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Biomedical subjects

I Hirata

Publications and source records attributed to I Hirata.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prostaglandin E2 inhibits lesion formation in dextran sodium sulphate-induced colitis in rats and reduces the levels of mucosal inflammatory cytokines.

Effects of rectally injected prostaglandin E2 (PGE2) in rats with dextran sodium sulphate (DSS)-induced colitis were investigated in terms of histopathology, local myeloperoxidase (MPO) activity, local mRNA expression of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and growth-regulated gene produced/cytokine-induced neutrophil chemoattractant (GRO/CINC)-1, and secretion of TNF-alpha and GRO/CINC-1. In animals with no PGE2 treatment, DSS-induced erosion and ulceration were particularly severe in the rectum and extended to the proximal colon. Neutrophil infiltration was characteristically present in the lesions and surrounding mucosa. MPO activity at lesion sites was increased. IL-1beta and GRO/CINC-1 mRNA expression was increased, while TNF-alpha mRNA expression was significantly decreased. GRO/CINC-1 secretion was increased but a similar elevation of TNF-alpha was not detected. In the PGE2-treated group, lesion formation was inhibited grossly and microscopically. Neutrophil infiltration and MPO activity in and around lesions were lessened. The reduction in TNF-alpha mRNA expression and secretion was not affected by PGE2. The expression of mRNA for IL-1beta and GRO/CINC-1 was reduced, as was the secretion of GRO/CINC-1. As mRNA expression and secretion of cytokines in lesions of non-PGE2-treated animals was similar to that reported in human ulcerative colitis, rectal injection of PGE2 may prove to be an effective therapy.

Animals↗
PubMed2000

Enprostil, a prostaglandin-E(2) analogue, inhibits interleukin-8 production of human colonic epithelial cell lines.

We previously reported that intracolonic administration of enprostil, a prostaglandin-E(2) (PGE(2)) analogue, had therapeutic effects on acute colitis induced in rodents by dextran sulfate sodium (DSS). In addition, production of growth-regulated gene product/cytokine-induced neutrophil chemoattractant-1 [GRO/CINC-1; an interleukin(IL)-8 like cytokine] was suppressed in the inflamed tissues. In the present study we used a human colon cancer cell line (HT-29) to investigate enprostil effects on the IL-8 production of intestinal epithelial cells stimulated by various stimulants. In a MTT assay, concentrations of enprostil >10(-5)M had cytotoxitic effects on HT-29 cells. Furthermore, 10(-6) M enprostil suppressed IL-8 production in HT-29 cells, SW620 and CaCo2 stimulated with interleukin-1 beta (IL-1 beta) or lipopolysaccharide (LPS), but did not suppress this response when cells were stimulated with tumour necrosis factor (TNF)-alpha. These results suggest that enprostil affects a point in the pathway between the IL-1 receptor or LPS receptor and nuclear factor-kappa B(NF-kappa B), without affecting the pathway between the TNF receptor and NF-kappa B, with the latter factor being required for the IL-8 gene transcription. The therapeutic effect of exogenous enprostil on DSS colitis may involve the inhibition of IL-8 production in colonic epithelial cells stimulated by IL-1 beta or LPS.

Colitis, Ulcerative↗
PubMed2000

Radiation enteritis: a rare complication of the transverse colon in uterine cancer.

Radiation therapy is a powerful method for the control of cancer. The utilization of abdominal or pelvic radiation has been extended, and the incidence of radiation enteritis appears to be increasing. The majority of the induced lesions is in the distal ileum, sigmoid colon, or rectum. Reported here is an unusual case of radiation enteritis which caused a severe sequelae of stricture in the transverse colon as a long-term effect of therapeutic irradiation for uterine cancer, and required a surgical resection.

Abdominal Pain↗
PubMed2000

Comparison of tests for fecal lactoferrin and fecal occult blood for colorectal diseases: a prospective pilot study.

OBJECTIVE: This prospective pilot study was conducted to compare the usefulness of measuring fecal lactoferrin (Lf) to that of fecal occult blood (FOB) test for detection of colorectal diseases. PATIENTS AND METHODS: The subjects were 351 patients who underwent colonoscopy. A fecal sample was obtained on the day before colonoscopy. Fecal Lf was measured by enzyme-linked immunosorbent assay. The FOB test was performed by combined assay (latex agglutination) of hemoglobin and transferrin. RESULTS: The specificities of the fecal Lf and FOB tests were the same (88.7%). For patients with colorectal cancer (13), colorectal polyp (69), ulcerative colitis (18), Crohn's disease (13), non-specific colitis (8), internal hemorrhoids (60), colon diverticulum (27), and miscellaneous diseases of the colon (10), the rates of positivity for fecal Lf were 7/13, 14/69, 12/18, 7/13, 4/8, 22/60, 8/27, and 6/10, respectively. The corresponding rates for FOB were 8/13, 12/69, 11/18, 4/13, 4/8, 9/60, 2/27, and 1/10. For patients with internal hemorrhoids, the rate of positivity for fecal Lf was significantly higher than that for FOB. In other disease groups, there was no significant difference in the rate of positivity between fecal Lf and FOB. CONCLUSION: These findings suggest that measurement of fecal Lf is as useful as FOB in detecting colorectal diseases.

Colonic Diseases↗
PubMed1999

A novel amino acid substitution at the receptor-binding site on the hemagglutinin of H3N2 influenza A viruses isolated from 6 cases with acute encephalopathy during the 1997-1998 season in Tokyo.

We analyzed the hemagglutinin (HA) genes of influenza A viruses consisting of 6 strains isolated from cerebrospinal fluids of patients with encephalopathy and 3 isolates from throat washes of patients without central nervous system symptoms during the 1997-1998 season in Tokyo. Aligned 9 amino acid sequences showed 7 common substitutions compared with A/Wuhan/359/95 (vaccine strain used in the season in Japan), which were allocated to three different antigenic sites on the H3 HA molecule. It is noted that a novel substitution at the receptor-binding site (Tyr-137 to Phe) was found exclusively in the isolates from the patients with encephalopathy.

Amino Acid Sequence↗
PubMed1999

First case of missense mutation (LDH-H:R171P) in exon 4 of the lactate dehydrogenase gene detected in a Japanese patient.

Complete deficiency of lactate dehydrogenase (LDH) subunit H was identified in a 41-year-old woman with paralysis of her left lower limb. The propositus had extremely low LDH activity and five of her family members had levels of LDH activity that ranged from lower than normal to normal level. A transversion mutation at codon 171 (CGC-->CCC), resulting in an Arg-->Pro substitution was identified in her DNA sequence. A new NruI restriction site was introduced into the polymerase chain reaction (PCR) product by PCR-primer introduced restriction analysis (PCR-PIRA) using a specific mismatched primer. Digestion with NruI revealed that the propositus and her mother were, respectively, homozygous and heterozygous for this mutation.

Adult↗
PubMed1999

Left gastric vein hemodynamics and variceal recurrence in patients undergoing prophylactic endoscopic ligation of high-risk esophageal varices.

BACKGROUND: Early recurrence of esophageal varices remains problematic after endoscopic variceal ligation. To evaluate the efficacy of prophylactic endoscopic ligation for esophageal varices at high risk for bleeding, the relationship between left gastric vein hemodynamics and variceal recurrence was investigated. METHODS: Thirty-five patients with cirrhosis underwent endoscopic variceal ligation. Angiography was performed in all patients before treatment and after eradication of varices to study left gastric vein hemodynamics. RESULTS: Before treatment, 12 patients had hepatopetal flow in the left gastric vein (type I), 17 had hepatofugal flow (type II), and 6 had hepatofugal flow with an extra-esophageal shunt (type III). In type I and III patients, the direction of blood flow in the left gastric vein did not change after eradication of varices. Type II patients showed bi-directional flow in the left gastric vein after treatment. Varices recurred in all but one type II patient and in one type I patient during follow-up (mean 36.7 months). The 2-year recurrence-free rate was higher in type I patients (p = 0.0001) and type III patients (p = 0.0002) than in type II patients. CONCLUSIONS: Prophylactic ligation seems to be a safe and useful procedure, especially in patients with type I or III hemodynamics in the left gastric vein before treatment.

Angiography, Digital Subtraction↗
PubMed1999

Overexpression of rck/p54, a DEAD box protein, in human colorectal tumours.

The RCK gene is a target of the t(11;14)(q23;q32) chromosomal translocation observed in human B-cell lymphoma, and the overexpression of its protein (rck/p54) by the translocation was shown to cause malignant transformation. The rck/p54 protein belongs to the DEAD box protein/RNA helicase family, which has a variety of functions such as translation initiation, pre-mRNA splicing and ribosome assembly. The expression of rck p54 in colorectal adenocarcinoma cells was examined by immunohistochemistry and Western blot analysis. The rck/p54 protein was found to be overexpressed in tumour tissues resected from 13 (50%) out of 26 cases of colorectal adenocarcinomas and two out of two (100%) cases of colonic severe dysplastic adenomas. In view of activities of rck/p54 determined in other tissue types, we suggest that rck/p54 may contribute to the cell proliferation and carcinogenesis at the translational level in the development of colorectal tumours.

Adenocarcinoma↗
PubMed1999

Inhibition of dextran sulphate sodium (DSS)-induced colitis in mice by intracolonically administered antibodies against adhesion molecules (endothelial leucocyte adhesion molecule-1 (ELAM-1) or intercellular adhesion molecule-1 (ICAM-1)).

We examined the effect of intracolonic administration of anti-adhesion molecule antibodies on DSS-induced colitis in mice. Immunohistochemical staining in mice with colitis showed increased expression of ELAM-1 and ICAM-1 on endothelial cells of vessels in the lamina propria and submucosa at sites of inflamed lesions. Intracolonic administration of anti-ELAM-1 or anti-ICAM-1 antibody decreased bloody stools, anaemia, and histologically evident damage, as well as myeloperoxidase activity and IL-1beta content. We concluded that adhesion molecule expression is important in the development of DSS-induced colitis in mice and that intracolonic administration of anti-adhesion molecule antibodies, especially anti-ELAM-1 antibody, effectively inhibits the colonic inflammation. Intracolonic administration of anti-adhesion molecule antibodies may show therapeutic promise in ulcerative colitis.

Animals↗
PubMed1999

Discrimination of cruzipain, the major cysteine proteinase of Trypanosoma cruzi, and mammalian cathepsins B and L, by a pH-inducible fluorogenic substrate of trypanosomal cysteine proteinases.

The substrate specificity of cruzipain, the major cysteine proteinase of Trypanosoma cruzi, was investigated using a series of dansyl-peptides based on the putative autoproteolytic sequence of the proteinase (VVG-GP) located at the hinge region between the catalytic domain and the C-terminal extension. Replacing Val with Pro at P2 in this sequence greatly improved the rate of cleavage by cruzipain. Tyr and Val residues are preferred at P3 by all cysteine proteinases whatever their origin, whereas only cruzipain and cathepsin L cleaved substrate with a His at that position. The combination of a Pro at P2 and His at P3 abolished cleavage by cathepsin L, so that only cruzipain was able to cleave the HPGGP peptide at the GG bond. A substrate with intramolecularly quenched fluorescence was raised on this sequence (Abz-HPGGPQ-EDDnp) which was also specifically cleaved by cruzipain (kcat/Km of 157 000 m-1. s-1) and by a homologous proteinase from Trypanosoma congolense. The pH activity profile of cruzipain on Abz-HPGGPQ-EDDnp showed a narrow peak with a maximum at pH 5.5 and no cleavage above pH 6.8, although trypanosomal cysteine proteinases remain active at basic pH. The lack of activity at neutral and basic pH was due to a decrease in kcat, while the Km remained essentially unchanged, demonstrating that the substrate still binds to the enzyme and therefore behaves as an inhibitor. Changing the substrate into an inhibitor depended on the deprotonation of the His residue in the substrate, as deduced from a comparison of the pH activity profile with that of a related, but uncharged, substrate. Abz-HPGGPQ-EDDnp also inhibited mammalian cathepsins B and L but was not cleaved by these proteinases at any pH. The importance of the His residue at P3 for cleavage by cruzipain was confirmed by substituting Lys for His at that position. The resulting peptide was not cleaved by cruzipain in spite of the presence of a positively charged group at P3, but still interacted with the enzyme. It was concluded that the presence of an imidazolium group at P3 was essential to endow the HPGGPQ sequence with the properties of a cruzipain substrate.

Animals↗
PubMed1999

Histologic and immunohistochemical analysis of early submucosal invasive carcinoma of the colon and rectum.

To investigate the development and progression of colorectal carcinoma, submucosal invasive carcinoma (SMC) with residual intramucosal neoplasm was studied histopathologically. Intramucosal neoplasm was confirmed by immunohistochemical staining against anti-alpha-smooth muscle actin antibody. Submucosal invasive carcinoma was classified into polypoid growth-type carcinoma (PGC) and non-polypoid growth-type carcinoma (NPGC), depending on the presence of intramucosal tumor proliferation. Tumors were > 15 mm in size in 78.2% of the PGC lesions studied, but the degree of submucosal invasion was minimal (invasion of the upper 500 microm of the submucosal layer) in 52.9% of the PGC lesions. Conversely, 64.4% of NPGC lesions were 15 mm in size and the degree of submucosal invasion was moderate or severe (involving the middle and deeper layer of the submucosa) for 72.9% of NPGC. In other words, lesions of NPGC were significantly smaller in size but showed deeper infiltration than PGC lesions. Furthermore, PGC was derived from intramucosal polypoid carcinoma (including carcinoma with adenoma) and was morphologically identical to polyp cancer as reported previously. However, NPGC was derived from the flat and/or depressed type of intramucosal carcinoma classified not as polyp type, but as the superficial type. Typical NPGC was, therefore, also of the superficial type. In addition, approximately 25% of PGC lesions were identified as having an adenoma-carcinoma sequence. There was no coexistence with adenoma in the NPGC lesions, suggesting de novo development. When the degree of histologic atypia in the two types of intramucosal carcinoma was compared, 74.7% of PGC lesions showed low-grade carcinoma, regardless of tumor size, while 62.7% of NPGC lesions showed high-grade carcinoma in the intramucosal lesion. Approximately 25% of carcinomas with low-grade atypia were positive for p53 (as were the high-grade lesions), but it was not expressed in the adenoma. Therefore, tumor development and the degree of invasion differed significantly between the two types of carcinoma.

Actins↗
PubMed1999

Balloon-occluded retrograde transvenous obliteration of high risk gastric fundal varices.

OBJECTIVE: Balloon-occluded retrograde transvenous obliteration is an effective new method for treating gastric fundal varices, but subsequent occurrence of esophageal varices creates a problem. The relationship between portal hemodynamics and the occurrence of esophageal varices after prophylactic balloon-occluded retrograde transvenous obliteration was investigated. METHODS: Ten cirrhotic patients considered to have high risk gastric fundal varices underwent angiography. Six patients showed a communication between blood flow in gastric wall vessels and that in the gastrorenal shunt (type I), whereas the others (type II) did not. Depending on the flow direction in the left gastric vein, the two groups were further divided into hepatopetal (a) and hepatofugal (b) subgroups. The therapeutic effect on portal hemodynamics and the relationship between pretreatment portal hemodynamics and posttreatment occurrence of esophageal varices were investigated. RESULTS: Fundal varices disappeared endoscopically in all 10 patients and the gastrorenal shunt was also occluded after the procedure. No patient showed worsening of liver function or systemic complications during follow-up. The increase in portal blood flow was more significant in type Ib patients than in the others. Esophageal varices occurred in all type I patients, and as to those in type Ib, high risk varices developed within 6 months after treatment. On the other hand, esophageal varices did not occur in type II patients. CONCLUSIONS: This procedure was effective for treating gastric fundal varices. However, type Ib patients are likely to develop high risk esophageal varices after occlusion of the gastrorenal shunt.

Adult↗
PubMed1999

Antineutrophil cytoplasmic antibodies in Japanese patients with inflammatory bowel disease: prevalence and recognition of putative antigens.

OBJECTIVE: Our aim was to investigate the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in Japanese patients with ulcerative colitis (UC) and Crohn's disease (CD), and the putative antigens recognized by perinuclear staining pattern ANCA (p-ANCA)-positive sera. METHODS: Sera from UC (n = 52) and CD (n = 43) patients, and from healthy controls (n = 74) were studied. The indirect immunofluorescence (IIF) method was used for the detection of ANCA and its binding pattern. p-ANCA-positive sera were studied further for putative antigens. ELISAs using lactoferrin (Lf), myeloperoxidase (MPO), and cathepsin G (Cat G) as antigens were performed. RESULTS: ANCA was positive in 40 of the 52 (76.9%) UC (p-ANCA in 33) and in 32 of the 43 (74.4%) CD (p-ANCA in 31) patients. UC and CD patients showed significantly higher titers of p-ANCA than controls; however, no significant difference was observed between UC and CD. In UC, 23, 17, and nine of the 33 patients with p-ANCA-positive sera showed reactivity with Lf, MPO, and Cat-G, respectively. In CD, 21, 20, and 11 of the 31 patients with p-ANCA-positive sera showed reactivity with Lf, MPO, and Cat-G, respectively. Fourteen of the UC and six of the CD patients showed reactivity with two different antigens, and seven of the UC and 11 of the CD patients showed reactivity with all three antigens. The presence of anti-Lf and anti-MPO antibodies was further confirmed by Western blotting. CONCLUSIONS: ANCA is useful in distinguishing patients with IBD from normal subjects but is not sufficient for the differential diagnosis of CD and UC. p-ANCA reactivity might be derived from the recognition of heterogeneous neutrophil-associated antigens.

Adult↗
PubMed1999

Fecal eosinophil granule-derived proteins reflect disease activity in inflammatory bowel disease.

OBJECTIVES: The aims of this study were: 1) to examine whether the fecal levels of eosinophil granule-derived proteins reflect disease activity in inflammatory bowel disease (IBD); and 2) to examine the extracellular release of these proteins from eosinophils and their stability in feces by an in vitro study. METHODS: We investigated 42 patients with ulcerative colitis (UC), 37 patients with Crohn's disease (CD), and 29 control subjects. The stool samples were collected at 4 degrees C over 48 h and were homogenized. The fecal levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured by radioimmunoassay. Fecal Hb (Hb), alpha1-antitrypsin (AT), and lactoferrin (Lf) were also measured by ELISA. RESULTS: Fecal ECP and EPX concentrations were significantly increased in both active UC and active CD compared to inactive UC and inactive CD, respectively. Fecal EPX concentration correlated with the fecal Hb, AT, and Lf concentrations more closely than fecal ECP concentration. Even in the inactive stage, CD patients who relapsed within the following 3 months showed higher fecal ECP and EPX concentrations compared to the patients who did not. EPX was released extracellularly more efficiently than ECP (18.6% vs 6.3%, after incubation for 15 min at 25 degrees C). EPX was more stable in the feces than ECP. CONCLUSIONS: The measurement of eosinophil granule-derived proteins in feces is useful for evaluating disease activity and predicting relapse in patients with IBD. EPX may be more suitable than ECP as a fecal eosinophil marker.

Adult↗
PubMed1999

[A case of gastric carcinoma treated effectively with 5'-DFUR].

A 79-year-old male was admitted to our hospital for further examination on gastric carcinoma (1' type) in the cardia. The histology of biopsied tissue was moderately differentiated adenocarcinoma (tub2). The patient refused a gastrectomy and received three cycles of local injection therapy with OK-432 + Beriplast into the tumor. However, the tumor showed no decrease in size. Considering the quality of life, the patient was given out patient treatment with 5'-DFUR (Furtulon, 800 mg/day). Three months later, the patient showed a partial response (PR) on the basis of gastric X-ray and endoscopic findings. No adverse reactions to the drug were seen. The patient has been receiving the same drug since then, and has continued to show PR for 15 months. Biopsied tissues were checked immunohistochemically for expression of thymidine phosphorylase (TdRPase), and changes in tissue TdRPase level were examined by ELISA. The TdRPase level decreased with shrinking of the tumor. These results suggest that the shrinking of tumor following 5'-DFUR therapy is closely related to TdRPase.

Adenocarcinoma↗