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Biomedical subjects

T Kudoh

Publications and source records attributed to T Kudoh.

At least 55 records · Page 3Linked to original sources
PubMed1997

Metabolism substrate with negative myocardial uptake of iodine-123-BMIPP.

UNLABELLED: Iodine-123-BMIPP is an iodinated methyl-branched-chain fatty acid. Low uptake of BMIPP relative to thallium or other perfusion tracer indicates metabolically damaged but viable myocardium (for example, ischemic but viable myocardium). In some cases, however, negative myocardial uptake of BMIPP is observed. The main purposes of this study were to assess the frequency of such BMIPP findings and to clarify metabolism of such cases by using PET. METHODS: Among the 1258 patients who underwent BMIPP scintigraphy, 11 patients (0.9%) showed negative myocardial uptake of BMIPP. Under fasting condition, PET using [11C]palmitate, 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and [11C]acetate was performed in nine of these 11 patients. RESULTS: Global myocardial uptake of [11C]palmitate, expressed as the standardized uptake value, was significantly lower in the patients than in control (3.62 +/- 0.44 versus 5.49 +/- 1.62; p < 0.01). However, the early phase clearance rate of [11C]palmitate and oxidative metabolism was not significantly different. In the fasting state, PET studies showed increased FDG accumulation in seven of nine patients (high group) and decreased accumulation in two patients (low group). In the high group patients, glucose metabolism in the fasting state was similar to that in the normal volunteers after glucose loading (Kcomplex: 0.050 +/- 0.016 versus 0.038 +/- 0.015; p = ns). However, low glucose metabolism was noted in the low group patients (Kcomplex: 0.007 and 0.005). CONCLUSION: Negative myocardial uptake of BMIPP is occasionally, but not often, observed. Global uptake of [11C]palmitate was decreased in these patient. The majority of these patients showed "metabolic switching" from normal free fatty acid metabolism to abnormally enhanced glucose metabolism in the fasting state. However, some patients showed decreases in both exogenous glucose utilization and free fatty acid uptake in the fasting state.

Acetates↗
PubMed1997

[New method for closure of median sternotomy: usefulness of barbed staple].

In this report, 15 cases using straight staple (group A) and 35 cases using barbed staple (group B) were compared for the purpose of investigating efficacy for median sternal closure. The staples were placed by a Stapilizer powered metaphyseal staple system following partial transsternal fixation with two wires. As a means of assessing the status of back out, which is a major cause of poor fixation, the back out rate (BOR) was measured on lateral sternal radiographies. The average BOR was found to be 33.8% in group A and 21.2% in group B (p < 0.001). Barbed staples seemed to be more useful for sternal fixation than straight staples. This method of applying barbed staples had the advantages of speed, ease of insertion and noninvasion of the retrosternal region. It should be recommended in cases with severe adhesion of the retrosternal region after coronary operation.

Adult↗
PubMed1996

Constitutive expression of the Wilms tumor suppressor gene WT1 in F9 embryonal carcinoma cells induces apoptotic cell death in response to retinoic acid.

The product of the Wilms tumor suppressor gene, WT1, is thought to be a tissue specific transcription factor regulating cell growth and differentiation. To elucidate the function of WT1 in cellular differentiation, we examined the changes in the level of WT1 expression during retinoic acid induced-differentiation of embryonal carcinoma F9 cells into parietal endoderm cells. We found that, in response to retinoic acid addition, the expression of WT1 increased significantly after 12--24 h of incubation, then decreased and finally disappeared after 4 days, by which time most of the cells had differentiated into primitive endoderm cells. To examine the significance of these changes in WT1 expression, we established cell lines constitutively expressing one of the WT1 splicing variants. These cell lines showed a phenotype very similar to parental F9 cells in the absence of retinoic acid. However, in the presence of retinoic acid, they failed to differentiate into primitive endoderm cells and underwent apoptotic death 36 h after the addition of retinoic acid. These results suggest that downregulation of WT1 expression is necessary for normal differentiation of F9 cells into parietal endoderm cells.

3T3 Cells↗
PubMed1996

Persistent activation of CDK4 during neuronal differentiation of rat pheochromocytoma PC12 cells.

It has been shown that suppression of cyclin-dependent kinase 4 (CDK4) expression or its kinase activity is a critical event for the differentiation of hematopoietic and myoblastic cells. To investigate the role of CDK4 during NGF-mediated neuronal differentiation of PC12 cells, we examined the changes in the expression and kinase activity of CDK4. Unexpectedly, both the expression of CDK4 and its kinase activity remained high throughout 10 days of exposure to NGF. Furthermore, constitutive overexpression of the human CDK4 did not inhibit the differentiation. These results suggest that suppression of CDK4 is not required for the NGF-induced neuronal differentiation of PC12 cells.

Animals↗
PubMed1996

Growth inhibition of human leukemic cells by WT1 (Wilms tumor gene) antisense oligodeoxynucleotides: implications for the involvement of WT1 in leukemogenesis.

We have previously reported expression of WT1 in acute leukemia. To elucidate its biological significance, we examined the effect of the suppression of the WT1 expression by WT1 antisense oligomers on the growth of the leukemic cells expressing WT1. When 20 different WT1 antisense (AS) oligomers covering from the 5' cap sites of the WT1 gene to the 3' end were examined for the inhibitory effect on the growth of K562 cells expressing WT1, four WT1 AS oligomers inhibited the cell growth, whereas WT1 sense and random sequence oligomers had no effect on the cell growth of K562. Moreover, WT1 AS oligomers significantly inhibited the growth of the clonogenic cells of fresh leukemic cells in six of 14 patients with acute myeloid leukemia, in one of two patients with chronic myelogenous leukemia (CML) chronic phase, and in one of one patient with CML blastic crisis. However, these oligomers did not inhibit normal colony-forming unit-granulocyte-macrophage. Western blot analysis clearly demonstrated the significant reduction in the WT1 protein levels in the K562 and fresh leukemic cells that were treated with the WT1 AS oligomers, confirming that the inhibitory effect of the WT1 AS oligomers on the cell growth operates via the reduction in the WT1 protein levels. These results show that WT1 plays an important role in leukemogenesis.

Base Sequence↗
PubMed1996

Human parvovirus B19 infection associated with acute hepatitis.

BACKGROUND: Human parvovirus (HPV) B19 infection produces a range of clinical manifestations including erythema infectiosum in children. Here we describe seven children who had acute hepatitis with HPV B19 infection. METHODS: Hepatic dysfunction was noted in three children referred to our hospital during the course of erythema infectiosum caused by HPV B19 infection diagnosed by ELISA and PCR. The role of HPV B19 in the pathogenesis of hepatic involvement was investigated retrospectively by PCR assay of stored serum samples from 773 patients admitted to our hospital. FINDINGS: 15 patients admitted to our hospital from January, 1991, to June, 1992, were HPV B19 DNA positive, of whom four had acute hepatitis of unknown origin. These four patients were aged between 7 months and 5 years. Of the seven patients, infection with hepatitis A, B, or C viruses or Epstein-Barr virus was ruled out in six by virological examinations. INTERPRETATION: Epidemiological evidence suggests that HPV B19 can be the cause of acute hepatitis.

Acute Disease↗
PubMed1996

Prognostic value of iodine-123 labelled BMIPP fatty acid analogue imaging in patients with myocardial infarction.

This study was undertaken to evaluate the prognostic value of iodine-123 labelled 15-iodophenyl-3-R,S-methyl pentadecanoic acid (BMIPP) imaging in patients with myocardial infarction. BMIPP is an iodinated methyl branched fatty acid analogue which is trapped in the myocardium with little washout, thereby reflecting fatty acid utilization in the myocardium. We previously reported that in patients with myocardial infarction, regions are often observed where reduced BMIPP uptake is seen relative to thallium-201 perfusion at rest. However, the clinical significance of such discordant BMIPP uptake remains unknown. Fifty consecutive patients with chronic myocardial infarction referred for stress thallium scan and coronary arteriography underwent BMIPP imaging at rest. Each patient was in a stable condition at the time of the radionuclide study. Follow-up was performed at a mean interval of 23 months to investigate the prognostic implications of the radionuclide studies. Nine patients had cardiac events during the follow-up period. Univariate analysis showed that the number of discordant BMIPP versus 201TL uptake segments was the best predictor of future cardiac events (P=0.0245), followed by the presence of discordant BMIPP uptake (P=0.0388) and the number of 201TL redistribution segments (P=0.0444). When all the clinical and radionuclide variables were analysed by Cox regression analysis, the presence of discordant BMIPP uptake was the best, and an independent, predictor of future cardiac events (chi 2=8.5) followed by the number of coronary stenoses on angiography (chi 2=3.9). These preliminary data suggest that decreased BMIPP uptake relative to 201TL is a valuable predictor of future cardiac events in patients with myocardial infarction. Areas with such discordant BMIPP uptake may contain jeopardized myocardium where fatty acid utilization has been severely suppressed relative to myocardial perfusion.

Aged↗
PubMed1996

Veno-occlusive disease of the liver following bone marrow transplantation: a clinical-pathological study of autopsy cases.

A total of 28 patients with leukemia underwent intensive therapy with megadose chemotherapy and stem cell transplantation. Of 16 patients who had busulfan therapy, 2 developed the clinical syndrome of veno-occlusive disease of the liver (VOD) characterized by progressive abnormalities in liver function, abdominal pain, and ascites. Postmortem findings showed VOD of the central and sublobular hepatic vein. Immunohistochemical analysis using anti-actin and CD34 mAb was employed in an attempt to clarify the process of fibrosis. Actin positive cells had accumulated around the central vein. Ito cell activation might be responsible for secondary fibrosis following endothelial injury. We report autopsy findings and immunohistochemical results.

Adolescent↗
PubMed1996

Generator-produced copper-62-PTSM as a myocardial PET perfusion tracer compared with nitrogen-13-ammonia.

UNLABELLED: The purpose of this study was to determine the suitability of 62Cu-pyruvaldehyde bis(N4-methylthiosemicarbazone) (62Cu-PTSM) for estimating myocardial blood flow (MBF) over a wide range of flow by comparison with 13N-ammonia (13NH3). METHODS: PET studies using 62Cu-PTSM and 13NH3 were performed at rest and after pharmacological vasodilatation in 9 normal subjects and 13 patients with coronary artery disease (CAD). According to the microsphere method, values for the product of the extraction fraction and MBF (ExMBF) were calculated using both tracers. In static images, the percent uptake (normalized to the peak count) of each tracer was measured in patients with CAD. RESULTS: The myocardial tracer distribution in the normal subjects was significantly higher in the inferior wall in the 62Cu-PTSM studies and lower in the lateral wall in the 13NH3 studies. The ExMBF values showed linear correlation for both tracers in a low flow range. In a high flow range, however, the ExMBF values for 62Cu-PTSM were nonlinearly proportional to the increase of those for 13NH3 (y = 1.1 x -0.21x2, r = 0.81). The percent uptake for both tracers at baseline well correlated linearly (y = 10.4 + 0.88x, R = 0.91). After pharmacological vasodilatation underestimation of blood flow with 62Cu-PTSM was noted compared to that with 13NH3 at high flows (y = 31.8 + 0.63x, r = 0.76). CONCLUSION: These results suggest that the MBF estimates using 62Cu-PTSM in a low flow range may be as accurate as those with 13NH3. In a high flow range, however, the extraction fraction of 62Cu-PTSM is considered to be lower than that of 13NH3, and this may limit the estimation of MBF with 62Cu-PTSM after pharmacological vasodilatation.

Ammonia↗
PubMed1996

Assessment of fatty acid uptake in ischemic heart disease without myocardial infarction.

UNLABELLED: To assess the clinical value of 123I fatty acid analog, 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) was imaged at rest in coronary patients without prior myocardial infarction. The BMIPP findings were compared with various clinical parameters. METHODS: Thirty-one patients with ischemic heart disease (19 with unstable angina, 12 with stable angina), without myocardial infarction underwent BMIPP SPECT at rest, coronary arteriography, rest/stress thallium SPECT and left ventriculography exams. RESULTS: Regional decrease of BMIPP was seen in 63% of the myocardial areas at risk, whereas regional perfusion decrease at rest was observed only in 35% (p < 0.01). The BMIPP decrease was more often seen in the unstable group (79%) than stable group (38%) (p < 0.01). Stress-induced ischemia was seen in 77% of segments with decreased BMIPP uptake in unstable group and in 57% in the stable group. Frequency and severity of BMIPP abnormality increased with the severity of stress-induced ischemia (p < 0.005) and the severity of coronary artery stenosis (p < 0.005). In addition, regional BMIPP abnormality was related to severity of wall motion abnormalities (p < 0.005). While 67% of segments with a wall motion abnormality showed BMIPP decrease, 36% with normal wall motion also showed BMIPP decrease (p < 0.01). CONCLUSION: Abnormal fatty acid metabolism was often observed at rest in patients with ischemic heart disease without history of myocardial infarction, and the abnormalities were related to severe myocardial ischemia and regional wall motion abnormalities.

Aged↗
PubMed1996

Regional abnormality of iodine-123-MIBG in diabetic hearts.

UNLABELLED: Autonomic neuropathy along with cardiac denervation is one of the prognostic factors of diabetic patients. The aim of this study was to establish qualitative and quantitative assessment of diabetic cardiac denervation using [123I]metaiodobenzylguanidine (MIBG). METHODS: The study population consisted of 31 diabetic patients and 12 control subjects (C). Diabetic patients were classified into the following three groups according to their presentation of neuropathy: NO, without neuropathy; N1, mild neuropathy; N2, severe neuropathy. All subjects underwent triple-phase MIBG scanning, including dynamic planar imaging as well as early and delayed planar and SPECT imaging. Myocardial uptake ratios of MIBG and heart-to-mediastinum count ratios (H/M) were calculated as global uptake indices. Inferior-to-anterior count ratios and coefficients of variation were calculated as regional distribution indices. The washout rate of the inferior wall and whole myocardium were also studied. RESULTS: MIBG abnormalities were obvious in the inferior wall, which gradually spread to the adjacent segments. All indices of regional uptake showed a significant difference (p < 0.01) among the groups, while only the H/M of the late image showed significant differences in the two global uptake indices (p = 0.02). the washout rate of the inferior wall was enhanced with neuropathy. CONCLUSION: Diabetic neuropathy involves an MIBG abnormality in its early stages. Since this abnormality occurs in the inferior segment, an inferior-to-anterior count ratio, an index of regional MIBG uptake could be suitable for the evaluation of this condition because of its superior sensitivity.

3-Iodobenzylguanidine↗
PubMed1996

[Nephrotic syndrome related to chronic graft versus host disease after allogeneic bone marrow transplantation in a patient with malignant lymphoma].

A 13-yr-old boy was diagnosed as T cell lymphoma. After the second remission, he underwent BMT from an HLA-identical, MLC negative sibling donor. After BMT, he developed grade II acute GVHD. GVHD was improved by pulsed steroid therapy using prednisolone. About 12 months after BMT, he developed bronchiolitis obliterans, sicca syndrome, and leukoderma, which were related to chronic GVHD. Pulsed steroid therapy was carried out twice, and his condition improved. Twenty-seven months after BMT, he developed nephrotic syndrome. A renal biopsy was performed, and the diagnosis was histologically membranous nephropathy and focal glomerular sclerosis. The response to steroids was not satisfactory. After 5 weeks, dipyridamole was added, but proteinuria persisted. Proteinuria disappeared 8 weeks after the addition of cyclosporine. The second biopsy after 5 months of treatment revealed an improvement in the renal lesions. The patient showed a low T4 to T8 ratio of T-lymphocytes at the onset of nephrotic syndrome. However after treatment with cyclosporine, the ratio gradually increased. These findings suggested the nephrotic syndrome in this patient was related to renal involvement in the course of chronic GVHD.

Adolescent↗
PubMed1995

Constitutive overexpression of CDK2 inhibits neuronal differentiation of rat pheochromocytoma PC12 cells.

Changes in the levels of cyclins A, D, and E, p21, and cyclin-dependent kinase 2 (CDK2) were examined in rat pheochromocytoma PC12 cells during neuronal differentiation induced by nerve growth factor (NGF). Expression of cyclin A decreased to an undetectable level after 5 days of exposure to NGF, while expression of CDK2 decreased gradually after day 3. In contrast, the levels of cyclins D1 and E increased gradually through day 10, yet the amount of cyclin E associated with CDK2 decreased concomitant with a decrease in the CDK2 protein level. p21 expression increased gradually after day 7, while the level of CDK2-associated p21 remained unchanged. When human cDNAs encoding cyclins and CDK2 were introduced into PC12 cells, only CDK2 overexpression inhibited NGF-induced differentiation. The cell lines overexpressing CDK2 showed stable and high levels of CDK2 kinase activity during differentiation, whereas parental and vector-transfected cell lines displayed a marked decline in CDK2 kinase activity 1 day after NGF treatment. In cell lines overexpressing cyclins A, D, and E, this reduction of the kinase activity was not apparent until day 3. These results suggest that down-regulation of CDK2 activity is a crucial event for the neuronal differentiation of PC12 cells.

Adrenal Gland Neoplasms↗
PubMed1995

G1 phase arrest induced by Wilms tumor protein WT1 is abrogated by cyclin/CDK complexes.

WT1, the Wilms tumor-suppressor gene, maps to the human chromosomal region 11p13 and encodes a transcriptional repressor, WT1, implicated in controlling normal urogenital development. Microinjection of the WT1 cDNA into quiescent cells or cells in early to mid G1 phase blocked serum-induced cell cycle progression into S phase. The activity of WT1 varied significantly depending on the presence or absence of an alternatively spliced region located upstream of the zinc finger domain. The inhibitory activity of WT1 was abrogated by the overexpression of cyclin E/CDK2 as well as cyclin D1/CDK4. Furthermore, both CDK4- and CDK2-associated kinase activities were downregulated in cells overexpressing WT1, whereas the levels of CDK4, CDK2, and cyclin D1 expression were unchanged. These findings suggest that inhibition of the activity of cyclin/CDK complexes may be involved in mediating the WT1-induced cell cycle block.

3T3 Cells↗