Biomedical subjects

Toru Horie

Publications and source records attributed to Toru Horie.

8 recordsLinked to original sources

PubMed2007

Rectal angiolipoma diagnosed after surgical resection: a case report.

Angiolipoma is a common benign tumor with a characteristic vascular component that usually occurs in subcutaneous tissue. Although lipomas are frequently encountered at colonoscopy as submucosal tumors, angiolipomas are rarely found in the gastrointestinal tract including the large intestine. Here we report a 77-year old Japanese man who underwent transanal resection of a tumor that was diagnosed tentatively as a leiomyoma. Histologically, the tumor consisted of mature fat cells and blood vessels. Immunohistochemically, the tumor cells were negative for c-kit and HMB-45, which are consistently expressed in tumors such as gastrointestinal stromal tumor and angiomyolipoma. The tumor was therefore diagnosed as an angiolipoma. This is thought to be the first case report of a surgically resected angiolipoma of the rectum.

Aged↗

PubMed2006

Total colectomy improves altered distribution of regulatory T cells in patients with ulcerative colitis.

BACKGROUND: It is now generally believed that regulatory T cells (Tregs) play an important role in peripheral tolerance, and a defect in Tregs is considered one of the most important factors in the induction of various kinds of autoimmune disease including ulcerative colitis (UC). Here, we examined the change in frequency of Tregs phenotype in five patients with UC whose condition had not been controllable by conventional conservative therapy and who were scheduled for total colectomy. AIMS: The aim of this study was to elucidate the role of Tregs in the pathogenesis of UC in a clinical setting. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from five patients with UC, and the change in frequency of Tregs was analyzed by flow cytometry before total colectomy and on postoperative days 1, 7, and 20. Tregs were defined as CD4+ CD25+ CD45RA+ T cells, and data (%) were expressed as frequency of Tregs/CD4+ T cells. Peripheral blood mononuclear cells (PBMCs) from healthy blood donors (n = 5) and from patients undergoing other types of major surgery (n = 5) were used as controls. RESULTS: Comparison with normal subjects showed that generation of Tregs was suppressed in UC patients before they underwent total colectomy (0.95 versus 5.06; P = 0.009). The frequency of Tregs increased shortly after total colectomy. The frequency at postoperative days 1, 7, and 20 was 3.81%, 8.13%, and 3.76%, respectively. There were significant differences in the change in frequency in the period before surgery and postoperative day 1, between postoperative days 1 and 7, and between days 7 and 20. CONCLUSIONS: Elimination of targeted antigens residing in the colorectal mucosa by total colectomy improved the suppressed distribution of Tregs in UC patients. The present study provides the first direct clinical evidence that Tregs play a pivotal role in the pathogenesis of UC.

Adult↗

PubMed2006

Characterization of humanized liver from chimeric mice using coumarin as a human CYP2A6 and mouse CYP2A5 probe.

Coumarin 7-hydroxylation (COH), which is catalyzed almost solely by human CYP2A6 and mouse CYP2A5, shows large differences in activity (humans>>mice) and inhibitor specificity between mice and humans. To differentiate human and mouse liver functions of chimeric mice (CM1, CM2 and CM3) prepared with hepatocytes from 3 donors, the microsomal COH activities were measured with and without benzaldehyde and undecanoic gamma-lactone as a specific inhibitor of human CYP2A6 and mice CYP2A5, respectively. The replacement % to human hepatocytes designated as replacement index (RI) was calculated from human specific cytokeratin 8/18 expression in the liver section. The COH activities correlated well with RIs in CM2 (R(2)=0.98) and CM3 (R(2)=0.94), except CM1 whose genotype of donor is CYP2A6*4/*4. However, the COH activities expressed as % of donor activities were not always coincident with RIs, and the inhibition pattern of CM2 and CM3 was human-type after RI exceeded approximately 50%. Subsequently, our attempts to use % of COH activities or inhibition patterns as an accurate functional replacement index were unsuccessful. Since the detection of human CYP2A6 protein in the liver and the steep increase of human albumin (hAlb) levels in the blood were begun from almost RI=50% similarly to the changes of inhibition pattern, RI=50% is the turning point for chimeric mice to have humanized liver function.

Animals↗

PubMed2005

Variations of the CFTR gene in the Hanoi-Vietnamese.

In order to investigate polymorphic backgrounds of the cystic fibrosis transmembrane conductance regulator gene (CFTR) in the Vietnamese, we analyzed 495 blood samples of randomly selected healthy individuals in Hanoi for the delta F508 mutation and TG-repeats, poly-T, and M470V polymorphisms. We compared their distributions with those of Caucasians and other Asian populations. No delta F508 mutation was found, being consistent with the extremely low incidence of cystic fibrosis (CF) in Vietnam. Allele frequency of the T5 allele promoting exon 9 skipping was 0.037. Greater number of TG-repeats, which is known to facilitate this aberrant splicing, was a predominant trend in the Vietnamese and other Asians. A "T5-TG12-V470" haplotype was most common (29/37) among T5-bearing haplotypes. Three major haplotypes, T7-TG12-M470, T7-TG11-V470, and T7-TG12-V470, estimated by PHASE program, related to 92% of the population. This is the first study of the CFTR gene among the Vietnamese.

Adolescent↗

PubMed2005

In vivo induction of human cytochrome P450 enzymes expressed in chimeric mice with humanized liver.

The induction and inhibition of human cytochrome P450 (P450) enzymes are clinically responsible for drug interactions. Although the induction of P450s is investigated using human hepatocytes in the drug development process, there are some disadvantages, such as the decline of the enzyme activity during culture. In the present study, we examined the in vivo induction potency in chimeric mice with humanized liver, which was recently established in Japan to clarify whether this chimeric mouse model would be more suitable for human induction studies. Rifampicin and 3-methylcholanthrene (3-MC) were used in vivo as typical P450 inducers in the chimeric mice. The expression levels of human CYP3A4 mRNA and CYP3A4 protein and dexamethasone 6-hydroxylase activity, specific for human CYP3A4, were increased 8- to 22-, 3- to 10-, and 5- to 12-fold, respectively, by treatment with rifampicin. In addition, the expression levels of human CYP1A2 mRNA and CYP1A2 protein were also increased 2- to 9- and 5-fold, respectively, by treatment with 3-MC. Although other human P450s are expressed in the chimeric mice, there were few effects by the treatment of rifampicin and 3-MC on the mRNA, protein, and enzyme activity of those P450s. It was demonstrated that human P450s expressed in the chimeric mice with humanized liver were induced by rifampicin and 3-MC. This chimeric mouse model may be a useful animal model to estimate and predict the in vivo induction of P450s in humans.

Animals↗

PubMed2005

Induction of human CYP1A2 and CYP3A4 in primary culture of hepatocytes from chimeric mice with humanized liver.

Chimeric mice with near-completely humanized liver were constructed by transplantating hepatocytes from a Japanese and Caucasian donor. In the present study, we investigated the induction of human CYP1A2 and CYP3A4 mRNA in a primary culture of the cryopreserved chimeric mouse hepatocytes. beta-naphthoflavone (beta-NF) and rifampicin (Rif) were used as typical cytochrome P450 (CYP) inducers for CYP1A2 and CYP3A4, respectively. Analysis was performed by the real-time reverse-transcription polymerase chain reaction method. CYP1A2 mRNA in the primary culture of chimeric mouse hepatocytes in mice No. 1, 2, and 3 was significantly increased 3.8-, 6.3-, and 3.3-fold by 5 microM beta-NF exposure, respectively, compared with the 0.1% DMSO treated control (p<0.01). CYP3A4 mRNA in the primary culture of chimeric mouse hepatocytes in mice No. 1, 2, and 3 was significantly increased 8.4-fold (p<0.001), 2.2-fold (p<0.01), and 2.3-fold (p<0.05) by 50 microM Rif exposure, respectively, compared with the 0.1% DMSO treated control. The present study demonstrated that a primary culture of cryopreserved hepatocytes from chimeric mice with humanized liver could be used for evaluating the induction of drug metabolizing enzymes in human. This in vitro method may be a useful method for screening the induction potency of new drug candidates on drug metabolizing enzymes.

Adolescent↗

PubMed2004

Expression of human cytochromes P450 in chimeric mice with humanized liver.

Recently, a chimeric mouse line in which the liver could be replaced by more than 80% with human hepatocytes was established in Japan. Because the chimeric mouse produces human albumin (hAlb), replacement by human hepatocytes could be estimated by the hAlb concentration in the blood of chimeric mice. In this study, we investigated human major cytochrome P450 (P450) in the livers of chimeric mice by mRNA, protein, and enzyme activity using real-time polymerase chain reaction, Western blot analysis, and high-performance liquid chromatography, respectively. Chimeric mice with humanized liver generated using hepatocytes from a Japanese and white donor were used. Human P450 mRNAs were expressed in the liver of chimeric mice, and major human P450 proteins such as CYP1A2, CYP2C9, and CYP3A4 were detected. The expression of P450 mRNA and protein was correlated with the hAlb concentration in the blood. The enzyme activities such as diclofenac 4'-hydroxylase activity, dexamethasone 6-hydroxylase activity, and coumarin 7-hydroxylase activity, activities that are specific to human P450 but not to murine P450, were increased in a hAlb concentration-dependent manner. The chimeric mice with nearly 90% replacement by human hepatocytes demonstrated almost the same protein contents of human P450s and drug-metabolizing enzyme activity as those of the donor. It was confirmed that genomic DNA from the livers of the chimeric mice and that from the liver of the donor exhibited the same genotype. In conclusion, the chimeric mice exhibited a similarly efficient capacity of drug metabolism as humans, suggesting that they could be a useful animal model for drug development.

Alleles↗

PubMedDate not supplied

Total intraoperative enteroscopy using a colonoscope for detecting the bleeding point.

We report a case of bleeding in the small intestine of a 59-year-old man that was successfully diagnosed and treated by total intraoperative enteroscopy. The patient was admitted to our hospital because of gastrointestinal bleeding. Gastroscopy, colonoscopy and mesenteric arteriography could not identify the bleeding point. Technetium-99m-labeled red blood cell scintigraphy suggested bleeding from the small intestine but could not reveal the precise lesion. As the patient presented melena and went into a state of shock, we performed emergency laparotomy with total intraoperative enteroscopy using a colonoscope. A small ulceration was found at the jejunum, and subsequently partial resection of the jejunum was performed. The lesion was diagnosed histopathologically as angiodysplasia. The patient recovered uneventfully and was discharged on the 24th postoperative day. Bleeding in the small intestine is rare and difficult to diagnose but it sometimes induces a severe condition. Total intraoperative enteroscopy using a colonoscope is effective for detecting the bleeding point in the small intestine and can be performed at most centers without special fiberscopes and techniques.

Angiodysplasia↗