM). mTOR plays a critical role in controlling translational effectors such as p70 S6 kinase alpha (p70 alpha) and eukaryotic initiation factor 4E binding protein 1 (4EBP1). RESULTS: We show that the C-terminal region of mTOR, which is highly conserved among the PI-kinase-related kinases, plays a critical role in the mTOR protein kinase activity. Deletion of the C-terminal residues did not adversely affect the expression of mTOR, but caused a nearly complete loss of the mTOR protein kinase activity toward both 4EBP1 and p70 alpha in vitro. These deletions also abolished the ability of a rapamycin-resistant mTOR mutant to rescue the activity of p70 alpha from inhibition induced by rapamycin in vivo. Furthermore, replacement of Trp2545, a conserved residue in the C-terminal region throughout the PI-kinase-related kinase family, abolished the function of the mTOR kinase, both in vivo and in vitro. However, substitution of 32 C-terminal residues of mTOR with those of ATM did not restore the mTOR function. CONCLUSIONS: These findings define an indispensable role for the noncatalytic C-terminal region of mTOR and indicate that, although this highly conserved region may be important throughout the PI-kinase-related kinase family, it is not functionally interchangeable within the family.

Amino Acid Sequence↗

PubMed2000

A stress distribution analysis of a ceramic lunate replacement for Kienbock's disease.

To determine the usefulness of a ceramic lunate replacement for the wrist joint as a possible treatment for Kienböck's disease, stress distribution of five wrist joint models (a normal wrist, one with the lunate bone removed, one with a coiled tendon replacement, one with a coiled tendon replacement with a ceramic core, and one with a ceramic lunate replacement coated with sheets of tendon) were analysed by the finite element method. The results of finite element method analyses were compared with those of pressure distribution analyses on the wrist joint using pressure-sensitive film and measurement of pressure on the radio-lunate joint with a tactile sensor. Both the coiled tendon model and ceramic core model were unable to resist applied force. Stress and pressure were well-distributed in the wrist joint of the ceramic lunate implant model. These results indicate that the ceramic lunate implant could be expected to prevent carpal collapse.

Cadaver↗

PubMed2000

Penetration by a giant gastric ulcer induced by a nonsteroidal anti-inflammatory drug.

A patient presented with penetration by a giant gastric ulcer resulting from treatment with a nonsteroidal anti-inflammatory drug. A test for Helicobacter pylori proved negative. Treatment with a combination of an inhibitor of gastric acid secretion and prostaglandin substitution therapy with misoprostol resulted in closure of the perforation and cicatrization of the gastric ulcer without the need for laparotomy.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

A novel method of virtual histopathology using laser-scanning confocal microscopy in-vitro with untreated fresh specimens from the gastrointestinal mucosa.

BACKGROUND AND STUDY AIMS: Histopathological examination for superficial gastrointestinal lesions has been mainly based upon the light microscopic examination of thin-slice specimens with hematoxylin and eosin (H&E) staining. However, it takes at least a couple of days to create a slide-glass for microscopic study. In order to obtain immediate microscopic images for untreated specimens, the authors used laser-scanning confocal microscopy (LCM) to study fresh samples of gastrointestinal mucosa. MATERIALS AND METHODS: Fresh untreated mucosal specimens from the esophagus, stomach, and colon, obtained by endoscopic pinch biopsy, polypectomy, or endoscopic mucosal resection (EMR), were fixed in normal saline and examined by LCM collecting the reflective light of a 488-nm wavelength argon laser beam. Findings from the LCM image were compared with those of conventional H&E staining in all specimens. For objective evaluation of the similarity of both pictures, the nucleus-to-cytoplasm ratio (N/C) of normal mucosa and that of cancer of the esophagus were calculated and statistically analyzed. The overall diagnostic accuracy for cancer was evaluated. RESULTS: The average scanning time to obtain the LCM image of a specimen was 1.6 seconds. The LCM images acquired corresponded well to the conventional H&E light microscopic images in the esophagus, stomach, and colon. Cell wall, nucleus, cytoplasm, and tissue structural elements were simultaneously visualized by LCM scanning. A difference in N/C ratios between normal mucosa and cancer in the esophagus was statistically apparent when Welch's test (P=0.05) was applied. The overall diagnostic accuracy of the LCM study for cancer was 89.7%. CONCLUSIONS: This novel method enables us to obtain an immediate serial virtual microscopic section through a fresh specimen, which has not actually been cut, although the resolution of the image obtained is still limited. These early results encourage us to develop imaging relevant to conventional histopathology alongside the development of LCM technology in the near future. We should aim at the in vivo application of LCM coupled to probes which can be introduced through the working channel of endoscopes.

Colon↗

PubMed2000

A new face-mounted display system: pilot trial of clinical application in therapeutic endoscopy.

BACKGROUND AND STUDY AIMS: Since fiber endoscopes evolved into video endoscopes, there has been no remarkable progression in the optical system for endoscopy. The current optical system provided by fixed cathode-ray tube (CRT) display is a monitor-oriented system. In this study, we evaluate the practical usefulness of the face-mounted display (FMD), which provides us with an operator-oriented optical system. PATIENTS AND METHODS: The FMD device, weighing 110 g, is designed for consumer video home use, consisting of two active matrix liquid crystal color panels with 180,000-pixel resolution. With the picture-in-picture capability, FMD provided us with image-navigated endoscopic procedure. Fourteen patients were enrolled in this study; seven patients for endoscopic mucosal resection, two for insertion of an esophageal metallic stent, three for clipping for the bleeding and two for dilatation of anastomotic strictures. RESULTS: The FMD device allowed us to use an ultra large screen as if there has been a 62-inch screen 2 m ahead. During endoscopy, we could concentrate more on the procedures. There were no complications attributable to the use of the device. CONCLUSION: We are convinced of a new evolution in the optical system for therapeutic endoscopy with the FMD device.

Endoscopes, Gastrointestinal↗

PubMed2000

Localization of insulinomas. Comparison of conventional arterial stimulation with venous sampling (ASVS) and superselective ASVS.

PURPOSE: To examine the value of superselective arterial stimulation venous sampling (ASVS) to localize insulinomas. MATERIAL AND METHODS: Superselective ASVS (SS-ASVS) was performed in 9 patients with insulinoma. Injection of secretagogue (calcium gluconate: 0.01 mEq Ca++/kg) was performed into the gastroduodenal, splenic (proximal and distal), and superior mesenteric arteries in 9 patients and additionally into the dorsal pancreatic artery in 6 patients. Sampling from the hepatic vein was performed to measure serum insulin concentrations at 30, 60 and 120 s after each injection of secretagogue into these arteries. SS-ASVS results were correlated with surgical findings, compared to those of conventional ASVS. RESULTS: Insulinomas were correctly localized to the head, body or tail of the pancreas by SS-ASVS in 8 patients (89%). Conventional ASVS detected insulinomas in 7 patients (78%), although it could not distinguish whether the insulinoma was located in the pancreatic body or tail in 4 of the 7 patients. There were eight-fold or more increases in serum insulin levels in hepatic venous samples related to the artery supplying the tumor in 8 patients. Localization of the insulinomas was verified at surgery in all patients. CONCLUSION: SS-ASVS is a useful method for detailed evaluation of overproduction of insulin from pancreatic insulinomas and their localization. When the pancreatic insulinoma is situated in the pancreatic body or tail, the localization is more accurately made by SS-ASVS than by conventional ASVS.

Aged↗

PubMed2000

Hepatic falciform artery. Angiographic findings in 25 patients.

PURPOSE: To determine the frequency of hepatic falciform artery (HFA) occurrence on celiac or hepatic angiograms and elucidate the anatomy and clinical importance. MATERIAL AND METHODS: Among 1,250 patients who underwent celiac or hepatic arteriography, we encountered 25 patients (2%) with a HFA. Prospectively, CT hepatic falciform arteriography (CTHA) was performed in 4 patients. Indigocarmine dye was injected into the HFA in 6 patients to evaluate whether the abdominal skin was stained. Embolization of the HFA before chemoembolization for hepatocellular carcinoma was performed in 4 patients to prevent abdominal wall injury. RESULTS: Among 25 patients, the HFA arose as a terminal branch of the middle hepatic artery in 14 patients (56%) and of the left hepatic artery in 11 patients (44%). The vessel was single in 18 patients (72%) and double in 7 patients (28%). Two vessels ran side by side along the hepatic falciform ligament. On CTHA, the HFA ran within the hepatic falciform ligament and the branches were connected with the liver around the hepatic falciform ligament. After indigocarmine dye injection, the stain of abdominal skin was recognized in all 6 patients. No abdominal wall injury occurred in any of the 4 patients who were subjected to hepatic chemoembolization. CONCLUSION: HFA is an extrahepatic pathway which runs to the abdominal wall. Before chemoembolization of the middle or left hepatic artery for hepatic malignancy, the HFA should be recognized.

Abdominal Muscles↗

PubMed2000

Radiation-induced mutations in the spleen and brain of lacZ transgenic mice.

PURPOSE: To study the dose-response and molecular nature of radiation-induced mutations in the spleen and brain of lacZ transgenic mice. MATERIALS AND METHODS: Line 60 transgenic mice containing the bacterial lacZ gene in a plasmid background were used. Mutants were selected using phenyl-beta-D-galactoside. The nature of mutants was determined by sequencing DNAs of mutant lacZ genes found in control and irradiated tissues. RESULTS: X-ray irradiation at 50 and 100 Gy showed linear dose-responses for mutation induction in both tissues. The slope, however, was about twice as steep in spleen than in brain. DNA sequence analyses showed that the predominant type of mutation induced by radiation in both tissues were large deletions. CONCLUSIONS: Radiation induces mutations in spleen and brain at different efficiencies but the molecular nature of the induced mutations are similar in the two issues.

Amino Acid Sequence↗

PubMed2000

Characterization of a bone morphogenetic protein-responsive Smad-binding element.

Bone morphogenetic proteins (BMPs) are pleiotropic growth and differentiation factors belonging to the transforming growth factor-beta (TGF-beta) superfamily. Signals of the TGF-beta-like ligands are propagated to the nucleus through specific interaction of transmembrane serine/threonine kinase receptors and Smad proteins. GCCGnCGC has been suggested as a consensus binding sequence for Drosophila Mad regulated by a BMP-like ligand, Decapentaplegic. Smad1 is one of the mammalian Smads activated by BMPs. Here we show that Smad1 binds to this motif upon BMP stimulation in the presence of the common Smad, Smad4. The binding affinity is likely to be relatively low, because Smad1 binds to three copies of the motif weakly, but more repeats of the motif significantly enhance the binding. Heterologous reporter genes (GCCG-Lux) with multiple repeats of the motif respond to BMP stimulation but not to TGF-beta or activin. Mutational analyses reveal several bases critical for the responsiveness. A natural BMP-responsive reporter, pTlx-Lux, is activated by BMP receptors in P19 cells but not in mink lung cells. In contrast, GCCG-Lux responds to BMP stimulation in both cells, suggesting that it is a universal reporter that directly detects Smad phosphorylation by BMP receptors.

Activins↗

PubMed2000

Crystal structure of the pyridoxal 5'-phosphate dependent L-methionine gamma-lyase from Pseudomonas putida.

L-Methionine gamma-lyase (MGL) catalyzes the pyridoxal 5'-phosphate (PLP) dependent alpha,gamma-elimination of L-methionine. We have determined two crystal structures of MGL from Pseudomonas putida using MAD (multiwavelength anomalous diffraction) and molecular replacement methods. The structures have been refined to an R-factor of 21.1% at 2.0 and 1.7 A resolution using synchrotron radiation diffraction data. A homotetramer with 222 symmetry is built up by non-crystallographic symmetry. Two monomers associate to build the active dimer. The spatial fold of subunits, with three functionally distinct domains and their quarternary arrangement, is similar to those of L-cystathionine beta-lyase and L-cystathionine gamma-synthase from Escherichia coli.

Amino Acid Sequence↗

PubMed2000

Monoclonal antibodies recognizing surface residues of the beta subunit of Escherichia coli F(1) ATPase: functional importance of the epitope residues.

Two monoclonal antibodies, beta 208 and beta 210, against the beta subunit of the F(1) ATPase from Escherichia coli reacted with an intact beta subunit and also a peptide corresponding to a portion of beta between residues 1 and 145. Mutations at Ala-1, Val-15, Glu-16, Phe-17, Leu-29, Gly-65, or Leu-66, and His-110 or Arg-111 for beta 210 and beta 208, respectively, caused decreased antibody binding to beta, suggesting that these residues form the epitopes and are thought to lie close together on the surface of the beta subunit. The topological locations of the corresponding residues in the atomic structure of the bovine beta subunit agree well with these expectations, except for Ala-1 and Leu-29. beta 210 binds to two beta strands including the epitope residues that are 50 residues apart, indicating that this antibody recognizes the tertiary structure of the N-terminal end region. Mutations in the epitope residues of beta 210 do not affect the F(1) ATPase activity, suggesting that surfaces of the two beta strands in the amino-terminal end region are not functionally essential. To analyze the functional importance around His-110 recognized by beta 208 we introduced site specific mutations at residues His-110 and Ile-109. Ile-109 to Ala or Arg, and His-110 to Ala or Asp caused defective assembly of F(1). However, the His-110 to Arg mutation had no effect on molecular assembly, suggesting that Ile-109 and His-110, especially the positive charge of His-110 are essential for the assembly of F(1). The His-110 to Arg mutation caused a large decrease in F(1)-ATPase activity, suggesting that a subtle change in the topological arrangement of the positive charge of His-110 located on the surface of beta plays an important role in the catalytic mechanism of the F(1)-ATPase.

Amino Acid Sequence↗

PubMed2000

Correlation between Bcl-2 overexpression and H-ras mutation in naturally occurring hepatocellular proliferative lesions of the B6C3F1 mouse.

The correlation between the mutation at codon 61 of the H-ras gene and the expression of the Bcl-2 protein was investigated in naturally occurring hepatocellular proliferative lesions in B6C3F1 mice. Specimens of histologically diagnosed neoplastic or preneoplastic lesions of the liver, obtained from the control mice used for 2-year carcinogenicity studies, were examined by immunohistochemical techniques. All of 25 lesions confirmed to be hepatocellular carcinomas stained positive for the Bcl-2 protein. Three of 12 foci of cellular alterations, as well as 24 of 42 hepatocellular adenomas, stained weakly positive. Bcl-2 protein was expressed to a greater degree in hepatocellular carcinomas as opposed to adenomas and confirmed by Western blot analysis. Seven of 18 hepatocellular adenomas that stained positive for Bcl-2 and three of 16 hepatocellular adenomas that stained negative had a mutation at codon 61 of the H-ras gene. Overexpression of Bcl-2 protein is likely to enhance the malignant turnover of the neoplastic cells, following a mutation at codon 61 of the H-ras gene particularly. These findings suggest that Bcl-2 overexpression and the mutation at codon 61 of the H-ras gene may be critical factors in the development of naturally occurring hepatocellular tumors in B6C3F1 mice.

Animals↗

PubMed2000

Sulfated glycosaminoglycan synthesis and its regulation by transforming growth factor-beta in rat clonal dental pulp cells.

Dental pulps contain sulfated glycosaminoglycans (GAGs), such as chondroitin 4-sulfate (CSA/4CS), dermatan sulfate (CSB/DS), and chondroitin 6-sulfate (CSC/6CS). Sulfated GAGs play important roles in mineralization and collagen fibrillogenesis during primary, secondary, and reparative dentin formations. Transforming growth factor-beta (TGF-beta) is a potent regulator for several extracellular matrix (ECM) components and modulates the proliferation and differentiation. Using rat clonal dental pulp cells (RPC-C2A), we investigated the constituents of GAGs synthesized by the cells and the effect of TGF-beta on their synthesis by measuring the radioactivity of [35S]sulfate incorporated into GAG fractions. Cellulose acetate electrophoresis analysis revealed that RPC-C2A cells synthesized CSA and CSB but not CSC and that 10 ng/ml of TGF-beta increased the production of CSA and CSB in the cell/ECM fraction. Measurement of [35S]sulfate incorporation showed a significant increase in the amount of GAGs by TGF-beta, 1.3-fold CSA, and 1.2-fold CSB in the cell/ECM fraction. In the medium fraction the most secreted GAG was CSA, whereas CSB was stored in the cell/ECM fraction. Secreted CSA in the medium was markedly increased by 10 ng/ml of TGF-beta (1.7-fold). These findings indicate that CSA and CSB are major sulfated GAGs synthesized by RPC-C2A cells and that TGF-beta acts as a stimulator of sulfated GAG synthesis in dental pulp cells.

Animals↗

PubMed2000

Glibenclamide inhibits accumulation of cholesteryl ester in THP-1 human macrophages.

Glibenclamide is an adenosine triphosphate (ATP)-sensitive potassium channel inhibitor that is widely used in treating diabetes mellitus. However, the effects of this drug on cholesterol metabolism and atherogenesis are not well known. We investigated the effects of this agent on the cellular cholesterol metabolism in cultured human macrophages. The effect of glibenclamide was evaluated by the measurement of the cellular contents of total cholesterol, free cholesterol, and cholesteryl ester in the presence of low-density lipoprotein (LDL). The effect on the degradation and association of 125I-labeled LDL (125I-LDL) also were determined. Cholesterol efflux was measured in the absence and the presence of high-density lipoprotein (HDL). The secretion of apolipoprotein E also was determined. The synthesis and hydrolysis of cholesteryl ester were evaluated. Glibenclamide stimulated both synthesis and hydrolysis of cholesteryl ester, and inhibited the net accumulation of cholesteryl ester by LDL in a concentration-dependent manner and even decreased its content compared with time 0 control. This drug had no effect on the degradation or association of 125I-LDL. Glibenclamide promoted the HDL-independent cholesterol efflux by decreasing esterified cholesterol and increasing the release of free cholesterol and secretion of apolipoprotein E into the medium. The other potassium channel inhibitors or openers had no effect on the cellular cholesterol levels. These results suggest that glibenclamide inhibits the accumulation of cholesteryl ester in macrophages by enhancing the hydrolysis of cholesteryl ester as well as by increasing cholesterol efflux, and possibly, by increasing the secretion of apolipoprotein E. These effects appeared to be unrelated to an effect on the potassium channel. Inhibition of accumulation of cellular cholesterol by glibenclamide might be favorable for the prevention of atherosclerotic disease.

Analysis of Variance↗

PubMed2000

L-myc restriction fragment length polymorphism in Japanese patients with esophageal cancer.

L-myc polymorphism is a representative genetic trait related to an individual's susceptibility to several cancers. However, there have been no reports concerning the association between esophageal cancer and L-myc polymorphism. To analyze the distribution of polymorphism in Japanese patients with esophageal cancer, a molecular genotyping method using a polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was used. Based on an analysis of 65 Japanese patients with esophageal cancer and 107 healthy control subjects, a significant difference was observed in either the distribution of genotypes (P=0.012) or of allele frequencies between the two groups (P=0.004). The relative risk of esophageal cancer for genotypes including the shorter allele was 2.9 compared to the longer allele homozygote. Furthermore, the patients with S-allele had a tendency for poor prognosis among those with three genotypes. A significant difference between the distribution of genotypes and the incidence of lymph node metastasis was found based on the clinicopathological features of the cancers. These results suggest that L-myc polymorphism may be implicated as a genetic trait affecting an individual's susceptibility to esophageal cancer, at least among Japanese patients.

Esophageal Neoplasms↗

PubMed2000

Association of poor prognosis with loss of 12q, 17p, and 18q, and concordant loss of 6q/17p and 12q/18q in human pancreatic ductal adenocarcinoma.

OBJECTIVE: Pancreatic cancer is one of the diseases with the poorest prognosis, but the associated genetic alterations are not yet well understood. The genetic alterations reported to date in pancreatic cancer include frequent mutations of the KRAS, TP53, p16, and SMAD4 genes. Mutation of the TP53 gene was reported to be associated with a poor prognosis. In this study, we analyzed the association of loss of heterozygosity (LOH) with clinicopathological features to attempt to devise effective methods in the future for clinically applying our results to diagnosis and treatment. METHODS: A total of 55 tumors from patients with primary pancreatic ductal carcinomas (34 men and 21 women, mean average age 63.9 yr) in which all the relevant clinical and pathological data were available were analyzed. A total of 46 cases were surgically resected, and nine cases were not. Tumor cells as well as corresponding normal cells were collected by microdissection under a microscope, and DNAs were purified. Allelotype analysis was performed by the PCR-based method, and the results were statistically analyzed. RESULTS: LOH of > or =30% were observed on chromosome arms 17p (47%, 17/36), 9p (45%, 14/31), 18q (43%, 15/35), 12q (34%, 10/29), and 6q (30%, 10/33). LOH of 12q, 17p, and 18q were significantly associated with a poor prognosis. Concordant losses of 6q with 17p and 18q were significantly associated with a poor prognosis. Concordant losses of 6q with 17p and of 12q with 18q were also found. CONCLUSIONS: Because LOH of 12q, 17p, and 18q are significantly associated with a poor prognosis, mutation of the putative tumor suppressor genes on these chromosome arms may play significant roles in the disease progression. Concordant losses of 6q with 17p and of 12q with 18q suggest that protein products of putative tumor suppressor genes on 6q and 12q may function in association with TP53 and SMAD4, respectively.

Alleles↗