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Biomedical subjects

H Saito

Publications and source records attributed to H Saito.

At least 73 records · Page 4Linked to original sources
PubMed2003

Validity of simple mucosal biopsy criteria combined with endoscopy predicting patients with ulcerative colitis ultimately requiring surgery: a multicenter study.

BACKGROUND: Recent mucosal biopsy criteria combined with endoscopy effectively differentiate patients with ulcerative colitis ultimately requiring surgery (UC-S) from those receiving medication alone (UC-M). However, the criteria were inconvenient in practical use because of the need for complicated calculations, and the validity has not been verified in other institutes where the indications for surgery may differ. The aims of this multicenter study were to propose simple criteria in which calculation can be performed by mental arithmetic and to measure their validity. METHODS: Based on the above original criteria, we constructed simple criteria in which coefficients and constant were simplified to integral numbers. The criteria consisted of the diagnostic categories, highest-risk, high-risk, unpredictable, low-risk, and lowest-risk of surgery. The validity of these proposed criteria was evaluated in 121 patients with UC-S and 186 with UC-M from 11 institutes. RESULTS: The categories of high-risk and low-risk had sensitivities exceeding 86.0% and specificities exceeding 95.2%, and the validities were maintained at high levels in most individual institutes. There was little difference in validity between the proposed and original criteria when testing using the same patients. CONCLUSIONS: Despite simplified coefficients and constant, the proposed criteria reliably predicted the eventual clinical outcome of patients with ulcerative colitis and would be helpful in determining the necessity of surgery.

Adolescent↗
PubMed2003

Isolation of peptides useful for differential diagnosis of Crohn's disease and ulcerative colitis.

BACKGROUND: Phage displayed random peptide technology has been utilised to identify binding epitopes of antibodies or receptor ligands. AIM: To isolates peptides from a phage library which are specifically recognised by antibodies in serum from patients with Crohn's disease (CD). METHODS: A phage displayed random peptide library composed of nine amino acids was established and sequentially screened using serum immunogloblin G obtained from CD patients. RESULTS: Five different CD specific peptides were isolated from the phage library. No homology in amino acid sequences was observed among four (CDP-1, -3 to -5) of the five peptides exhibiting different binding characteristics with each CD patient's serum. In contrast, two peptides (CDP-1 and -2) had similar amino acid sequences and similar binding characteristics. Four multiple antigenic peptides (MAP, CDP-1, -3 to -5) were synthesised, and an enzyme linked immunosorbent assay (ELISA) using the four peptides was developed to detect serum antibodies against them. Fifty two of 92 CD patients (56.5%) were detected by ELISA, none of 20 ulcerative colitis (UC) patients, only one of 25 duodenal ulcer patients, and only three of 48 healthy subjects. CONCLUSIONS: ELISA using the four peptides isolated in this study may be useful for the differential diagnosis of CD and UC.

Amino Acid Sequence↗
PubMed2003

[Surgical treatment for pulmonary metastases from colorectal cancer].

Blalock first reported pulmonary resection for metastatic colorectal cancer in 1944. Since then, surgical resection of pulmonary metastases has been generally accepted as a standard therapeutic procedure in properly selected cases. Recently, the criteria of eligibility have been progressively expanded according to the development of radiological diagnosis using helical computed tomography (CT), widespread of minimum invasive video-assisted thoracic surgery. In this review summarized the surgical treatment of pulmonary metastases from colorectal cancer based on the recent literatures. Major areas of controversy remain with respect to the following aspects: prognostic factors (i.e., number of metastases, size of tumor, disease free interval, preoperative serum carcinoembryonic antigen level), procedure of operation (i.e., role of video-assisted thoracic surgery, lymphonode dissection), indication of surgical treatment on metastases both lung and liver, role of repeat thoracotomy for recurrence. For all above-mentioned points it appeared reasonable to try to the cooperative multicentric clinical prospective study.

Colorectal Neoplasms↗
PubMed2003

[Comparative study of hypothermic circulatory arrest and normothermic distal perfusion for thoracoabdominal aortic aneurysm repair].

BACKGROUND: Hypothermic bypass with circulatory arrest for thoracoabdominal aortic aneurysm (TAAA) repair is employed for its protective effect on spinal cord function and because it avoids clamping the diseased aorta. However, organ dysfunction caused by reperfusion injury as well as bleeding tendencies due to deep hypothermia have been described. In this paper we compared the efficacies of the hypothermic and normothermic operations. METHODS: Between February 1996 and June 2000, 28 patients underwent thoracoabdominal aortic repair. Twenty-three patients were men, 5 were women, and the median age was 55.3 (range 23 to 75 years). Fourteen patients had aortic dissection, and 7 had Marfan syndrome. Fourteen patients required reconstruction of visceral arteries. Twelve patients underwent TAAA repair under deep hypothermic circulatory arrest (H group), and 15 under normothermic distal perfusion (N group), while 1 patient underwent a simple clamp procedure. Perioperative data and early outcomes were compared between groups. RESULTS: The overall 30-day mortality rate was 0%, but 3 patients (25.0%) in II group, and 1 patient (6.3%) in N group died during hospital stay. Operation time and bypass time were longer in H group than N group (operative time 793 min vs. 481 min (p < 0.05): cardiopulmonary bypass (CPB) time 255 min vs. 102 min (p < 0.05). Also, more intraoperative bleeding was found in H group than in N group (3,506 ml vs. 1,220 ml). Spinal cord neurologic deficit did not occur in either group. Respiratory failure occurred in 3 patients (25.0%) in H group and one (6.3%) in N group. Renal failure occurred in 3 (25.0%) in H group, and none in N group. CONCLUSION: Early and mid-term outcome of TAAA repair was almost satisfactory and without neurospiral complications. The deep hypothermic operation is more likely to induce postoperative respiratory and renal dysfunction than the normothermic operation. TAAA repair using deep hypothermic circulatory arrest should be limited to patients with TAAA involving the distal arch or a severely calcified aortic wall.

Adult↗
PubMed2003

[Left superior segmental resection for lung cancer with anomalous branching of the left A4 + 5; report of 2 cases].

We experienced with two cases of left superior segmental resection for lung cancer with the left A4 + 5 which arose from pars mediastinalis. Left superior segmental resection was performed on a 67-year-old female and an 81-year-old male. In both cases we divided A4 + 5 temporarily and anastomosed to pars interlobaris of the left pulmonary artery. As a result, it was able to perform safe division of bronchus. In cases with A4 + 5 arising from pars mediastinalis, operation is difficult and risky because A4 + 5 locates in front of the left upper lobe bronchus. It is safer to reconstruct A4 + 5 on pars interlobaris of the left pulmonary artery in such cases.

Adenocarcinoma↗
PubMed2002

Production of active bovine cathepsin C (dipeptidyl aminopeptidase I) in the methylotrophic yeast Candida boidinii.

The heterologous production of active bovine cathepsin C (CTC; dipeptidyl aminopeptidase I) was investigated. Attempts to express CTC in Escherichia coli were hampered by formation of inclusion bodies that were partially degraded. To overcome this impediment, secretion of recombinant CTC was attempted in the methylotrophic yeast Candida boidinii. A DNA fragment encoding bovine procathepsin C was synthesized based on preferred codon usage in C. boidinii and placed downstream of the C. boidinii proteinase A signal sequence resulting in secretion of active CTC into the culture medium. The gene was expressed under the control of the methanol-inducible formate dehydrogenase gene promoter. Production levels were significantly improved by using a protease-deficient strain, changing medium composition, and by lowering the temperature of induction. When the recombinant C. boidinii was grown for 90 h in a jar-fermenter, active CTC was secreted with a yield of up to approximately 12 mg/l.

Amino Acid Sequence↗
PubMed2002

Enhanced tumor cell selectivity of adriamycin-monoclonal antibody conjugate via a poly(ethylene glycol)-based cleavable linker.

A novel linker consisting of poly(ethylene glycol) (PEG) and dipeptide was used for conjugation of adriamycin with tumor-specific monoclonal antibody, NL-1, to confirm that the linker can be cleaved selectively with the tumor specific enzyme to express cytotoxicity of the anti-tumor agent. Initially, adriamycin-conjugated PEG linkers through different amino acid compositions, alanyl-valine (Ala-Val), alanyl-proline (Ala-Pro), and glycyl-proline (Gly-Pro) sequences, were prepared to confirm selective digestion with model enzymes. Adriamycin was released by particular model endoproteases, thermolysin and proline endopeptidase, from the linkers with different efficiency. When conjugates were prepared using these adriamycin-bound linkers, conjugates had no loss of binding affinity and specificity for common acute lymphoblastic leukemia antigen (CALLA) expressed on the Daudi cell surfaces as the target of NL-1 antibody. In addition, adriamycin release from the conjugates was also confirmed by incubating them with specific proteases. Tumor cell growth was inhibited dose-dependently for the conjugates carrying Ala-Val and Gly-Pro linkers, whereas significant inhibitory effect was abolished for the conjugate carrying Ala-Pro linker, indicating that cytotoxic effect can be controlled by specificity of antibody and composition of linker peptide. IC(50) for Ala-Val linked conjugate was approximately 3.5 microg/ml and that for Gly-Pro linked conjugate was 5.2 microg/ml. PEG-dipeptidyl linker demonstrated here will be an effective tool for the preparation of immunoconjugate, especially specific activation of anti-tumor agents at desired tumor tissues.

Antibodies, Monoclonal↗
PubMed2002

Halitosis prevention campaign: a report of oral health promotion activities in Japan.

A local dental association, Hakodate Dental Association, has been conducting an oral health promotion campaign, 'Good-bye Bad Breath', in a local community since April 1998. The purpose of this campaign was not only to prevent oral malodour but also to raise people's awareness about oral health. Oral health education has been provided at schools and through television commercials, radio programmes and newspaper articles. Campaign posters and leaflets on bad breath have also been distributed to drug stores, medical clinics and schools, as well as dental clinics. It has been emphasised that oral malodour is a preventable condition and that the dentist can provide adequate advice and suitable treatment. Medical and pharmaceutical associations have cooperated with the Dental Association in running the campaign. Dental care was provided free of charge to the local residents. The free services provided included the assessment of oral malodour using a portable sulphide detector, instructional programmes, and consultations with dentists. This campaign offered a good opportunity to encourage people to visit the dentist for regular check-ups. The number of regular check-ups and halitosis patients has increased in 70% of the clinics belonging to the Dental Association.

Counseling↗
PubMed2002

New endo-beta-1,4-glucanases from the parabasalian symbionts, Pseudotrichonympha grassii and Holomastigotoides mirabile of Coptotermes termites.

Abstract. An endo-beta-1,4-glucanase (EG) was purified from the hindgut of an Australian mound-building termite, Coptotermes lacteus. The hindgut extract had a peak separate from those for extracts obtained from the salivary glands and the midgut based on sephacryl S-200 gel chromatography, and also demonstrated an origin different from the endogenous EGs of the termite itself. The recovery was further purified by SDS-PAGE, and its N-terminal amino acid sequence analyzed. This showed high homology to EGs from glycoside hydrolase family (GHF) 7. PCR-based cloning methods were applied to the hindgut contents of C. lacteus and individual protozoan symbionts from C formosanus. cDNAs encoding putative EGs homologous to GHF7 members were then identified. The functionality of one of the putative proteins was confirmed by its expression in Escherichia coli.

Amino Acid Sequence↗
PubMed2002

Topographical analysis of lymphatic pathways from the meso- and hypopharynx based on minute cadaveric dissections: possible application to neck dissection in pharyngeal cancer surgery.

To facilitate the development of new operative procedures for pharyngeal cancer, it is important to understand the precise location of the lymph nodes and their pathways. Minute dissection of 22 neck-halves (11 adult cadavers) was undertaken to determine the location and topographical relationships of the lymphatics of the pharynx. Four groups of lymph nodes on the drainage pathways from the meso- and hypopharynx to the internal jugular nodes were classified according to their topographical relationships to the carotid arteries: lateral pharyngeal, superior thyroid, lateral retropharyngeal and medial retropharyngeal nodes. Lymphatics from the mesopharynx passed laterally to lateral pharyngeal or jugulodigastric nodes or slightly upward to lateral retropharyngeal nodes. Lymphatic drainage from the hypopharynx was multidirectional with the pathways being classified as follows: ascending pathway to the lateral pharyngeal and lateral retropharyngeal nodes, lateral pathway to the internal jugular chain, and descending pathway connecting to the uppermost vessels ascending from the recurrent laryngeal nerve chain. In addition, a contralateral pathway was found originating from the hypopharynx extending to the contralateral internal jugular chain. These findings provide valuable information for comparison with CT and MRI studies, as well as with clinicopathological data, to clarify the precise mode of metastasis in head and neck cancers. These results are also applicable to neck dissection in meso- and hypopharyngeal cancers.

Aged↗
PubMed2002

Prognostic significance of the null genotype of glutathione S-transferase-T1 in patients with acute myeloid leukemia: increased early death after chemotherapy.

We investigated the prognostic significance of genetic polymorphism in glutathione-S transferase mu 1 (GSTM1), glutathione-S transferase theta 1 (GSTT1), NAD(P)H:quinone oxidoreductase (NQO1) and myeloperoxidase (MPO), the products of which are associated with drug metabolism as well as with detoxication, in 193 patients with de novo acute myeloid leukemia (AML) other than M3. Of the patients, 64.2% were either homozygous or heterozygous for GSTT1 (GSTT1(+)), while 35.8% showed homozygous deletions of GSTT1 (GSTT1(-)). The GSTT1(-) group had a worse prognosis than the GSTT1(+) group (P = 0.04), whereas other genotypes did not affect the outcome. Multivariate analysis revealed that GSTT1(-) was an independent prognostic factor for overall survival (relative risk: 1.53; P = 0.026) but not for disease-free survival of 140 patients who achieved complete remission (CR). The rate of early death after the initiation of chemotherapy was higher in the GSTT1(-) group than the GSTT1(+) group (within 45 days after initial chemotherapy, P = 0.073; within 120 days, P = 0.028), whereas CR rates and relapse frequencies were similar. The null genotype of GSTT1 might be associated with increased toxicity after chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Selective apoptosis of tandemly duplicated FLT3-transformed leukemia cells by Hsp90 inhibitors.

An internal tandem duplication of the juxtamembrane (JM) domain of FLT3, a family of ligand-activated receptor tyrosine kinases, has been found in 20% of cases of acute myeloid leukemia (AML), and this mutation is correlated with leukocytosis and a poor prognosis. As a therapeutic approach, we previously reported that herbimycin A (HA) inhibited the growth of tandemly duplicated FLT3 (TDFLT3)-transformed cells (Leukemia 2000; 14: 374). Here, we have investigated the mechanism behind the cytotoxicity of HA, an ansamycin derivative which is now known to target Hsp90. The treatment with HA or another Hsp90 inhibitor, radicicol, induced selective apoptosis in TDFLT3-transformed 32D cells (TDFLT3/32D). The tyrosine-phosphorylation of TDFLT3 was inhibited by HA, whereas FLT3 ligand-induced phosphorylation of wild-type FLT3 (WtFLT3) was not. The downstream signal molecules MAPK, Akt and STAT5a were also dephosphorylated by HA in TDFLT3/32D. Immunoprecipitation analysis showed that TDFLT3 but not WtFLT3 formed a complex with Hsp90, and that the HA treatment dissociated TDFLT3 from the Hsp90 chaperone complex. These findings imply that targeting of Hsp90 will facilitate the development of anti-TDFLT3 therapy, and that Hsp90 is closely involved in the oncogenic activation of FLT3.

Animals↗
PubMed2002

Characterization of 'adult-type' mast cells derived from human bone marrow CD34(+) cells cultured in the presence of stem cell factor and interleukin-6. Interleukin-4 is not required for constitutive expression of CD54, Fc epsilon RI alpha and chymase, and CD13 expression is reduced during differentiation.

BACKGROUND: In vitro-derived human mast cells exhibit different properties, depending in part on the source of progenitor cells. Most investigations have used fetal liver, cord blood or peripheral blood. Few have used adult bone marrow. OBJECTIVE: Human mast cells derived in vitro from the CD34(+) progenitors in bone marrow and cord blood that had been cultured with recombinant human stem cell factor (rhSCF) and recombinant human interleukin-6 (rhIL-6) were compared. METHODS AND RESULTS: After 12 weeks of culture, nearly all of the cells were mast cells, and nearly all of these had cytoplasmic granules containing both tryptase and chymase (MCTC type), stained metachromatically with acidic toluidine blue, and expressed CD117 on the cell surface. Both tryptase protein and mRNA were detected by two weeks of culture. Chymase mRNA and protein were detected at 4 weeks but not at 2 weeks of culture. By 12 weeks, chymase content per cell, measured by ELISA, was significantly higher (P < 0.05) in human bone marrow-derived mast cells (HBMMC) (5.6 +/- 0.9 pg) than in cord blood-derived mast cells (CBMC) (2.4 +/- 0.9 pg), whereas histamine and tryptase levels were not significantly different. Of the cluster designations tested, CD29, CD49d, CD51 and CD61 were strongly expressed on HBMMC. CD54 and Fc epsilon RI alpha also were expressed constitutively. Approximately half of CD34-sorted cells at day 0 were CD13(+) and this diminished as mast cell maturation occurred. Electron microscopy revealed that 12-week-old HBMMC had many secretory granules that contained spherical electron dense cores surrounded by electron lucent space, consistent with previous reports of immature MCTC cells developing in vivo. CONCLUSIONS: CD34(+) progenitors of human bone marrow are a rich source of mast cell progenitors capable of expressing granule and surface markers of mature mast cells in the presence of rhSCF and rhIL-6.

Antigens, CD↗
PubMed2002

Transmural pressure induces IL-6 secretion by intestinal epithelial cells.

Although intestinal epithelial cells (IECs) are known as an important source for IL-6, it is not known whether mechanical forces affect IL-6 production. We investigated how transmural pressure modulates IL-6 synthesis and activation of transcription factors in IECs. Pressure was loaded onto IEC-18 cells by introducing compressed helium gas into the cell culture flask for 1-48 h. IL-6 release into the culture media was determined by cell proliferation bioassay using an IL-6-dependent mouse hybridoma cell line (7TD1). Exposure to pressure (80 mmHg) significantly enhanced IL-6 release into the culture media from IEC-18 cells at 12 h. Under control conditions, IL-6 secretion was directed to the basolateral side, but after exposure to pressure IL-6 secretion was increased in both the apical and basolateral sides. A nuclear factor kappa B (NF-kappaB) decoy reversed completely the pressure-induced increase of IL-6 secretion by IEC-18 cells. Pressure treatment enhanced IL-6 mRNA expression in IECs within 6 h. Pressure loading significantly enhanced the activation of both NF-kappaB and NF-IL-6 from 1h in the nuclear protein of IEC-18 cells as assessed by the electrophoretic mobility shift assay using FITC-conjugated specific primers. Increased phosphorylation of I-kappa B was also demonstrated in the cytosol of IEC cells within 1h by Western blot analysis. These results suggest a possible role for pressure loading in immune modulation of the intestinal mucosa by the stimulation of IL-6 release from intestinal epithelial cells.

Animals↗