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Biomedical subjects

H Takayama

Publications and source records attributed to H Takayama.

At least 145 records · Page 8Linked to original sources
PubMed1997

Synthesis and biological activity of a 1 alpha,25-dihydroxyvitamin D2 analog bearing an amide group in the side-chain.

Synthesis of a 1 alpha,25-dihydroxyvitamin D2 analog (3), in which the double bond in the side-chain is replaced by an amide group, is described. Condensation of a carboxylic acid (8) with an amine (6) gave an amide (9), which in turn led to 3 via several steps. The analog (3) could not bind to the chick cytosol vitamin D receptor, which indicated the importance of the hydrophobic interaction of the C(22)-C(23) double bond in 1 alpha,25-dihydroxyvitamin D2 (2) with the vitamin D receptor.

Ergocalciferols↗
PubMed1997

[Urethral recurrence of bladder cancer 16 years after total cystectomy. A case report].

A 74-year-old man was admitted to our hospital. Diagnosis of invasive bladder cancer was made and a total cystectomy was performed on January, 30, 1980. Histological examination showed transitional cell carcinoma, grade 2, pT1 is N0M0. After 16 years, when he suffered left femur, he had right inguinal lymphnode swelling. On the biopsy of the inguinal mass, histology was transitional cell carcinoma. The urethral washing cytology was positive. Lung CT scan dem onstrated multiple lesions. He was diagnosed of the urethral recurrence, right inguinal lymphnode metastasis and lung metastasis of bladder cancer. This case is the 5th case of urethral recurrence of bladder cancer following cystectomy in our hospital.

Aged↗
PubMed1997

Qualitative platelet 12-lipoxygenase abnormality in a patient with essential thrombocythemia.

Quantitative platelet 12-lipoxygenase (12-LOX) deficiency has been reported in some patients with myeloproliferative disorders (MPD). We report here for the first time a novel qualitative abnormality of the 12-LOX enzyme of platelets from a patient with essential thrombocythemia. The anti-12-LOX immunoprecipitates from the patient's platelet homogenates showed a deficiency of 12-LOX activity, but contained normal amount of 12-LOX protein. There was no difference in subcellular localization of the enzyme between the patient's platelets and normal ones. This 12-LOX protein lacking its enzyme activity showed slightly larger electrophoretic mobility than normal one, suggesting a molecular abnormality of the enzyme. However, we could not detect any genetic mutation causing such abnormalities in all exons of 12-LOX gene by sequencing the patient's PCR-amplified DNA. Thus, our results indicate that the deficient activity of this abnormal 12-LOX protein is probably due to a posttranslational modification, and the possibility that platelets of some MPD patients have qualitative abnormality of the 12-LOX enzyme besides quantitative ones.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1997

Renal tubular hyperplasia, polycystic disease, and glomerulosclerosis in transgenic mice overexpressing hepatocyte growth factor/scatter factor.

Hepatocyte growth factor/scatter factor (HGF/SF) has been implicated as a renotrophic agent, capable of stimulating renal regeneration after unilateral nephrectomy or acute kidney failure. However, evaluation of the therapeutic utility of HGF/SF requires thorough analysis of its effects in an appropriate in vivo model system. To this end, the renal structure and function in HGF/SF transgenic mice were examined. Mice overexpressing HGF/SF in the kidney and serum demonstrated prominent tubular cystic disease and progressive glomerulosclerosis, and were susceptible to premature death from renal failure. The tubular phenotype appeared to result from HGF/SF-Met autocrine stimulation of the tubular epithelium and consequent hyperplasia. Electron microscopic examination of glomeruli, which also showed enhanced cellular proliferation, revealed ultrastructural features consistent with focal segmental glomerulosclerosis: an increase in mesangial matrix, effacement of foot processes, and thickening of basement membrane. These changes were not present at birth but developed progressively with age, which is consistent with the notion that HGF/SF may not be essential for the early stages of nephrogenesis, but may play an important role in renal epithelial renewal and regeneration. Thus, HGF/SF transgenic mice could be a useful model for dissecting the molecular mechanisms leading to polycystic disease and focal segmental glomerulosclerosis. Moreover, our results suggest that caution should be used when considering HGF/SF as a future therapeutic agent.

Animals↗
PubMed1997

Twin-stage procedure. Part 1: A new method to reproduce precise eccentric occlusal relations.

The condylar path, the incisal path, and the cusp angle determine the amount of disocclusion during eccentric movement. In prosthodontics, the condylar path has been used as the main determinant of occlusion. However, the method to derive the incisal path and cusp angle from the condylar path is not known, and thus it has been difficult to scientifically reproduce the amount of disocclusion on a restoration. This study describes the Twin-Stage Procedure, in which the cusp angle is used as the main determinant of occlusion because of its reliability. It is possible to accurately control the amount of disocclusion on the restoration without measuring condylar path.

Dental Articulators↗
PubMed1997

Twin-Stage Procedure. Part 2: A clinical evaluation test.

The Twin-Stage Procedure was used to measure the amount of disocclusion reproduced on the articulator (in vitro) and in the mouth (in vivo). The results almost coincided, even without measurement of the condylar path By using this new procedure, quantitative control of the amount of disocclusion, which was previously impossible, has become a reality in daily clinical procedures. The amount of disocclusion occurring on an articulator coincided with the amount of disocclusion intraorally; therefore, the Twin-Stage Procedure is considered to be highly reliable.

Crowns↗
PubMed1996

Central antinociceptive effects of mitragynine in mice: contribution of descending noradrenergic and serotonergic systems.

Mitragynine is a major alkaloidal constituent of young leaves of Mitragyna speciosa Korth, that is known to exhibit narcotic-like activity. In this study, we investigated the roles of central monoaminergic systems in the antinociceptive action of mitragynine by means of the tail-pinch and hot-plate tests in mice. Mitragynine (1.0-10 micrograms) injected i.c.v. exerted a dose-dependent antinociceptive activity in both tests. The activity of mitragynine (10 micrograms, i.c.v.) in the tail-pinch test was antagonized by reserpine, 6-hydroxydopamine plus nomifensine, and p-chlorophenylalnine treatment, whereas the antinociceptive activity of morphine (3 micrograms) given i.c.v. in this test was attenuated by 6-hydroxydopamine plus nomifensine but not by p-chlorophenylalanine treatment. Moreover, the activity of i.c.v. mitragynine was also antagonized by the alpha 2-adrenoceptor antagonist, idazoxan (10 micrograms), and cyproheptadine (1 microgram) administered intrathecally (i.t.). On the other hand, the antinociceptive action of i.c.v. mitragynine (10 micrograms) in the hot-plate test was abolished by reserpine and 6-hydroxydopamine plus nomifensine, but not by p-chlorophenylalanine treatment. This action was also antagonized by i.t. injection of idazoxan (10 micrograms). These results suggest that both descending noradrenergic and serotonergic systems are involved in the antinociceptive activity of supraspinally administered mitragynine on the mechanical noxious stimulation, while the descending noradrenergic system predominantly contributes to the effect of supraspinal mitragynine on the thermal noxious stimulation. The mechanisms underlying the suppressive action of mitragynine on the nociceptive response may differ from those of morphine in mice.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1996

Lack of requirement for SHP-1 in both Fas-mediated and perforin-mediated cell death induced by CTL.

The Fas (CD95)-transmitted cell death signal has been reported to involve a protein tyrosine phosphatase, SHP-1. We analyzed the role of SHP-1 in the Fas-dependent as well as the perforin-dependent pathways of CTL-mediated killing using target cells prepared from SHP-1-deficient motheaten mice. Con A blast targets prepared from both a motheaten mouse and a phenotype-normal littermate were equally sensitive to the cytolysis and DNA fragmentation induced by both perforin-deficient Fas-dependent CTL and Fas ligand-deficient perforin-positive CTL. Fas-induced DNA degradation detected by the terminal deoxynucleotide transferase reaction was also observed in the killing of motheaten thymocytes by a Fas-based CTL as well as by anti-Fas mAb. These data cast doubt on the involvement of SHP-1 in Fas-induced lymphoid cell death.

Animals↗
PubMed1996

Scatter factor/hepatocyte growth factor as a regulator of skeletal muscle and neural crest development.

Factors that regulate cellular migration during embryonic development are essential for tissue and organ morphogenesis. Scatter factor/hepatocyte growth factor (SF/HGF) can stimulate motogenic and morphogenetic activities in cultured epithelial cells expressing the Met tyrosine kinase receptor and is essential for development; however, the precise physiological role of SF/HGF is incompletely understood. Here we provide functional evidence that inappropriate expression of SF/HGF in transgenic mice influences the development of two distinct migratory cell lineages, resulting in ectopic skeletal muscle formation and melanosis in the central nervous system, and patterned hyperpigmentation of the skin. Committed TRP-2 positive melanoblasts were found to be situated aberrantly within defined regions of the transgenic embryo, including the neural tube, which overproduced SF/RGF. Our data strongly suggest that SF/HGF possesses physiologically relevant scatter activity, and functions as a true morphogenetic factor by regulating migration and/or differentiation of select populations of premyogenic and neural crest cells during normal mammalian embryogenesis.

Animals↗
PubMed1996

Concanamycin A, a powerful tool for characterization and estimation of contribution of perforin- and Fas-based lytic pathways in cell-mediated cytotoxicity.

Perforin- and Fas-based cytolytic pathways are two major mechanisms of cell-mediated cytotoxicity. Recently, we have shown that an inhibitor of vacuolar type H+-ATPase, concanamycin A (CMA), inhibits perforin-based cytotoxic activity, mostly due to accelerated degradation of perforin by an increase in the pH of lytic granules. Here we show that CMA failed to inhibit the cytolytic activity of CD4+ CTL clone and perforin-deficient CD8+ CTL clone, which exclusively mediate Fas-based cytotoxicity, although CMA inhibited acidification and induced drastic vacuolation of cytoplasmic granules in these clones. In a wide range of alloantigen-specific CTL, a significant amount of the lysis of Con A blasts from normal mice and of Fas-positive tumor cells remained unaffected even in excess concentrations of CMA. However, CMA almost completely inhibited the lysis of Con A blasts from lpr mice and of Fas low expressing or negative tumor cells. Cytolysis by alloantigen-specific CD8+ CTL derived from gld mice was completely prevented by CMA. Furthermore, CMA-insensitive cytolysis exerted by CD8+ CTL clone was completely inhibitable by soluble Fas molecules. Thus, these data clearly indicate not only that CMA-insensitive cytolysis mediated by alloantigen-specific CTL is Fas dependent, but also that CMA is a selective inhibitor to block only the perforin-based killing pathway. In contrast, brefeldin A blocked the Fas-based cytotoxicity, but only marginally reduced the perforin-based cytotoxicity. Moreover, CMA and brefeldin A in combination completely abrogated all cytolytic activity of alloantigen-specific CTL. Taken together, these results reveal that CTL mainly exert perforin-based cytotoxicity and complementary Fas-based cytotoxicity, and that CMA is a powerful tool to clarify the contributions of the two distinct cytolytic pathways.

Animals↗
PubMed1996

Antinociceptive action of mitragynine in mice: evidence for the involvement of supraspinal opioid receptors.

Mitragynine is a major alkaloidal constituent extracted from the young leaves of Mitragyna speciosa Korth. (Rubiaceae). We investigated an antinociceptive activity of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) injection of this alkaloid by the tail-pinch and hot-plate tests in mice, and evaluated the mechanisms of the action using naloxone, an opioid receptor antagonist. Mitragynine (5.0-30 mg/kg, i.p. and 1.0-10 micrograms/mouse, i.c.v.) exerted a dose-dependent antinociceptive activity which was maximal at 15-45 min after injection in the tail-pinch and hot-plate tests, but it did not induce a morphine-like behavioral change. the antinociceptive actions of i.p. mitragynine were completely abolished by both s.c. (2 mg/kg) and i.c.v (10 micrograms/mouse) naloxone. The action of i.c.v. mitragynine (10 micrograms/mouse) was also antagonized by i.c.v. naloxone (10 micrograms/mouse). These results indicate that mitragynine itself can induce antinociception by acting in the brain, and that the supraspinal opioid systems are at least partly involved in the antinociceptive action of mitragynine in mice.

Analgesia↗
PubMed1996

Anti-HIV-1 activity of thiadiazole derivatives: structure-activity relationship, reverse transcriptase inhibition, and lipophilicity.

The structure-activity relationship of the non-nucleoside HIV-1-specific reverse transcriptase (RT) inhibitors 4-phenyl-1,2,5-thiadiazol-3-yl N,N-dialkylcarbamate (TDA) derivatives was investigated with respect to their anti-HIV-1 activity, RT inhibition, and lipophilicity. 4-Phenyl-1,2,5-thiadiazol-3-yl N,N-dimethylcarbamate inhibited HIV-1-induced cytopathic effect (CPE) by 50% at a concentration of 28.8 microM in MT-4 cells. The activity increased more than 100-fold when the hydrogens at the 2-position and the 6-position in phenyl moiety were substituted by chlorines. However, the derivative with a chlorine at the 4-position of phenyl moiety did not show any inhibition of HIV-1 replication at its non-toxic concentrations. All of the 4-(2,6-dichlorophenyl)-1,2,5-thiadiazol-3-yl N-methyl-N-alkylcarbamates proved inhibitory to HIV-1 replication in the nanomolar concentration range. The TDA derivatives that showed anti-HIV-1 activity also inhibited RT activity in an enzymatic assay. However, the TDA derivatives did not show any specific inhibition of a non-nucleoside RT inhibitor (NNRTI)-resistant mutant and its RT activity. When the TDA derivatives were examined for their inhibitory effect on HIV-1 replication in the presence of 50% human serum, the activity significantly decreased depending on-their lipophilicity.

Anti-HIV Agents↗
PubMed1996

Acute myeloblastic leukaemia in a cow.

A myeloblastic leukaemia was found in a 6-year-old Holstein cow. Although macroscopical lesions were not found in parenchymal organs, the animal had many neoplastic cells in the peripheral blood, bone marrow, lymph nodes, and spleen. By light microscopy most neoplastic cells appeared to be agranular blast cells, but some cells contained acidophilic granules and stained positively for naphthol AS-D chloroacetate esterase and lysozyme. Ultrastructural examination revealed that many of the blast cells had a few peroxidase-positive granules and corresponded to early promyelocytes.

Animals↗
PubMed1996

Behavioral studies on alkaloids extracted from the leaves of Hunteria zeylanica.

The effects of a crude methanol extract, butanol- and chloroform-fractions, and a pure compound, corymine, extracted from the leaves of H. zeylanica on locomotor activity and rearing, pentobarbital-induced sleep, and drug-induced convulsions were studied in mice. The methanol extract dose-dependently decreased rearing without a significant effect on locomotor activity at doses of 15, 60 and 120 mg/kg. It did not significantly prolong the sleeping time but potentiated the convulsions induced by strychnine, but not that by either picrotoxin or pentylenetetrazole, at a dose of 120 mg/kg. The butanol-fraction significantly prolonged sleeping time at a dose of 125 mg/kg but did not affect either of the convulsive drugs. The chloroform fraction prolonged sleeping time at doses of 62.5 and 125 mg/kg and potentiated the convulsions induced by either strychnine or picrotoxin, but not that by pentylenetetrazole, at doses of 15, 30, 60 and 120 mg/kg. Corymine did not significantly prolong sleeping time, but potentiated the convulsions induced by either strychnine or picrotoxin, not by pentylenetetrazole, at doses of 2, 8 and 15 mg/kg. These results suggest that crude alkaloidal extracts of H. zeylanica leaves produce biphasic effects on the central nervous system (CNS), depression and stimulation, while the pure compound, corymine, has a unique central stimulatory effect in mice.

Alkaloids↗
PubMed1996

Electromagnetic interference of an external temporary pacemaker during maxillofacial and neck surgery.

Indirect inhibition of an external temporary pacemaker by electrocautery is reported. Before induction of general anesthesia for a hemimaxillectomy and radical neck dissection, a temporary transvenous demand pacemaker was inserted into a patient with a first-degree atrioventricular block and complete left bundle-branch block. Although we provided common precautions to prevent electromagnetic interference by electrocautery, pacing failure still occurred. It was thought to be caused by current dispersing from the active electrocautery electrode. This case suggests that occipital placement of the electrocautery ground plate should be considered during neck surgery in a patient requiring a temporary pacemaker.

Aged↗
PubMed1996

[A case of de novo aneurysm of the distal posterior inferior cerebellar artery with intraventricular hemorrhage].

A case is presented of a de novo aneurysm of the distal posterior inferior cerebellar artery with intraventricular hemorrhage. A 67-year-old woman was admitted to our hospital with sudden onset of severe headache and loss of consciousness. Computed tomography (CT) scans showed subarachnoid hemorrhage. Angiography demonstrated three aneurysms: an aneurysm of the right vertebral-posterior inferior cerebellar artery, an aneurysm of the bifurcation of the basilar artery, and an aneurysm of the left middle cerebral artery. Considering the distribution of the hemorrhage on CT scans, we concluded that the cause of the hemorrhage was rupture of the vertebral-posterior inferior cerebellar aneurysm. The vertebral-posterior inferior cerebellar aneurysm and the middle cerebral aneurysm were successfully clipped, postoperative angiograms showing the complete clippings. At that time, however, there were no abnormal findings in the left posterior inferior cerebellar artery. Six years later, she was readmitted to our hospital because of sudden onset of headache, nausea, and vertigo. CT scans showed an intraventricular hemorrhage, especially in the fourth ventricle, although subarachnoid hemorrhage was not clearly found. Angiography revealed an aneurysm of the left distal posterior inferior cerebellar artery. She underwent clipping of the aneurysm verified by postoperative angiograms. However she had bacterial meningitis and died from pneumonia and disseminated intravascular coagulopathy. De novo aneurysms of the anterior circulation have often been reported. Carotid, ligation, smoking, the use of oral contraceptives, congenital anomalies and hypertension are major risk factors in the formation of aneurysms. A de novo aneurysm of the distal posterior inferior cerebellar artery is, however, extremely rare. In this case, the right posterior inferior cerebellar artery disappeared when the de novo aneurysm was found. So it is supposed that hemodynamic changes caused by the clipping of the right vertebral-posterior inferior cerebellar aneurysm and the left middle cerebral aneurysm had contributed to the formation of the de novo aneurysm of the left distal posterior inferior cerebellar artery. In the present study, we review the literature on the aneurysm at the distal posterior inferior cerebellar artery and on the de novo aneurysm of the vertebrobasilar artery, and discuss the radiological findings and features.

Aged↗
PubMed1996

Hepatocellular carcinoma with pleural metastasis complicated by hemothorax.

Hemothorax can be caused by rupture of hepatocellular carcinoma (HCC). Hemoperitoneum is a well-known cause of death caused by rupture of a primary HCC lesion. Rupture of a HCC metastasis has not been adequately described. This is the first report of a HCC patient who died of hemothorax due to rupture of a pleural metastasis. The patient, a woman, died in respiratory failure 2 wk after rupture of her HCC metastasis in the pleura. Autopsy revealed moderately differentiated HCC in the liver, lung, and pleura. We discuss treatment options for ruptured pleura-based HCC metastases.

Adult↗