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Biomedical subjects

Y Horie

Publications and source records attributed to Y Horie.

At least 55 records · Page 3Linked to original sources

Role of nitric oxide in endotoxin-induced hepatic microvascular dysfunction in rats chronically fed ethanol.

BACKGROUND: Nitric oxide (NO) appears to be involved in the pathogenesis of endotoxin-induced liver injury. However, little is known about how NO acts on the hepatic microcirculation, especially in alcohol-fed animals. We examined the roles of NO in endotoxin-induced hepatic microvascular dysfunction in control and ethanol-fed rats. METHODS: One lobe of the liver was observed with an intravital microscope. Flow velocity of fluorescein isothiocyanate-labeled erythrocytes in sinusoids was measured with an off-line velocimeter. Portal pressure and mean arterial pressure also were measured. RESULTS: After administration of endotoxin to control, the flow velocity decreased after 30 min. Portal pressure increased after 45 min. However, in ethanol-fed rats, both the flow velocity and portal pressure temporarily increased in the early phase. Thereafter, the flow velocity decreased and portal pressure increased. At 30 min after administration of the endotoxin, pretreatment with 10 mg/kg of an NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), enhanced the endotoxin-induced decrease in the velocity of erythrocytes in the midzonal region of both control and ethanol-fed rats. Although 0.5 mg/kg of L-NMMA enhanced the endotoxin-induced reduction of erythrocyte velocity in the midzonal region of ethanol-fed rats, L-NMMA enhanced the endotoxin-induced reduction of erythrocyte velocity in the pericentral region of control rats. At 60 min after the endotoxin administration, L-NMMA did not affect the endotoxin-induced decrease of erythrocyte velocity in either control or ethanol-fed rats. Although 10 mg/kg of L-NMMA increased mean arterial pressure both in control and ethanol-fed rats, 0.5 mg/kg of L-NMMA did not change mean arterial pressure in either control or ethanol-fed rats. CONCLUSIONS: These results suggest that NO is involved in endotoxin-induced hepatic microvascular dysfunction, which may contribute to the sequential liver injury, especially in alcohol-fed animals.

Animals↗

[Anatomical variations of Koch's triangle in patients with atrioventricular nodal reentrant tachycardia: usefulness of the left anterior oblique view].

OBJECTIVES: Several anatomical distances of Koch's triangle including the ablation site were measured and correlated with clinical features and slow pathway potentials in patients with atrioventricular nodal reentrant tachycardia to improve the avoidance of complete atrioventricular block. METHODS: Sixty consecutive patients (24 males and 36 females, mean age 47 +/- 12 years) with successfully eliminated atrioventricular nodal reentrat tachycardia were studied. The distances between the His-bundle area and the base of the coronary sinus ostium (Dis HBE-CS) and the distances between the successful ablation site and the base of the CS ostium (Dis SP-CS) were measured in both right anterior oblique and left anterior oblique views, and used to define the dimensions of Koch's triangle. The relationship between the slow pathway potentials at the successful ablation site and anatomical distances was estimated. RESULTS: The Dis HBE-CS in the right anterior oblique view was negatively correlated with patient age (r = -0.759, p < 0.001) and body mass index. In contrast, the Dis HBE-CS in the left anterior oblique view had only weak correlations with patient age and body mass index. The mechanism of the short Dis HBE-CS in the right anterior oblique view in elderly obese patients tended to change the shape of the tricuspid annulus from a circle to an ellipse, compressed by the ascending aorta and diaphragma. The Dis SP-CS in the right anterior oblique view associated with the low frequency potential (Haissaguerre's slow pathway potential) was longer than that associated with the high frequency potential (Jackman's slow pathway potential). CONCLUSIONS: Elderly obese patients had shorter distances between the proximal His-bundle area and the base of the coronary sinus ostium in the right anterior oblique view. In contrast, the Dis HBE-CS in the left anterior oblique view was not so narrow. Therefore, slow pathway ablation can be performed safely without complicated complete atrioventricular block, using both the slow pathway potential guided approach and the anatomical guided approach, especially in the left anterior oblique view.

Adolescent↗

Factors affecting the volume of umbilical cord blood collections.

OBJECTIVE: Our purpose was to find factors that may help increase the number of the HSC (CD34+) collected from umbilical cord blood for transplantation. STUDY DESIGN: We assessed the effect of cesarean sections and vaginal deliveries on the volume of the umbilical cord blood collected from 155 healthy term neonates retrospectively. RESULTS: The volume of umbilical cord blood obtained in 29 cesarean deliveries was 103.9 +/- 33.6 ml compared with 84.2 +/- 25.3 ml collected in 126 vaginal deliveries. Although the percentage of CD34+ cells was comparable in both groups, the absolute number of CD34+ cells was significantly higher in the cesarean section group because of the larger volume collected. CONCLUSIONS: Cesarean sections may allow collection of significantly increased volumes of umbilical cord blood and numbers of CD34+ cells compared to vaginal deliveries.

Adult↗

Diarrhea induction by rotavirus NSP4 in the homologous mouse model system.

Comparison of the NSP4 amino acid sequences from 31 strains of mammalian rotaviruses revealed the presence of four distinct NSP4 alleles; i.e., the Wa, KUN, AU-1, and EW alleles. The EW allele consists only of NSP4s from murine rotavirus strains and is divergent from other NSP4 alleles from the evolutionary perspective. There have been conflicting reports regarding the enterotoxigenic activity of NSP4 in the mouse model system; heterologous simian and porcine rotavirus NSP4s function as an enterotoxin in mice, while a homologous EC NSP4 does not play a dominant role as an enterotoxin in the cystic fibrosis conductance regulator knockout mice. To further examine the enterotoxigenic activity of NSP4, we expressed in Escherichia coli a recombinant protein consisting of glutathione S-transferase and amino acid residues 86-175 of the EW NSP4. We found that this fusion protein caused diarrhea in the majority (8/14) of 5- to 6-day-old CD1 mice. This study confirmed and extended that group A rotavirus NSP4s were able to induce diarrhea in neonatal mice and had an enterotoxigenic activity.

Alleles↗

A splicing mutation in the hydroxymethylbilane synthase gene in a Japanese family with acute intermittent porphyria.

OBJECTIVES: Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease caused by a decreased activity of hydroxymethylbilane synthase (HMBS). As far as the gene abnormalities of the HMBS, many different mutations have been reported. In this work, we investigated the presence of mutations in a Japanese family with AIP. DESIGN AND METHODS: A 44-year-old Japanese male and nine members of his family were investigated. All of them were screened by traditional biochemical markers. Mutational analysis was performed using polymerase chain reaction-single strand conformation polymorphism method followed by DNA sequencing. A reliable restriction enzyme cleavage assay was established for the pedigree analysis. RESULTS: The mutation was a splicing mutation, a C to G transversion at position -3 of the acceptor site of intron 11 of the HMBS gene, resulting in the exon 12 skipping. The patient is heterozygous for the mutation, and his father appeared to be the source of the mutant allele. This mutation created a new cleavage site of the Nla III restriction enzyme and could be screened by a amplified fragment from genomic DNA with digestion. Using this cleavage assay, an asymptomatic carrier in the family was definitively identified. CONCLUSIONS: This mutation was first found among Japanese AIP patients, but happened to be the same as reported previously from Europe. A similarity of gene abnormality may suggest that those European and Japanese AIP families have a common ancestor. Molecular investigations on the family members should be applied not only for more accurate diagnosis, but also for understanding the molecular genetic heterogeneity underlying this dominantly inherited enzymopathy.

Adult↗

Artificial insemination using trypsin-treated sperm in the silkworm, Bombyx mori.

A new method was developed for artificial insemination of the silkworm. Virgin females artificially inseminated by this method oviposited fertilized eggs at a rate almost similar to that of females mated with males. Using inactive sperm collected from the seminal vesicles, we confirmed the previous finding by Omura, S., 1936a, Artificial insemination of Bombyx mori, Journal of Faculty of Agriculture, Hokkaido Imperial University 38, 135-150, and Omura, S., 1938, Studies of the reproductive system of the male of Bombyx mori II, Post-testicular organs and post-testicular behaviour of the spermatozoa, Journal of Faculty of Agriculture, Hokkaido Imperial University 40, 129-170, that the sperm of B. mori requires the secretion of the glandula prostatica for activation. Sperm also could be activated by trypsin. At an optimal concentration, 0.3 &mgr;g trypsin/ml in 50% semen solution, the fertilization rate as well as the number of eggs oviposited was almost equivalent to that obtained in normally mated moths. These results may contribute not only to basic studies on fertilization and reproduction in Lepidoptera but also to the development of long-term preservation of genetic resources by using cryopreserved sperm of B. mori and other Lepidoptera insects.

Journal Article↗

Pseudovascular squamous cell carcinoma of the uterine cervix: a lesion that may simulate an angiosarcoma.

A case of pseudovascular squamous cell carcinoma in the uterine cervix of a 64-year-old woman was examined. Histologically, the lesion consisted of atypical, large, non-keratinizing squamous cells that exhibited not only acantholytic changes but also pseudovascular changes. Immunohistochemically, these tumor cells were positive for cytokeratin, epithelial membrane antigen and carcinoembryonic antigen, but none of them were positive for Factor VIII-related antigen or CD34. To our knowledge, pseudovascular carcinoma of the uterine cervix has not been described in the literature. Pathologists should be aware of this unusual form of cervical squamous cell carcinoma, particularly in the differential diagnosis of angiosarcoma.

Biomarkers, Tumor↗

Juvenile hemangioma (infantile hemangioendothelioma) of the parotid gland associated with cytomegalovirus infection.

A case of parotid juvenile hemangioma associated with cytomegalovirus infection is reported. A growing lobulated mass, measuring 30 x 20 mm, was extirpated from the left parotid gland in a 4-month-old male. Histologically, the tumor consisted of cellular plump endothelial cells, stromal cells and residual ductal and acinar elements of the parotid gland. Numerous intranuclear and cytoplasmic inclusions were observed in the ductal cells of the whole parenchymal part of the parotid gland and the residual part of the tumor. Immunohistochemically, some nuclei of the ductal cells possessing these inclusions were positive for the anti-cytomegalovirus antibody but there were no positive findings in the endothelial or stromal cells. Although the present lesion may suggest that the human cytomegalovirus plays some role in the etiology of juvenile hemangioma, it is unknown whether or not this association is incidental.

Antibodies, Viral↗

Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome.

Dubin-Johnson syndrome (DJS) is an autosomal recessive disease characterized by conjugated hyperbilirubinemia. Previous studies of the defects in the human canalicular multispecific organic anion transporter gene (MRP2/cMOAT) in patients with DJS have suggested that the gene defects are responsible for DJS. In this study, we determined the exon/intron structure of the human MRP2/cMOAT gene and further characterized mutations in patients with DJS. The human MRP2/cMOAT gene contains 32 exons, and it has a structure that is highly conserved with that of another ATP-binding-cassette gene, that for a multidrug resistance-associated protein. We then identified three mutations, including two novel ones. All mutations identified to date are in the cytoplasmic domain, which includes the two ATP-binding cassettes and the linker region, or adjacent putative transmembrane domain. Our results confirm that MRP2/cMOAT is the gene responsible for DJS. The finding that mutations are concentrated in the first ATP-binding-cassette domain strongly suggests that a disruption of this region is a critical route to loss of function.

ATP-Binding Cassette Transporters↗

Evidence for ethanol oxidation by Kupffer cells.

Ethanol oxidation in Kupffer cells was investigated by measuring 14C-acetate formation from 14C-ethanol, and the role of aldehyde dehydrogenase 2 (ALDH2) in this process was also examined. Formation of 14C-acetate from 20 mM of 14C-ethanol was significantly increased in medium-containing Kupffer cells (9,003 +/- 2,066 cpm/5 x 10(6) cells), compared with medium containing no cells (1,826 +/- 46 cpm, p < 0.01), or containing acid-killed Kupffer cells (1,629 +/- 210 cpm, p < 0.01). Ethanol formation was significantly attenuated when 20 and 200 microM cyanamide or 2 microM disulfiram were given. Reverse transcriptase-polymerase chain reaction demonstrated that Kupffer cells carry mRNA for ALDH2. These findings indicate that Kupffer cells can oxidize ethanol to acetate. ALDH2 may participate in this process, especially in the conversion of acetaldehyde to acetate.

Acetaldehyde↗

Isolation of a human rotavirus strain with a super-short RNA pattern and a new P2 subtype.

Super-short rotavirus strains that have a rearranged gene segment 11 are rarely found in humans, and only five isolates, all from Southeast Asia, have been described in the literature. We report the first isolation in Japan from an infant with severe diarrhea of a rotavirus possessing a super-short RNA pattern. This strain, designated AU19, had a G1 VP7 and is also the first isolate in Japan that possesses a P2[6] VP4. Furthermore, the P2[6] VP4 carried by AU19 was divergent in the hypervariable region of the amino acid sequence from the P2A[6] VP4s carried by asymptomatic neonatal strains or from the P2B[6] VP4 carried by porcine rotavirus strain Gottfried. Thus, AU19 is likely to represent a new VP4 subtype, which we propose to call P2C. Given the recent emergence of the P2[6] VP4s in India, Brazil, and the United States and the role of VP4 in protective immunity, further scrutiny is justified to see whether the emergence of the previously underrepresented P2[6] VP4 serotype is related to this new P2 subtype.

Base Sequence↗

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↗

Ischemia-reperfusion induced microvascular responses in LDL-receptor -/- mice.

The objective of this study was to determine whether the microvascular responses to ischemia and reperfusion (I/R) are altered in an animal model of atherosclerosis, the low-density lipoprotein-receptor knockout (LDLr -/-) mouse. Intravital video microscopy was used to monitor venular wall shear rate, leukocytes rolling velocity, the number of rolling, adherent and emigrated leukocytes, and albumin leakage in cremasteric postcapillary venules of wild-type (B6129) and LDLr -/- mice exposed to 60 min of ischemia and 60 min of reperfusion. The postcapillary venules of LDLr -/- mice exhibited two- to threefold larger increments in the number of adherent leukocytes and a more profound albumin leakage response to I/R than venules in wild-type mice. The exaggerated inflammatory responses noted in LDLr -/- mice placed on a normal diet were not exacerbated by a high-cholesterol diet. Treatment of LDLr -/- mice with either a platelet-activating factor (PAF) receptor antagonist (WEB-2086) or a monoclonal antibody (YN-1) against the endothelial cell adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), markedly attenuated the I/R-induced leukocyte adherence and albumin leakage. These findings indicate that atherogenic mice are more vulnerable to the deleterious microvascular effects of I/R and that PAF-mediated, ICAM-1-dependent leukocyte adhesion contributes to this exaggerated response to I/R.

Animals↗

Prognosis for pedunculated hepatocellular carcinoma.

We retrospectively compared the outcome of 13 patients at our institution and that of 163 reported cases of pedunculated hepatocellular carcinoma (HCC) with that of conventional HCC subdivided by tumor diameter (group A: less than 2 cm; group B: 2-5 cm, group C: more than 5 cm). The survival of patients with pedunculated HCC in the 163 reported cases was no different from that of group B, but less favorable than in group A (p < 0.01) and more favorable than in group C (p < 0.01). Among the 163 patients with pedunculated HCC, the 113 cases of surgically treated patients had higher survival than the 21 patients treated with transcatheter arterial embolization (n = 16) or transcatheter arterial infusion chemotherapy (n = 5) (p < 0.01) and than 29 conservatively treated patients (p < 0.001). A total of 70 patients out of 163 (42%) died within 1 year after diagnosis. Additionally, almost all cases of pedunculated HCC showed histologically moderately or poorly differentiated characteristics according to Edmondson and Stainer's classification or the WHO classification. These results suggest that pedunculated HCC has not a favorable prognosis if appropriate surgical resection has not been performed very early within a few months because of its rapid progressive nature.

Adult↗

Quantitative analysis of surface P-wave morphology in isthmus ablation for type 1 atrial flutter: differentiation between complete isthmus block and slow isthmus conduction.

Changes in P-wave morphology in inferior leads during atrial pacing at the margins of the carvo-tricuspid isthmus have been reported to be useful for predicting the creation of isthmus block in radiofrequency (RF) ablation of type I atrial flutter (AFL). However, it is not known whether these changes in P-wave morphology allow the clinician to differentiate between complete isthmus block and slow isthmus conduction. P-wave morphology during low lateral right atrial (LLRA) pacing, as well as during coronary sinus ostium (PCS) pacing, was evaluated prior to ablation, during slow isthmus conduction, and after complete isthmus block in 30 patients with AFL. Changes in P-wave morphology during LLRA pacing were not sufficient to differentiate between complete isthmus block and slow isthmus conduction. While changes in P-wave morphology in lead II from inverted to biphasic during PCS pacing were observed in both slow isthmus conduction and complete isthmus block, the ratio of the positive component to the total P-wave amplitude (P-wave ratio) was significantly different between slow isthmus conduction (20+/-17%) and complete isthmus block (40+/-11%) (P<0.0001). When the P-wave ratio in lead II during PCS pacing was more than 75% of the F-wave ratio in lead II during AFL, bilateral complete isthmus block was predicted with a sensitivity of 88%, a specificity of 71%, a positive predictive value of 75%, and a negative predictive value of 85%. These results indicate that a P-wave ratio greater than 20% or a P-wave ratio during PCS pacing greater than 75% of the F-wave ratio during AFL may predict a bidirectional complete isthmus block.

Aged↗

Neuroendocrine carcinoma of the posterior mediastinum: a possible primary lesion.

A paravertebral mass was noted in the posterior mediastinum in a 47-year-old man. Microscopically, the tumor showed solid and trabecular patterns and consisted of poorly differentiated atypical cells that often formed Flexner-Wintersteiner rosettelike glands. Immunohistochemically, the tumor cells expressed both epithelial and neuroendocrine markers, including cytokeratin (AE1/3), carcinoembryonic antigen, epithelial membrane antigen, neuron-specific enolase, chromogranin A, and synaptophysin, but were negative for CD99 (MIC2). Ultrastructurally, numerous desmosomes and neurosecretory granules were identified in the tumor cells. The present lesion was a primary neuroendocrine carcinoma of the posterior mediastinum-an unusual site for such a lesion.

Biomarkers, Tumor↗