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Biomedical subjects

T Kudoh

Publications and source records attributed to T Kudoh.

At least 37 records · Page 2Linked to original sources
PubMed1999

BMIPP compared with PET metabolism.

I-123 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) was introduced as an approved radiopharmaceutical in Japan in 1993. This article reviews our clinical comparisons between BMIPP and PET metabolism conducted at Kyoto University. BMIPP uptake was suggested to reflect exogenous fatty acid utilization in the myocardium. By the comparison between FDG PET and BMIPP SPECT, reduced uptake of BMIPP relative to thallium was considered metabolically damaged but viable myocardium in ischemic coronary artery disease. In hypertrophic cardiomyopathy, reduction of BMIPP uptake was shown to precede suppression of oxidative or glucose metabolism. Occasionally we encounter subjects with absent myocardial BMIPP uptake. The majority of these subjects showed metabolic switching from normal free fatty acid metabolism to abnormally enhanced glucose metabolism in the fasting state. Thus, BMIPP provides us with the valuable metabolic information which is unattainable using a perfusion tracer.

Cardiomyopathies↗
PubMed1999

An ultrashort 1-day protocol of Tc-99m tetrofosmin.

PURPOSE: This study describes a new 1-day protocol with Tc-99m tetrofosmin that requires only 100 minutes to obtain both stress and resting cardiac images by using a double-injection and subtraction method. METHODS: This procedure was performed in 48 consecutive patients. Rest-rest double injections were performed in eight patients (five men, three women; mean age, 69 +/- 9.8 years ) to evaluate count and image reproducibility (subprotocol A), and stress-rest and additional resting perfusion images (true rest) were done on a different day in 11 patients (five men, six women; mean age, 63 +/- 5.9 years) to confirm the validity of the new protocol (subprotocol B). RESULTS: Image quality scores of the resting image were excellent (35 of 48, or 72.9%), good (7 of 48, or 14.6%), fair (3 of 48, or 6.3%), and poor (3 of 48, or 6.3%). The scintigraphic findings with the new protocol corresponded closely with those of angiography in 26 of 34 cases (76.5%), with a tendency for underestimation (in 5 of 34 cases, or 14.7%) rather than overestimation (in 3 of 34 cases, or 8.8%). In subprotocol A, count reproducibility between the two resting images was excellent (r = 0.95; P < 0.0001); and in subprotocol B, the early-rest images were concordant visually and quantitatively with the true rest images (r = 0.89, P < 0.0001). CONCLUSION: Although there are some limitations, this protocol can be used as a routine stress-rest protocol.

Aged↗
PubMed1999

[The control survey in CD marker analysis of leukemic cells].

Analysis of cell surface antigens is thought to be more objective compared to classification by the morphology. However, it has been indicated that the evaluated data are different each other between institutes. Therefore, we performed a control survey of CD marker analysis in leukemia cells using flow cytometry in six commercial laboratories. The expression of CD2, 4, 5, 7, 8, 10, 13, 14, 19, 20, 33, 34, 38, and 71, HLA-DR in tumor cells from megakaryoblastic leukemia, lymphoblastic crisis of CML, and ALL patients, were examined. There were large differences in the results of CD marker analysis among the six commercial laboratories. One possible reason for this result is the differences in gating condition and monoclonal antibodies used in each laboratory. However, there were the differences in the results even when the same gating condition and antibodies were used. The reasons for the difference in transport or treatment conditions for samples remain a matter of considerable controversy. In the present condition, it was suggested that the exchange of information about the origin of tumor cells between the physician in charge and examination experts is thought to be the best way to analyze proper cell surface antigen expression. Further, no national survey has been carried out, but the establishment of a standard assay is preferred to obtain proper data for the patients and medical parties concerned.

Adolescent↗
PubMed1999

[Unrelated bone marrow transplantation in two severe aplastic anemia patients preconditioned with a regimen of cyclophosphamide, antithymocyte globulin, and total body irradiation].

We report our experiences with HLA-matched unrelated bonemarrow transplantation combining a preconditioning regimen of cyclophosphamide, antithymocyte globulin (ATG), and total body irradiation for two patients with severe aplastic anemia (SAA) who had already undergone repeated blood transfusions. Short-term methotrexate and cyclosporine were administered for graft-versus-host disease (GVHD) prophylaxis. Both patients achieved rapid engraftment within 3 weeks, furthermore, neither acute nor chronic GVHD developed. Our conditioning regimen appeared to be well-suited for unrelated bone marrow transplantation in heavily transfused SAA patients. However, both patients experienced bouts of fever about 20-30 and 40-50 days after transplantation, and it was difficult to differentiate whether they were affected by acute GVHD, cytomegalovirus (CMV) infections, or serum sickness. Because weakly positive CMV antigenemia was detected, both patients were given ganciclovir. Although their fever did not respond initially, it gradually subsided following the combined administration of prednisolone. These outcomes suggest it is essential that attention be devoted to the potential for serum sickness and the high risk of herpes virus infections, particularly by CMV, following the use of intensive preconditioning regimens that include ATG.

Adolescent↗
PubMed1999

Application of homogeneous time-resolved fluorescence (HTRFTM) to monitor poly-ubiquitination of wild-type p53.

Rapid degradation of wild-type p53 in the human uterine cervix is induced by the infection of high-risk human papilloma virus (HPV) types 16 and 18. HPV-E6 protein plays a critical role in the poly-ubiquitination of wild-type p53 by mediating the association of p53 with E6-associated protein (E6AP). As a result, the poly-ubiquitinated p53 is rapidly and selectively degraded by the 26S proteasome. We have established a high throughput assay system to monitor poly-ubiquitination of wild-type p53 using a new fluorescence homogeneous technology known as Homogeneous Time-Resolved Fluorescence (HTRFTM). The Europium Cryptate [Eu(K)]-labeled ubiquitins are incorporated into poly-ubiquitin chains conjugated with the biotinylated p53. In the HTRF assay, Europium cryptate-labeled ubiquitin and streptavidin-labeled allophycocyanin (XL665) are used as the fluorescence donor and acceptor, respectively. The biotinylated p53 is ubiquitinated by ubiquitination enzymes, then by the addition of streptavidin-labeled XL665, the donor and acceptor molecules are brought in close proximity, thereby generating fluorescent signals. This time-resolved fluorescence assay system shows a sufficient signal for its application in synthetic compound screening and having almost the same level of sensitivity as that monitored by the scintillation proximity assay (SPA) using 125I-labeled ubiquitin. The detection of poly-ubiquitination of wild-type p53 by using the HTRFTM or SPA systems described here is much easier and quicker than by using conventional methods. Therefore, these new systems would be appropriate for high throughput screening of compounds for the discovery of new inhibitors of poly-ubiquitination of wild-type p53.

Biopolymers↗
PubMed1999

Simultaneous assessment of myocardial free fatty acid utilization and left ventricular function using 123I-BMIPP-gated SPECT.

UNLABELLED: This study was designed to evaluate the methodological feasibility of 123I-labeled beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP)-gated SPECT to assess regional and global left ventricular (LV) function in comparison with 99mTc-sestamibi (methoxyisobutyl isonitrile [MIBI])-gated SPECT and first-pass radionuclide angiography (FPRNA). METHODS: Forty-four patients with stable coronary artery disease underwent rest BMIPP-gated SPECT (111 MBq, 60 s/step) and rest MIBI-gated SPECT (600 MBq, 40 s/step) within a week. From both gated SPECT studies, regional defect scores (DS), wall motion scores (WMS) and wall-thickening scores (WTS) were evaluated visually using 4-point scales for nine segments, and LV ejection fraction (EF) (%) was automatically calculated using Quantitative Gated SPECT (QGS) software. FPRNA was also performed on injection of MIBI. RESULTS: Exact agreement between the two gated SPECT studies was 84.1% (kappa = 0.706, r = 0.907, P < 0.0001) in WMS and 87.1% (kappa = 0.662, r = 0.884, P < 0.0001) in WTS. LVEF obtained from BMIPP-gated SPECT linearly correlated with those from MIBI-gated SPECT (y = -0.27 + 0.944x, r = 0.948, SEE = 5.00, P < 0.0001) and FPRNA (y = -7.32 + 1.042x, r = 0.919, SEE = 6.19, P < 0.0001). Even in 21 patients with mismatch segments (BMIPP DS > MIBI DS), agreement was considered to be acceptable in WMS (81.5%, kappa = 0.707, r = 0.853, P < 0.0001) and in WTS (76.7%, kappa = 0.526, r = 0.754, P < 0.0001), and correlation in LVEF remained good between BMIPP-gated SPECT and MIBI-gated SPECT (y = -1.24 + 0.955x, r = 0.938, SEE = 6.25, P < 0.0001) or FPRNA (y = -6.03 + 1.024x, r = 0.913, SEE = 7.38, P < 0.0001). CONCLUSION: BMIPP-gated SPECT can evaluate regional and global LV function with the QGS software. Therefore, BMIPP-gated SPECT offers the opportunity for simultaneous assessment of myocardial free fatty acid utilization and LV function.

Aged↗
PubMed1998

CMV retinitis after cessation of ganciclovir therapy for CMV antigenemia in an unrelated BMT recipient.

An 11-year-old boy with severe aplastic anemia underwent unrelated BMT following TBI, antithymocyte globulin and CY. On day +23, CMV antigenemia was detected which resolved with ganciclovir. Eight days after discontinuing ganciclovir, he complained of impaired visual acuity. Ophthalmologic findings and a positive PCR study using anterior chamber fluid from the right eye confirmed the presumptive diagnosis of CMV retinitis, although CMV antigenemia and PCR studies using PBMC were then negative. He was successfully re-treated with ganciclovir. CMV retinitis should be considered even when CMV antigenemia is not present or PCR using PBMC is negative.

Anemia, Aplastic↗
PubMed1998

Impairment of BMIPP uptake precedes abnormalities in oxygen and glucose metabolism in hypertrophic cardiomyopathy.

UNLABELLED: Impairment of fatty acid uptake is shown to precede myocardial perfusion abnormality using 123I-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) in an experimental model of hypertrophic cardiomyopathy (HCM) and in human studies. We have recently demonstrated that abnormalities of both glucose and oxidative metabolism precede the reduction of blood flow in HCM. The main purposes of this study were to assess the frequency of abnormal findings in FDG uptake, BMIPP uptake and oxygen metabolism and to clarify the relationship among these metabolic parameters by using PET and SPECT. METHODS: Twenty-eight subjects with HCM underwent FDG- and acetate-PET and thallium- and BMIPP-SPECT studies at rest, respectively. After correcting for partial volume effect, real percentages of FDG and BMIPP uptake were calculated. In addition, the clearance rate constant (K mono) of acetate was measured and normalized (%) to estimate the oxygen metabolism. RESULTS: There were various metabolic abnormalities observed in patients with HCM. BMIPP uptake was often impaired without significant reduction of K mono values or FDG uptake. Thus, abnormality of BMIPP uptake was more frequently observed than that for FDG uptake or K mono values (p < 0.0001, respectively). FDG uptake was relatively maintained even in the segments with reduced K mono values and reduced BMIPP uptake. CONCLUSION: HCM shows a variety of metabolic patterns; however, the results of our study suggest that reduction of BMIPP uptake appears to be the most sensitive indicator of metabolic abnormalities followed by reduction of oxidative metabolism in patients with HCM.

Acetates↗
PubMed1998

First-pass radionuclide angiography using iodine-123 myocardial tracers and a multicrystal gamma camera.

UNLABELLED: The purpose of this study was to validate the accuracy of the assessment of ventricular function by first-pass radionuclide angiography (FPRNA) with 123I myocardial tracers and a multicrystal gamma camera. METHODS: Left ventricular ejection fraction (LVEF) and right ventricular ejection fraction were measured in 69 patients by FPRNA using 123I myocardial tracers (126 +/- 7 MBq) and 99mTc tracers (541 +/- 141 MBq) on a multicrystal gamma camera with a high-sensitivity collimator. For 44 patients, ejection fraction values measured by 123I-FPRNA were compared to those estimated by equilibrium radionuclide angiography (ERNA). Visual wall-motion analysis was also performed to judge clinical acceptability of 123I-FPRNA images for identification of wall-motion abnormality. RESULTS: Mean LVEFs (%) estimated by 123I-FPRNA and by 99mTc-FPRNA were 49.6 +/- 13.6 and 49.1 +/- 14.1, respectively (nonsignificant p value). An excellent correlation was found between LVEFs estimated by 123I-FPRNA and 99mTc-FPRNA (r = 0.96, s.e.e. = 1.9%). Values of LVEF measured by 123I-FPRNA also demonstrated excellent correlation with those measured by ERNA (r = 0.95, s.e.e. = 2.2%). A good correlation was also noted between right ventricular ejection fractions measured by 123I-FPRNA and 99mTc-FPRNA (r = 0.72, s.e.e. = 4.0%). The Spearman rank correlation coefficient between 123I-FPRNA and ERNA wall-motion scores was 0.87 (n = 135, p < 0.001). CONCLUSION: Resting ventricular function can be reliably measured with 123I-FPRNA in combination with a multicrystal gamma camera. This indicates that the assessment of ventricular function is feasible in conjunction with 123I myocardial imaging without an increase in cost or radiation dose to patients.

Adult↗
PubMed1998

Analysis of genetic diversity in the VP1 unique region gene of human parvovirus B19 using the mismatch detection method and direct nucleotide sequencing.

To assess the prevalent genetic types of human parvovirus B19 strains derived from various sources and their relation to particular clinical symptoms, the genetic diversity in the VP1 unique region, which is important for the neutralizing response to human parvovirus B19, was examined by the mismatch detection method using the Non-isotopic RNase Cleavage Assay (NIRCA) and direct nucleotide sequencing. Twenty three samples obtained between 1986 and 1997 were examined. Three electrophoresis patterns were observed with NIRCA. The nucleotide sequence showed that there were 14 nucleotide changes and 4 amino acid substitutions in comparison with Au strains employed as a standard strain. The nucleotide variability of all samples ranged from 0.3 to 2.7% and the amino acid variability ranged from 1.0 to 3.0%. They were classified into three types according to NIRCA. Types 1 and 3 had similar sequences, but the type 2 sequence was quite different. Although there were some nucleotide variations in the same NIRCA type, these were silent. However, there was no relationship between the clinical features and NIRCA types or between clinical features and the nucleotide sequence. All samples obtained before 1987 were NIRCA type 2. On the other hand, 19 of 20 samples obtained after 1989 were NIRCA type 1. The other sample obtained in 1992 was type 3. The results suggest that the B19 strain of type 2 disappeared by 1988 and changed to other B19 strains such as type 1 and type 3 after 1988, indicating a correlation between genome type and prevalence. NIRCA is a convenient method for screening mutations due to its simplicity and quickness.

Adolescent↗
PubMed1998

Abnormality of myocardial oxidative metabolism in noninsulin-dependent diabetes mellitus.

UNLABELLED: The purpose of this study was to evaluate oxidative metabolism and its response by dobutamine in patients with noninsulin-dependent diabetes mellitus (NIDDM) using 11C-acetate PET. METHODS: We studied 16 patients with NIDDM (9 men, 7 women; mean age 53.7 +/- 12.8 yr) and 6 healthy male control subjects (mean age 41.8 +/- 17.2 yr). None of them had an abnormality on stress-perfusion SPECT. The 11C-acetate clearances (Kmono) were compared regionally for five myocardial segments in all subjects at rest and during low-dose dobutamine stress in 13 patients (8 patients with NIDDM, age 51.9 +/- 13.6 yr; 5 healthy male control subjects, age 45.6 +/- 16.3 yr). Correlation between regional Kmono and rate-pressure product (RPP) was also studied. RESULTS: At rest, the clearance of 11C-acetate was slightly heterogeneous for both patients with NIDDM and healthy control subjects, with smaller values in the apex and inferior wall in both groups. The difference became significant during dobutamine stress in the patients. The RPP-to-Kmono (average for five segments) ratio at rest was slightly smaller in the patients (1042.7 +/- 559.1 x 0.01) than in the healthy control subjects (1391.4 +/- 209.6 x 0.01, not significant), and those during dobutamine stress were almost the same in the two groups (1457.3 +/- 737.4 x 0.01 and 1486.0 +/- 211.8 x 0.01, respectively). A significant correlation was seen between regional Kmono and RPP in every segment in the healthy control subjects (average; r = 0.89; p < 0.01), whereas more scattered correlation with greater regional variation was observed in the patients (average; r = 0.31; p value was not significant). CONCLUSION: Patients with NIDDM showed slight regional heterogeneity in myocardial oxidative metabolism. They also had more scattered correlation between myocardial oxidative metabolism and cardiac work (RPP) than healthy control subjects, with the smallest correlation coefficient observed in the inferior wall. These findings may help the understanding of dynamics in myocardial oxidative metabolism of NIDDM hearts.

Acetates↗
PubMed1997

The Wilms tumor suppressor gene WT1 induces G1 arrest and apoptosis in myeloblastic leukemia M1 cells.

WT1 was isolated as a tumor suppressor gene of Wilms tumor. However, high expression of WT1 correlates with poor prognosis in acute leukemia. In addition suppression of WT1 expression by WT1 anti-sense oligonucleotide inhibits proliferation of leukemia cells, suggesting that WT1 is important for their proliferation. To further elucidate the biological significance of WT1 in leukemic cell growth, we overexpressed exogenous WT1 in murine M1 myeloblastic leukemia cells using the isopropyl-beta-D-thiogalactoside (IPTG)-controlled expression system. We found that induction of one splicing variant of WT1 [WT1-17AA(+)-KTS(-)] in M1 cells induces cell cycle arrest and apoptotic cell death. These results suggest that the role of WT1 is different depending on the type of leukemia cell in which it is expressed.

Animals↗
PubMed1997

Recent advances in nuclear cardiology in the study of coronary artery disease.

A variety of new radiopharmaceutical agents have been introduced to probe myocardial function in vivo. This review will introduce these new techniques which have recently been available in Japan. Tc-99m perfusion imaging agents provide excellent myocardial perfusion images which may enhance diagnostic accuracy in the study of coronary artery disease. In addition, greater photon flux from the tracer permits simultaneous assessment of regional perfusion and function with use of first-pass angiography or ECG-gated acquisition. Positron emission tomography enables metabolic assessment in vivo. Preserved FDG uptake indicates ischemic but viable myocardium which is likely to improve regional dysfunction after revascularization. In addition, FDG-PET seems to be valuable for selecting a high risk subgroup. Recently I-123 BMIPP, a branched fatty acid analog, has been clinically available in Japan. Less uptake of BMIPP than thallium is often observed in the ischemic myocardium. Such perfusion metabolic mismatch which seems to be similarly observed in FDG-PET is identified in the stunned or hibernating myocardium with regional dysfunction. Both of them are likely to recover afterwards. Severe ischemia is identified as reduced BMIPP uptake at rest, suggesting its role as an ischemic memory imaging. I-123 MIBG uptake in the myocardium reflects adrenergic neuronal function in vivo. In the study of coronary artery disease, neuronal denervation is often observed around the infarcted myocardium and post ischemic region as well. More importantly, reduced MIBG uptake in these patients can identify high risk for ventricular arrhythmias and assess severity of congestive heart failure. These new techniques will provide insights into new pathological states in the ischemic heart disease and enable to select optimal treatment in these patients.

Adrenergic Fibers↗
PubMed1997

The Wilms tumor protein is persistently associated with the nuclear matrix throughout the cell cycle.

In order to investigate the subnuclear interactions of the WT1 gene product, nuclear fractionation analyses were performed with human osteosarcoma HOS and myelogenous leukemia K562 cells. The WT1 protein was tightly associated with the nucleus and was resistant to high-salt or detergent extraction and DNase I digestion. Both the expression level and stability of WT1 and its resistance to high salt and DNase I treatments remained constant during the cell cycle. In addition, human WT1 ectopically expressed in mouse NIH3T3 cells was also resistant to these treatments. These results suggest that WT1 functions in tight association with the nuclear matrix.

3T3 Cells↗