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Biomedical subjects

T Hibi

Publications and source records attributed to T Hibi.

At least 91 records · Page 5Linked to original sources
PubMed1999

[A model of quality of life in the patients with Crohn's disease].

PURPOSE: To identify the integrated impact of psychological, social, and clinical factors onto the quality of life (QOL) in the patients with Crohn's disease. SUBJECTS AND METHODS: Two hundred twenty two out-patients participated in a cross-sectional questionnaire survey in which health-related QOL (SF36), disease-specific symptoms, psychological adaptation and social support were measured. Multi-variable regression models were used to test the impact of clinical, psychological, and social factors on the patient's QOL and symptom reports. RESULTS: The patient's symptoms and health-related QOL were significantly associated not only with disease activities, but also with the patient's psychological adaptation and the quality of social support. CONCLUSION: The results strongly suggest that a psychoeducational intervention may be useful in combination with a clinical intervention to improve the patient's QOL.

Adult↗
PubMed1999

Laparoscopically assisted bowel resection for primary mucosa-associated lymphoid tissue lymphoma of the cecum.

We present the first report of laparoscopic resection for colorectal mucosa-associated lymphoid tissue (MALT) lymphoma. A 76-year-old man was found to have MALT lymphoma of the cecum during colonoscopy. He underwent a laparoscopically assisted ileocecal resection after admission and was discharged 9 days postoperatively without any complications. Colorectal MALT lymphoma is a rare neoplasm that responds favorably to locally directed therapy, because it tends to remain localized for prolonged periods. Laparoscopic surgery for colorectal MALT lymphoma is considered feasible because it is minimally invasive, making it suitable for treatment of low-grade malignancies, such as MALT lymphoma, which cannot be removed endoscopically.

Aged↗
PubMed1998

Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa.

We have demonstrated that intestinal epithelial cells produce interleukin 7 (IL-7), and IL-7 serves as a potent regulatory factor for proliferation of intestinal mucosal lymphocytes expressing functional IL-7 receptor. To clarify the mechanism by which locally produced IL-7 regulates the mucosal lymphocytes, we investigated IL-7 transgenic mice. Here we report that transgenic mice expressing murine IL-7 cDNA driver by the SRalpha promoter developed chronic colitis in concert with the expression of SRalpha/IL-7 transgene in the colonic mucosa. IL-7 transgenic but not littermate mice developed chronic colitis at 4-12 wk of age, with histopathological similarity to ulcerative colitis in humans. Southern blot hybridization and competitive PCR demonstrated that the expression of IL-7 messenger RNA was increased in the colonic mucosal lymphocytes but not in the colonic epithelial cells. IL-7 protein accumulation was decreased in the goblet cell-depleted colonic epithelium in the transgenic mice. Immunohistochemical and cytokine production analysis showed that lymphoid infiltrates in the lamina propria were dominated by T helper cell type 1 CD4+ T cells. Flow cytometric analysis demonstrated that CD4+ intraepithelial T cells were increased, but T cell receptor gamma/delta T cells and CD8alpha/alpha cells were not increased in the area of chronic inflammation. Increased IL-7 receptor expression in mucosal lymphocytes was demonstrated in the transgenic mice. These findings suggest that chronic inflammation in the colonic mucosa may be mediated by dysregulation of colonic epithelial cell-derived IL-7, and this murine model of chronic colitis may contribute to the understanding of the pathogenesis of human inflammatory bowel disease.

Animals↗
PubMed1998

CD45RChighCD4+ intestinal mucosal lymphocytes infiltrating in the inflamed colonic mucosa of a novel rat colitis model induced by TNB immunization.

To clarify the role of CD4(+) intestinal mucosal lymphocytes in chronic intestinal inflammation, we developed a new rat colitis model by immunization with 2,4,6-trinitrobenzenesulfonic acid (TNB) in an emulsion with an adjuvant followed by transrectal administration of a low dose of TNB. Moreover, we assessed the therapeutic effect of anti-CD4 monoclonal antibody (mAb) on this model. In concert with the development ofserum anti-TNB Abs, transmural and segmental colitis that mimics some characteristics of human Crohn's disease was induced in the immunized rats. Immunohistochemical analysis showed the increase of infiltrating lamina propria CD4(+) T cells. Flow-cytometric analysis of isolated cells from inflamed mucosa revealed that CD45RChighCD4(+) T cells were significantly increased. Interestingly, intraperitoneal administration of anti-CD4 mAbs could suppress severe inflammation in the model with decrease of anti-TNB Ab titer. After the treatment with anti-CD4 mAbs, CD45RChighCD4(+) T cells in the lamina propria and interferon-gamma mRNA expression in the colonic lamina propria CD4(+) T cells were decreased. These results indicated that Th1 CD4(+) intestinal mucosal T cells have a role in the progress of inflamed lesions in chronic enteritis. They implicate that a therapy targeting mucosal T cells expressing CD4 may be feasible in the treatment of human Crohn's disease.

Animals↗
PubMed1998

The genome organization of the broad bean necrosis virus (BBNV).

The genome of the broad bean necrosis virus Oita-isolate (BBNV-O) [RNA1 (6.0 kb), RNA2 (2.8 kb) and RNA3 (2.4 kb)] was cloned and sequenced. Computer analysis indicates that methyltransferase, helicase and RNA-dependent RNA polymerase (RdRp) motifs are present in RNA1. The viral capsid protein (CP) cistron is located at the 5' terminal end of RNA2 and the Mr of CP (20 K) is close to that determined by SDS-PAGE analysis. An ochre codon (UAA) in the CP cistron is thought to be partially suppressed to produce a large readthrough protein. RNA3 possesses typical motifs of triple gene block proteins, which are also reported in several other plant viruses. The furovirus genome organization and phylogenetic analysis using RdRp and CP amino acid sequences suggest that BBNV is closely related to potato mop-top virus (PMTV), but is relatively distantly related to other furoviruses. The data also suggest that the genus Furovirus should be separated into several genera: the prototypical genus Furovirus, which excludes the following viruses: the PMTV group including BBNV; the beet necrotic yellow vein virus (BNYVV) group; and the peanut clump virus (PCV) group.

Amino Acid Sequence↗
PubMed1998

A novel donor splice site mutation in the C1 inhibitor gene of a patient with type I hereditary angioneurotic edema.

We studied the molecular genetic basis of a C1 inhibitor deficiency in a patient with type I hereditary angioneurotic edema using both the polymerase chain reaction and nucleotide sequencing. A single nucleotide change (T-->A) at the GT 5' donor splice recognition motif in the seventh intron of the C1 inhibitor gene was detected. A restriction site analysis of the C1 inhibitor gene in the patient's family indicated that this mutation is correlated with a decreased level of C1 inhibitor activity. A northern blot analysis demonstrated C1 inhibitor mRNA to have a normal size, but its contents were reduced by about 50% compared with a normal subject. As the donor splice site is essential for an excising of the intron during mRNA processing, aberrant mRNA splicing may cause a rapid degradation of the transcript, thus resulting in the onset of hereditary angioneurotic edema.

Adult↗
PubMed1998

Gastric urease activity is inversely associated with the success of treatment for Helicobacter pylori: effect of sofalcone.

Eradication therapy for Helicobacter pylori (H. pylori) has been established. However, the physiological factors influencing the success of treatment remain unclear. The aim of this study was to analyze these factors and to evaluate the efficacy of sofalcone on H. pylori eradication therapy. Forty-four H. pylori-infected and peptic ulcer patients were enrolled in this study. Twenty-seven patients were treated with lansoprazole (LPZ, 30 mg o.d. for 1-8 weeks) and amoxicillin (AMPC, 500 mg q.i.d, 1-2 weeks), followed by 8 weeks of treatment with famotidine (FAM, 20 mg o.d.). Moreover, sofalcone (SOF, 100 mg t.i.d) was administered to 17 patients throughout the therapeutic period. Endoscopic and serologic evaluations and the urea breath test (UBT) were performed before therapy. At the endoscopic examination, mucosal samples were biopsied and then tissue myeloperoxidase (MPO) content, an index of neutrophil infiltration was measured. Cure of H. pylori infection was determined 8 weeks after the cessation of LPZ. This eradication regimen afforded an overall cure rate of 63.0% (17/27) without SOF and 76.5% (13/17) with SOF. In the control group, treatment success was inversely associated with pre-UBT value (gastric urease activity), whereas this association was not observed in the SOF group. Furthermore, in the patients exhibiting a high preUBT value (>40%), a twofold higher eradication rate was obtained by the administration of SOF. In patients who were successfully eradicated, mucosal MPO level was slightly higher than those of unsuccessful cases, whereas there was no significant association with serum pepsinogen (PG I, PG II) concentration and its ratio (PG I/PG II). These results suggest that a low UBT value is a factor predicting treatment success. SOF administration may improve the eradication rate, especially in the high-UBT subgroup.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Augmented levels of gastric mucosal leucocyte activation by infection with cagA gene-positive Helicobacter pylori.

The possession of the cytotoxin-associated gene (cagA) of Helicobacter pylori is thought to be highly associated with peptic ulcer disease. However, the pathogenic role of cagA is still unknown. We have emphasized the importance of the interrelationship between H. pylori-derived ammonia and oxygen radicals from infiltrated leucocytes. The aim of the present study was to explore the relationship between oxygen radical production and H. pylori strain diversity based on cagA possession. An endoscopic examination and gastric mucosal biopsy were performed in 30 H. pylori-infected patients with gastric ulcer. Myeloperoxidase (MPO) content and the luminol-dependent chemiluminescence value in the biopsied gastric specimens were measured as an index for leucocyte infiltration and oxygen radical production. From the precipitates of cultured bacterial isolates of biopsied specimens, bacterial DNA was purified and analysed by polymerase chain reaction to characterize the possession of cagA. While all patients had ureC-positive strains, 22 had cagA-positive and eight had cagA-negative strains. In patients with cagA-positive strains, MPO contents as well as chemiluminescence values in the gastric corpus were significantly higher than those in patients with cagA-negative strains. Gastric mucosal leucocyte recruitment and activation are suggested to be enhanced by cagA gene-positive H. pylori infection.

Adult↗
PubMed1998

Predictive factors of response to leukocytapheresis therapy for ulcerative colitis.

Leukocytapheresis (LCAP) using a leukocyte removal filter was performed for 8 patients with moderate to severe ulcerative colitis (UC). Significant clinical improvement was attained in 5 of 8 patients (62.5%). All of them had been suffering from moderately active colitis and received corticosteroid therapy. On the other hand, 3 patients with severely active disease and treated with little or no corticosteroid were resistant to LCAP. This result indicates that LCAP is an effective treatment for steroid-resistant cases of UC when combined with steroid therapy. LCAP alone, however, seems to have little efficacy for severely active UC.

Adult↗
PubMed1998

A novel ATP-binding cassette transporter involved in multidrug resistance in the phytopathogenic fungus Penicillium digitatum.

Demethylation inhibitor (DMI)-resistant strains of the plant pathogenic fungus Penicillium digitatum were shown to be simultaneously resistant to cycloheximide, 4-nitroquinoline-N-oxide (4NQO), and acriflavine. A PMR1 (Penicillium multidrug resistance) gene encoding an ATP-binding cassette (ABC) transporter (P-glycoprotein) was cloned from a genomic DNA library of a DMI-resistant strain (LC2) of Penicillium digitatum by heterologous hybridization with a DNA fragment containing an ABC-encoding region from Botrytis cinerea. Sequence analysis revealed significant amino acid homology to the primary structures of PMR1 (protein encoded by the PMR1 gene) and ABC transporters of Saccharomyces cerevisiae (PDR5 and SNQ2), Schizosaccharomyces pombe (HBA2), Candida albicans (CDR1), and Aspergillus nidulans (AtrA and AtrB). Disruption of the PMR1 gene of P. digitatum DMI-resistant strain LC2 demonstrated that PMR1 was an important determinant of resistance to DMIs. The effective concentrations inhibiting radial growth by 50% (EC50s) and the MICs of fenarimol and bitertanol for the PMR1 disruptants (Deltapmr1 mutants) were equivalent to those for DMI-sensitive strains. Northern blot analysis indicated that severalfold more PMR1 transcript accumulated in the DMI-resistant strains compared with those in DMI-sensitive strains in the absence of fungicide. In both DMI-resistant and -sensitive strains, transcription of PMR1 was strongly enhanced within 10 min after treatment with the DMI fungicide triflumizole. These results suggested that the toxicant efflux system comprised of PMR1 participates directly in the DMI resistance of the fungus.

4-Nitroquinoline-1-oxide↗
PubMed1997

Human IgGFc binding protein (FcgammaBP) in colonic epithelial cells exhibits mucin-like structure.

Cloning a cDNA for human IgGFc binding protein (FcgammaBP) from human colonic epithelial cells reveals an mRNA and coding region of 17 and 16.2 kilobases, respectively. The predicted amino acid sequence contains 12 occurrences of a 400-amino acid cysteine-rich unit resembling that found in mucin. A motif (CGLCGN) in FcgammaBP is conserved in MUC2 and prepro-von Willebrand factor. The N-terminal 450-amino acid sequences are necessary and sufficient to confer IgG Fc binding activity. FcgammaBP mRNA is expressed only in placenta and colonic epithelial cells. These results suggest that FcgammaBP may play an important role in immune protection and inflammation in the intestines of primates.

Amino Acid Sequence↗
PubMed1997

Pectinolytic enzymes from Pseudomonas marginalis MAFF 03-01173.

Two pectinolytic enzymes were purified from the culture broth of Pseudomonas marginalis pv. marginalis MAFF 03-01173 with total 33% recovery of the initial activity. From the substrate specificities against pectin and polygalacturonic acid, the requirement of calcium ion for the enzymatic activity, and the N-terminal sequences, the enzymes were identified as pectin lyase and pectate lyase. The M,s of pectin lyase and pectate lyase were estimated to be 34,000 and 43,000, respectively, by SDS polyacrylamide gel electrophoresis. Both enzymes showed almost the same pH dependent activity curves with the highest activity at pH 8.3

Amino Acid Sequence↗
PubMed1997

The serum factor from patients with ulcerative colitis that induces T cell proliferation in the mouse thymus is interleukin-7.

The disturbance of immune regulatory T cells is related to the pathogenesis of ulcerative colitis. Here we demonstrated and characterized the serum factor from ulcerative colitis patients that induced proliferation of intrathymic T cells. The factor isolated from the patient sera by a combination of gel filtration and anion-exchange chromatography induced proliferation of CD4+CD8- intrathymic T cells in the organ-cultured embryonic mouse thymus. Purification and amino acid sequence analysis of the serum factor demonstrated that the N-terminal 12 sequence was homologous to that of interleukin-7. SDS-PAGE and Western blot confirmed that purified serum factor was interleukin-7. Enzyme immunoassay demonstrated that the serum interleukin-7 concentration was significantly increased in the patients. PCR and Southern blot hybridization demonstrated that interleukin-7 mRNA expression was increased in the thymus tissues from patients but decreased in the colonic mucosa. Since interleukin-7 is a crucial cytokine for proliferation and differentiation of T cells in the thymus, the present study indicates that interleukin-7 may contribute to the disturbance of immune regulatory T cells in ulcerative colitis.

Amino Acid Sequence↗
PubMed1997

Enhancement of neutrophil infiltration in the corpus after failure of Helicobacter pylori eradication.

Neutrophil accumulation plays an important role in Helicobacter pylori-associated gastric mucosal injury. In this study, the mucosal content of myeloperoxidase (MPO), which is a measure of neutrophil accumulation and interleukin-8 (IL-8) was assayed and changes in MPO and IL-8 content were determined before and after H. pylori eradication therapy. Thirty-seven H. pylori-positive patients (11DU/26GU) underwent H. pylori eradication therapy with lansoprazole (30 mg/day, 6 weeks) and amoxicillin (2 g/day, 2 weeks), followed by famotidine (20 mg/day, 8 weeks). H. pylori-infection status was evaluated by routine endoscopic examinations (culture, CLO, histology). Immediately and 8 weeks after cessation of the anti-H. pylori therapy, these tests were repeated. Intragastric urease activity was estimated by delta 13CO2, which was obtained by the [13C]urea breath test (UBT). Mucosal samples were taken and tissue MPO and IL-8 contents were assayed by EIA and ELISA, respectively. Histologic examination was also performed. Among the 37 patients, 21 cases of H. pylori infection were eradicated (56.8%). Intragastric urease activity was dramatically reduced immediately after the anti-H. pylori therapy, whereas, it was re-elevated 8 weeks later in the relapsed cases. Antral MPO content was decreased in the eradicated and relapsed cases. MPO in the corpus was also decreased in the eradicated cases. Nevertheless, it was enhanced (3.5-fold) in the relapsed cases at 8 weeks after therapy. Changes in mucosal IL-8 content were similar to those of MPO. In eradicated cases, neutrophil infiltration is improved in both the antrum and corpus. However failure of eradication therapy results in the enhancement of neutrophil accumulation in the corpus. Further study is necessary to clarify the mechanism of neutrophil accumulation after therapy for H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Synthesis and antinociceptive activity of [D-Ala2]Leu-enkephalin derivatives conjugated with the adamantane moiety.

Based on the physicochemical and pharmacological properties of drugs having an adamantane skeleton, an adamantane-based moiety was evaluated as a drug carrier for poorly absorbed compounds, including peptides, active towards the central nervous system (CNS). Seven [D-Ala2]Leu-enkephalin derivatives conjugated with an adamantane-based moiety at the C-terminus or N-terminus were prepared by the solution-phase method and their biological activities were examined. The compounds derivatized at the C-terminus through an ester or amide linkage were much more lipophilic than the parent peptide and exhibited moderate in vitro opioid activity (guinea-pig ileum assay). Among them, four derivatives (1, 2, 4, 5), exhibited significant antinociceptive effects in an in vivo assay (mouse tail-pressure test) after subcutaneous administration. This result suggests that the introduction of the lipophilic adamantane moiety into [D-Ala2]Leu-enkephalin would improve the permeation of the poorly absorbed parent peptide through the blood-brain-barrier (BBB) without loss of antinociceptive effect.

Adamantane↗