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Biomedical subjects

Y Horie

Publications and source records attributed to Y Horie.

At least 19 recordsLinked to original sources
PubMed1999

Anti-inflammatory drugs and endothelial cell adhesion molecule expression in murine vascular beds.

BACKGROUND: Inflammatory bowel diseases (IBD) are characterised by an intense infiltration of leucocytes that is mediated by adhesion molecules expressed on the surface of activated endothelial cells. AIMS: To determine whether drugs used in the treatment of IBD, specifically dexamethasone (DEX), 5-aminosalicylic acid (5-ASA), methotrexate (MTX), and 6-mercaptopurine (6-MP), alter the expression of endothelial cell adhesion molecules (ECAMs). METHODS: The expression of P-selectin, E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular CAM 1 (VCAM-1) in different vascular beds of C57Bl/6J mice was measured using the dual radiolabelled monoclonal antibody technique. RESULTS: Lipopolysaccharide (LPS) elicited a profound increase in the expression of all ECAMs in the mesentery, small intestine, caecum, and distal colon. The LPS induced increase in CAM expression was not significantly affected by prior treatment with either MTX or 6-MP. However, pretreatment with either DEX or 5-ASA significantly attenuated LPS induced increases in expression of P- and E-selectin, and VCAM-1 in the majority of tissues evaluated. DEX also blunted the LPS induced increase in ICAM-1 expression in the caecum and distal colon. DEX, but not 5-ASA, largely abolished the rise in plasma tumour necrosis factor alpha elicited by LPS. CONCLUSIONS: These findings suggest that DEX and 5-ASA may exert their beneficial therapeutic action in IBD, at least in part, by inhibiting the expression of ECAMs which mediate leucocyte adhesion and transmigration in the microvasculature.

Animals↗
PubMed1998

Transgenic mice with increased copper/zinc-superoxide dismutase activity are resistant to hepatic leukostasis and capillary no-reflow after gut ischemia/reperfusion.

The objectives of this study were to (1) determine whether transgenic (Tg) mice overexpressing copper/zinc-superoxide dismutase (CuZn-SOD) are protected from the deleterious effects of gut ischemia/reperfusion (I/R) and (2) compare the effectiveness of Tg SOD overexpression in attenuating I/R injury to intravascularly administered CuZn-SOD or manganese (Mn)-SOD. The accumulation of fluorescently labeled leukocytes and number of nonperfused sinusoids were monitored by intravital microscopy in livers of wild-type mice (C57BL/6), CuZn-SOD Tg mice, and wild-type mice receiving either CuZn-SOD or Mn-SOD. All parameters were measured for 1 hour after release of the occluded (for 15 minutes) superior mesenteric artery. Gut I/R in wild-type mice led to an increased number of stationary leukocytes, while reducing the number of perfused sinusoids (capillary no-reflow). All of these responses were significantly blunted in CuZn-SOD Tg mice, with a corresponding attenuation of liver enzyme release into plasma. Exogenously administered SOD had little or no effect on gut I/R-induced leukostasis or capillary no-reflow in the liver. These observations suggest a role for superoxide in gut I/R-induced leukostasis and hypoxic stress in the liver. Furthermore, the findings suggest that cellular localization of SOD activity is an important determinant of the protective actions of this enzyme in experimental models of I/R injury.

Analysis of Variance↗
PubMed1998

No Mycobacterium paratuberculosis detected in intestinal tissue, including Peyer's patches and lymph follicles, of Crohn's disease.

To clarify the etiologic significance of Mycobacterium paratuberculosis in Crohn's disease, we investigated whether M. paratuberculosis was detected in intestinal tissues, including Peyer's patches, where M. paratuberculosis invades, and colonic lymph follicles, where early lesions appear. Fifty-one samples of intestinal tissues, either therapeutically resected or biopsied, including 34 specimens from 30 patients with Crohn's disease, were studied. Four Peyer's patches and eight lymph follicles were included in the intestinal tissue samples of Crohn's disease. They were visualized by acetic acid fixation. DNA extracted from intestinal tissues by proteinase K treatment was used for nested polymerase chain reaction (PCR) for detection of IS900, which is specific for M. paratuberculosis. PCR products were analyzed by agarose gel electrophoresis and subsequent Southern blot analysis. Our amplification system could detect 7.5 fg of M. paratuberculosis DNA. None of the tissue samples showed positive IS900 amplification, whereas they all showed amplification of the positive control human leukocyte antigen (HLA)-DQA DNA. Spiked experiments of tissue samples with M. paratuberculosis demonstrated that inhibitors of IS900 amplification were not present in the samples. Our study does not support the etiologic significance of M. paratuberculosis in Crohn's disease.

Adolescent↗
PubMed1998

Listeria monocytogenes in Crohn's disease.

BACKGROUND: In an immunohistochemical study a higher rate of reactivity of intestinal tissues to the antibody against Listeria monocytogenes was reported in Crohn's disease as compared with controls. METHODS: Seventy-six intestinal tissues, either therapeutically resected or biopsied, from 31 patients with Crohn's disease, 20 with ulcerative colitis, and 21 with non-inflammatory bowel disease were studied. DNA extracted from intestinal tissues by proteinase K treatment was used for nested polymerase chain reaction (PCR), using two sets of primers. PCR products were analyzed with agarose gel electrophoresis and subsequent Southern blot analysis. RESULTS: Our amplification system could detect 9 pg of L. monocytogenes DNA. L. monocytogenes was detected in only one sample, that from a patient with ulcerative colitis. CONCLUSIONS: Our study does not support the etiologic significance of L. monocytogenes in Crohn's disease.

Adult↗
PubMed1998

Simple electrocardiographic criteria for identifying the site of origin of focal right atrial tachycardia.

UNLABELLED: To construct an algorithm for identifying the precise site of origin of focal right atrial tachycardia (RAT), we analyzed the P wave configuration in 32 patients with RAT who underwent successful radiofrequency catheter ablation. The RA was divided into three areas in the left anterior oblique view: superolateral, inferolateral, and inferomedial. There were 17 RATs arising from the crista terminalis (CT-AT), 12 from the tricuspid annulus (TA-AT), and 3 from the septum away from the TA (Sep-AT). A negative P wave in lead aVR identified CT-AT with a sensitivity (sens) of 100% and a specificity (spec) of 93%. In CT-ATs, positive P waves in the inferior leads differentiated superolateral AT from inferolateral AT with a sens of 86% and a spec of 100%. In any type of AT with inferomedial or inferolateral foci, the P wave deflections in at least one of the inferior leads was negative, and negative P waves in leads V5 and V6 identified inferomedial AT with a sens of 92% and a spec of 100%. In ATs near the apex of Koch's triangle, the P wave duration in the inferior leads was shorter than during sinus rhythm. CONCLUSIONS: (1) the P wave configuration in lead aVR can easily differentiate CT-AT from TA-AT and Sep-AT; (2) the P wave configuration in the inferior leads helps to determine a superior versus inferior origin in any type of AT; (3) in inferior AT, the P wave polarity in leads V5 and V6 is useful in determining a lateral versus medial origin; (4) this algorithm can predict accurately the origin of AT.

Algorithms↗
PubMed1998

Nitric oxide modulates gut ischemia-reperfusion-induced P-selectin expression in murine liver.

Reperfusion of ischemic intestine is associated with P-selectin-dependent adhesion of leukocytes in the liver microcirculation. The objective of this study was to define the contribution of nitric oxide (NO) to the enhanced P-selectin expression and increased leukocyte rolling elicited by gut ischemia-reperfusion (I/R). Leukocyte rolling (monitored by intravital microscopy) in the terminal hepatic venules (THV) and P-selectin expression (measured using the dual-radiolabeled monoclonal antibody technique) were determined in mice after 15 min of superior mesenteric artery occlusion and 30 min of reperfusion. After 30 min of reperfusion, P-selectin expression was significantly increased in the liver, intestine, and lung, with a corresponding increase in the number of rolling leukocytes (in THV). The NO synthase inhibitor NG-monomethyl-L-arginine exaggerated the gut I/R-induced increases in both rolling leukocytes and P-selectin expression (in liver and intestine), responses that were not detected with coadministration of L-arginine or in P-selectin-deficient mice. The NO donor diethylenetriamine/NO and L-arginine were both effective in attenuating the gut I/R-induced increases in rolling leukocytes (in THV) and P-selectin expression (in liver, intestine, and lung). These findings indicate that NO modulates gut I/R-induced recruitment of rolling leukocytes in THV via an action on P-selectin expression.

Animals↗
PubMed1998

Superior sagittal sinus thrombosis associated with primary antiphospholipid syndrome--case report.

A 36-year-old female with a history of recurrent pregnancy loss experienced sudden onset of disturbance in consciousness, with right hemiparesis and total aphasia. Computed tomography revealed a massive hemorrhage in the left frontal lobe, and angiography showed occlusion of the anterior two-thirds of the superior sagittal sinus. Laboratory investigations detected the presence of lupus anticoagulant, elevation of the anticardiolipin beta 2-glycoprotein I complex antibody level, and a decreased protein S activity level. There were no underlying conditions, such as connective tissue disorders, malignancies, infectious diseases, and drug-induced disorders, so the diagnosis was primary antiphospholipid syndrome. Primary antiphospholipid syndrome should be considered in the evaluation of patients with "idiopathic" or "primary" sinus and cerebral venous thrombosis.

Adult↗
PubMed1998

Induction of major histocompatibility complex class II antigens on human colonic epithelium by interferon-gamma, tumor necrosis factor-alpha, and interleukin-2.

Class II antigens are strongly expressed on the inflamed colonic epithelium in inflammatory bowel disease. However, the mechanism of this epithelial class II antigen induction is not fully understood. Increased activities of interferon (IFN)gamma, tumor necrosis factor (TNF)alpha, and interleukin (IL)2 have been shown in the inflamed mucosa of inflammatory bowel disease. Therefore, we studied whether these cytokines could induce class II antigens on the human colonic epithelium. By an organ culture technique, 284 normal colonic biopsy specimens obtained from 49 individuals were cultured in media containing different concentrations of cytokines with/without anti-IFNgamma R antibody. Colonic epithelial class II antigens were identified by the indirect immunoperoxidase staining method with anti-human leukocyte antigen (HLA)-DR, DP, and DQ monoclonal antibodies. IFNgamma, TNFalpha, and IL2 induced epithelial class II antigens in 16 of 16 cases (100%), 2 of 16 cases (12.5%), and 6 of 17 cases (35%), respectively. Epithelial class II antigen expression in response to TNFalpha was induced via IFNgamma but not via IL2. This is the first demonstration that: (i) the induction of class II antigens on the colonic epithelium in response to TNFalpha is mediated via IFNgamma, and (ii) that IL2 induces class II antigens.

Epithelial Cells↗
PubMed1998

Mutation in the exon 10 (R173W) of the hydroxymethylbilane synthase gene in two unrelated Japanese families with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an inherited disorder characterized by a deficiency of hydroxymethylbilane synthase (EC 4.3.1.8.; HMBS), the third enzyme in the heme biosynthetic pathway. To date, 113 different HMBS gene mutations have been reported in the world. However, there were a few reports of the gene mutations in the Japanese AIP patients. We studied the gene mutation in two unrelated AIP families in the San-in district, a local area of Western Japan. The overlapping 6 fragments of the HMBS gene, amplified by the reverse transcript-polymerase chain reaction, were analyzed by the single-strand conformation polymorphism with silver staining technique. The abnormal fragment from a member of one family was sequenced to detect the C to T substitution at 517 nucleic acid position of cDNA, which led to a missense mutation of arginine to tryptophan exchange at an amino acid level (R173W). This mutation located in exon 10 created a new site of the MSP 1 restriction endonuclease and was screened by the amplified fragment of exon 10 from genomic DNA with the MSP 1 digestion. The mutation was detected totally in three members of the family and interestingly also in two patients of an unrelated family. This mutation has been reported widely in the world independently, such as in a Swedish, a Canadian, a Finnish, and a French family, but is the first in Japanese patients. The screening method for this mutation is useful for diagnosis in Japanese AIP patients.

Adult↗
PubMed1997

Induction of megamitochondria by some chemicals inducing oxidative stress in primary cultured rat hepatocytes.

Effects of hydrazine, hydrogen peroxide and bromobenzene, inducers of free radicals, and those of erythromycin and cycloheximide, inhibitors of protein synthesis on structural changes of mitochondria in primary monolayer culture of rat hepatocytes were examined using laser confocal microscope and electron microscope. After 22 h of incubation of hepatocytes with 0.2 mM hydrogen peroxide or 10 microg ml-1 of erythromycin, mitochondria became extremely enlarged. Mitochondria of hepatocytes isolated from control rats became slightly to moderately enlarged in the presence of 2 mM hydrazine, while those of hepatocytes isolated from phenobarbital-pretreated animals became extremely enlarged in the presence of 2 mM hydrazine. Cycloheximide (0.5-10.0 microg ml-1) and bromobenzene (0.1-1.0 mM) failed to induce structural changes of mitochondria. The level of cytochrome P-450 in freshly prepared hepatocytes from phenobarbital-treated rats was 2.5 times higher than that from the control rats, and remained about three times higher than the latter after 22 h of incubation with 2 mM hydrazine. The level of malondialdehyde was invariably elevated when megamitochondria were induced. These results may suggest that oxidative stress is intimately related to the mechanism of the formation of megamitochondria and that the inhibition of cytoplasmic protein synthesis seems not to contribute the phenomenon. However, the detailed mechanism by which free radicals may induce megamitochondria remains to be elucidated.

Animals↗
PubMed1997

Lymphocytes mediate TNF-alpha-induced endothelial cell adhesion molecule expression: studies on SCID and RAG-1 mutant mice.

TNF-alpha is known to elicit a rapid increase in the expression of specific endothelial cell adhesion molecules (ECAMs) within different vascular beds. The aim of this study was to determine whether lymphocytes contribute to the increased ECAM expression elicited by TNF-alpha. A dual radiolabeled mAb technique was used to quantify constitutive and TNF-alpha-induced expression of ICAM-1, VCAM-1, E-selectin, and P-selectin in different vascular beds (lung, heart, stomach, mesentery, small intestine, large intestine, and muscle) in wild-type and SCID mice. In reconstitution experiments, either whole splenocytes, T cell-enriched splenocytes, or B cell-enriched splenocytes were injected into SCID mice 48 h before TNF-alpha administration. Although the constitutive expression of ECAMs differed only slightly between wild-type and SCID mice, TNF-alpha-induced ECAM expression was markedly blunted in SCID mice compared with wild-type mice. This blunted response to TNF-alpha was also demonstrated for VCAM-1 in recombination activating gene (RAG)-1 mutant mice. Reconstitution studies revealed that administration of 50 x 10(6) splenocytes in SCID mice at 48 h before cytokine treatment restored the TNF-alpha-induced expression of VCAM-1 to levels normally observed in wild-type mice. Reconstitution with T cell- but not B cell-enriched splenocytes, also restored the TNF-alpha-induced expression of VCAM-1 in SCID mice to wild-type levels. These results implicate circulating T lymphocytes as modulators of the increased ECAM expression elicited by TNF-alpha.

Animals↗
PubMed1997

Hepatic leukostasis and hypoxic stress in adhesion molecule-deficient mice after gut ischemia/reperfusion.

The concept that leukocyte-endothelial cell adhesion (LECA) is a major determinant of the tissue injury elicited by ischemia/reperfusion (I/R) is largely based on studies employing adhesion molecule-specific monoclonal antibodies. The objective of this study was to assess the contribution of LECA to I/R injury using mutant mice (all on a C57B1 background) that are deficient in either intracellular adhesion molecule-1, P-selectin, or CD11/CD18. The accumulation of fluorescently labeled leukocytes and the number of nonperfused sinusoids in livers of control and adhesion molecule-deficient mice were monitored by intravital microscopy for 1 h after release of the occluded (for 15 min) superior mesenteric artery. Autofluorescence of pyridine nucleotide (NADH) was measured as an indicator of mitochondrial O2 consumption and redox status. The number of stationary leukocytes in the liver after gut I/R was significantly elevated compared with baseline values in C57B1 (control) mice. Autofluorescence of NADH was also significantly increased (indicating hypoxia) after I/R in these mice, especially in the pericentral region. Intercellular adhesion molecule-1-, CD11/CD18-, and P-selectin-deficient mice all exhibited a blunted leukosequestration response to I/R and smaller increments in nonperfused sinusoids, relative to C57B1 mice. All adhesion molecule-deficient mice also exhibited an attenuated increment in NADH autofluorescence in the pericentral region, relative to control mice. These results from adhesion molecule-deficient mice provide additional support for the view that LECA is an important determinant of the liver dysfunction induced by gut I/R.

Animals↗
PubMed1997

Role of Kupffer cells in gut ischemia/reperfusion-induced hepatic microvascular dysfunction in mice.

Kupffer cells (KCs) have been implicated in the leukocyte recruitment and microvascular dysfunction associated with liver inflammation. The overall objective of this study was to assess the role of KCs in the leukocyte adhesion and oxidative stress elicited in the liver by gut ischemia/reperfusion (I/R). The accumulation of rhodamine-6G-labeled leukocytes and the number of nonperfused sinusoids (NPS) were monitored (by intravital microscopy) in mouse liver for 1 hour after a 15-minute period of normothermic intestinal ischemia. Autofluorescence of pyridine nucleotide [NAD(P)H] was measured as an index of mitochondrial O2 consumption and redox status. Leukostasis, as well as increases in NPS and NAD(P)H autofluorescence (indicating hypoxia), were observed in the liver at 60 minutes after gut I/R. Pretreatment with gadolinium chloride (GdCl3), which reduces KC function, attenuated the liver leukostasis and NPS elicited by gut I/R. The platelet activating factor (PAF) antagonist, WEB2086, and a tumor necrosis factor (TNF)-alpha-specific antibody were also effective in attenuating the gut I/R-induced leukostasis and NAD(P)H autofluorescence. The findings of this study suggest that KCs play an important role in mediating the leukocyte recruitment, impaired sinusoidal perfusion, and tissue hypoxia elicited in the liver after gut I/R. These KC-mediated responses appear to involve the participation of both PAF and TNF-alpha.

Alanine Transaminase↗
PubMed1997

Crohn's disease associated with renal amyloidosis successfully treated with an elemental diet.

We report a case of Crohn's disease associated with nephrotic syndrome due to renal amyloidosis in a 21-year-old man in whom remission of both Crohn's disease and the nephrotic syndrome has been maintained with an elemental diet. The patient developed toxic megacolon and nephrotic syndrome due to renal amyloidosis. Intensive intravenous prednisolone therapy with total parenteral nutrition was dramatically effective in treating the toxic megacolon and inducing remission in Crohn's disease and afterward, remission of the nephrotic syndrome. Remission of both conditions has been maintained for more than 2 years with the elemental diet. To our knowledge, this is the first confirmed case of Crohn's disease complicated with renal amyloidosis in which only slight proteinuria (below 0.3 g/day) was shown with an elemental diet used for a long period.

Adult↗
PubMed1997

Three cases of familial ulcerative colitis--in a mother and two of her sons.

A pedigree of familial ulcerative colitis with their HLA haplotypes is reported. The mother and two children, the eldest and second of three sons were affected. The mother developed proctitis at age 35, and the lesion extended to the entire colon at the time of a relapse. The two sons developed ulcerative colitis in a similar fashion; total colitis, of moderate severity, developing at age 16 in both. The analysis of HLA haplotypes of all five family members suggested that the HLA responsible for ulcerative colitis in this family was not HLA B, C, or DR, but Aw24 and DQw1. The third son had the same HLA haplotype as the second son, and it was presumed that he would develop ulcerative colitis in the future. These cases, together with other cases of familial ulcerative colitis indicate that Aw24 and DQw1 are critical phenotypes for ulcerative colitis in Japan.

Adolescent↗
PubMed1997

Effect of lipopolysaccharides on erythrocyte flow velocity in rat liver.

Although endotoxin exacerbates hepatic microcirculatory disturbance, little is known of the way in which it acts on the hepatic microcirculation. We measured endotoxin-induced changes in hepatic microcirculation and investigated the effect of endotoxin on hepatic microcirculation in rats. After male Wistar rats were anesthetized, a lobe of the liver was observed with an inverted intravital microscope. Erythrocytes (RBC) were labeled with fluorescein isothiocyanate (FITC) and injected. The flow velocity (FV) of FITC-RBC in sinusoids was measured with an off-line velocimeter. Portal pressure (PP) and mean arterial pressure (MAP) were measured with a catheter cannulated in the portal vein and the left carotid artery, respectively. After a small dose (1 mg/kg) of endotoxin had been administered intravenously, FV decreased and PP increased gradually after 30 min. MAP showed no significant change, except for an initial decrease. However, when 5 mg/kg of endotoxin was administered, FV and PP increased, with a peak at 10 min, which was not observed with the small dose. In the late phase, FV decreased and PP increased, as was seen with the small dose. Endotoxin increased serum aspartate aminotransferase and lactate dehydrogenase activities. These results suggest that endotoxin induces hepatic microcirculatory disturbance, which may cause liver injury.

Alanine Transaminase↗
PubMed1997

Metastatic Crohn's disease involving the penis.

Metastatic Crohn's disease is a rare complication in Crohn's disease and there have been only several cases of metastatic Crohn's disease involving the penis. We report one such case. A 22-year-old male student developed anal pain and alternative constipation and diarrhea in December, 1985, followed by diarrhea and lower abdominal pain in January, 1986. He was diagnosed as having Crohn's disease of ileocolitis type. He was admitted to our hospital in July, 1987 because of exacerbation of Crohn's disease. He had anal tags. Soon after admission, two red swollen lesions with central ulcer and erosions were demonstrated at the eversion of the foreskin adjacent to coronal sulcus. Histology of the lesions revealed granulomas with epithelioid cells and giant cells. The lesion responded to a topical steroid. Eight cases of metastatic Crohn's disease involving the penis are briefly reviewed.

Adult↗