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Biomedical subjects

T Yamazaki

Publications and source records attributed to T Yamazaki.

At least 523 records · Page 29Linked to original sources
PubMed1994

[Relapse of acute leukemia after allogeneic bone marrow transplantation].

The relapses of 45 acute leukemia patients who underwent allogeneic bone marrow transplantation between April 1976 and February 1992 were analyzed clinically. The relapse rates of acute nonlymphocytic leukemia (ANLL) and acute lymphocytic leukemia (ALL) were 4/26 (15%) and 9/19 (47%), respectively. Although multivariate analysis could not be done, a high frequency of leukemia relapse was significantly associated with ALL, a younger age, history of extramedullary leukemia and blood-type identity. Chromosomal abnormalities at diagnosis, interval from diagnosis to bone marrow transplantation (BMT) and graft-versus-host disease (GVHD) prophylaxis were likely to be predictive of relapse. On the other hand, neither stage of leukemia at BMT, acute GVHD, sex, nor WBC count at diagnosis was a predictive factor. Eight of 10 relapsed patients achieved complete remission posttransplant, but the duration of remission was only 138 days on average. Four second BMT procedures for relapsed leukemia were carried out but were associated with many complications. However, one is alive well over 6 years after the second transplantation. There is a high treatment-related mortality following second BMT, but there is some possibility of long survival in some patients.

Adolescent↗
PubMed1994

[A case of left atrial free-floating ball thrombus].

A rare case of left atrial free floating ball thrombus with mitral stenosis is reported. A 66-year-old woman was admitted for epigastralgia and acute heart failure without atrial fibrillation and previous embolization. The patient was treated successfully with removal of ball thrombus and mitral valve replacement. Intraoperative transesophageal echocardiography was effective for monitoring of mobile left atrial thrombus.

Aged↗
PubMed1993

Time-resolved fluorescence spectroscopy and photolysis of the photoreceptor blepharismin.

Blepharismin is the photoreceptor for the photophobic response in the ciliate Blepharisma japonicum (Scevoli, P., Bisi, F., Colombetti, G., Ghetti, F., Lenci, F., and Passarelli, V. (1987) J. Photochem. Photobiol.: B. Biol. 1, 75-84; Lenci, F., Ghetti, F., Gioffre, D., Heelis, P.F., Thomas, B., Phillips, G.O., and Song, P.-S. (1989) J. Photochem. Photobiol.: B. Biol. 3, 449-453). Blepharismin was solubilized from the red cells with 2% n-octylglucopyranoside. A crude pigment-protein preparation was then successively subjected to Bio-Gel A1.5 filtration, FPLC/hydroxyapatite and FPLC/DEAE ion-exchange chromatography. At least two spectrally distinct forms of blepharismin, with the respective absorbance maxima at 597 +/- 1 and 601 +/- 1 nm, were resolved. The steady state fluorescence emission maxima were at 602.5 and 617.5 nm, respectively. The fluorescence decay curves for these pigments were non-exponential. The major component possesses relatively short fluorescence lifetime (200-500 ps) for the former, according to a global analysis. This analysis suggests that the excited state of the shorter wavelength-absorbing form of blepharismin undergoes primary photoprocess faster than that of the free parental chromophore hypericin. Photolysis of blepharismin in solution yielded a irreversible product, accompanied by a 10-12 nm bathochromic shift of the absorbance maximum. However, the mechanistic nature of the time-resolved fluorescence and the photochemistry of blepharismin remains to be elucidated.

Animals↗
PubMed1993

An immunohistochemical study of the c-erbB-2 oncogene product in intraductal mucin-hypersecreting neoplasms and in ductal cell carcinomas of the pancreas.

BACKGROUND: Intraductal mucin-hypersecreting neoplasm of the pancreas (IMHN) is a unique tumor that has a tendency to spread intraductally. The clinical outcome of IMHN generally is far better than that of pancreatic ductal cell carcinoma. Because of the presence of various cell atypia within the same tumor, it sometimes is difficult to make an accurate histopathologic diagnosis and, therefore, predict its biologic behavior. It has been shown that overexpression of c-erbB-2 protein in breast cancer with lymph node metastases is related to a poor prognosis. Overexpression of c-erbB-2 protein has been reported as an infrequent event in pancreatic ductal cell carcinoma, but little is known in the case of IMHN. METHODS: The expression of c-erbB-2 protein was immunohistochemically investigated in the formaldehyde-fixed, paraffin-embedded tissues of 17 cases of IMHN, and 14 cases of pancreatic ductal cell carcinoma (8 cases with lymph node metastasis), using polyclonal and monoclonal c-erbB-2(p185) antibodies by the avidin-biotin method. RESULTS: Both the polyclonal and monoclonal antibodies showed similar immunostaining for the c-erbB-2 product. Overexpression of the c-erbB-2 product was observed frequently in IMHN (13/17), especially in that with moderate- to high-grade cell atypia (12/12), whereas it was detected in only 1 of 14 cases of pancreatic ductal cell carcinoma (1/14). Among eight cases of pancreatic ductal cell carcinoma with lymph node metastases, overexpression of the c-erbB-2 product in metastatic lesions was detected in two, one of whose primary lesions also overexpressed the oncogene product. CONCLUSIONS: These observations suggest the genetic expression of c-erbB-2 is related to the pathogenesis of IMHN.

Adenocarcinoma, Mucinous↗
PubMed1993

Mechanical loading activates mitogen-activated protein kinase and S6 peptide kinase in cultured rat cardiac myocytes.

The molecular mechanisms by which overloaded cardiac myocytes increase the cell size (hypertrophy) remain unknown. We have previously shown that mechanical loading increased the protein synthesis and the expression of proto-oncogene c-fos mRNA (Komuro, I., Kaida, T., Shibazaki, Y., Kurabayashi, M., Katoh, Y. Hoh, E., Takaku, F., and Yazaki, Y. (1990) J. Biol. Chem. 265, 3595-3598; Komuro, I., Katoh, Y., Kaida, T., Shibazaki, Y., Kurabayashi, M., Hoh, E., Takaku, F., and Yazaki, Y. (1991) J. Biol. Chem. 266, 1265-1268). It has been known that both mitogen-activated protein (MAP) kinase and S6 kinase can be activated by many kinds of growth factors. To clarify whether MAP kinase(s) and S6 kinase(s) are associated with the intracellular signaling of cardiac hypertrophy induced by mechanical loading, we cultured neonatal rat cardiac myocytes in deformable dishes and imposed an in vitro mechanical loading by stretching the adherent myocytes. In this study, we demonstrated that 1) myocyte stretching maximally activated a kinase activity toward myelin basic protein (MBP) at 10 min after stretching, and the kinase activity returned to the control level at 30 min after stretching; 2) kinase assays in MBP-containing gel, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, revealed that stretch-induced MBP kinase activity mainly migrated at 42 kDa in the immunoprecipitated fraction of anti-MAP kinase antibody, suggesting that the stretching mainly increased the 42-kDa MAP kinase activity in cardiac myocytes; 3) phosphorylation of MAP kinase was induced after stretching cardiac myocytes; 4) when protein kinase C was depleted by preincubating myocytes with 100 nM 12-O-tetradecanoyl-phorbol-13-acetate for 24 h or 2 nM staurosporine for 30 min, stretch-induced MBP kinase activity was decreased by approximately 60-70% as compared with the kinase activity in myocytes without protein kinase C depletion; 5) although the receptor tyrosine kinases were depleted by preincubating myocytes with 50 microM tyrphostin or 20 microM genistein for 30 min, there was no change in the stretch-induced MBP kinase activity; 6) stretch-induced MBP kinase activity was partially dependent on transsarcolemmal influx of Ca2+; 7) myocyte stretching also increased S6 peptide (RRLSSLRA) kinase activity in the anti-S6 kinase II antibody immunoprecipitates. From these results, we conclude that myocyte stretching increases the activities of MAP kinase and S6 peptide kinase, which may play an important role in the induction of the specific genes and the increase in the protein synthesis.

Alkaloids↗
PubMed1993

A phenotypically neutral dimorphism of protein S: the substitution of Lys155 by Glu in the second EGF domain predicted by an A to G base exchange in the gene.

During the course of structural gene analysis of a family with type III protein S deficiency, we found a novel DNA polymorphism: an A or G variation at nucleotide 732 in exon 6 of the PS-alpha gene. This A to G mutation would lead to a substitution of Lys155 by Glu in the second EGF domain. Linkage study with restriction enzyme analysis using mutagenic PCR strategy showed that the same mutation was also present in three other members of the patient's family and two individuals from an unrelated kindred, while they all had normal amounts of both immunological and functional PS levels. Restriction enzyme analysis of 182 normal Japanese genomic samples showed that 1.65% of normal population were heterozygotes for this variant allele. These findings suggest that this substitution in exon 6 is not responsible for the type III protein S deficiency but a phenotypically neutral polymorphism. Hereby we designate this polymorphism as PS-732.

Adolescent↗
PubMed1993

Complete assignments of magnetic resonances of ribonuclease H from Escherichia coli by double- and triple-resonance 2D and 3D NMR spectroscopies.

Assignments of 1H, 15N, and 13C magnetic resonances for ribonuclease H from Escherichia coli have been completed using double- and triple-resonance 2D and 3D NMR experiments. These assignments include all types of 1H, 15N, and 13C nuclei detectable by NMR. The enzyme used, which cleaves the RNA moiety of an RNA-DNA duplex, consists of 155 amino acid residues and has 1962 nuclei (227 nitrogen, 762 carbons, and 973 protons) observable independently by NMR. Among those, 1868 nuclei (95%) have been assigned. Two methods, 3D HCH and 13C-13C-1H heteroSQC/homoSQC, were newly devised to complete the side chain assignments. These methods were used to elucidate the -CH2- and -C-CH-substructures. Triple-resonance experiments to detect other types of substructures, (e.g., -N-CH- and -C-NH-) were also applied. In total, 10 kinds of 3D NMR experiments were used to complete the assignments. The chemical shifts obtained through the assignments were analyzed in terms of the tertiary structure of the protein molecule. Among the 13C chemical shifts, larger secondary shifts (deviations from shifts at the random coil state) were observed for the C alpha, C beta, and C' nuclei, which reflect the local structures on the backbone, that is, the alpha-helix, beta-sheet, and left-handed helix, respectively.

Amino Acid Sequence↗
PubMed1993

Determination of aspoxicillin in broncho-alveolar lavage fluid by high-performance liquid chromatography with photolysis and electrochemical detection.

A determination method for the penicillin antibiotic aspoxicillin in broncho-alveolar lavage fluid has been developed, involving high-performance liquid chromatography and post-column photolysis. The method enabled the determination of aspoxicillin at concentrations below 100 ng/ml, with a linear calibration curve at concentrations of 1-1000 ng/ml for 100 microliters of lavage fluid. The detection limit was 1 ng/ml at a signal-to-noise ratio of 3:1.

Amoxicillin↗
PubMed1993

A topochemical approach to explain morphiceptin bioactivity.

A topochemical model to explain the bioactivity of morphiceptin (Tyr1-Pro2-Phe3-Pro4-NH2) was developed by taking account of accessible conformations around rotatable bonds which define relative spatial arrangements of opioid pharmacophores, the amine and phenolic groups of tyrosine and the aromatic ring of phenylalanine, necessary for receptor recognition. For this purpose, 1H-NMR measurements and computer simulations were extensively carried out on 10 stereoisomeric analogs related to morphiceptin: Tyr-Pro-(L and D)-Phe- (L and D)-Pro-NH2; Tyr-Pro-(L and D)-(NMe)Phe-(L and D)-Pro-NH2; Tyr-(NMe)Ala-Phe-D-Pro-NH2; and Tyr-Ala-Phe-D-Pro-NH2. These analogs are structurally close to one another but display various opiate potencies from highly active to inactive. The conformation of each rotatable bond has been specifically identified by measuring accessible space for the analogs, in which the difference in composition is observed in the specific site affecting only the conformation around the target bond. The most interesting characteristic of the model is a requirement of a cis amide bond linking residues 1 and 2. The model also requires the side chains in a trans conformation (chi 1 = 180 degrees) for the Tyr and Phe residues. The distances between the three pharmacophores, d1 (Tyr N to Tyr OH), d2 (Tyr N to the center of the aromatic ring of the third residue), and d3 (Tyr OH to the center of the aromatic ring of the third residue), were found to be approximately 8, approximately 7, and approximately 11-13 A, respectively. This model should aid in pharmaceutical design of peptide and nonpeptide ligands with opioid potencies.

Analgesics↗
PubMed1993

Role of protein kinase system in the signal transduction of stretch-mediated protooncogene expression and hypertrophy of cardiac myocytes.

To examine the molecular mechanisms by which mechanical stimuli induce protooncogene expression and hypertrophy of cardiac myocytes directly, we cultured rat neonatal cardiac myocytes in deformable dishes and imposed mechanical load on adherent cultured cardiac myocytes by stretching the dishes. Myocyte stretching increased total cell RNA content and mRNA levels of c-fos and skeletal alpha-actin followed by the amino acid incorporation into cardiac proteins. CAT assay analysis indicated that the sequences containing serum response element were required for the efficient transcription of c-fos gene by stretching. This accumulation of c-fos mRNA by myocyte stretching was inhibited markedly by down-regulation of protein kinase C. Moreover, myocyte stretching increased inositol phosphate levels. These findings suggests that mechanical stimuli might directly induce protooncogene expression possibly via protein kinase C activation. Furthermore, we observed the activation of MAP kinase by myocytes stretching. This result suggests that MAP kinase activation induced by mechanical stimuli might increase the efficiency of protein synthesis on ribosomes induced by mechanical stimuli.

Actins↗
PubMed1993

Measurement of two- and three-bond 13C-1H J couplings to the C delta carbons of leucine residues in staphylococcal nuclease.

A new 1H-detected 3D NMR experiment is described that permits quantitative measurement of two- and three-bond 13C-1H couplings in proteins with selectively 13C-enriched methyl sites. The method is demonstrated for staphylococcal nuclease selectively [5,5 13C]-labeled in all 11 leucine positions and ligated with thymidine 3',5'-biphosphate and Ca2+. Two- and three-bond 13C methyl-proton couplings are reported and, together with the measured three-bond JC alpha C delta in uniformly 13C-enriched staphylococcal nuclease, the chi 2-angles and the stereospecific assignments of the C delta methyl group with respect to the prochiral beta-protons were determined. The same residues that were previously found to have high degrees of internal mobility on the basis of 13C relaxation times have measured coupling constants that are indicative of motional averaging.

Amino Acid Sequence↗
PubMed1993

The point mutation of c-Ki-ras at codon 12 in carcinoma of the pancreatic head region and in intraductal mucin-hypersecreting neoplasm of the pancreas.

In order to clarify whether the detection of a point mutation in the c-Ki-ras gene at codon 12 in tumor tissues can assist in predicting the tumor's biological grade of malignancy, two types of tumors were investigated; one was called "carcinoma in the pancreatic head region," and the other was intraductal mucin-hypersecreting neoplasm of the pancreas (IMHN). Dot hybridization and a modified PCR technique developed by Haliassos et al. were employed. Among 16 cases of tumors in the pancreatic head region, the point mutation was detected with a high frequency only in pancreatic ductal cell carcinomas (five out of six cases, 83.3%), but was not detected in extrahepatic bile duct carcinomas (0/5) or in ampullary carcinomas (0/5). In pancreatic ductal cell carcinomas, no relation was found between the occurrence of the point mutation and the histological type of the tumor. Among 20 cases of IMHNs, the point mutation was found in 11 cases (55%). No relation was found between the occurrence of the mutation and the size of IMHNs. However, as the grade of cell atypia increased, the frequency of the mutation tended to become higher. These results suggest that detection of this point mutation might be useful for distinguishing pancreatic ductal cell carcinoma from those of other origins in the pancreatic head region, and for the determination of the histopathological grade of malignancy in IMHNs.

Aged↗
PubMed1993

Ultrastructural localization of amyloid beta/A4 protein precursor in the normal rat brain.

The ultrastructural localization of amyloid beta/A4 protein precursor (APP) was studied immunohistochemically in normal rat brains using antibodies against different portions of APP. In cerebral cortical neurons and Purkinje cells. APP reaction products were located in the cytoplasm and on cell surface membranes. Some Golgi apparatuses and rough endoplasmic reticulum also showed APP immunoreactivity on their membranes and some vesicles near the trans face of the Golgi apparatuses were stained. In the neuropil of the cerebral cortex and the cerebellar molecular layer, many cell processes, which surrounded synapses and were considered to be astrocytic, were APP-positive. Foot processes around capillaries and subpial astrocytic processes were also immuno-positive. At the ultrastructural level, APP-positive astrocytic processes were identified.

Amyloid beta-Peptides↗
PubMed1993

Effects of halothane on carotid occlusion in rabbits.

Effects of halothane on the carotid sinus baroreflex control of circulation were studied in chronically instrumented rabbits. The carotid sinus baroreflex was evaluated by the hemodynamic responses to bilateral carotid occlusion (BCO). Either 0.5 or 1.0 MAC of halothane inhalation did not alter mean arterial pressure (MAP) or total peripheral resistance (TPR), but significantly increased heart rate (HR). Carotid occlusion produced a significant increase in MAP and HR, and both responses were attenuated dose-dependently by halothane. Halothane depressed the reflex gain of arterial pressure from 3.5 +/- 0.3 at conscious state to 1.3 +/- 0.2 at 1.0 MAC halothane. Response of cardiac output (CO) to BCO was attenuated significantly only at 1.0 MAC compared with those responses at conscious state and at 0.5 MAC. Response of TPR was attenuated at both 0.5 and 1.0 MAC halothane as compared with at conscious state but no significant difference existed between the two concentrations of halothane. These data suggested that halothane could attenuate the carotid occlusion responses to various degrees in the involved effector components. 0.5 MAC halothane attenuated MAP response to BCO predominantly by attenuating reflex peripheral vasoconstriction. The reduced CO response was mainly responsible for further attenuation of MAP response at 1.0 MAC halothane.

Journal Article↗
PubMed1993

Molecular and biochemical analyses of combining sites of monoclonal anti-morphine antibodies.

V region nucleotide sequences were determined by mRNA sequencing for 11 monoclonal anti-morphine antibodies with slightly different specificities for morphine-related opiates. The VH region nucleotide sequences of the antibodies MOR8, MOR33, MOR35, MOR44, MOR83, and MOR76 were classified into the VH-5 (7183) family, while the antibodies MOR39, MOR115, MOR131, MOR158 and MOR180 used VH-1 (J558) family genes. MOR39, MOR115 and MOR131 used the V lambda-1 gene for their L chain V region. MOR158 and MOR180 used the Vk-10 gene. MOR8, MOR33, OR35, MOR44, MOR76 and MOR83 used VK-21D. The antibody sets MOR158 and MOR180; MOR39 and MOR131; and MOR8, MOR33, MOR35, MOR44, MOR76 and MOR83 appeared to be somatic mutants derived from the same clones since they showed the same VH/VL usage and V(D)J recombination pattern. The pH-reactivity profiles for these antibodies revealed that the binding of morphine to the antibodies is highly dependent on the pH value of the assay solution, suggesting the importance of the electrostatic interaction between the positive charge of morphine and the negative charges at or near the combining sites. Direct UV-photoaffinity labeling with 3H-morphine was carried out in order to estimate the orientation of morphine in the combining sites. The H chains were preferentially labeled in MOR8, MOR33, MOR35, MOR76, and MOR83, whereas most of the crosslinked hapten was found in the L chains in MOR39, MOR115, MOR131, MOR158 and MOR180. Thus, these 11 antibodies were classified into two types in terms of reactivity in the photoaffinity labeling.

Affinity Labels↗
PubMed1993

Effects of vasopressin on the response to carotid occlusion in conscious rabbits.

To investigate the interaction between arginine vasopressin and the carotid sinus baroreflex, hemodynamic responses to bilateral carotid occlusion and to controlled reductions in carotid sinus pressure were examined. In the control state and during vasopressin infusion in conscious rabbits, mean arterial pressure, heart rate, mean aortic flow and total peripheral resistance were measured. Vasopressin infusion at 5 or 10 ng/kg/min did not raise arterial pressure, but increased resistance, and decreased heart rate and aortic flow in a dose-dependent manner. The pressure and resistance responses to carotid occlusion or changes in carotid pressure were not altered by vasopressin. The heart rate response was augmented significantly from 23 +/- 5 (mean +/- S.E.) to 40 +/- 8 and 43 +/- 8 beats/min with infusion of 5 and 10 ng/kg/min of vasopressin. Vasopressin did not augment the gain of carotid sinus reflex control of arterial pressure (3.7 +/- 0.5 in control and 3.5 +/- 0.5 during 5 ng/kg/min of vasopressin). With vasopressin infusion at 5 ng/kg/min, following vagal blockade with methylatropine both the arterial pressure and the heart rate responses to carotid pressure changes decreased to 73% and 32% of the response before blockade. The data indicate that vasopressin has little effect on control of arterial pressure by the carotid sinus baroreflex in conscious rabbits when vagal responses are activated.

Animals↗