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Biomedical subjects

M Hattori

Publications and source records attributed to M Hattori.

At least 19 recordsLinked to original sources
PubMed2006

BCR/ABL and IL-3 activate Rap1 to stimulate the B-Raf/MEK/Erk and Akt signaling pathways and to regulate proliferation, apoptosis, and adhesion.

The Ras family small GTPase Rap1 is activated by hematopoietic cytokines, such as interleukin (IL)-3, to induce beta1 integrin-mediated cell adhesion or by the BCR/ABL fusion tyrosine kinase to stimulate the MEK/Erk signaling pathway. Here, we demonstrate that the abrogation of Rap1 activation by SPA-1, a Rap1-specific GAP, inhibits activation of B-Raf, MEK, Erk, and Akt in a murine hematopoietic cell line, Ton.B210, stimulated with IL-3 or inducibly expressing BCR/ABL. Furthermore, Rap1 inactivation had an inhibitory effects on proliferation and survival of Ton.B210 cells, which were more remarkable when cells were stimulated by BCR/ABL than by IL-3. Induction of BCR/ABL expression increased adhesion of Ton.B210 cells to fibronectin in a manner at least partly dependent on its kinase activity, and Rap1 inhibition by SPA-1 partially inhibited BCR/ABL-induced adhesion of cells. Thus, IL-3- or BCR/ABL-induced activation of Rap1 may play important roles in regulation of cell proliferation and survival through activation of the B-Raf/MEK/Erk and Akt signaling pathways and in induction of integrin-mediated cell adhesion. Furthermore, as compared with IL-3, BCR/ABL is more dependent on Rap1-mediated signaling to induce cell proliferation and survival and, thus, Rap1 may represent an attractive target for novel therapies for leukemias caused by BCR/ABL.

Animals↗
PubMed2005

Carbonate-containing hydroxyapatite derived from calcium tripolyphosphate gel with urea.

Carbonate containing hydroxyapatite (CO3HAp) is one of the candidate materials as a bioresorbable bone substitute. In the present work, CO3HAp was efficiently prepared by a hydrothermal treatment of calcium tripolyphosphate gel with urea at 140 degrees C for 24 h. Chemical potential plots of the CO3HAp for estimation of its dissolution behavior suggested that the CO3HAp is more soluble than hydroxyapatite (HAp) and is as soluble as octacalcium phosphate (OCP) and/or beta -tricalcium phosphate (TCP). This material is expected to be applied to bioresorbable materials such as bone fillers.

Absorbable Implants↗
PubMed2005

Epitope analysis of myeloperoxidase-specific antineutrophil cytoplasmic autoantibodies (MPO-ANCA) in childhood onset Graves' disease treated with propylthiouracil.

AIM: This study aimed to elucidate the relationship between epitope profiles and clinical manifestations of patients with myeloperoxidase antineutrophil cytoplasmic autoantibodies-(MPO-ANCA) positive childhood onset Graves' disease treated with propylthiouracil (PTU). METHODS: Sixteen patients were studied. The patients were grouped into ten without clinical vasculitis and nephritis (non-vasculitis group) and six with biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis (vasculitis group). Epitope analysis was performed on serum samples by an enzyme-linked immunosorbent assay (ELISA) using a panel of recombinant deletion mutants of MPO. RESULTS: The high frequency sites were region upstream of Met341 (Ha region) near the N-terminus of the heavy chain, and regions downstream of Gly598 (Hf and Hg regions) near the C-terminus. Most patients in the non-vasculitis group had polyclonal MPO-ANCA recognizing both the above linear sites and other epitope sites of the heavy chain of MPO. Only one of ten patients in the non-vasculitis group, and four of six patients in the vasculitis group had MPO-ANCA recognizing only the linear sites of the heavy chain of the MPO molecule (Ha, Hf and/or Hg). Of the four patients in the vasculitis group, two had nephritis, like rapidly progressive glomerulonephritis and one had alveolar hemorrhage. CONCLUSION: These findings suggest that most patients with childhood onset Graves' disease treated with PTU who manifest no vasculitis have polyclonal MPO-ANCA recognizing both the linear and other epitope sites of the heavy chain of MPO. However, some patients who develop nephritis have MPO-ANCA recognizing only the linear sites of the heavy chain of MPO. This clonality of MPO-ANCA may be a risk factor that induces clinical vasculitis and nephritis in patients treated with PTU. Therefore, patients exposed to PTU should be monitored for MPO-ANCA level and epitopes.

Adolescent↗
PubMed2004

DNA sequence and comparative analysis of chimpanzee chromosome 22.

Human-chimpanzee comparative genome research is essential for narrowing down genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language. Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee chromosome 22. By comparing the whole sequence with the human counterpart, chromosome 21, we found that 1.44% of the chromosome consists of single-base substitutions in addition to nearly 68,000 insertions or deletions. These differences are sufficient to generate changes in most of the proteins. Indeed, 83% of the 231 coding sequences, including functionally important genes, show differences at the amino acid sequence level. Furthermore, we demonstrate different expansion of particular subfamilies of retrotransposons between the lineages, suggesting different impacts of retrotranspositions on human and chimpanzee evolution. The genomic changes after speciation and their biological consequences seem more complex than originally hypothesized.

Animals↗
PubMed2004

Transplantation of pediatric cadaveric kidneys into adult or pediatric recipients.

In Japan, nationwide cadaveric organ sharing for kidney transplantation by the Japan Organ Transplant Network (JOTN) has operated since April 1995. This study retrospectively analyzed the long-term results of single pediatric donor kidneys transplanted into adult or pediatric recipients at a single center. From March 1983 to December 2002, 281 cadaveric renal allografts were transplanted at our center, including, 17 recipients of cadaveric kidneys from donors aged less than 16 years. We divided these 17 recipients into two groups: 10 adult recipients (group 1; G1) and seven pediatric recipients (group 2; G2). HLA-AB, -DR mismatches were 1.3 +/- 1.3, 0.7 +/- 0.5 in G1 and 2.6 +/- 1.3, 1.4 +/- 0.8 in G2, respectively (P < .05 for both). The end of the observation of this study was March 2003. Among G1, two recipients died with functioning grafts and one died after graft loss. Among G2, no recipients died. Patient survival rates at 1 and 5 years were 90% and 80% in G1 and 100% and 100% in G2, respectively. At the end of the observation in this study, five recipients among G1 and six recipients among G2 had functioning grafts. Graft survival rates at 1 and 5 years were 90% and 80% in G1 and 85.7% and 85.7% in G2, respectively. Our results demonstrate that transplantation of pediatric cadaveric kidneys into pediatric recipients was excellent compared to adult recipients in terms of survival. Priority to pediatric patients should be given especially in cases of pediatric donors.

Adolescent↗
PubMed2004

Thiotepa/cyclophosphamide/TBI as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome.

In all, 18 patients (30-56 years; median 49) with MDS underwent allogeneic HSCT from related (n=12) or unrelated (n=6) donors after a conditioning regimen comprising thiotepa, cyclophosphamide, and TBI. GVHD prophylaxis consisted of cyclosporine (n=15) or tacrolimus (n=3) with short-course methotrexate. Four patients had low-risk disease (refractory anemia or complete remission after chemotherapy) and 14 patients had high-risk disease (RAEB, RAEB-t, or AML). Grade II-IV acute GVHD developed in six patients and chronic GVHD in 10. With a median follow-up of 31 months, the 2-year survival probability is 75% for low-risk patients and 57% for high-risk patients. One patient died of leukemia and six of treatment-related causes. This conditioning regimen requires further study in patients with MDS.

Adult↗
PubMed2004

Mechanical properties of cast Ti-6Al-4V-XCu alloys.

The mechanical properties of Ti-6Al-4V-XCu (1, 4 and 10 wt% Cu) alloys were examined. The castings for each alloy were made in a centrifugal titanium casting machine. Two shapes of specimens were used: a dumbbell (20 mm gauge length x 2.8 mm diameter) for mechanical property studies, and a flat slab (2 mm x 10 mm x 10 mm) for metallography, microhardness determination and X-ray diffractometry. Tensile strength, yield strength, modulus of elasticity, elongation and microhardness were evaluated. After tensile testing, the fracture surfaces were observed using scanning electron microscopy. The tensile strengths of the quaternary alloys decreased from 1016 MPa for the 1% Cu alloy to 387 MPa for the 10% Cu alloy. Elongation decreased with an increase in the copper content. The 1% Cu alloy exhibited elongation similar to Ti-6Al-4V without copper (3.0%). The results also indicated that the copper additions increased the bulk hardness of the quaternary alloy. In particular, the 10% Cu alloy had the highest hardness and underwent the most brittle fracture. The mechanical properties of cast Ti-6Al-4V alloy with 1 and 4% Cu were well within the values for existing dental casting non-precious alloys.

Alloys↗
PubMed2003

Wear resistance of experimental Ti-Cu alloys.

After using cast titanium prostheses in clinical dental practice, severe wear of titanium teeth has been observed. This in vitro study evaluated the wear behavior of teeth made with several cast titanium alloys containing copper (CP Ti+3.0 wt% Cu; CP Ti+5.0 wt% Cu; Ti-6Al-4V +1.0 wt% Cu; Ti-6Al-4V+4.0 wt% Cu) and compared the results with those for commercially pure (CP) titanium, Ti-6Al-4V, and gold alloy. Wear testing was performed by repeatedly grinding upper and lower teeth under flowing water in an experimental testing apparatus. Wear resistance was assessed as volume loss (mm(3)) at 5kgf (grinding force) after 50,000 strokes. Greater wear was found for the six types of titanium than for the gold alloy. The wear resistance of the experimental CP Ti+Cu and Ti-6Al-4V+Cu alloys was better than that of CP titanium and Ti-6Al-4V, respectively. Although the gold alloy had the best wear property, the 4% Cu in Ti-6Al-4V alloy exhibited the best results among the titanium metals. Alloying with copper, which introduced the alpha Ti/Ti(2)Cu eutectoid, seemed to improve the wear resistance.

Alloys↗
PubMed2003

Quantitative analysis of the resorption and osteoconduction process of a calcium phosphate cement and its mechanical effect for screw fixation.

The clinical application of calcium phosphate cements (CPCs) composed of tetracalcium phosphate and dicalcium phosphate anhydrous has been limited because of its longer setting time, so that we developed the CPC in which the setting time was shortened to approximately 10 min. Aiming at clinical application, we evaluated the histological response in the bone quantitatively and the biomechanical effectiveness of this substance. The CPC was implanted in the rabbit femoral condyle up to 52 weeks for histological evaluation. In mechanical testing, small cancellous screws were inserted into the condyle, both with and without augmentation with the CPC, and the pull-out strength was measured. The micro-computed tomography finding demonstrated that the cross-sectional area of the implanted CPC at 24 weeks was approximately two-thirds of the initial area. The amount of newly calcified bone around the CPC was significantly greater than that of the sintered hydroxyapatite. Histologically, the new bone was formed on the surface of the implanted CPC 1 week after the implantation and resorption of the CPC was evident at 3 weeks. The pull-out strength was enhanced significantly by augmentation with the CPC and the initial strength was maintained for a 6 week period. This CPC showed good osteoconductivity and was resorbed without adverse inflammation. Using the CPC as augmentation may be capable of useful treatment options in fractures with poor bone quality.

Animals↗
PubMed2003

Invasive colorectal cancer detected up to 3 years after a colonoscopy negative for cancer.

BACKGROUND AND STUDY AIMS: Colonoscopy has replaced barium enema as the primary method for direct diagnosis of colorectal cancer, but detection may fail, and the reasons for this are not completely understood. PATIENTS AND METHODS: In order to analyze the accuracy of colonoscopy for detecting invasive colorectal cancer, 7365 colonoscopic examinations were matched with the most accurate local government population-based cancer registry in Japan. RESULTS: In 15 colonoscopic examinations, patients were not diagnosed as having invasive colorectal cancer, but disease of this type was detected within 3 years of the examinations (false-negative examinations). During the same period, 233 colonoscopies were identified as true-positive examinations. The false-negative rate for detecting invasive colorectal cancer with colonoscopy was 6% at 3 years. The false-negative rate was significantly higher in individuals between 60 and 69 years of age and in invasive cancers located to the right of the splenic flexure. CONCLUSIONS: Colonoscopists should receive adequate training in achieving easy cecal intubation, detecting small or flat lesions, and carrying out adequate biopsies.

Colonoscopy↗
PubMed2003

Prospective randomized pilot trial of selective biliary cannulation using pancreatic guide-wire placement.

BACKGROUND AND STUDY AIMS: In difficult cases of selective bile duct cannulation, several expanded techniques are available which have only been partially evaluated in randomized studies. This study describes a prospective, randomized trial investigating a further technique for obtaining selective biliary access--pancreatic duct wire placement. PATIENTS AND METHODS: During a six-month study period, 107 consecutive patients required deep selective biliary cannulation. Accessing the bile duct using a catheter failed within 10 min in 53 of the patients, who were randomly assigned to either pre-insertion of a guide wire into the pancreatic duct or persistence with a conventional catheter. The success rate and complication rate were compared between these two groups. RESULTS: In the pancreatic duct-guide wire group (n=27), the success rate was significantly greater than in the conventional group (93% vs 58%). No pancreatitis complications occurred within either group. CONCLUSIONS: Inserting a guide wire into the pancreatic duct to facilitate deep selective bile duct cannulation is better than persisting with a conventional catheter. Further studies will be needed to confirm these results and to compare this method with other sophisticated techniques for obtaining selective access to the bile duct.

Adult↗
PubMed2003

Measurement of plasma procyanidin B-2 and procyanidin B-3 levels after oral administration in rat.

Using a high-performance liquid chromatographic method and mass spectrometry analysis, we successfully measured the absorption of orally administered procyanidin B-2 and procyanidin B-3 isolated from Cinnamonomi cortex (the bark of Cinnamomum cassia Blume) in the rat plasma. This method used a TSK- GEL ODS-80TS column, two solvents (A: 0.01% acetic acid; B: methanol with 0.01% acetic acid) in a linear gradient at a flow-rate of 1.0 ml/min, and fluorescence detection at excitation and emission wavelengths of 220 and 327 nm.

Administration, Oral↗
PubMed2003

Dedifferentiation and decreased expression of adhesion molecules, E-cadherin and ZO-1, in colorectal cancer are closely related to liver metastasis.

Carcinoma cells with high metastatic potential often show a dedifferentiated phenotype at the primary site. In this study, a total of 48 cases (24 primary tumors of colorectal cancer (Pr-CRC) with liver metastasis, 24 without) were examined for E-cadherin and ZO-1 expression by immunohistochemical staining, and for their dedifferentiated phenotype. The expression levels of E-cadherin and ZO-1 were markedly decreased in the cancer cells of tumors with liver metastasis. Moreover, dedifferentiation of cancer cells, which was evaluated by the modified Gleason score, was also related to liver metastasis. However, none of the conventional clinicopathologic parameters of invasion, except lymph node metastasis, showed any relationship with liver metastasis. These results indicate that dedifferentiation and a decreased expression of E-cadherin and ZO-1 are closely related to liver metastasis.

Cadherins↗
PubMed2002

Endoscopic surveillance for gastric remnant cancer after early cancer surgery.

BACKGROUND AND STUDY AIMS: The aims of this article were to clarify the incidence of gastric remnant cancer after surgery for early gastric cancer, and to develop surveillance programs for patients who have undergone partial gastrectomy in order to detect such lesions at an early stage. PATIENTS AND METHODS: A total of 642 patients with partial gastrectomy for early gastric cancer were enrolled in a surveillance program for gastric remnant cancer between 1985 and 1996. In 509 patients, the interval between endoscopic examinations was no more than 2 years. RESULTS: Among the 509 patients examined periodically, 15 patients were diagnosed as having gastric remnant cancer; in 12 patients, the cancers were detected at an early stage. All gastric remnant cancers were found distant from the site of the anastomosis, and in eight patients the cancers were located on the lesser curvature. The cumulative 5-year prevalence rate was estimated as 2.4 % and the 10-year prevalence rate as 6.1 %. The initial tumors in the patients with gastric remnant cancer were of the microscopically intestinal type, without exception. The interval between the preceding examination and diagnosis was shorter in the patients with early cancer than in those with advanced cancer ( P < 0.01). CONCLUSIONS: Periodical surveillance endoscopy for gastric remnant cancer is recommended after surgery for early gastric cancer, particularly in patients whose cancers are of the intestinal type. The examinations can be repeated at 2 - 3-year intervals, and special attention should be given to the lesser curvature away from the anastomotic site.

Aged↗
PubMed2002

Development of a health guidance support system for lifestyle improvement. Committee of Health Evaluation Support System Council of Japan AMHTS Institutions.

OBJECTIVE: To provide automated advice for lifestyle adjustment based on an assessment of the results of a questionnaire and medical examination or health checkup data. METHODS: A system was developed that gathers data based on questions regarding weight gain, exercise, smoking, sleep, eating habits, salt intake, animal fat intake, snacks, alcohol, and oral hygiene; body mass index, resting blood pressure, fasting blood sugar, total cholesterol, triglycerides, uric acid and liver function tests. Based on the relationships between the lifestyle data and the health checkup data, a health assessment sheet was generated for persons being allocated to a multiple-risk-factor syndrome group. RESULTS: Health assessment and useful advice for lifestyle improvement were automatically extracted with the system, toward the high risk group for lifestyle related diseases. The system is operational. CONCLUSIONS: We developed a health guidance support system for lifestyle improvement. In comparison with conventional, limited advice methods, we developed a practical system that defined the necessity for lifestyle improvement more clearly, and made giving advice easier.

Counseling↗
PubMed2001

Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing the ability of producing secondary metabolites.

Streptomyces avermitilis is a soil bacterium that carries out not only a complex morphological differentiation but also the production of secondary metabolites, one of which, avermectin, is commercially important in human and veterinary medicine. The major interest in this genus Streptomyces is the diversity of its production of secondary metabolites as an industrial microorganism. A major factor in its prominence as a producer of the variety of secondary metabolites is its possession of several metabolic pathways for biosynthesis. Here we report sequence analysis of S. avermitilis, covering 99% of its genome. At least 8.7 million base pairs exist in the linear chromosome; this is the largest bacterial genome sequence, and it provides insights into the intrinsic diversity of the production of the secondary metabolites of Streptomyces. Twenty-five kinds of secondary metabolite gene clusters were found in the genome of S. avermitilis. Four of them are concerned with the biosyntheses of melanin pigments, in which two clusters encode tyrosinase and its cofactor, another two encode an ochronotic pigment derived from homogentiginic acid, and another polyketide-derived melanin. The gene clusters for carotenoid and siderophore biosyntheses are composed of seven and five genes, respectively. There are eight kinds of gene clusters for type-I polyketide compound biosyntheses, and two clusters are involved in the biosyntheses of type-II polyketide-derived compounds. Furthermore, a polyketide synthase that resembles phloroglucinol synthase was detected. Eight clusters are involved in the biosyntheses of peptide compounds that are synthesized by nonribosomal peptide synthetases. These secondary metabolite clusters are widely located in the genome but half of them are near both ends of the genome. The total length of these clusters occupies about 6.4% of the genome.

Base Sequence↗
PubMed2001

DNA demethylase is expressed in ovarian cancers and the expression correlates with demethylation of CpG sites in the promoter region of c-erbB-2 and survivin genes.

The objectives of this study were to examine DNA demethylase (dMTase) expression in ovarian cancers and evaluate methylation of CpG sites in the promoter of the c-erbB-2 gene and survivin gene exon 1. Forty-three epithelial ovarian cancers and 43 non-cancerous ovarian tissues were studied for dMTase expression by RT-PCR. Genomic DNA was extracted and digested with HindIII and then HpaII. CpG site-sensitive primers were constructed to amplify the promoter of the c-erbB-2 gene and survivin gene exon 1. Immunohistochemical evaluation of ErbB-2 protein and RT-PCR for survivin were also performed. dMTase was positive in 88.4% of ovarian cancers but only in 9.3% of non-cancerous ovaries (P<0.001, Fisher's exact test). The expression was similarly observed in both early stage (stage I+II: 17/19) and advanced stage (stage III+IV: 21/24) groups of ovarian malignancy. It was found that 78.9% of dMTase-positive cancers had both c-erbB-2 promoter and survivin gene exon 1 unmethylated, whereas 40% of dMTase-negative cancers had both sites methylated. In non-cancerous ovaries, these sites were mostly methylated (90.6%) and the difference from cancer cases was highly significant (P<0.001). Immunohistochemical evaluation of ErbB-2 showed significant correlation of unmethylated c-erbB-2 promoter and ErbB-2 expression. The RT-PCR for survivin expression showed that 86% of cancers were positive and six cases were negative. Exon 1 was methylated in 83% of the survivin-negative cases. This is the first report of dMTase expression in ovarian cancers. The correlation of dMTase expression with unmethylation of c-erbB-2 promoter and survivin gene exon 1 suggests that these sites may be targets for demethylation by the enzyme. The up-regulation of oncogenes may be the consequence of epigenetic control of gene expression by the dMTase.

Adolescent↗