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T Yamauchi

Publications and source records attributed to T Yamauchi.

At least 199 records · Page 11Linked to original sources
PubMed1998

Renal c-fos expression induced by angiotensin II is enhanced in spontaneously hypertensive rats.

We compared the effect of a bolus injection of angiotensin II (Ang II) on the expression of protooncogene c-fos in the renal cortex and medulla of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Intravenous infusion of 5 ng/kg body weight of Ang II resulted in an immediate rise in systolic blood pressure (SBP) in both SHR and WKY rats. The percent rise in SBP was similar in both strains. Pretreatment with Ang II type 1 (AT1)-receptor antagonist, L-158,809 (1 mg/kg) abolished the pressor response in both strains. Competitive reverse transcription-polymerase chain reaction (RT-PCR) showed that administration of Ang II increased the expression of c-fos mRNA within 10 min in both the renal cortex and medulla of SHR significantly higher than WKY rats. Moreover, the enhanced c-fos mRNA expression due to Ang II was significantly suppressed by the pretreatment of L-158,809 in both strains. These findings indicate that c-fos expression in the kidney is mediated by AT1-receptors and that the renal c-fos response to exogenous Ang II was significantly augmented in SHR compared with WKY rats, suggesting that this hyperresponsiveness on renal AT1-action may partly contribute to the progression of renal injury in SHR.

Angiotensin II↗
PubMed1998

Minor daphnane-type diterpenoids from Wikstroemia retusa.

In addition to huratoxin, pimelea factor P2, and wikstroelides A-G from the fresh bark, eight daphnane-type diterpenoids, wikstroelides H-O, were isolated from the bark and stem, and their structures established. Cytotoxicity was assayed on some wikstroelides.

Animals↗
PubMed1998

Idarubicin and idarubicinol are less affected by topoisomerase II-related multidrug resistance than is daunorubicin.

We investigated the cytotoxicity and cellular pharmacology of idarubicin (IDA), idarubicinol (IDAol) and daunorubicin (DNR) in K562/VP-H2 cells, which show topoisomerase II-related multidrug resistance but do not overexpress P-glycoprotein. K562/VP-H2 cells were less resistant to IDA and IDAol than to DNR. There was no significant difference in the accumulation of each drug between K562 and K562/VP-H2 cells. The cleavage of DNA induced by each drug was decreased in K562/VP-H2 cells, however, the decrease in cleavage in K562/VP-H2 cells was less with IDA and IDAol than with DNR. These results suggest that IDA and IDAol have more cytotoxic potency than DNR in topoisomerase II-related multidrug-resistant leukemia cells.

Antineoplastic Agents↗
PubMed1998

Syntheses and preventive effects of analogues related to 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71) on bone mineral loss in ovariectomized rats.

Analogues related to 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71) (2), 26,27-dimethyl ED-71 (3) and 26,27-diethyl ED-71 (4), were synthesized from lithocholic acid (5). In the study of the preventive effects of these analogues and ED-71 (2) on bone mineral loss in ovariectomized rats, 26,27-dimethyl ED-71 (3) showed the most potent activity.

Animals↗
PubMed1998

Neurite outgrowth of neuroblastoma cells overexpressing alpha and beta isoforms of Ca2+/calmodulin-dependent protein kinase II-effects of protein kinase inhibitors.

Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) is one of the most abundant protein kinases in the brain and has a broad substrate specificity [M.K. Bennett, N.E. Erondu, M.B. Kennedy, Purification and characterization of a calmodulin-dependent protein kinase that is highly concentrated in brain, J. Biol. Chem. 258 (1983) 12735-12744 [1]; J.R. Goldenring, B. Gonzalez, J.S. McGuire, Jr., R.J. DeLorenzo, Purification and characterization of a calmodulin-dependent kinase from rat brain cytosol able to phosphorylate tubulin and microtubule-associated proteins, J. Biol. Chem. 258 (1983) 12632-12640 [4]; M.B. Kennedy, P. Greengard, Two calcium/calmodulin-dependent protein kinases, which are highly concentrated in brain, phosphorylate protein I at distinct sites, Proc. Natl. Acad. Sci. U.S.A. 78 (1981) 1293-1297 [10]; T. Yamauchi, H. Fujisawa, Evidence for three distinct forms of calmodulin-dependent protein kinases from rat brain, FEBS Lett. 116 (1980) 141-144 [20]; T. Yamauchi, H. Fujisawa, Purification and characterization of the brain calmodulin-dependent protein kinase (kinase II), which is involved in the activation of tryptophan 5-monooxygenase, Eur. J. Biochem. 132 (1983) 15-21 [21]]. The alpha and beta isoforms of CaM kinase II are known to be expressed almost exclusively in the brain [P.I. Hanson, H. Schulman, Ca2+/calmodulin-dependent protein kinases, Annu. Rev. Biochem. 61 (1992) 559-601 [7]]. To elucidate the cellular function of CaM kinase II, we introduced cDNA of wild-type CaM kinase II alpha- or beta-isoform, and of mutant alpha-isoform (Ala-286 kinase) into two different types of neuroblastoma, Neuro2a (Nb2a) and NG108-15, thus generating cell lines stably producing elevated levels of these kinases. The mutant alpha-isoform is markedly suppressed in its autophosphorylation by replacement of Thr-286 with Ala [Y.-L. Fong, W.L. Taylor, A.R. Means, T.R. Soderling, Studies of the regulatory mechanism of Ca2+/calmodulin-dependent protein kinase II. Mutation of threonine 286 to alanine and aspartate, J. Biol. Chem. 264 (1989) 16759-16763 [3]; P.I. Hanson, M.S. Kapiloff, L.L. Lou, M.G. Rosenfeld, H. Schulman, Expression of a multifunctional Ca2+/calmodulin-dependent protein kinase and mutational analysis of its autoregulation, Neuron 3 (1989) 59-70 [6]; S. Ohsako, H. Nakazawa, S. Sekihara, A. Ikai, T. Yamauchi, Role of Threonine-286 as autophosphorylation site for appearance of Ca2+-independent activity of calmodulin-dependent protein kinase II alpha subunit, J. Biochem. 109 (1991) 137-143 [15]]. We provided evidence that CaM kinase II played a role in regulating neurite outgrowth and growth cone motility in these cells, and that the autophosphorylation is essential for the kinase to sufficiently exert its cellular function in vivo [Y. Goshima, S. Ohsako, T. Yamauchi, Overexpression of Ca2+/calmodulin-dependent protein kinase II in Neuro2a and NG108-15 neuroblastoma cell lines promotes neurite outgrowth and growth cone motility, J. Neurosci. 13 (1993) 559-567 [5]]. Neurite outgrowth was further stimulated by treatment with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) or chelerythrine, inhibitors of protein kinase C [T. Nomura, K. Kumatoriya, Y. Yoshimura, T. Yamauchi, Overexpression of alpha and beta isoforms of Ca2+/calmodulin-dependent protein kinase II in neuroblastoma cells-H-7 promotes neurite outgrowth, Brain Res. 766 (1997) 129-141 [14]]. The morphological change stimulated with protein kinase inhibitors was rapid and was greater in the beta than alpha cells. Some substrates of CaM kinase II related to neurite outgrowth were detected in cells overexpressing the kinase stimulated with H-7. These results suggest that CaM kinase II and protein kinase C play an important role in the control of cell change. (c) 1998 Elsevier Science B.V. All rights reserved.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

A method that preserves circulation during preparation of the pectoralis major myocutaneous flap in head and neck reconstruction.

The present article describes a method that preserves circulation during the preparation of the pectoralis major myocutaneous flap used in head and neck reconstruction. The major disadvantage of this flap is its poor circulation and consequent partial necrosis. To solve this problem, we analyzed the circulation and hemodynamics of the pectoralis major myocutaneous flap (the perforator of the anterior intercostal branch located about 1 to 2 cm medial to the areola in the fourth intercostal space is important), evaluated the safe donor sites in the chest wall for a skin island (the perforator is included on the skin island's central axis), improved the surgical procedure for elevating flaps (for preventing perforator injuries), and devised a means to transfer flaps, thereby increasing the range of the flaps (the transfer route is under the clavicle). Using this technique, head and neck reconstruction was performed on 62 patients. The diagnosis included oral cancer (21), oropharyngeal carcinoma (10), parotid carcinoma (10), hypopharyngeal carcinoma (9), and other head and neck malignant tumors (12). Of these, partial or marginal necrosis of the flap caused by circulatory problems was detected in three patients (5 percent). Using our method, the problems associated with inadequate circulation in the pectoralis major myocutaneous flap were greatly alleviated, thus reconfirming the usefulness of this flap in head and neck reconstruction.

Adult↗
PubMed1998

Possible mechanism for the anti-atherosclerotic action of the calcium channel blocker AE0047 in cholesterol-fed rabbits.

1. The present study was designed to investigate the anti-atherosclerotic effect of AE0047, a calcium channel blocker, and to compare it with that of nilvadipine in cholesterol-fed rabbits. Furthermore, the effects of AE0047 on low-density lipoprotein (LDL) oxidation were studied in vitro. 2. A 7 week treatment period with AE0047 (3 and 10 mg/kg, p.o.) led to a dose-dependent reduction in the lipid deposition area by Oil Red-O staining (surface index) without affecting serum lipid levels. There was no reduction in the surface index following treatment with the same dose of nilvadipine (10 mg/kg). 3. In a vehicle-administered high-fat diet group of rabbits, levels of total cholesterol (TC) and esterified cholesterol (EC) and calcium content in the aorta were increased approximately two- to three-fold over those of the normal diet group. Increased levels of TC and EC and calcium content were reduced to the same levels as the normal diet group by AE0047 treatment, whereas nilvadipine did not affect TC and EC levels. 4. In an in vitro study, AE0047 (10 micromol/L) inhibited LDL oxidation and the aggregation of apolipoprotein (Apo) B-100 induced by Cu2+. Furthermore, AE0047 inhibited the degradation of oxidized LDL by macrophages. In contrast, the same dose of nilvadipine (10 micromol/L) did not inhibit either LDL oxidation or the aggregation of ApoB-100. 5. In summary, AE0047 inhibited LDL oxidation, resulting in a decrease of its uptake into macrophages and an inhibition of cholesterol esterification. This leads to an anti-atherosclerotic effect of AE0047. Thus, AE0047 may have therapeutic potential in preventing cardiovascular disease in hypertensive patients.

Animals↗
PubMed1998

Education of psychiatry in Japan.

This paper discusses the problems of Japanese under- and postgraduate education of psychiatry, and indicates several important points for psychiatric education. Most medical schools give lectures on psychiatry to fourth and fifth graders. Lecturing hours average 2.3% of the total lecture time for medical students. However, the hours have tended to decrease recently, and lectures by the Department of Psychiatry are spreading to the first and second graders. These lectures include behavioral science, psychology and science for human relationships. The following problems should be solved urgently: (i) undergraduate psychiatric education should focus on the majority of medical students who will not be psychiatrists; (ii) clarification should be made of the minimum required psychiatric knowledge for medical doctors; (iii) promotion of the use of efficient educational strategies; (iv) increases in practical training. The Department of Psychiatry has an important role to play in primary education of psychiatrists in most cases. Every university educates using different curriculums; however, the programs are mostly similar in their primary training. However, there is no standardized educational system and Board of Certification for psychiatrists in Japan. Minimum requirements and a certification system for psychiatrists are urgently needed. I will discuss the global review on the issues of under- and postgraduate psychiatric education in Japan, then highlight the problems that should be targeted in the future.

Cross-Cultural Comparison↗
PubMed1998

Impairment of consciousness during epileptic seizures with special reference to neuronal mechanisms.

Two neuronal structures, i.e., the cerebral cortex and the subcortical structures, were shown by clinical observations to be involved in maintaining consciousness. The alteration of consciousness during epileptic seizures is discussed with respect to these findings: Alterations of consciousness during epileptic seizures may be produced by subcortical, i.e., reticular formation, and/or cortical dysfunction followed by excessive, hypersynchronous neuronal discharges. An impairment of consciousness during absence seizures may be due mainly to cortical dysfunction; during complex partial seizures (CPS), it may be due to dysfunctional subcortical neuronal structures. The mechanisms underlying an alteration of consciousness are defined as causing "irritative" functional disturbances and/or as having "inhibitory" effects on consciousness-related structures.

Brain↗
PubMed1998

[Early manifestation of septic shock and disseminated intravascular coagulation complicated by acute myocardial infarction in a patient suspected of having Legionnaires' disease].

Legionellosis is an important cause of severe pneumonia in the community. Inadequate therapy will lead to respiratory distress syndrome, disseminated intravascular coagulation (DIC) and finally fatal multiple organ failure. We encountered a rare case in which early manifestation included septic shock and DIC complicated by acute myocardial infarction (AMI) suspected to be derived from Legionnaires' disease. A 54-year-old healthy female complained of lumbago, high fever and dry cough 10 days after visiting a hot spring spa. She was emmergently admitted due to shock. Physical examination demonstrated hypotension, high fever, course creakle in the right lower lung. Hepatosplenomegaly, lymphadenopathy and eruption were not found. WBC count was 34600/microliters with nuclear shift. CRP elevated. FDP, D dimer and TAT also elevated CPK elevated with dominance of the MB isozyme. Chest roentogenography revealed congestive heart failure, pleural effusion and obscure pneumonic shadow and EKG showed ST segment elevation in leads I, II, III, aVF, V4, V5, and V6. The patient was diagnosed as having septic shock, DIC and AMI. She was treated with gabexate mesilate, high dose methyl prednisolone and dopamine hydrochloride as well as piperacillin, meropenem, isepamycin and fluconzaole. Despite intensive care, the blood pressure fell again and pneumonia had progressed on the 8th hospital day. These antibiotics appeared to be ineffective. Erythromycin was then administered and a dramatic effect. was obtained as the patient recovered. Serum titer of Legionella pneumophila (serogroup 1) rose to 128-fold 2 weeks after the onset. Other serum titers such as Chlamydia psittaci, Rickettsia, Mycoplasma were all negative. Cultures obtained from the sputum, throat swab, urine and blood did not yield any microorganisms. Although the diagnosis could not be confirmed because the titer did not elevate over 256-fold of 4-fold within 2 weeks after the onset, Legionella infection was highly suspected from the clinical features. This is a rare case in which septic shock and DIC with AMI preceded pulmonary symptoms in a non-immunocompromised patient.

Diagnosis, Differential↗
PubMed1998

Cross sectional observation of the effects of carbon disulphide on arteriosclerosis in rayon manufacturing workers.

OBJECTIVE: A prospective cohort study was designed to clarify the relations between occupational exposure to carbon disulphide (CS2) and its effects on arteriosclerosis in workers in 11 Japanese rayon manufacturing factories. This report is a cross sectional baseline observation in the first study year. METHODS: Study subjects were 432 male rayon workers (mean (range) age 35.5 (19.1-47.8); duration of exposure 13.4 (0.3-29.0)) and 402 male referent workers (age 35.8 (18.9-49.8)). Exposure to CS2 was assessed by determining the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine. Mean (SD) TTCA was 3.42 (2.73) mg/g creatinine (Cr) (n = 422). About a quarter of the urine samples were > 5 mg/g Cr, a biological exposure index recommended by the American Conference of Governmental Industrial Hygienists. Health effects on arteriosclerosis were evaluated by measuring blood pressure, serum lipids, pulse wave velocity of the aorta, stiffness and blood flow of the carotid artery, and blood coagulation and fibrinolysis indices, and by use of brain magnetic resonance imaging, electrocardiogram (at rest and after exercise), ophthalmograph, and Rose's questionnaire. Information on potential confounding factors was collected by self administered questionnaire. RESULTS: Prevalence of microaneurysm of the retinal artery was significantly higher in workers exposed to CS2 (8.1%) than in referent workers (3.4%), and increased with age. Other examinations did not show any differences between the two groups even after allowance for confounding factors. CONCLUSIONS: Significant effects of CS2 on arteriosclerosis were not found in current rayon manufacturing workers, with the exception of induction of microaneurysm of the retinal artery.

Adult↗
PubMed1998

Aggravating action of zymosan on acute liver damage in perfused liver of rats treated with D-galactosamine.

To study the role of Kupffer cells in the aggravation of liver injury, effects of zymosan on acute liver damage were explored using perfused livers of rats 24 h after intraperitoneal injection of D-galactosamine (800 mg/kg). The leakage of lactate dehydrogenase and aspartate aminotransferase into the effluent was used to indicate acute liver damage. Infusion of zymosan (30 microgram/ml) into the portal vein rapidly increased the leakage of lactate dehydrogenase and aspartate aminotransferase from galactosamine-treated liver with decreased perfusion flow. Pretreatment of animals with gadolinium, which diminished an immunostaining of resident macrophages in the injured liver, significantly attenuated the flow reduction induced by zymosan, whereas it did not affect the increases in enzyme leakage. Infusions of PGF2alpha, PGE2, and leukotriene D4, the eicosanoids mainly produced by Kupffer cells, decreased perfusion flow without rapid augmentation of enzyme leakage from galactosamine-treated liver. These results indicate that zymosan potentiates acute liver damage after galactosamine injection and suggest that certain types of nonparenchymal cells other than Kupffer cells are mainly involved in the action of zymosan.

Acute Disease↗
PubMed1998

Effects of chronic inhibition of ACE and AT1 receptors on glomerular injury in dahl salt-sensitive rats.

To elucidate the contribution of the renin-angiontensin system (RAS) to glomerular injury in salt-sensitive hypertension, we investigated the chronic effects of the angiotensin I-converting enzyme inhibitor cilazapril and the angiotensin II type 1-receptor antagonist (AT1a) TCV-116 in Dahl-Iwai rats. Dahl salt-sensitive (S) rats receiving 8% salt diet for 6 wk were simultaneously treated with cilazapril (n = 6), TCV-116 (n = 6), or saline (n = 14). The 8% salt diet markedly increased systolic blood pressure (SBP), urinary protein, and N-acetyl-beta-glucosaminidase (NAG) excretion compared with 0.3% salt-treated S (n = 6) or salt-resistant (n = 6) rats. Although neither cilazapril nor TCV-116 reduced the elevated SBP, TCV-116 significantly lowered urinary protein and NAG excretion. Histologically, 8% salt treatment in S rats induced progressive sclerotic and proliferative glomerular changes, which were ameliorated by both drugs. TCV-116 increased the glomerular diameter. Immunofluorescence demonstrated the increased level of type III collagen in the mesangium of 8% salt-treated S rats, which was completely reversed by TCV-116. Competitive RT-PCR of mRNA extracted from the glomeruli revealed that 8% salt treatment significantly increased the levels of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor B-chain and that TCV-116 significantly reduced the levels of PCNA and transforming growth factor-beta1 (TGF-beta1). Thus, although the chronic RAS-inhibition in salt-sensitive hypertension exerted a histologically renoprotective effect by both ways without lowering blood pressure, the RAS inhibition due to AT1a had more beneficial advantages of reducing proteinuria and attenuating the levels of glomerular TGF-beta1 and extracellular matrix.

Acetylglucosaminidase↗
PubMed1998

Generation of immortalized murine forebrain cell lines expressing an alpha isoform of Ca2+/calmodulin-dependent protein kinase II.

Immortalized hybrid cells were generated by the somatic fusion of the cells from the forebrain of embryonic mouse with N18TG2 neuroblastoma cells. Three monoclonal hybrid cell lines, designated NF26, NF81, and NF83 (neuroblastoma forebrain hybrid cells), expressing an alpha isoform of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) were isolated, and their expression was demonstrated by immunoblotting and immunocytochemistry using a monoclonal antibody specific to the a isoform of the enzyme. The kinase activity of the hybrid cells was 2- to 3-fold higher than that of the parent neuroblastoma line N18TG2 cells. The neuronal origin of these lines was shown by their immunoreactivity to neurofilament protein, a neuron specific marker. Lines NF26, NF81, and NF83 are the first cell lines to express the gene of the alpha isoform of CaM kinase II in the brain.

Animals↗
PubMed1998

Further investigation of phenanthroindolizidine alkaloids from Tylophora tanakae.

In addition to ten alkaloids previously described, we have isolated two alkaloid N-oxides from Tylophora tanakae MAXIM. (Asclepiadaceae). Further, the polar fraction of the leaves and caules of this plant cultivated in a farm afforded two new polar alkaloids. The structures of the four products were determined. The relation between the structure and cytotoxic activity of this group of alkaloids is discussed.

Alkaloids↗
PubMed1998

Hypocalcemia due to spontaneous infarction of parathyroid adenoma and osteomalacia in a patient with primary hyperparathyroidism.

A 49 year-old Japanese woman had subjected enlargement of a cervical tumor, and also suffered two bone fractures in 2 years. The cervical tumor had enlarged further in the month prior to admission, becoming warm and tender. Endocrinological examination revealed that the serum intact PTH concentration was remarkably high at 400 pg/mL despite the low serum calcium concentration, and that the serum vitamin Ds concentration was decreased. Bone roentgenograms revealed severe osteolytic changes compatible with osteitis fibrosa cystica and a pathologic fracture of the humerus. Under a diagnosis of primary hyperparathyroidism, parathyroidectomy was performed, followed by fixation surgery for the pathologic fracture. Histologically, the cervical tumor was a parathyroid chief-cell adenoma with massive necrosis, and the bone pathology by iliac bone biopsy revealed the existence of osteomalacia. She was treated with calcium, vitamins D and K2 and calcitonin after the surgery. This case is a rare condition manifesting hypocalcemia with catastrophic osteoporosis under the coexistence of spontaneous infarction of parathyroid adenoma with osteomalacia, suggesting that the clinical features of hyperparathyroidism are modified by both the autoparathyroidiectomy and the existence of osteomalacia due to vitamin D deficiency.

Adenoma↗
PubMed1998

Growth hormone-induced tyrosine phosphorylation of EGF receptor as an essential element leading to MAP kinase activation and gene expression.

GH binding to its receptor, which belongs to the cytokine receptor superfamily, activates Janus kinase (JAK) 2 tyrosine kinase, thereby activating a number of intracellular key proteins such as STAT (signal transducers and activators of transcription) proteins and mitogen-activated protein (MAP) kinases, which finally lead to GH's biological actions including gene expression. In contrast to receptor tyrosine kinases, the signalling pathways leading to MAP kinase activation by GH are poorly understood but appear to involve Grb2 and Shc. We now show that GH stimulated tyrosine phosphorylation of epidermal growth factor receptor (EGFR) and its association with Grb2, and concomitantly stimulated MAP kinase activity in liver, a major target tissue. Expression of EGFR and its mutants into CHO-GH receptor (GHR) cells revealed that GH-induced full activation of MAP kinase and c-fos expression required tyrosine phosphorylation sites of EGFR but not its intrinsic tyrosine kinase activity. Moreover, by also using dominant negative JAK2 and in vitro kinase assay, we demonstrated that tyrosine 1068 of EGFR was evidently one of the major phosphorylation and Grb2 binding sites stimulated by GH via JAK2. These data suggest that the role of EGFR in GH signalling is to be phosphorylated by JAK2, thereby providing docking sites for Grb2 and activating MAP kinases and gene expression. This novel cross talk pathway may provide the first example of the hormone and cytokine receptor superfamily transducing signals via associated nonreceptor tyrosine kinase by phosphorylating growth factor receptor and utilizing it as a docking protein independent of its receptor tyrosine kinase activity.

Adaptor Proteins, Signal Transducing↗