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Biomedical subjects

H Hatanaka

Publications and source records attributed to H Hatanaka.

At least 37 records · Page 2Linked to original sources
PubMed2001

Comparison of mechanical properties of polyvinylidene fluoride and polypropylene monofilament sutures used for flexor tendon repair.

We performed an experimental study to evaluate the mechanical properties of polyvinylidene fluoride sutures and to compare their use with that of standard polypropylene sutures for the circumferential, epitendinous suture of a flexor tendon repair. Polyvinylidene fluoride sutures had a smaller suture diameter, a greater knot pull strength and less delayed extension when under creep testing, than polypropylene sutures. Tendons repaired using polyvinylidene fluoride sutures had significantly greater gap and breaking strengths than those repaired using polypropylene sutures.

Animals↗
PubMed2001

Comparison of postoperative early active mobilization and immobilization in vivo utilising a four-strand flexor tendon repair.

We evaluated a technique of four-strand double-modified locking Kessler flexor tendon repair in healing tendons. Seventy-two canine flexor digitorum profundus tendons in Zone 2 were repaired and evaluated following either active mobilization or immobilization at 0, 7, 14, 28 and 42 days after surgery. Fifty-six tendons were examined for gap and ultimate strength using a tensile testing machine and 16 were evaluated with standard hematoxylin and eosin, and Masson's trichrome staining. All tendons healed without rupture or gap formation of more than 1 mm, thus demonstrating that this repair technique has enough tensile strength to withstand early active mobilization. The gap and ultimate strength of actively mobilized tendons did not decrease significantly during the first 7 days, and were significantly greater than those of immobilized tendons throughout the 42-day study period. Actively mobilized tendons healed without the extrinsic adhesions and large tendon calluses that were found in immobilized tendons.

Animals↗
PubMed2001

Analysis of tyrosine phosphorylation-dependent protein-protein interactions in TrkB-mediated intracellular signaling using modified yeast two-hybrid system.

Activated receptor tyrosine kinases induce a large number of tyrosine phosphorylation-dependent protein-protein interactions through which they mediate their various ligand-exerted functions including regulation of proliferation, differentiation and survival. TrkB receptor tyrosine kinase activated by binding of brain-derived neurotrophic factor (BDNF) also stimulates various protein interactions in a tyrosine phosphorylation-dependent manner in neuronal cells. To examine tyrosine phosphorylation-dependent interactions stimulated by active TrkB, we developed a modified yeast two-hybrid system, which we call the yeast two-and-a-half-hybrid system. In this system, yeast was engineered to express a tyrosine kinase domain of TrkB as an effector, in addition to two fusion proteins with GAL4 DNA-binding and GAL4 activation domains as bait and prey proteins, respectively. Using this system with Shp2 as the bait, we demonstrated that Shp2 interacts directly with BIT/SHPS-1 (also called SIRP) and Grb2 depending on tyrosine phosphorylation mediated by TrkB. Furthermore, we screened an adult human brain cDNA library with the yeast two-and-a-half-hybrid system in order to identify other Shp2-binding proteins in TrkB-stimulated tyrosine phosphorylation signaling. We found that fibroblast growth factor receptor substrate 2beta (FRS2beta), also called SNT2, interacts with Shp2 dependently on TrkB-mediated tyrosine phosphorylation of FRS2beta/SNT2. Therefore, we show that the two-and-a-half-hybrid system is a powerful tool for studying tyrosine phosphorylation-dependent protein-protein interactions in intracellular signaling pathways stimulated by TrkB receptor tyrosine kinase.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Abnormality of the myocardial sympathetic nervous system in a patient with Becker muscular dystrophy detected with iodine-123 metaiodobenzylguanidine scintigraphy.

PURPOSE: This study was performed to determine whether I-123 metaiodobenzylguanidine (MIBG) scintigraphy can depict myocardial sympathetic nerve abnormalities in Becker muscular dystrophy. MATERIALS AND METHODS: A 34-year-old man with Becker muscular dystrophy underwent Tl-201 and I-123 MIBG scintigraphy sequentially before and 4 months after the beginning of oral administration of enalapril maleate, an angiotensin-converting enzyme inhibitor. RESULTS: Before and during treatment, stress Tl-201 scintigraphy revealed nonreversible myocardial perfusion defects in the anterior, inferoposterior, and apical walls, and I-123 MIBG scintigraphy depicted a region with decreased sympathetic nerve function or innervation. Before treatment, the I-123 MIBG heart count- mediastinum count (H:M) ratio was 2.1 and the washout rate was 21% on delayed images obtained 4 hours after the injection of I-123 MIBG, indicating hyperactivity of the sympathetic nervous system in the myocardium. During treatment, the H:M ratio was 3.0 and the washout rate was 15%. CONCLUSION: With I-123 MIBG scintigraphy it is possible to evaluate an abnormality of the myocardial sympathetic nervous system and the efficacy of administration of an angiotensin-converting enzyme inhibitor in this disease.

Adult↗
PubMed2001

Purification, characterization, and gene cloning of purine nucleosidase from Ochrobactrum anthropi.

A bacterium, Ochrobactrum anthropi, produced a large amount of a nucleosidase when cultivated with purine nucleosides. The nucleosidase was purified to homogeneity. The enzyme has a molecular weight of about 170,000 and consists of four identical subunits. It specifically catalyzes the irreversible N-riboside hydrolysis of purine nucleosides, the K(m) values being 11.8 to 56.3 microM. The optimal activity temperature and pH were 50 degrees C and pH 4.5 to 6.5, respectively. Pyrimidine nucleosides, purine and pyrimidine nucleotides, NAD, NADP, and nicotinamide mononucleotide are not hydrolyzed by the enzyme. The purine nucleoside hydrolyzing activity of the enzyme was inhibited (mixed inhibition) by pyrimidine nucleosides, with K(i) and K(i)' values of 0.455 to 11.2 microM. Metal ion chelators inhibited activity, and the addition of Zn(2+) or Co(2+) restored activity. A 1.5-kb DNA fragment, which contains the open reading frame encoding the nucleosidase, was cloned, sequenced, and expressed in Escherichia coli. The deduced 363-amino-acid sequence including a 22-residue leader peptide is in agreement with the enzyme molecular mass and the amino acid sequences of NH(2)-terminal and internal peptides, and the enzyme is homologous to known nucleosidases from protozoan parasites. The amino acid residues forming the catalytic site and involved in binding with metal ions are well conserved in these nucleosidases.

Amino Acid Sequence↗
PubMed2001

Serum levels of vascular endothelial growth factor and cavity formation in active pulmonary tuberculosis.

BACKGROUND: In active pulmonary tuberculosis, certain cytokines have been postulated to be related to cavity formation, although the detailed mechanism of cavity formation is not yet known. OBJECTIVE: We examined the relationship between cavity formation in pulmonary tuberculosis and vascular endothelial growth factor (VEGF), which functions as an angiogenesis factor. METHODS: Forty-eight patients with active pulmonary tuberculosis were divided into two groups according to cavity formation as evaluated by chest high-resolution computed tomography. We evaluated serum VEGF levels by enzyme immunoassay. RESULTS: Group A (with cavities) was comprised of 22 patients and group B (without cavities) was comprised of 26 patients. The serum levels of VEGF were significantly higher in group B (58.733 +/- 21.612 pg/ml) than those in normal individuals (8.739 +/- 3.656 pg/ml) and in group A (13.053 +/- 8.670 pg/ml) (Mann-Whitney U test, p = 0.0149 and p = 0.0481, respectively). Serum levels of interleukin-8 and tumor necrosis factor-alpha were not significantly different between the two groups. CONCLUSION: These findings suggested that increased serum VEGF levels subdue cavity formation in active pulmonary tuberculosis.

Adolescent↗
PubMed2001

N-Acetyltransferase 2 genotype correlates with sulfasalazine pharmacokinetics after multiple dosing in healthy Japanese subjects.

Sulfapyridine (SP) is metabolized by polymorphic N-acetyltransferase 2 (NAT2) [EC 2.3.1.5]. In this study, the correlation between the NAT2 genotype and the pharmacokinetics of SP after multiple oral dosing of sulfasalazine (SASP) was examined to elucidate the effect of multiple dosing on the predictability of the phenotype by NAT2 genotyping. Seven healthy subjects were classified into two groups; the homozygotes for the wild-type allele, NAT2*4/*4 (Group I) and the compound heterozygotes for the mutant allele (NAT2*4/*6A or NAT2*4/*7B) (Group II). All received once-daily 1 g of SASP (Salazopyrin) orally for 8 d. Plasma concentrations and urinary recoveries of SASP, SP and N-acetylsulfapyridine (AcSP) were monitored for 8 d. At 24 h on Day 1, the plasma concentration of SASP was lower and those of SP and AcSP were higher in Group II compared with Group I, but there was no significant difference. The plasma concentration ratio of AcSP to SP (AcSP/SP) tended to be lower in Group II. Urinary recoveries of SP and AcSP were increased in Group II, and their ratio was slightly reduced in Group II. Multiple dosing for 8 d resulted in an increase in the plasma concentrations of SASP, SP and AcSP. The difference between Group I and II was marked compared with single dosing, resulting in a significant difference in the plasma concentration of SP and the ratio of AcSP/SP. The simple input-output pharmacokinetic model applied for the analysis of plasma concentrations and urinary recoveries of SP and AcSP suggested the acetylation of SP into AcSP was 2.7-fold reduced in Group II (p=0.064).

Acetylation↗
PubMed2001

N-Acetyltransferase2 genotype correlated with isoniazid acetylation in Japanese tuberculous patients.

Isoniazid (INH) is metabolized by polymorphic N-acetyltransferase2 (NAT2). In the present study, the relationship between the NAT2 genotype and the INH acetylator phenotype was examined in Japanese tuberculous patients and compared with healthy subjects. Subjects were classified according to the genotyping into NAT2*5B (allele4), NAT2*6A (allele3) and NAT2*7B (allele2), using the PCR-RFLP method. Twelve healthy subjects and 7 tuberculous patients participated in the INH acetylator phenotyping study, in which each subject was administered an oral dose of INH, followed by urine sampling for 24 h. Urinary concentrations of INH and N-acetylisoniazid (AcINH) were measured by the HPLC method. The urinary recoveries of INH (% of dose) in healthy subjects in relation to NAT2 genotyping were as follows: 6.4+/-2.2 in the homozygotes for the wild-type allele, 10.7+/-2.2 in the compound heterozygotes for the mutant allele, and 38.6+/-6.4 in the homozygotes for the mutant allele. In the patients study, the findings in the corresponding three groups were 4.0+/-1.7, 8.8 and 18.3+/-9.3. Although no significant difference was found because of the lower systemic exposure of INH in patients compared with healthy subjects, there were differences in the disposition kinetics of INH between subjects with and without mutations in the NAT2 gene, and these findings were observed not only in healthy subjects but also in patients who had comedicated drugs and hepatic dysfunctions. The findings indicated that the metabolism of INH by NAT2 is clearly impaired in subjects with mutations in the NAT2 gene, and thus genotyping for three NAT2 point mutations was adequate to predict the metabolism of INH in Japanese tuberculous patients as well as healthy subjects. This NAT2 genotyping could become a useful alternative to TDM for INH.

Acetylation↗
PubMed2001

Effects of double mutation at two distant IgE-binding sites in the three-dimensional structure of the major house dust mite allergen Der f 2 on IgE-binding and histamine-releasing activity.

Recently, we reported that introduction of mutations that induced conformational changes of the major mite allergen Der f 2 was an efficient strategy to reduce the allergenicity for safer allergen-specific immunotherapy. In this study, we evaluated another strategy, disruption of two independent IgE epitopes without inducing conformational change. We analyzed allergenicities of the wild-type Der f 2, two single mutants with a mutation at either of the two IgE-binding sites (K15A and K77A), and a double mutant with mutations at both of the sites (K15/77A). Purified recombinant forms of Der f 2 expressed in Escherichia coli had correct disulfide bonds, equivalent apparent molecular masses of approximately 15 kDa, and similar secondary structures. The mutants of Der f 2 had less IgE reactivities than the wild-type Der f 2 and reduced inhibitory activities for IgE-binding to the wild-type Der f 2. However, the mutations did not significantly reduce histamine-releasing activity.

Allergens↗
PubMed2001

Gene expression of angiogenesis related factors in glioma.

Angiogenesis plays an important role in growth and proliferation of cancer. Various angiogenic and angiostatic factors regulate angiogenesis. In this study, we examined gene expression of the angiopoietin family including angiopoietin 1 (Ang1) and angiopoietin 2 (Ang2) in 39 gliomas and 5 glioma-xenografts by RT-PCR. Ang1 and Ang2 genes were expressed in 54%, and 77% of gliomas, respectively. The expression of Ang1 was significantly correlated with the expression of Ang2. Both Ang1 and Ang2 were shown to be expressed in the glioma cells. Ang2 gene expression was correlated with VEGF gene expression. Angiopoietin molecules may synergistically cooperate in growth and vascularization in glioma.

Angiopoietin-1↗
PubMed2001

Interleukin 10 expression is correlated with thrombospondin expression and decreased vascular involvement in colon cancer.

Interleukin 10 (IL-10) is an immuno-suppressive cytokine produced by T-lymphocytes, and a regulatory molecule for angiogenesis in various cancers. We examined IL-10 gene expression in 53 colon cancer patients who underwent surgical resection. IL-10 gene expression was correlated with TSP1 and TSP2 gene expression (P=0.0049, P=0.0285). Colon cancer with IL-10 gene expression (19/53) showed significantly decreased venous involvement (P=0.0433). The mean vessel counts in the colon cancers with IL-10 gene expression were significantly lower than those without IL-10 gene expression (P<0.001). These results suggested that IL-10 stimulates angiostatic factor gene expression, and results in suppression of venous involvement.

Adenocarcinoma↗
PubMed2001

Interleukin-10 expression is correlated with growth fraction in human non-small cell lung cancer xenografts.

We examined IL-10 and IL-10 receptor (IL-10R) gene expression in 44 xenografts of human non-small cell lung cancer (NSCLC) by reverse transcription-polymerase chain reaction (RT-PCR) assay with human-specific primers. IL-10 gene expression was detected in 10 (22.7%) of 44 xenografts (0/11 adenocarcinomas, 6/19 squamous cell carcinomas, 4/14 large cell carcinomas) and IL-10R expression in 8 (18.2%) xenografts. The IL-10-positive xenografts immunohistochemically showed significantly increased growth fractions of neoplastic cells (471.0 +/- 112.2) relative to IL-10-negative xenografts (208.4 +/- 96.3) (p=0.009, Mann-Whitney U test), and showed significantly increased vascular number (p=0.008, Mann-Whitney U test). These results suggested that IL-10 expression is correlated with growth features in human NSCLC.

Animals↗
PubMed2001

Significant correlation between interleukin 10 expression and vascularization through angiopoietin/TIE2 networks in non-small cell lung cancer.

The expression of interleukin 10 (IL-10) is correlated with clinical prognosis in non-small cell lung cancer [NSCLC (H. Hatanaka et al., ANN: ONCOL:, 11: 815--819, 2000)]. However, the effects of IL-10 expression on vascularization in NSCLC are not apparent. We examined the gene expression of IL-10/IL-10 receptor and various angiogenic/angioinhibitory factors in 95 NSCLC samples to determine the correlation between IL-10 production and vascularization. Vascular endothelial growth factor, angiopoietin [Ang (Ang-1 and Ang-2)], thrombospondin, brain-specific angiogenesis inhibitor 1, vascular endothelial growth factor receptors (KDR and flt-1), and Ang receptor (TIE2) gene expression were evaluated by reverse transcription-PCR. The cellular localization of these factors and vascularity in the cancer stroma were examined immunohistochemically. Seventy-eight (82.1%) and 93 (97.9%) of these 95 NSCLCs were positive for IL-10 and IL-10 receptor, respectively. Ang-1, Ang-2, and TIE2 gene expression was seen in 76 (97.4%), 73 (93.6%), and 78 (100%) of 78 IL-10-positive NSCLCs, respectively, and was significantly correlated with IL-10 gene expression (P < 0.0088, <0.0008, and 0.0305, respectively; Fisher's exact method). The localizations of Ang-1, Ang-2, and TIE2 were confirmed within tumor cells immunohistochemically. Vascular number and measurement area were significantly higher in the IL-10-positive NSCLCs (33.500 +/- 9.299/microm(2) and 4.742 +/- 1.287%) as compared with IL-10-negative NSCLCs (10.611 +/- 2.839/microm(2) and 0.718 +/- 0.331%; Mann-Whitney U test, P = 0.0039). The IL-10 expression did not show any significant correlation with the expression of other factors. These results suggested that tumor-produced IL-10 promotes stromal vascularization through expression of Ang-1, Ang-2, and TIE2.

Angiogenesis Inhibitors↗
PubMed2000

p38 mitogen-activated protein kinase regulates low potassium-induced c-Jun phosphorylation and apoptosis in cultured cerebellar granule neurons.

Cultured rat cerebellar granule neurons are widely used as a model system for studying neuronal apoptosis. After maturation by culturing in medium containing 26 mm potassium (high K(+)), changing to medium containing 5 mm potassium (low K(+); LK) rapidly induces neuronal apoptosis. Then over 50% of granule cells die within 24 h. However, the molecular mechanisms by which the LK-induced apoptosis occurs in cultured cerebellar granule cells remain unclear. In the present study, we found that p38 MAP kinase (p38) was an important factor for LK-induced apoptosis. Three hours after changing to LK medium, p38 was markedly activated. In addition, SB203580, a specific inhibitor of p38, strongly inhibited the phosphorylation and expression of c-Jun in LK-induced apoptosis of cultured cerebellar granule cells. In vitro kinase assay using glutathione S-transferase-c-Jun as a substrate showed that p38 directly phosphorylated c-Jun. Furthermore, in the presence of SB203580, about 80% of neurons survived. These results indicate that p38 regulates LK-induced apoptosis of cerebellar granule neurons.

Animals↗
PubMed2000

Unlocking the allergenic structure of the major house dust mite allergen der f 2 by elimination of key intramolecular interactions.

We report on the structural background of the remarkable reduction of allergenicity in engineering of the major house dust mite allergen Der f 2. Disruption of intramolecular disulfide bonds in Der f 2 caused extensive conformational change that was monitored by circular dichroism and gel-filtration analysis. The degree of conformational change correlated well with the degree of reductions in the capacity to bind IgE and to induce histamine release from basophils in mite-allergic patients. Loosening the rigid tertiary structure by elimination of key intramolecular interactions is an effective strategy to reduce the number of high affinity IgE epitopes of allergen vaccine.

Animals↗