PubMed Health⌕ Search

Biomedical subjects

H Seno

Publications and source records attributed to H Seno.

At least 19 recordsLinked to original sources

Chromosomal instability by beta-catenin/TCF transcription in APC or beta-catenin mutant cells.

Adenomatous polyposis coli (APC/Apc) gene encodes a key tumor suppressor whose mutations activate beta-catenin/T-cell factor (TCF)-mediated transcription (canonical Wnt signaling). Here, we show that Wnt signaling can cause chromosomal instability (CIN). As an indicator of CIN, we scored anaphase bridge index (ABI) in mouse polyps and ES cells where Wnt signaling was activated by Apc or beta-catenin mutations. We found three to nine times higher ABI than in wild-type controls. Furthermore, karyotype analysis confirmed that the Wnt signal-activated ES cells produced new chromosomal aberrations at higher rates; hence CIN. Consistently, expression of dominant-negative TCFs in these cells reduced their ABI. We also found that Wnt signal activation increased phosphorylation of Cdc2 (Cdk1) that inhibited its activity, and suppressed apoptosis upon exposure of the cells to nocodazole or colcemid. The data suggest that Wnt signaling stimulates the cells to escape from mitotic arrest and apoptosis, resulting in CIN. In human gastric cancer tissues with nuclear beta-catenin, ABI was significantly higher than in those without. These results collectively indicate that beta-catenin/TCF-mediated transcription itself increases CIN through dysregulation of G2/M progression.

Adenoma↗

Hypoxia induced by benign intestinal epithelial cells is associated with cyclooxygenase-2 expression in stromal cells through AP-1-dependent pathway.

Cyclooxygenase-2 (COX-2) plays important roles in tumor development. Especially in the early-stage colorectal tumors, COX-2 expression is often observed in the tumor stroma. However, the mechanism regulating such stromal expression of COX-2 remains unknown. In the present study, we simulated the indirect interaction between epithelial cells and stromal cells in the process of colorectal tumor development using an in vitro co-culture model in which NIH3T3 fibroblasts were co-cultured with 'sparsely' or 'densely' populated intestinal epithelial cells, Intestine-407 as a model of premalignant or benign intestinal epithelial cells, and DLD-1 and Caco-2 as models of malignant epithelial cells. COX-2 expression in NIH3T3 fibroblasts was upregulated when co-cultured with the 'dense' epithelial cells regardless of their character. Interestingly, there was pericellular hypoxia in the vicinity of NIH3T3 fibroblasts when co-cultured with 'dense' epithelial cells, and the recovery of the partial pressure of oxygen level resulted in the reduction of enhanced COX-2 expression only in NIH3T3 fibroblasts co-cultured with 'dense' Intestine-407 cells. Furthermore, COX-2 expression was also reduced by the inhibition of transcription factor AP-1. Thus, pericellular hypoxia of the stromal cells caused by densely populated epithelial cells may be one of the potent COX-2 enhancers before completion of malignant transformation during intestinal tumor development.

Animals↗

Group size determined by fusion and fission. A mathematical modelling with inclusive fitness.

We consider a mathematical model for the group size determination by the intra-reactions, self-growth, ostracism and fission within a group, and by the inter-reactions, immigration and fusion between two groups. In some group reactions, a conflict between two groups occurs about the reaction to change the group size. We construct a mathematical model to consider such conflict, taking into account the inclusive fitness of members in each group. In the conflict about the fusion between two groups, our analysis shows that the smaller group wants to fuse, while the larger does not. Also the criterion to resolve the conflict is discussed, and some numerical examples are given, too. It is concluded that, depending on the deviation in the total cost paid for the conflict by counterparts, the group reactions could result in a terminal group size different from that reached only by a sequence of outsider's immigrations into a group.

Animals↗

Effect of CYP2C19 polymorphism on the safety and efficacy of omeprazole in Japanese patients with recurrent reflux oesophagitis.

BACKGROUND: The polymorphic enzyme cytochrome P450 2C19 affects omeprazole metabolism. This influence on metabolism might affect serum gastrin levels, and safety, during long-term treatment of reflux oesophagitis. AIM: To examine the relationship between cytochrome P450 2C19 genotype and the safety profile of long-term omeprazole treatment. METHODS: A total of 119 Japanese patients with recurrent reflux oesophagitis underwent cytochrome P450 2C19 genotyping prior to receiving daily omeprazole 10 mg or 20 mg for 6-12 months, during which adverse event frequency, serum gastrin levels and endoscopic findings were monitored. RESULTS: The incidences of adverse events, serious adverse events and adverse events leading to withdrawal did not differ between homozygous extensive metabolizer (n = 46), heterozygous extensive metabolizer (n = 53) or poor metabolizer (n = 20) groups. In all genotype groups, serum gastrin increased during the first 3 months of dosing but stabilized thereafter. No significant differences were seen either in the rate of reflux oesophagitis healing or symptom improvement among genotype groups. CONCLUSIONS: Long-term treatment with omeprazole was well-tolerated in Japanese patients, irrespective of their cytochrome P450 2C19 metabolic genotype, indicating that dose adjustment depending on metabolic genotype is not required during treatment with omeprazole.

Adult↗

Possible role of REG Ialpha protein in ulcerative colitis and colitic cancer.

BACKGROUND AND AIMS: Although regenerating gene (REG) Ialpha protein may be involved in the inflammation and carcinogenesis in the gastrointestinal tract, its pathophysiological role in ulcerative colitis (UC) and the resulting colitic cancer remains unclear. We investigated expression of the REG Ialpha gene and its protein in UC and colitic cancer tissues. We examined whether cytokines are responsible for REG Ialpha gene expression and whether REG Ialpha protein has a trophic and/or an antiapoptotic effect on colon cancer cells. METHODS: Expression of REG Ialpha mRNA and its gene product in UC tissues was analysed by real time reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. The effects of cytokines on REG Ialpha promoter activity were examined in LoVo cells by luciferase reporter assay. The effects of REG Ialpha protein on growth and H(2)O(2) induced apoptosis were examined in LoVo cells by MTT and TUNEL assays, respectively. RESULTS: REG Ialpha protein was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of REG Ialpha mRNA expression in UC tissues correlated significantly with severity of inflammation and disease duration. REG Ialpha promoter activity was enhanced by stimulation with interferon gamma or interleukin 6. REG Ialpha protein promoted cell growth and conferred resistance to H(2)O(2) induced apoptosis in LoVo cells. REG Ialpha protein promoted Akt phosphorylation and enhanced Bcl-xL and Bcl-2 expression in LoVo cells. CONCLUSIONS: The REG Ialpha gene is inducible by cytokines and its gene product may function as a mitogenic and/or an antiapoptotic factor in the UC-colitic cancer sequence.

Adenoma↗

Ischemic duodenitis.

Explore the source record for details and available documents.

Arteriosclerosis Obliterans↗

Usefulness of famotidine in functional dyspepsia patient treatment: comparison among prokinetic, acid suppression and antianxiety therapies.

BACKGROUND: The treatment of functional dyspepsia is controversial. AIM: The purpose of this paper is to clarify the initial effect of prokinetic, acid suppression and antianxiety treatment for functional dyspepsia patients. PATIENTS AND METHODS: Sixty-four functional dyspepsia patients without Helicobacter pylori infection were randomly assigned to 15 mg/day of mosapride, 40 mg/day of famotidine, or 30 mg/day of tandospirone during an 8-week treatment. Individual functional dyspepsia symptoms were evaluated with 4 cm visual analogue scale before and at 2, 4 and 8 weeks after treatment. RESULTS: Among 64 enrolled patients, 62 completed the study. Within 2 weeks, visual analogue scale score in the mosapride-treated group decreased from 2.29 +/-0.14 to 1.57 +/- 0.20; in the famotidine from 2.04 +/- 0.16 to 1.09 +/- 0.12 (mean +/- S.E.). Therefore, there were significant improvements of functional dyspepsia symptoms in mosapride- and famotidine-treated patients (P <0.01). Furthermore, famotidine was significantly more effective than mosapride (P < 0.05). On the contrary, visual analogue scale score in the tandospirone therapy was 2.23 +/- 0.20 and 2.13 +/- 0.22 before and at 2 weeks, respectively, without any significant improvement. CONCLUSIONS: A treatment regimen of famotidine at 40 mg/day had a significant favourable effect on the clinical outcome in functional dyspepsia patients.

Anti-Anxiety Agents↗

Jaw-opening dystonia (Brueghel's syndrome) associated with cavum septi pellucidi and Verga's ventricle - a case report.

Jaw-opening dystonia (oromandibular dystonia with jaw-opening; Brueghel's syndrome) is a rare condition, and only a limited number of cases have been reported in the literature. However, many patients may remain undiscovered or misdiagnosed, like a patient described previously. A case (40-year-old man) of jaw-opening dystonia (oromandibular dystonia with jaw-opening; Brueghel's syndrome) is reported. In this case, brain anomalies, cavum septi pellucidi and Verga's ventricle, were observed on magnetic resonance imaging of the brain. This case and a review of the literature indicate the presence of organic factors in the etiology of Brueghel's syndrome. The etiological relationship of brain anomalies in Bruegel's syndrome is discussed.

Adult↗

Involvement of tumor necrosis factor alpha in intestinal epithelial cell proliferation following Paneth cell destruction.

BACKGROUND: An intravenous injection of diphenylthiocarbazone (dithizone), a zinc chelator, induces selective killing of Paneth cells which have a large amount of zinc in their cytoplasmic granules. A transient wave of intestinal epithelial cell proliferation occurs at 12 h after the injection. Paneth cells have tumor necrosis factor (TNF)-alpha protein in their cytoplasmic granules, and TNF-alpha has a proliferative effect on intestinal epithelial cells in vitro. The aim of this study is to clarify the in vivo role of TNF-alpha in intestinal epithelial cell proliferation using a dithizone-treated rat model. METHODS: Male Wistar rats received a dithizone (100 mg/kg of body weight) injection with or without TNF-alpha inhibitor, pentoxifylline (100 mg/kg), neutralizing anti-TNF-alpha antibody (2 mg/kg), or nuclear transcription factor kappaB (NF-kappaB) inhibitors: pyrrolidine dithiocarbamate (100 mg/kg) or N-acetyl-L-cystein (100 mg/kg). The activation of NF-kappaB was examined by the electrophoretic mobility shift assay, and cellular proliferation by BrdU labeling. RESULTS: Without any inhibitors, dithizone treatment evoked NF-kappaB activation in the ileal mucosa with its peak level at 2 h after the injection. TNF-alpha inhibition reduced the NF-kappaB activation, and blocked a transient wave of epithelial cell proliferation 12 h after the injection. NF-kappaB inhibitors also reduced the NF-kappaB activation and epithelial cell proliferation. CONCLUSIONS: TNF-alpha released from degenerated Paneth cells was, in part, responsible for the intestinal cell proliferation through the activation of NF-kappaB, suggesting its proliferative effect on intestinal epithelial cells.

Animals↗

Regression of fundic gland polyps following acquisition of Helicobacter pylori.

The prevalence of Helicobacter pylori infection is very low in patients with fundic gland polyps (FGPs) of the stomach. We report here two cases with multiple FGPs that regressed following new H pylori acquisition. Patient Nos I and II had multiple FGPs in normal fundic mucosa without inflammatory changes or atrophy. Both were not infected with H pylori. Following acquisition of H pylori infection however, all FGPs in both patients completely disappeared except for one FGP in patient No I. Although the size of the remaining polyp in patient No I was greatly reduced after H pylori acquisition, it became enlarged again after eradication. Interestingly, in the remaining polyp, we found an activating beta-catenin gene mutation whereas no such mutations were detected in FGPs of patient No II. Thus H pylori infection may have an inhibitory effect on the development of FGPs.

Adult↗

A curious autopsy case of a car crash in which self-strangulation and lung collapse were found: a case report.

A curious autopsy case following the car crash of a 20-year-old male, in which self-strangulation and lung collapse were observed, is presented. His motor vehicle had crashed into a restaurant as a result of self-strangulation using an electrical cord wound four times around his neck. At autopsy, we found small rupture holes of spontaneous bullae in both lung apices, which had probably taken place upon collision during driving, petechial hemorrhages in the face skin and the absence of severe injuries. Since it seemed unlikely that the small holes in both lung apices caused fatal pneumothorax instantly, the cause of his death was judged to be asphyxia due to self-strangulation. It is not clear whether the self-strangulation was suicidal or autoerotic, because neither traces of suicidal intent nor circumstances suggesting either of them were disclosed.

Accidents, Traffic↗

CDX2 expression in the stomach with intestinal metaplasia and intestinal-type cancer: Prognostic implications.

CDX2, a transcriptional factor expressed in the intestine, is implicated in the development and maintenance of the intestinal mucosa. Recent studies have demonstrated that CDX2 is expressed in the intestinal metaplasia of the stomach and intestinal-type gastric cancer, while it is not expressed in the normal gastric mucosa. To investigate the role of CDX2 in gastric cancer, we determined CDX2 expression and cell proliferation rate in various types of gastric cancer tissues by immunostaining. Surgically dissected gastric cancer tissues were collected from 40 patients. Consistent with previous reports, CDX2 was expressed in most gastric mucosa samples with intestinal metaplasia (89%, 16/18), although it was not found in the adjacent normal mucosa. CDX2 expression was also detected in 64% (18/28) of intestinal-type gastric cancer cases, whereas it was not observed in the diffuse-type gastric cancer (0/12). Moreover, the CDX2-positive gastric cancer samples showed significantly lower index for Ki-67 immunostaining, indicating reduced cell proliferation rates than in the CDX2-negative samples. Importantly, multivariate analysis for the overall survival rate revealed that the CDX2-positive gastric cancer patients survived significantly longer than the CDX2-negative patients. Even among the intestinal-type gastric cancer cases, the CDX2-positive group showed a lower Ki-67 index and longer postoperative survival than the CDX2-negative group. These results collectively indicate that CDX2 expression in gastric cancer tissues can be a novel prognostic marker for patient survival.

Aged↗

Sensitive determination of four general anaesthetics in human whole blood by capillary gas chromatography with cryogenic oven trapping.

Four general anaesthetics, sevoflurane, isoflurane, enflurane and halothane, in human whole blood, have been found measurable with very high sensitivity by capillary gas chromatography-flame ionization detection (GC-FID) with cryogenic oven trapping upon injection of headspace (HS) vapor sample. To a 7-ml vial, containing 0.48 ml of distilled water and 20 microl of internal standard solution (5 microg), a 0.5-ml of whole blood sample spiked with or without anaesthetics, was added, and the mixture was heated at 55 degrees C for 15 min. A measure of 10 ml HS vapor was injected into the GC in the splitless mode at -40 degrees C oven temperature, which was programmed up to 250 degrees C. All four peaks were clearly separated; no impurity peaks were found among their peaks. Their extraction efficiencies were about 10%. The calibration curves showed good linearity in the range of 0.5-20 microg/ml; their detection limits were 10-100 ng/ml, which are almost comparable to those by previous reports. The coefficients of intra-day and day-to-day variations were 6.5-9.8 and 7.3-17.2%, respectively. Isoflurane or enflurane was also measured from whole blood samples in which three volunteers inhaled each compound.

Adult↗

Identification of xanthine dehydrogenase/xanthine oxidase as a rat Paneth cell zinc-binding protein.

Paneth cells are zinc-containing cells localized in small intestinal crypts, but their function has not been fully elucidated. Previously, we showed that an intravenous injection of diphenylthiocarbazone (dithizone), a zinc chelator, induced selective killing of Paneth cells, and purified a zinc-binding protein in Paneth cells. In the present study, we further characterized one of these proteins, named zinc-binding protein of Paneth cells (ZBPP)-1. Partial amino acid sequences of ZBPP-1 showed identity with rat xanthine dehydrogenase (XD)/xanthine oxidase (XO). Anti-rat XD antibody (Ab) recognized ZBPP-1, and conversely anti ZBPP-1 Ab recognized 85 kDa fragment of rat XD in Western blotting. Messenger RNA and protein levels of XD were consistent with our previous data on the fluctuation of Paneth cell population after dithizone injection. Thus, ZBPP-1 is an 85 kDa fragment of XD/XO in Paneth cells. XD/XO in Paneth cells may play important roles in intestinal function.

Animals↗

Sensitive determination of pethidine in body fluids by surface ionization organic mass spectrometry.

We have presented a simple and sensitive method for determining pethidine, a narcotic analgesic drug in body fluids by gas chromatography (GC)/surface ionization organic mass spectrometry (SIOMS). Good linearity was obtained in the range of 0.625-25 ng/ml of whole blood and urine by mass chromatography, and in the range of 0.05-2 ng/ml of whole blood by selected ion monitoring (SIM). Pethidine and diphenylpyraline (internal standard) were extracted from body fluids with Bond Elut Certify cartridges; their recoveries were above 95%. The detection limits (signal-to-noise ratio=3) were estimated to be 0.2 ng/ml of whole blood or urine by mass chromatography, 0.02 ng/ml of whole blood by SIM.

Analgesics, Opioid↗

Profenofos metabolites in human poisoning.

Profenofos and its metabolites were determined in a case of fatal poisoning. Little profenofos and large amounts of metabolites were detected by gas chromatography/flame photometric detection in the acid extracts of blood and urine after methylation with diazomethane. Four major metabolites containing phosphorus were identified with the synthesized metabolites, namely, despropylated profenofos, desethylated profenofos and des-S-propylated profenofos, respectively. 4-Bromo-2-chlorophenol (BCP), an aryl moiety of profenofos, was also determined in blood and urine with high performance liquid chromatograph (HPLC) as free or conjugated metabolites.

Aged↗

A case of death due to rescue action by a power shovel after being buried alive.

We report a rare case of death due to rescue using a power shovel. A 41-year-old female was accidentally buried alive by a landslide of the earth and sand upon working at a construction site. One of her colleagues started to save her using a power shovel. However, she was dug out dead at the spot about 10 min after the accident with marked head and face injuries. The autopsy disclosed that there was extensive laceration across the face and head with marked skull bone fractures. Around these injuries, extensive hemorrhage could be observed as a vital reaction. Asphyxial death had to be taken into consideration, because she was buried under the earth and sand for about 10 min; but we finally judged that the cause of her death was head injury by the power shovel inflicted during the attempted rescue.

Journal Article↗