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Biomedical subjects

H Yamazaki

Publications and source records attributed to H Yamazaki.

At least 361 records · Page 20Linked to original sources

mRNA expression of KIF1A, KIF1B, KIF2, KIF3A, KIF3B, KIF4, KIF5, and cytoplasmic dynein during axonal regeneration.

Mouse brain expresses multiple kinesin superfamily proteins (KIFs), which are involved in vesicle transport. The expression of KIFs is developmentally regulated, and both the mRNA and proteins of KIF2 and KIF4 are expressed abundantly in the juvenile brain. To elucidate the role of individual kinesin superfamily motor proteins during regenerative outgrowth of axons, we examined the mRNA expression of KIF1A, KIF1B, KIF2, KIF3A, KIF3B, KIF4, and KIF5 in adult mouse dorsal root ganglion cells after sciatic nerve crush. Seven to fourteen days after the nerve crush, the mRNA expression pattern of neurofilament and beta-tubulin isotypes suggested that the regenerative outgrowth of axons was active. At these stages, levels of mRNA for KIF1A, KIF1B, KIF2, KIF3A, KIF3B, KIF4, and KIF5 were 50.80% of control. The levels of mRNA for KIF4, which are detected in juvenile brain but not in the adult, were under the detection limit in both control and regenerating dorsal root ganglion cells. Because mRNA of neither KIF2 nor KIF4 increased significantly, the results suggest that the gene expression of KIFs during regeneration does not recapitulate the embryonic development and support the hypothesis that different series of events take place during the regenerative and embryonic outgrowths of axons. In contrast, mRNA for cytoplasmic dynein was slightly increased, up to 140%. This is consistent with the hypothesis that retrograde transport plays critical roles in regeneration such as the transport of neurotrophic factors.

Age Factors↗

Late local recurrence after radiotherapy for tongue and early glottic carcinoma.

BACKGROUND/AIM: Late local recurrence after radiotherapy for tongue and early glottic carcinoma is rarely discussed. In the head and neck cancer, approximately 90% of local recurrence occurred within 2 years after radiotherapy. However, we found that late local recurrence after radiotherapy for glottic cancer was not rare. Our aim was to evaluate the late local recurrence after radiotherapy for early glottic and tongue cancer. PATIENTS AND METHODS: From 1967 through 1982, 633 patients with tongue carcinoma and 330 patients with early (T1T2N0) glottic carcinomas were treated at the Department of Radiology, Osaka University Hospital. Of these 821 patients, 329 patients with tongue carcinoma and 221 patients with early glottic carcinoma survived at 5 years after radiotherapy without local recurrence. For tongue carcinoma, patients were divided by T category. For early glottic carcinoma, patients were divided by the tumor response at 40 Gy. RESULTS: Late local recurrence occurred in 23 of 329 patients (7%) with tongue carcinoma, and in 9 of 221 (4%) with early glottic carcinoma. For tongue carcinoma, late recurrence occurred in 19 of 249 patients (8%) in stage I and II, and 4 of 80 patients (5%) in stage III and IV. For glottic carcinoma, late recurrence occurred in 8 of 137 patients (6%) with tumor clearance at 40 Gy and 1 of 63 patients (2%) with tumor persistence at 40 Gy. The incidence of double cancer was also evaluated. Of 329 5-year survivors with tongue carcinoma, 39 patients (12%) had another malignancy, and 26 patients of 221 5-year survivors with early glottic carcinoma (12%) had also another malignancy. Of 39 double primaries of tongue carcinoma, 10 patients (26%) had head and neck malignancies, and none of 26 double primaries of early glottic carcinoma. CONCLUSION: Late local recurrence was not rare in tongue and early glottic cancer. Poor prognostic group showed lower incidence of late recurrence than good prognostic group. This result suggests that secondary tumor at the same site of primary tumor is late local recurrence.

Carcinoma↗

[Perioperative fractionated high dose rate brachytherapy in bone and soft-tissue tumors].

The 13 lesions of 11 patients with bone and soft-tissue tumors (four primary and nine recurrent lesions) were treated with surgery and postoperative fractionated high dose rate (HDR) brachytherapy started on the 6-7th day after surgery. The total dose was 40-50 Gy/7-10 fr/6-7d(bid) at 5 mm from the source. Local control was achieved in eight of 13 lesions (62%). Four of the five uncontrolled lesions had macroscopic residual tumor after the surgery. There was one peripheral nerve damage as a side effect. This study indicates that the use of perioperative fractionated HDR brachytherapy is feasible and well tolerated.

Adolescent↗

Characterization of microsomal cytochrome P450 enzymes involved in the oxidation of xenobiotic chemicals in human fetal liver and adult lungs.

Levels and catalytic activities of cytochrome P450 (P450) enzymes involved in the oxidation of drugs and carcinogens were determined in human adult lungs and fetal livers and compared with those in microsomes from adult livers. P450s immunoreactive with anti-human P4501A1 and anti-human P4503A antibodies were detected in fetal liver microsomes by immunoblotting analysis, and P450s related P4501A1, 2A6, 2C9, 2E1, and 3A4 were determined in adult lung microsomes; all of these P450 enzymes were detected in much higher amounts in adult liver microsomes except that P4501A2 was only the 1A subfamily of P450 found in adult livers. Drug oxidation activities with the substrates ethoxyresorufin, coumarin, 7-ethoxycoumarin, bufuralol, and testosterone were determined in these microsomes, and we found that none of the activities were higher in microsomes of adult lungs and fetal livers than in adult livers. Activation of procarcinogens to reactive metabolites that induce umu gene expression in Salmonella typhimurium TA1535/pSK1002 or NM2009 was also examined and it was found that activities with (+)- and (-)-enantiomers of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene were higher in fetal liver microsomes than adult lung or liver microsomes. The adult liver and lung activities for these two procarcinogens were similar on the basis of microsomal protein contents despite the fact that p450 contents are higher in liver than lung microsomes. alpha-Naphthoflavone, a known inhibitor of P4501A-related activities, did not affect these procarcinogen activation in fetal liver microsomes. Fetal liver microsomes catalyzed activation of aflatoxin B1 and sterigmatocystin, two procarcinogens known to be activated by P4503A4/7 in humans, although activation of carcinogenic arylamines that are good substrates for P4501A2 was much lower in microsomes of fetal livers and adult lungs than in adult livers. These results suggest that in human fetal livers at least two P450 enzymes, a form of P450 that is immunoreactive P4501A1 and P4503A7, are actually expressed and these enzymes are suggested as being involved in the activation of the (+)- and (-)-enantiomers of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene and the carcinogenic mycotoxins, respectively. The exact nature of the former enzyme in fetal livers is unknown. In adult human lungs, several P450 enzymes are expressed, although the precise roles of these enzymes in the oxidation of xenobiotics were not determined due to the low level of expression of these P450s.

Antibodies↗

[Three-dimensional images of the cystic duct obtained with helical DIC CT].

Before laparoscopic cholecystectomy, it is important to clarify the anatomy of the cystic duct. This study assessed three-dimensional CT images (3D images) of the cystic duct obtained non-invasively using helical DIC CT and these images were compared with those obtained with ERCP and DIC. The three-dimensional technique using Helical DIC-CT was applied in 168 patients for laparoscopic cholecystectomy. The cystic duct detected by 3D imaging was evaluated for patency, length and bifurcation. Three-dimensional images showed the cystic duct in 157 of 168 cases (93.5%) and in 81 of 89 cases (91%) in which the cystic duct was not clearly visualized on DIC. Among the 23 cases in which were both 3D images and ERCP undergone, 3D images were equal to those of ERCP in detection of the cystic duct in 20 cases, superior to ERCP in two cases, and inferior to ERCP in one. The technique of 3D images proved useful in demonstrating the patency, length and variations in bifurcation of the cystic duct for surgeons performing laparoscopic cholecystectomy and might be substitute ERCP in preoperative assessment.

Cholangiopancreatography, Endoscopic Retrograde↗

[Development of collagen vascular diseases and production of autoantibodies in HTLV-I env-pX transgenic rats].

Human T lymphocyte virus type I (HTLV- I) is now known to be associated with a number of diverse clinical disorders, not only adult T cell leukemia but also HTLV- I associated myelopathy/tropical spastic paraparesis, HTLV- I -associated arthropathy, HTLV- I uveitis, and probably Sjögren's syndrome, T cell alveolitis, polymyositis, and infective dermatitis. To investigate virus-host interactions and pathogenetic mechanisms in these diverse disorders, inbred rat, which is susceptible to HTLV- I infection and develops HAM/TSP-like disease by HTLV- I infection, was used as a host of HTLV- I gene transfer model. HTLV- I LTR-env-pX-LTR construct was injected to rat ova, and two lines of the transgenic rat (env-pX rat) were established. Both lines of env-pX rats expressed HTLV- I env and pX genes in various tissues, and developed a wide spectrum of collagen vascular diseases, including chronic destructive arthritis similar to rheumatoid arthritis, necrotizing arteritis mimicking polyarteritis nodosa, myositis, myocarditis, and chronic sialoadenitis and dacryoadenitis resembling Sjögren's syndrome in humans. Thrombosis and thymic atrophy were also observed. These rats showed hyper-gamma globulinemia and a number of autoantibodies, including high titered rheumatoid factors, anti-dsDNA antibodies and anti-cardiolipin antibodies were presented in the serum. Results suggest that the HTLV- I env-pX gene may play a pathogenic role in development of collagen vascular diseases associated with autoimmune phenomenon. The env-pX rat appears to be a suitable animal model for elucidating pathogenetic mechanisms implicated in HTLV- I -induced diseases and also in various collagen vascular diseases of unknown etiology in humans.

Animals↗

Fatigue evaluation of lumbar muscles during repeated dynamic trunk exercise.

Muscle fatigue in the lumbar muscles for five normal subjects was investigated during repeated dynamic trunk exercise using a lumbar extension machine which is designed to isolated lumbar extension functions. The electromyogram (EMG) signal from erector spinae muscles at lumbar 1 (L1), lumbar 3 (L3) and lumbar 5 (L5) spinal level was detected by bipolar Ag-AgCl surface electrodes. Subjects were required to perform one set of variable resistance lumbar extensions through a 72 degrees range of motion (ROM) with a weight load (50% maximal voluntary contraction) that allowed 13 repetitions of fatigue contraction. Median frequency (MF) of EMG power spectrum was analyzed to compare the difference of fatigability between each lumbar muscle. The experimental results indicated: 1) each lumbar muscle has characteristic MF, especially at the beginning of the trunk exercise (i.e., L1 = 86 Hz, L3 = 96 Hz and L5 = 106 Hz); 2) Significant differences (P < 0.001) in MF between the beginning and the end of trunk exercise for all lumbar muscle sites; 3) Significant differences in the decreasing ratios of MF between L1, L3 and L5. Based on the theory that the decreasing ratio of MF is proportional to fatigability, L5 was more fatiguable than L1 and L3.

Adult↗

[Clinical study on urinary cytology in renal pelvic and ureteral tumors].

We analyzed the urinary cytology of 126 patients with renal pelvic and ureteral cancer who were initially treated during the last 10 years. Cytological specimens were stained by the Papanicolaou techniques. Urinary cytology was classified according to the Papanicolaou's classification. Classes IV and V were defined as positive. The cytologic findings were compared with the grade, shape, size, number and stage of tumors. The positive rates were 49.2% in renal pelvic and ureteral cancers. Higher positive rates were observed in high grade, non-papillary and large (> or = 3 cm) tumors. No correlation existed among the positive rates and number or stage of the tumor.

Adult↗

[Pulmonary aspergillosis: clinical findings and surgical treatment].

Between 1980 and 1995, 10 patients underwent thoracotomy for pulmonary aspergillosis. In six patients, hemoptysis and bloody sputum were the chief complaints. The other complaints were nonspecific. Six patients had a history of pulmonary tuberculosis, and two of those patients underwent upper lobectomy. Aspergillosis had developed in the residual space. A fungus ball was observed on the preoperative chest X-ray and CT scan films in seven patients. Lobectomy was done in three patients, segmentectomy in two, and partial pulmonary resection in four. The patients with lesions that had grown in the residual space underwent curettage with muscle plombage. Three patients underwent thoracoplasty. An additional operation was done in two patients because of poor residual lung expansion. No patient had recurrence. We conclude that surgical treatment should be based on symptoms and on pathological findings.

Adult↗

In vivo and in vitro characterization of CYP2E1 activity in Japanese and Caucasians.

Chlorzoxazone's disposition after oral administration was determined in 20 young healthy Caucasian men and a similar group of Japanese men. The drug's plasma concentrations were significantly higher and its rate of elimination slower in Japanese compared to Caucasian men. Accordingly, chlorzoxazone's oral clearance was smaller (40%) in Japanese men and a similar difference (30%) was still apparent after normalizing for body weight (3.74 +/- 1.23 versus 5.05 +/- 1.41 ml.min-1.kg-1, P < .05). This slower elimination was associated with a reduced (fractional) clearance by 6-hydroxylation (2.34 +/- 1.04 ml.min-1.kg-1 versus 3.23 +/- 1.10, P < .05). Because such metabolism is mediated by cytochrome P4502E1 (CYP2E1), these findings suggest a lower level of the enzyme's catalytic activity in Japanese men. This was confirmed by in vitro studies with microsomes prepared from livers of individuals representative of the two racial groups. CYP2E1 levels were lower (61% P < .002) and CYP2E1-mediated chlorzoxazone 6-hydroxylase (22%, P < .001) and aniline 4-hydroylase (35%, P < .0001) activities were reduced in Japanese preparations compared to those from Caucasians. No relationships were found between measures of CYP2E1 activity, both in vivo and in vitro, and genomic polymorphisms in the CYP2E1 gene identified by Rsal/Pstl and Dral restriction fragment length polymorphisms. Collectively, these data show an interracial difference in CYP2E1 activity. Because this enzyme is importantly involved in the activation of environmental procarcinogens, such a difference may account, in part, for the lower rate of some cancers, e.g., lung cancer, in Japanese compared to Caucasians men.

Adolescent↗

Effect of FR133605, a novel cytokine suppressive agent, on bone and cartilage destruction in adjuvant arthritic rats.

OBJECTIVE: We evaluated the effect of FR133605, a novel inhibitor of interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), on bone and cartilage destruction in adjuvant arthritic rats and compared it to corticosteroid, nonsteroidal antiinflammatory drugs (NSAID), and disease modifying antirheumatic drugs (DMARD). METHODS: The antiinflammatory responses were evaluated by measurement of hind paw swelling, body weight, femoral bone mineral density, and glycosaminoglycan content (GAG) in femoral condyles in adjuvant arthritic rats. RESULTS: FR133605 inhibited IL-1 and TNF-alpha production stimulated with lipopolysaccharide (LPS) in human monocytes. FR133605 also inhibited serum IL-1 and TNF-alpha concentrations in LPS treated mice. In contrast, among comparison antirheumatic drugs, only corticosteroid inhibited production at nontoxic concentrations. In adjuvant arthritis, FR133605 significantly inhibited paw swelling, bone and cartilage destruction, and increased body weight. On the other hand, indomethacin significantly inhibited paw swelling, but not bone and cartilage loss. Dexamethasone completely inhibited paw swelling and bone loss, but augmented cartilage breakdown. DMARD weakly restored the loss of GAG contents in articular cartilage. CONCLUSIONS: FR133605 improved bone loss and articular cartilage destruction in adjuvant arthritic rats and the inhibitory effect was closely correlated with the suppressive activity of IL-1 and TNF-alpha production.

Adrenal Cortex Hormones↗

Pharmacokinetics and tolerance of pantoprazole, a proton pump inhibitor after single and multiple oral doses in healthy Japanese volunteers.

The pharmacokinetics and tolerance of pantoprazole were investigated after single (20, 40, 80, and 120 mg) and multiple (80 mg once a day for 7 days) oral administration as enteric-coated tablet formulation to healthy male Japanese volunteers. Pantoprazole was well tolerated with no serious adverse events at all doses. Pantoprazole was rapidly absorbed in the fasted state. The mean maximum concentration in serum (Cmax) ranged from 1.77-9.25 micrograms/ml for the 20-120 mg dose and the mean time to reach Cmax (tmax) ranged from 1.92-2.42 h. The half-life (t1/2) ranged from 0.74-1.16 h. A good linear correlation was found between the administered doses (20-120 mg) and the resulting area under the concentration-time curve (AUC) and Cmax with the correlation coefficients of 0.9088 and 0.9263, respectively. Within 24 h, pantoprazole was excreted into urine as the unchanged drug to a negligible extent. In the multiple dose study, 2 apparent poor metabolizers (PMs) of pantoprazole were observed. The means of Cmax, AUC and t1/2 for these 2 PMs were 1.6, 6.7, and 6.8 times higher than those of the extensive metabolizers (EMs). The pharmacokinetic parameters such as Cmax, AUC, and t1/2 after the 7th oral dose were not significantly different from those after the 1st dose both in the PMs and the EMs, which indicated that there was virtually no drug accumulation.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effects of N-3554S, a polyprenyl phosphate, on B16-F10 mouse melanoma cells.

N-3554S, an optically active S-isomer of alpha-dihydrodecaprenyl phosphate, reduced the tumorigenicity of cultured B16-F10 mouse melanoma cells probably by affecting protein N-glycosylation. Accordingly, membrane glycoprotein samples were prepared from the melanoma cells cultured with or without N-3554S, and amounts and structures of N-linked sugar chains were determined. Analyses of the N-linked oligosaccharides released by hydrazinolysis from these samples and reduced with NaB3H4 revealed that the N-3554S-treated cells contain 1.5-1.8 times as much oligosaccharides as the control cells, and the relative amounts of high-mannose-type and bi-, tri- and tetra-antennary complex-type sugar chains are almost the same between two samples. Western blot analysis, however, showed that binding of L-PHA, which binds to oligosaccharides with the GlcNAc beta 1-->6(GlcNAc beta 1-->2)Man structure, is significantly reduced in 90 K, 96 K, 140 K, 155 K and 180 K glycoproteins in N-3554S-treated cells. Immunoblot analysis showed that the 140 K glycoprotein could be a fibronectin receptor. It was also shown that N-3554S treatment enhances the adhesiveness of the cells to fibronectin. These results indicate that N-3554S affects N-glycosylation of membrane glycoproteins and alters the cell surface properties of B16-F10 cells.

Animals↗

Mutagenic activation of 3-methoxy-4-aminoazobenzene by mouse renal cytochrome P450 CYP4B1: cloning and characterization of mouse CYP4B1.

A new P450 responsible for mutagenic activation of 3-methoxy-4-aminoazobenzene (3-MeO-AAB) which is a potent procarcinogen was purified from renal microsomes of male mice using an index of umu gene expression. The purified P450 had high bioactivation toward 3-MeO-AAB and also 2-aminofluorene and 2-aminoanthracene. The antibody against this P450 completely inhibited mutagenic activation of 3-MeO-AAB of mouse renal microsomes. With immunoblotting, this form was present abundantly in renal microsomes of male mice but not in those of female mice. This P450 was also present in pulmonary microsomes of male and female mice but not in hepatic microsomes. The NH2-terminal amino acid sequence analysis indicated that this form belonged to the CYP4B subfamily. Thus, mouse kidney cDNA library was screened with rat CYP4B1 probe. The cDNA-deduced amino acid sequence of isolated cDNA consisted of 511 amino acids and bore 90, 86, and 84% similarities to rat, rabbit, and human CYP4B1, respectively. The NH2-terminal amino acid sequence of the purified renal P450 and amino acid sequence of BrCN-digested peptides from the purified P450 agreed with the cDNA-deduced amino acid sequence. These results suggest that CYP4B1 is a major form in renal microsomes of male mice and plays a major role in mutagenic activation of 3-MeO-AAB. In extrahepatic tissue, CYP4B1 may contribute to chemical carcinogenesis.

Amino Acid Sequence↗

Roles of divalent metal ions in oxidations catalyzed by recombinant cytochrome P450 3A4 and replacement of NADPH--cytochrome P450 reductase with other flavoproteins, ferredoxin, and oxygen surrogates.

Recombinant cytochrome P450 (P450) 3A4 was most active in nifedipine and testosterone oxidation in a system including NADPH-P450 reductase, cytochrome b5 (b5), a semisynthetic phospholipid mixture plus cholate, glutathione, and MgCl2. The MgCl2 effect could be seen with high concentrations of Ca2+ or Sr2+ but not readily when these cations were replaced with monovalent cations. The divalent cation effect was also seen in liver microsomes. Part of the basis of this effect appears to be enhanced rates of b5 reduction, as judged from studies on deletions of reconstitution components and analysis of steady-state spectral studies. Rapid reduction of ferric P450 3A4 to ferrous was dependent upon the presence of substrate, either testosterone or ethylmorphine. When testosterone was present, reduction was also highly dependent upon the presence of b5 and Mg2+. In the case of the substrate ethylmorphine, the need to add b5 and Mg2+ to obtain optimal reduction rates was less pronounced. These patterns are consistent with the dramatic dependence of testosterone 6 beta-hydroxylation on b5 and the lack of dependence of ethylmorphine N-demethylation on b5. Our interpretation is that divalent cations stimulate electron transfer from NADPH-P450 reductase to several acceptors and that substrates and b5 can bind to P450 3A4 to influence its rate of reduction by the reductase. P450 3A4 catalyzed testosterone 6 beta-hydroxylation within Escherichia coli cells. The reactions could be supported by E. coli cytosol or by purified E. coli flavodoxin and NADPH-flavodoxin reductase. Spinach ferredoxin and NADPH-ferredoxin reductase also supported catalytic activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cytokine-producing mammary carcinomas in transgenic rats carrying the pX gene of human T-lymphotropic virus type I.

In two lines of transgenic rats (pX rats) from WKAH and F344 strains and carrying the human T-lymphotropic virus type I pX gene, undifferentiated mammary carcinomas developed predominantly in females starting at about 5 months of age, and there was massive infiltration of granulocytes in the tumor tissue. The incidence of the tumor reached about 40% when the rats were 12 months old. mRNAs of both pX and host genes Gro and MIP-2, which are granulocyte chemoattractants of the interleukin 8 family, were highly expressed in the tumor tissue. Since expression and point mutation of several oncogenes and the antioncogene were not demonstrated, hitherto unidentified novel oncogenic pathways may be transactivated by the pX transgene in these pX rats.

Animals↗

The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors.

Axonal transport has been intensively examined as a good model for studying the mechanism of organelle transport in cells, but it is still unclear how different types of membrane organelles are transported through the nerve axon. To elucidate the function of this mechanism, we have cloned KIF1A, a novel neuron-specific kinesin superfamily motor that was discovered to be a monomeric, globular molecule and that had the fastest reported anterograde motor activity (1.2 microns/s). To identify its cargo, membranous organelles were isolated from the axon. KIF1A was associated with organelles that contained synaptic vesicle proteins such as synaptotagmin, synaptophysin, and Rab3A. However, this organelle did not contain SV2, another synaptic vesicle protein, nor did it contain presynaptic membrane proteins, such as syntaxin 1A or SNAP-25, or other known anterograde motor proteins, such as kinesin and KIF3. Thus, we suggest that the membrane proteins are sorted into different classes of transport organelles in the cell body and are transported by their specific motor proteins through the axon.

Amino Acid Sequence↗