Biomedical subjects

K Tsuchiya

Publications and source records attributed to K Tsuchiya.

At least 109 records · Page 6Linked to original sources

PubMed2001

Signal transduction of reactive oxygen species and mitogen-activated protein kinases in cardiovascular disease.

Reactive oxygen species (ROS), generated by reduction-oxidation (redox) reactions, have been recognized as important chemical mediators that regulate signal transduction. It has been reported that increase in ROS generation may relate to a risk for cardiovascular diseases such as atherosclerosis, angina pectoris, and myocardial infarction. Therefore, understanding the ROS-generating biological processes and ROS-induced intracellular signaling will be informative to gain insights into the pathogenesis of these diseases. In this review, we focus on the sources and reactions of ROS in the cardiovascular system and the role of mitogen-activated protein (MAP) kinase pathway in redox-mediated signal transduction. Clinical implications of ROS and MAP kinase are then described to provide insight into the pathogenesis of various redox-sensitive cardiovascular diseases. The pathways responsible for ROS generation in the cardiovascular system may provide novel therapeutic targets.

Animals↗

PubMed2001

[A case of Down syndrome with ventricular septal defect and hemodynamical Eisenmenger syndrome].

A 10 month-old infant with Down syndrome having ventricular septal defect and pulmonary hypertension performed cardiac catheterization, which resulted in a slight increase in the pulmonary vascular resistance from 10.8 to 11.3 unit.m2. Lung biopsy findings showed at most an early grade 2 Heath-Edwards classification, and an index of pulmonary vascular disease of 1.1, both of which indicated operability for total correction. He underwent surgical correction and the pulmonary arterial pressure significantly decrease. Although he suffered chylothorax in 5th postoperative day, he did not developed pulmonary hypertension crisis.

Down Syndrome↗

PubMed2001

[A case of stent-graft implantation for distal arch aneurysm].

A 74-year-old woman was pointed out distal arch aneurysm 4 years ago in another hospital. As the diameter has gradually increased, the operation was considered. At first a pig tail catheter was inserted from the right femoral artery to aortic arch in the cardiac catheterization laboratory. In the operating room, stent-graft was inserted using pig tail catheter. Post operative CT showed clot formation outside the stent-graft. This procedure was thought to be less invasive and safe.

Aged↗

PubMed2001

[An autopsy case of pure autonomic failure with pathological features of Parkinson's disease].

Pure autonomic failure (PAF) is an uncommon disorder, characterized by autonomic failure without other neurological deficits. We report here an autopsy case of pure autonomic failure with pathological features of Parkinson's disease. At age 79, the patient developed slowly progressive severe orthostatic hypotension, followed by decreased sweating and constipation. On admission, his blood pressure dropped after standing (from 133/97 to 71/22 mmHg) without tachycardia. Neurological examination revealed neither parkinsonism, nor cerebellar symptoms. Supine plasma norepinephrine levels were low and intravenous norepinephrine administration showed denervation hypersensitivity. He was diagnosed as having PAF and treated by amezinium, midodrine, L-threodops, and fludrocortisone with elastic stockings but without any effects. He died of pneumonia about 2 years after the onset of the disease. Postmortem study revealed Lewy bodies in the nucleus basalis of Meynert, substantia nigra. Edinger-Westphal nucleus, locus ceruleus, and dorsal vagal nucleus. Neuronal loss was found in above-mentioned sites, except for Edinger-Westphal nucleus and intermediolateral nucleus. This is a rare and important report on a patient with PAF who satisfied the strict clinical criteria on PAF reported in 1996, and showed neuropathological findings, consistent with Parkinson's disease.

Aged↗

PubMed2001

[An autopsied case of presenile dementia with tangles].

We report an autopsied case of presenile dementia showing neuropathologically abundant neurofibrillary tangles(NFT) without senile plaques(tangle only dementia). A Japanese woman developed memory disturbance when she was 60 years old. At age of 65, her ability to understand deteriorated and euphoria and wandering manifested but neither psychotic symptoms, including hallucination and delusion nor a change in character were observed. The patient was hospitalized at age 66 and a cranial CT scan revealed bilateral moderate atrophy of the cortex and moderate enlargement of the lateral ventricle, especially in the inferior horn. No lobar atrophy was detected. She exhibited an oral tendency and became appallic at her final stage and died at the age of 75. Autopsy showed that her brain weighed 850 g and neuropathological study showed numerous NFT mainly in the entorhinal (trans-entorhinal) region, subiculum, CA1-CA4, dentate gyrus, amygdara, subthalamic nucleus, basal nucleus of Meynert, substantia nigra and locus coeruleus. Severe neuronal loss with gliosis was noted in the temporal lobes including the hippocampal region. No senile plaque was detected in any of the brain regions. There have been some recent reports of patients with abundant NFT with the predominant involvement of the allocortex but no or very little senile plaque. All the patients in the reported cases were very elderly at onset(over 80 years of age). In our case, the onset was presenile and we could exclude any other diseases, that usually present with NFT, and to our knowledge, this is the first report of a presenile dementia with tangles.

Aged↗

PubMed2001

Molecular cloning of the porcine insulin cDNA using a monolayer culture of pancreatic endocrine cells.

Porcine pancreatic endocrine cells are an attractive candidate for islet cell transplantation in view of the immunological properties and structural similarities of porcine insulin to human insulin. We recently established a method of isolation and a primary monolayer culture of porcine pancreatic endocrine cells. In this study, cloning of the porcine insulin cDNA was performed to clarify the genetic background of the purified isolated cells. A homology-based PCR cloning method was employed to determine the sequence using mRNA extracted from the monolayer-forming cells, and the candidate products were then determined by a homology search on the human insulin cDNA. According to the newly identified sequence, rapid amplification of cDNA ends was applied to the 5' and 3' ends, and the entire cDNA sequence was determined. Gene and protein expression was confirmed by Northern blotting, immunohistochemistry, and enzyme assay. To examine the transcriptional level, the cultured cells were incubated in a 20 mM D-glucose medium in the presence or absence of 5 microM forskolin. The porcine insulin cDNA exhibited a high homology to the human cDNA and showed 85% matching with the human amino acid sequence. D-Glucose at 20 mM stimulated the insulin secretion and mRNA expression, and further addition of 5 microM forskolin with the glucose was applied as the strongest stimulus in this culture system.

Amino Acid Sequence↗

PubMed2001

Quercetin inhibits Shc- and phosphatidylinositol 3-kinase-mediated c-Jun N-terminal kinase activation by angiotensin II in cultured rat aortic smooth muscle cells.

Angiotensin II (Ang II) induces vascular smooth muscle cell (VSMC) hypertrophy, which results in various cardiovascular diseases. Ang II-induced cellular events have been implicated, in part, in the activation of mitogen-activated protein (MAP) kinases. Although it has been proposed that daily intake of bioflavonoids belonging to polyphenols reduces the incidence of ischemic heart diseases (known as "French paradox"), the precise mechanisms of efficacy have not been elucidated. Thus, we hypothesized that bioflavonoids may affect Ang II-induced MAP kinase activation in cultured rat aortic smooth muscle cells (RASMC). Our findings showed that Ang II stimulated rapid and significant activation of extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38 in RASMC. Ang II-induced JNK activation was inhibited by 3,3',4',5,7-pentahydroxyflavone (quercetin), a major bioflavonoid in foods of plant origin, whereas ERK1/2 and p38 activation by Ang II were not affected by quercetin. Ang II caused a rapid tyrosine phosphorylation of Src homology and collagen (Shc), which was inhibited by quercetin. Quercetin also inhibited Ang II-induced Shc.p85 association and subsequent activation of phosphatidylinositol 3-kinase (PI3-K)/Akt pathway in RASMC. Furthermore, LY294002, a PI3-K inhibitor and a quercetin derivative, inhibited Ang II-induced JNK activation as well as Akt phosphorylation. Finally, Ang II-induced [(3)H]leucine incorporation was abolished by both quercetin and LY294002. These findings suggest that the preventing effect of quercetin on Ang II-induced VSMC hypertrophy are attributable, in part, to its inhibitory effect on Shc- and PI3-K-dependent JNK activation in VSMC. Thus, inhibition of JNK by quercetin may imply its usefulness for the treatment of cardiovascular diseases relevant to VSMC growth.

Angiotensin II↗

PubMed2001

[Serological diagnosis of pulmonary tuberculosis and nontuberculous pulmonary mycobacteriosis].

OBJECTIVE: The present study was undertaken to evaluate the utility of the serodiagnosis of pulmonary tuberculosis and nontuberculous pulmonary mycobacteriosis by ELISA using a Pathozyme-Myco kit (Myco kit) and a Pathozyme-TB complex kit (TB kit) (OMEGA Diagnostics Ltd.). STUDY POPULATION: The subjects comprised 256 healthy volunteers (HV, healthy hospital employees), 66 patients with sputum-positive active pulmonary tuberculosis (apTB), 14 patients with healed pulmonary tuberculosis (hpTB), 24 patients with nontuberculous pulmonary mycobacteriosis (NTM) and 32 patients with pulmonary diseases other than mycobacteriosis. RESULTS: 1) The serum IgG antibody titers determined with the Myco kit were significantly higher in the apTB group (p < 0.01), the hpTB group (p < 0.01), and the NTM group (p < 0.01) than those in the HV and the other pulmonary disease group. At a cut-off value of the mean + 2SD of the values obtained in the HV, the positive rate was 47.0% in patients with apTB, 50.0% in those with NTM, 21.4% in those with hpTB, 3.1% in those with other pulmonary diseases, and 1.6% in the HV. Analysis of ROC curves showed that the HV and the pulmonary mycobacteriosis group (apTB and NTM) were best distinguished by a cut-off value of -0.280 OD (log), with the sensitivity and the specificity being 83.3% and 78.5%, respectively. It was impossible to distinguish apTB from NTM. 2) The serum IgG antibody titers determined with the TB kit were significantly higher in the apTB group than those in the HV (p < 0.01), the NTM group (p < 0.05) and the other pulmonary disease group (p < 0.01). No significant difference was observed between the HV and the patients with NTM or those with other pulmonary diseases. Although the positive rate of the test was low in the apTB group (42.4%), there was a significant difference between apTB and NTM (12.5%) (p < 0.05), suggesting that apTB could be distinguished from NTM. 3) Since the serum antibody titers determined by the Myco kit showed no significant difference between apTB and NTM, and there was also no difference in the positivity between the two diseases, we performed serologic examination using the Myco kit to detect both diseases as pulmonary mycobacteriosis. After diagnosing pulmonary mycobacteriosis by the Myco kit, we then used the TB kit to separate apTB from NTM. In this case, the sensitivity and specificity of the test were 55.6% and 85.7%, respectively. Better methods should be developed to distinguish apTB from nontuberculous mycobacteriosis.

Adult↗

PubMed2001

[Anesthetic management in a patient with Simpson-Golabi-Behmel syndrome].

We report the anesthetic management of a 4-yr-old boy with Simpson-Golabi-Behmel syndrome. This syndrome is an X-linked condition characterized by pre- and postnatal overgrowth with visceral and skeletal anomalies. Affected males have a distinctive facial appearance with wide nasal bridge, anteverted nostrils, wide-open mouth, enlarged tongue, and large protruding maxilla and jaw. Although it had been speculated preoperatively that airway management would be complicated by the macroglossia, there was no difficulty in endotracheal intubation in the present patient. Preparations for difficult airway management should be made by the anesthesiologist before induction of anesthesia.

Abnormalities, Multiple↗

PubMed2000

Effect of endothelin-1(1-31) on p38 mitogen-activated protein kinase in cultured human mesangial cells.

It was reported that human chymase cleaves big endothelins (ETs) at the Tyr31-Gly32 bond and produces 31-amino acid ETs(1-31). In this study, we investigated the effect of ET-1(1-31) on p38 mitogen-activated protein kinase (p38-MAPK) activity in human mesangial cells (HMCs). By measuring the kinase activity, we demonstrated that ET-1 (1-31) activated the p38-MAPK dose-dependently (10(-9) M to 10(-7) M), which was inhibited by SB203580. The p38-MAPK activation induced by ET-1(1-31) peaked at 10 minutes. BQ123 almost abolished ET-1(1-31)-induced p38-MAPK activation, whereas BQ788 failed to inhibit it. These findings suggest that the stimulatory effect of ET-1(1-31) on p38-MAPK activation is mediated through ET(A) or ET(A)-like receptor. In conclusion, ET-1(1-31) induced increase in p38-MAPK activation in cultured HMCs.

Blotting, Western↗

PubMed2000

Physical aspects of a real-time tumor-tracking system for gated radiotherapy.

PURPOSE: To reduce uncertainty due to setup error and organ motion during radiotherapy of tumors in or near the lung, by means of real-time tumor tracking and gating of a linear accelerator. METHODS AND MATERIALS: The real-time tumor-tracking system consists of four sets of diagnostic X-ray television systems (two of which offer an unobstructed view of the patient at any time), an image processor unit, a gating control unit, and an image display unit. The system recognizes the position of a 2.0-mm gold marker in the human body 30 times per second using two X-ray television systems. The marker is inserted in or near the tumor using image guided implantation. The linear accelerator is gated to irradiate the tumor only when the marker is within a given tolerance from its planned coordinates relative to the isocenter. The accuracy of the system and the additional dose due to the diagnostic X-ray were examined in a phantom, and the geometric performance of the system was evaluated in 4 patients. RESULTS: The phantom experiment demonstrated that the geometric accuracy of the tumor-tracking system is better than 1.5 mm for moving targets up to a speed of 40 mm/s. The dose due to the diagnostic X-ray monitoring ranged from 0.01% to 1% of the target dose for a 2.0-Gy irradiation of a chest phantom. In 4 patients with lung cancer, the range of the coordinates of the tumor marker during irradiation was 2.5-5.3 mm, which would have been 9.6-38.4 mm without tracking. CONCLUSION: We successfully implemented and applied a tumor-tracking and gating system. The system significantly improves the accuracy of irradiation of targets in motion at the expense of an acceptable amount of diagnostic X-ray exposure.

Algorithms↗

PubMed2000

Adrenomedullin receptors in rat cerebral microvessels.

To characterize the sites of action of adrenomedullin (AM) in the cerebral microvasculature, we studied the effect of AM on cyclic AMP (cAMP) level as well as expression of AM and its receptor in the rat cerebral microvessels. The microvessels were prepared from rat cerebral cortex by albumin flotation and glass bead filtration technique. AM and calcitonin gene-related peptide (CGRP) increased cAMP level in the microvessels in a concentration-dependent manner. The effect of AM was more than 100 times more potent than that of CGRP. The accumulation of cAMP by AM was inhibited by AM[22-52], an AM receptor antagonist, but not by CGRP[8-37], a CGRP receptor antagonist, suggesting that AM increased cAMP accumulation by acting on receptors specific to AM. [125I]AM binding to the microvessels was displaced by AM and less potently by AM[22-52]. The displacing potencies of CGRP and CGRP[8-37] were very weak. mRNAs for AM as well as calcitonin-receptor-like receptor and receptor-activity-modifying protein 2 which form a receptor specific to AM, were highly expressed in the microvessels. These results provide biochemical and pharmacological evidence that AM is produced in and acts on the cerebral microvessels in an autocrine/paracrine manner and is involved in regulation of cerebral microcirculation.

Adrenomedullin↗

PubMed2000

alpha(1)-Adrenergic receptor subtypes in rat cerebral microvessels.

To identify alpha(1)-adrenergic receptor subtypes involved in the regulation of cerebral microcirculation, we studied alpha(1)-adrenergic receptor subtypes expressed in the rat cerebral microvessels. The microvessels were prepared from rat cerebral cortex by albumin flotation and glass bead filtration techniques. [(125)I]HEAT binding to the cerebral microvessels was displaced by low concentrations of 5-methylurapidil, a selective antagonist for alpha(1A)-receptors, and modified Scatchard analysis of the data revealed that half of alpha(1)-receptors is alpha(1A)-subtype, and that alpha(1B)- and/or alpha(1D)-receptors are also present. The K(i) value of the high-affinity component for 5-methylurapidil was 3.90+/-1.08 nM, which is comparable with the value obtained in the rat cerebral cortex (2.17+/-0.88 nM). Reverse transcription and polymerase chain reaction experiments showed that mRNAs of alpha(1A)- and alpha(1B)-receptors, but not alpha(1D)-receptors, were expressed in the cerebral microvessels. These results suggest that alpha(1)-receptors involved in the regulation of cerebral microvessel function are alpha(1A)- and alpha(1B)-receptor subtypes.

Adrenergic alpha-Antagonists↗

PubMed2000

Developmental expression of maf-1 messenger ribonucleic acids in rat kidney by in situ hybridization histochemistry.

maf is a family of oncogenes, originally identified from the avian oncogenic retrovirus AS42, which encodes a nuclear bZip transcription factor protein. It has been reported that maf family genes have critical roles in embryological development and cellular differentiation. In this study, the distribution of maf-1 genes, the rat homologues of mafB, was examined in rat kidneys at the embryonic stages from 13 days, gestation (E13) through E21 and then 1, 2, 4, and 8 weeks after birth by in situ hybridization with (35)S-labeled antisense riboprobes. The cellular localization was determined using double in situ hybridization. Expression of maf-1 mRNA appeared weakly on E15 and was restricted to glomerular visceral epithelial cells during the pre- and postnatal stages until 2 weeks after birth and then gradually diminished. Double in situ hybridization demonstrated that maf-1 mRNA-positive cells in glomerulus also expressed Pod-1 gene, suggesting that maf-1 mRNA was expressed in the podocyte. These findings suggest that the expression of maf-1 gene may be involved in embryological development and/or differentiation of the kidney.

Animals↗

PubMed2000

Appearance of tau-2 immunoreactivity in glial cells in human brain with cerebral infarction.

Appearance of tau epitopes in ischemic foci was investigated immunohistochemically on a series of autopsied human brains using a panel of anti-tau antibodies. While neurons were immunopositive for Alz-50, microglia and oligodendroglia around ischemic foci abundantly contained tau-2 immunoreactivity. Some astrocytes contained tau-2 immunoreactive granules in their cytoplasm. This difference suggests that neurons and glia react differently to an ischemic insult by exhibiting different tau epitopes. Immunohistochemical visualization tau-2 epitope represents its conformational change, as was reported with neurofibrillary tangles of Alzheimer type. Lack of argyrophilia in any of these tau-immunoreactive cells distinguishes them from tau-immunoreactive structures seen in various neurodegenerative disorders.

Aged↗

PubMed2000

Neurons containing Alz-50-immunoreactive granules around the cerebral infarction: evidence for the lysosomal degradation of altered tau in human brain?

Little is known about the metabolic process of tau and tau-derived substances. Alz-50- and tau 2-immunoreactivities in intracellular granules of neurons were observed in regions surrounding infarcted foci in the human cerebral cortex. Ultrastructurally, these granules in the fresh infarcted region exhibited primary lysosome-like structures, while those in old infarctions were lipofuscin. These findings indicate that tau is metabolized within lysosomes in neurons damaged by ischemic injury in human cortical penumbra. Alz-50-positive granules were more prominent in fresh infarction than in old infarction. After undergoing degradation and modification, altered tau might remain, at least partially, in secondary lysosomes.

Aged↗

PubMed2000

Impact of respiratory movement on the computed tomographic images of small lung tumors in three-dimensional (3D) radiotherapy.

PURPOSE: Three-dimensional (3D) treatment planning has often been performed while patients breathe freely, under the assumption that the computed tomography (CT) images represent the average position of the tumor. We investigated the impact of respiratory movement on the free-breathing CT images of small lung tumors using sequential CT scanning at the same table position. METHODS: Using a preparatory free-breathing CT scan, the patient's couch was fixed at the position where each tumor showed its maximum diameter on image. For 16 tumors, over 20 sequential CT images were taken every 2 s, with a 1-s acquisition time occurring during free breathing. For each tumor, the distance between the surface of the CT table and the posterior border of the tumor was measured to determine whether the edge of the tumor was sufficiently included in the planning target volume (PTV) during normal breathing. RESULTS: In the sequential CT scanning, the tumor itself was not visible in the examination slice in 21% (75/357) of cases. There were statistically significant differences between lower lobe tumors (39.4%, 71/180) and upper lobe tumors (0%, 0/89) (p < 0.01) and between lower lobe tumors and middle lobe tumor (8.9%, 4/45) (p < 0.01) in the incidence of the disappearance of the tumor from the image. The mean difference between the maximum and minimum distances between the surface of the CT table and the posterior border of the tumor was 6.4 mm (range 2.1-24.4). CONCLUSION: Three-dimensional treatment planning for lung carcinoma would significantly underdose many lesions, especially those in the lower lobe. The excess "safety margin" might call into question any additional benefit of 3D treatment. More work is required to determine how to control respiratory movement.

Adolescent↗

PubMed2000

Nitric oxide-forming reaction between the iron-N-methyl-D-glucamine dithiocarbamate complex and nitrite.

The objective of this study was to elucidate the origin of the nitric oxide-forming reactions from nitrite in the presence of the iron-N-methyl-D-glucamine dithiocarbamate complex ((MGD)(2)Fe(2+)). The (MGD)(2)Fe(2+) complex is commonly used in electron paramagnetic resonance (EPR) spectroscopic detection of NO both in vivo and in vitro. Although it is widely believed that only NO can react with (MGD)(2)Fe(2+) complex to form the (MGD)(2)Fe(2+).NO complex, a recent article reported that the (MGD)(2)Fe(2+) complex can react not only with NO, but also with nitrite to produce the characteristic triplet EPR signal of (MGD)(2)Fe(2+).NO (Hiramoto, K., Tomiyama, S., and Kikugawa, K. (1997) Free Radical Res. 27, 505-509). However, no detailed reaction mechanisms were given. Alternatively, nitrite is considered to be a spontaneous NO donor, especially at acidic pH values (Samouilov, A., Kuppusamy, P., and Zweier, J. L. (1998) Arch Biochem. Biophys. 357, 1-7). However, its production of nitric oxide at physiological pH is unclear. In this report, we demonstrate that the (MGD)(2)Fe(2+) complex and nitrite reacted to form NO as follows: 1) (MGD)(2)Fe(2).NO complex was produced at pH 7.4; 2) concomitantly, the (MGD)(3)Fe(3+) complex, which is the oxidized form of (MGD)(2)Fe(2+), was formed; 3) the rate of formation of the (MGD)(2)Fe(2+).NO complex was a function of the concentration of [Fe(2+)](2), [MGD], [H(+)] and [nitrite].

Dose-Response Relationship, Drug↗