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Biomedical subjects

T Katsube

Publications and source records attributed to T Katsube.

At least 19 recordsLinked to original sources

Correlation between microsatellite instability and metachronous disease recurrence after endoscopic mucosal resection in patients with early stage gastric carcinoma.

BACKGROUND: Since endoscopic treatment was first evaluated and established as a treatment for patients with early stage gastric carcinoma, metachronous disease recurrence at other sites in the stomach after endoscopic treatment has become a major problem. METHODS: A retrospective case-control study was conducted on 10 patients with metachronous recurrence of gastric carcinoma after undergoing successful endoscopic mucosal resection (EMR) therapy for early stage gastric carcinoma and on 14 patients without recurrence. Gastric mucosal tissues obtained during the initial EMR were dissected, and DNA samples from the tumor tissue and surrounding nonneoplastic mucosa were extracted separately. Microsatellite instability (MSI) was tested in five microsatellite markers (D2S137, D3S1067, TP53, TGFbetaRII, and BAX). The authors also looked for K-ras codon 12 point mutations in the tumor tissues. In addition, immunohistochemical staining was done to test for the presence of proliferating cell nuclear antigen (PCNA), p53, hMSH2, and hMLH1 in the mucosal tissues. Finally, the correlation between the presence or absence of metachronous recurrence and the characteristics of the primary tumor (MSI, K-ras, p53, etc.) were investigated. RESULTS: Three of 10 patients with recurrent disease showed MSI in more than two microsatellite markers among 3-5 investigated site (MSI-H), whereas none of the patients with nonrecurrent disease did so. There was no significant correlation between metachronous recurrence after EMR and immunohistochemical staining reactions, including those for PCNA, p53, hMSH2, and hMLH1. None of the patients showed K-ras mutations. CONCLUSIONS: Thirty percent of patients with recurrent disease showed MSI-H, whereas none of the patients with nonrecurrent disease did so.

Adaptor Proteins, Signal Transducing↗

Role of hiatus hernia and gastric mucosal atrophy in the development of reflux esophagitis in the elderly.

BACKGROUND AND AIMS: The pathogenetic mechanism responsible for the increased prevalence of reflux esophagitis in the elderly remains controversial. The aim of this study was to determine if an increased occurrence of hiatus hernia (HH) and/or a lower rate of gastric mucosal atrophy (GMA) are the main causes of the increased prevalence of reflux esophagitis in elderly patients. METHODS: The prevalence of HH, GMA, and reflux esophagitis was investigated by reviewing the endoscopic films of 2788 consecutive patients examined during a 3-year period. RESULTS: The prevalence of esophagitis in males was higher than in females (11.6% vs 7.6%, P< 0.0005). The prevalence of reflux esophagitis and HH was found to increase with age in females, but not in male patients. The prevalence of reflux esophagitis in hernia-positive patients also increased with age in women, but not in men. Age, male gender, presence of HH, and closed-type of GMA were significant risk factors for the prevalence of esophagitis (P=0.0001, 0.0229, <0.0001, <0.0001, respectively). In addition, the risk ratios of HH and low-grade GMA for reflux esophagitis increased with age, and this tendency was higher in female patients than in males. CONCLUSIONS: Aging, male gender, HH and closed-type GMA are most likely the risk factors of endoscopically proven reflux esophagitis in Japanese patients.

Adult↗

Prevalence of functional dyspepsia and its relationship with Helicobacter pylori infection in a Japanese population.

AIM: To investigate the prevalence of functional dyspepsia and Helicobacter pylori infection and their relationship in a Japanese population. METHODS: Two thousand five hundred people who visited Shimane Institute of Health Science for their annual medical check-up from September 1998 to August 1999 were prospectively enrolled in the study. After routine medical examination, including an upper gastrointestinal study and an ultrasonographic examination, all subjects were asked standard questions to check for the presence of any symptoms that suggested dyspepsia. Helicobacter pylori infection was determined by using a serum IgG antibody concentration with an ELISA. RESULTS: Of the 2,500 persons investigated, 2,263 showed no abnormal finding in any medical examination. The presence or absence of symptoms and H. pylori infection was investigated in these 2,263 cases. Of these, 201 people (8.9%) experienced nausea, fullness and/or early satiety and were diagnosed as having dysmotility-like dyspepsia, while 118 people (5.2%) experienced pain localized to the epigastrium and were diagnosed as having ulcer-like dyspepsia. The frequency of these symptoms had a tendency to decline with age, although this was not statistically significant. In contrast, the rate of H. pylori infection increased with age. There was no significant relationship between H. pylori infection and any type of functional dyspepsia. CONCLUSIONS: Helicobacter pylori infection does not influence the prevalence of the dysmotility-like and ulcer-like dyspeptic symptoms.

Adult↗

Lifting of lesions during endoscopic mucosal resection (EMR) of early colorectal cancer: implications for the assessment of resectability.

BACKGROUND AND STUDY AIMS: This study assessed the indications for and limitations of endoscopic mucosal resection (EMR) for early colorectal cancer, focusing on the way in which the lesion lifts after submucosal injection. PATIENTS AND METHODS: The study included 94 patients with early colorectal cancer who received EMR treatment. The lifting of the lesion after submucosal injection was analyzed (classified as completely lifted/soft; completely lifted/hard; incompletely lifted; and non-lifted) along with the endoscopic findings, pathological findings, and clinical course. RESULTS: Almost all completely lifted/soft lesions were mucosal cancers. Some of the completely lifted/hard lesions were staged as sm2. The incompletely lifted lesions included stages sm1 to sm3. Non-lifting lesions were almost always deeper than sm3. The lifting condition was significantly associated with the depth of invasion, and the lesion type was related to the extent of lifting but not to tumor size or recurrent disease. Recurrent disease was noted in three patients who underwent piecemeal EMR. CONCLUSIONS: The indication for EMR is easily assessed on the basis of the lifting characteristics of the tumor after submucosal injection, which was found to be significantly related to the depth of invasion. The factor limiting the indication for EMR is not the size of a tumor, but its lifting condition.

Aged↗

Genomic organization, transcription start sites, and chromosomal location of the Drosophila cortactin gene.

An actin filament binding protein cortactin was initially identified as a major phosphotyrosine-containing protein in v-Src-transformed chicken embryo fibroblast cells. The mouse, human, and Drosophila homologs were independently identified as a signaling molecule involved in a mitogenic response, as a product of a putative oncogene EMS1, and as a molecule interacting with a scaffolding protein ZO-1, respectively. In this report, we describe the cloning of the Drosophila cortactin gene, which consists of four exons and three introns, covering 3 kilobases in length. All exon-intron junctions are well matched with the GT/AG consensus sequence. S1 nuclease mapping revealed one major and several minor transcription start sites. The cytological location of the Drosophila cortactin gene is between chromosome segments 93B3 and 93B7.

Animals↗

Gastrointestinal stromal tumor with a novel mutation of KIT proto-oncogene.

The majority of human gastrointestinal mesenchymal tumors are gastrointestinal stromal tumors (GISTs). Recent reports have shown the existence of gain-of-function mutations in the juxta-membrane domain of receptor tyrosine kinase (KIT) in GISTs. We present a 77-year-old woman with GIST diagnosed by positive immunostaining of cluster designation (CD) 34 and KIT. This case had a novel mutation at codon 576 located in the juxta-membrane domain of KIT. Our results indicate the importance of mutations in this KIT region and suggest the possibility of the existence of other types of mutations in this region in GISTs.

Aged↗

Investigation into the mode of action of R-91650, an arylpiperazinyl fluoroquinolone, on feline immunodeficiency virus replication inhibitory activity.

The mode of action of R-91650, an arylpiperazinyl fluoroquinolone, on feline immunodeficiency virus (FIV) replication inhibitory activity was investigated. R-91650 inhibited replication of FIV at non-cytotoxic concentration levels in both acutely infected peripheral blood mononuclear cells and chronically infected P-CrFK cells. The compound reduced the intracellular p24 concentration levels in P-CrFK cells in a dose-dependent manner. Northern blot analysis revealed that R-91650 selectively prevented the accumulation of FIV mRNA in P-CrFK cells. However, the compound did not inhibit FIV-long terminal repeat (LTR) promoter activity in the reporter gene expression analysis. These data suggest that R-91650 is a novel inhibitor of FIV replication that inhibits a certain step or steps following transcription initiation of the FIV-LTR promoter.

Animals↗

Long-lasting binding of IT-066 to human histamine H2 receptor.

Based on animal models, IT-066, a histamine H2-receptor antagonist, is reported to possess potent and long-lasting antagonisms on histamine H2 receptor (H2R) -mediated effects. However, no reports have been published concerning its interaction with the human H2R. The aim of this study is to characterize its interaction with human H2R. Chinese hamster ovary cell lines stably expressing human H2Rs were obtained. The effects of IT-066, famotidine, and ranitidine on tiotidine binding and histamine-stimulated cAMP production were analyzed. IT-066 inhibited [3H]tiotidine binding and histamine-stimulated cAMP production more potently than famotidine or ranitidine. In addition, preincubation with 10(-5) M IT-066, but not with 10(-5) M famotidine or 10(-4) M ranitidine, had marked inhibitory effects long after extensive washing. Paraformaldehyde fixation of the cells blunted inhibition of [3H]tiotidine binding induced by preincubation with IT-066, but not that by preincubation with famotidine or ranitidine. IT-066 has potent and long-lasting antagonisms on human H2R. At least one of the IT-066 binding sites is not shared by famotidine, ranitidine, or tiotidine and is affected by paraformaldehyde fixation.

Animals↗

Helicobacter pylori infection influences nocturnal gastric acid breakthrough.

BACKGROUND: Nocturnal gastric acid breakthrough is defined as night-time periods when gastrin pH falls below 4.0 for greater than 1h during administration of a proton pump inhibitor. This phenomenon is a serious problem for patients who require strict control of their gastric acid secretions. AIM: To investigate the prevalence of nocturnal gastric acid breakthrough in Japanese subjects during administration of rabeprazole, and to clarify the relationship between Helicobacter pylori infection and nocturnal gastric acid breakthrough. METHODS: Thirty-one normal male volunteers were examined by ambulatory 24 h gastric pH monitoring four times: without medication, after a morning or an evening dose of 20 mg rabeprazole, and after administration of an H2-receptor antagonist at bedtime, in addition to the morning dose of rabeprazole. H. pylori infection was determined by the 13C-urea breath test and an assay for serum anti-H. pylori antibody. RESULT: Nocturnal gastric acid breakthrough was observed in 12 patients (39%) after the morning dose of 20 mg rabeprazole. In all cases, nocturnal gastric acid breakthrough was inhibited completely by administration of the H2-receptor antagonist at bedtime. Only one patient with nocturnal gastric acid breakthrough had H. pylori infection. CONCLUSION: The absence of H. pylori infection appears to be closely related to the occurrence of nocturnal gastric acid breakthrough during dosing with a proton pump inhibitor.

2-Pyridinylmethylsulfinylbenzimidazoles↗

CYP2C19 genotype status and intragastric pH during dosing with lansoprazole or rabeprazole.

BACKGROUND: CYP2C19 has an important role in the catabolism of several proton pump inhibitors. However, the relative contribution of CYP2C19-mediated metabolism varies among the different proton pump inhibitors. AIM: To determine the effect of CYP2C19 genotype status on intragastric pH during dosing with lansoprazole or rabeprazole. SUBJECTS AND METHODS: The subjects were 20 male volunteers without Helicobacter pylori infection. Their CYP2C19 genotype status was determined by a polymerase chain reaction-restriction fragment length polymorphism method. Twenty-four-hour monitoring of intragastric acidity was performed three times: once without medication, once on the last day of a 7-day course of rabeprazole, and once on the last day of a 7-day course of lansoprazole. RESULTS: Subjects were divided into three groups on the basis of their CYP2C19 genotype status: homozygous extensive metabolizers (homo-EMs, n=7), heterozygous extensive metabolizers (hetero-EMs, n=9), and poor metabolizers (PMs, n=4). The median pH during rabeprazole administration was not influenced by CYP2C19 genotype. On the other hand, the median pH in PMs during lansoprazole dosing was higher than in homo-EMs and hetero-EMs. The percentage of time with pH < 4.0 had a similar tendency to that of median pH. CONCLUSION: CYP2C19 genotype status influences gastric acid suppression by lansoprazole, but not by rabeprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Suppression of cellular immunity by surgical stress.

BACKGROUND: Suppression of cellular immunity is one of the host responses to surgical stress. In cancer patients this immunosuppression may accelerate the growth and metastasis of residual cancer cells, so it is desirable to restrict immunosuppression by surgical stress to a minimum. However, the extent and duration of immunosuppression caused by operations on gastrointestinal cancer, as well as the mechanisms involved, have not been determined. METHODS: To clarify these points, we investigated immunocyte function and measured the blood levels of hormones, cytokines, and acute phase reactants from before to after operation in 20 patients with stage I gastrointestinal cancer. RESULTS: In patients exposed to surgical stress, peripheral blood lymphocyte numbers and function were suppressed until at least 2 weeks postoperatively. This immunosuppression was mainly due to a decrease of helper-inducer T cells, cytotoxic T cells, natural killer cells, and interleukin-2 receptor-positive cells, as well as an increase of suppressor T cells. In addition, hypersecretion of cortisol and overproduction of immunosuppressive acidic protein were observed. CONCLUSIONS: Cellular immunosuppression by surgical stress was mainly due to an increase of lymphocyte subsets that depress cellular immunity coupled with a decrease of the subsets that promote it. Overproduction of cortisol and immunosuppressive acidic protein in response to surgical stress may play an important role in the development of immunosuppression.

Acute-Phase Proteins↗

Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier.

BACKGROUND: Stratum corneum lipids, particularly ceramides, are important components of the epidermal permeability barrier that are decreased in atopic dermatitis and aged skin. OBJECTIVES: We investigated the effects of nicotinamide, one of the B vitamins, on biosynthesis of sphingolipids, including ceramides and other stratum corneum lipids, in cultured normal human keratinocytes, and on the epidermal permeability barrier in vivo. METHODS: The rate of sphingolipid biosynthesis was measured by the incorporation of [14C]-serine into sphingolipids. RESULTS: When the cells were incubated with 1-30 micromol L-1 nicotinamide for 6 days, the rate of ceramide biosynthesis was increased dose-dependently by 4.1-5. 5-fold on the sixth day compared with control. Nicotinamide also increased the synthesis of glucosylceramide (7.4-fold) and sphingomyelin (3.1-fold) in the same concentration range effective for ceramide synthesis. Furthermore, the activity of serine palmitoyltransferase (SPT), the rate-limiting enzyme in sphingolipid synthesis, was increased in nicotinamide-treated cells. Nicotinamide increased the levels of human LCB1 and LCB2 mRNA, both of which encode subunits of SPT. This suggested that the increase in SPT activity was due to an increase in SPT mRNA. Nicotinamide increased not only ceramide synthesis but also free fatty acid (2.3-fold) and cholesterol synthesis (1.5-fold). Topical application of nicotinamide increased ceramide and free fatty acid levels in the stratum corneum, and decreased transepidermal water loss in dry skin. CONCLUSIONS: Nicotinamide improved the permeability barrier by stimulating de novo synthesis of ceramides, with upregulation of SPT and other intercellular lipids.

Acyltransferases↗

8-Difluoromethoxy-4-quinolone derivatives as anti-feline immunodeficiency virus (FIV) agents: important structural features for inhibitory activity of FIV replication.

The inhibitory activities of various 8-difluoromethoxy-4-quinolone derivatives against feline immunodeficiency virus (FIV) replication in the chronically infected cell line P-CrFK were investigated. Certain derivatives were found to inhibit FIV production from P-CrFK cells in a dose-dependent manner without exhibiting cytotoxic effects at inhibitory concentrations. Based on this study, the structures important for anti-FIV activity are suggested to be (i) a carboxyl group at position C-3, and (ii) an aromatic modification at position 4 of the C-7 piperazinyl moiety.

Animals↗

Prevalence of non-ulcer dyspepsia in the Japanese population.

BACKGROUND: Non-ulcer dyspepsia (NUD) is one of the most frequently encountered disorders in general practice in Western countries. The prevalence of this disorder in the Japanese, however, has not been fully investigated. This study is designed to clarify the characteristics and prevalence of dyspepsia in the Japanese. METHODS: The subjects were 1139 people who visited our institutes for their annual medical check up for gastric cancers. After routine medical examination, all subjects were asked standardized questions in order to check for the presence of any symptoms suggesting dyspepsia. RESULTS: The results of the study showed that dysmotility-like dyspepsia, characterized by the presence of nausea, fullness and early satiety, is the most frequently observed dyspepsia in Japanese and that this type of dyspepsia decreases with age. Ulcer-like dyspepsia, which is the major type of dyspepsia in Western countries, is the least frequently experienced dyspepsia in the Japanese. CONCLUSIONS: This study clarified that NUD is also one of the most prevalent disorders in the Japanese, although its characteristics may be somewhat different from those in Western countries.

Adult↗

Predictive factors for metachronous recurrence of early gastric cancer after endoscopic treatment.

Since endoscopic treatment has been evaluated and become established as treatment for early gastric cancer, metachronous recurrence has become a major problem. In this report, predictive factors for recurrence were studied using the Kaplan-Meier method and Cox's proportional hazards regression model in 76 patients who received endoscopic treatment. There were 48 men and 28 women age 69.6 +/- 8.3 years (mean +/- standard deviation), 5 of whom had synchronous multiple lesions and 71 who had a single lesion found during the initial endoscopic treatment. In all patients, periodic follow-ups were performed by endoscopy for more than 2 years after treatment. Helicobacter pylori infection was assessed in 55 of the 76 patients, and proved positive in 43 and negative in 12. Metachronous recurrence was detected significantly more frequently in patients whose synchronous multiple lesions were found during the initial treatment. In addition, age affected the recurrence positively. However, gender and H. pylori infection had no significant relationship with metachronous recurrence.

Adenocarcinoma↗

Accumulation of soybean glycinin and its assembly with the glutelins in rice

Saline-soluble glycinins and insoluble glutelins are the major storage proteins in soybean (Glycine max) and rice (Oryza sativa), respectively. In spite of their differences in solubility properties, both proteins are members of the 11S globulin gene family based on their similarities in primary sequences and processing of the coded protein. Wild-type and methionine-modified glycinin coding sequences were expressed in transgenic rice plants under the control of the rice glutelin GluB-1 promoter. Glycinins were specifically synthesized in the endosperm tissue and co-localized with glutelins in type II protein bodies. They assembled into 7S and 11S species, similar to what was observed in developing soybean seeds. This pattern was quite different from that displayed by the rice glutelins in untransformed plants, in which processed subunits sedimenting at 2S were apparent. In glycinin-expressing transgenic plants, however, glutelins were observed sedimenting at 7S and 11S with lesser amounts in the 2S region. A portion of the glycinins was also found associated in the insoluble glutelin fraction. Renaturation experiments suggested that the hybrid glycinin-glutelin oligomers were formed through specific interactions. Overall, these results indicate that despite significant differences in the assembly of soybean glycinin and rice glutelin, both proteins can assemble with each other to form soluble hexameric oligomers or insoluble aggregates.

Journal Article↗