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Biomedical subjects

J Hirai

Publications and source records attributed to J Hirai.

At least 19 recordsLinked to original sources

Hyperhomocysteinemia, diabetes mellitus, and carotid atherosclerosis independently increase atherosclerotic vascular disease outcome in Japanese patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) have high mortality from atherosclerotic/atherothrombotic vascular disease (AVD). However, the role of an elevated plasma total homocysteine (tHcy) level as a risk factor is uncertain in ESRD. METHODS: We enrolled 55 ESRD patients in a prospective follow-up study in order to evaluate the prognostic significance of their tHcy levels, common methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, and other atherosclerotic risk factors, in combination with the results of B mode ultrasound for carotid arteries. RESULTS: Mean intima-media thickness of the common carotid artery (CCA-IMT) in ESRD patients was thicker than that in 102 age- and sex-matched healthy controls. Carotid plaque was more frequently present in patients compared with controls, as was calcified plaque more common in patients (p < 0.001). Plasma tHcy levels (mean +/- SD) in patients (39.1 +/- 27.2 nmol/ml) were higher than that (8.8 +/- 2.7 nmol/ml) in controls (p < 0.001). Folic acid was the major determinant of elevated tHcy levels in ESRD patients. During the follow-up period of 31 +/- 3 months, 14 patients had one or more AVD complications, and 10 consequently died from AVD causes. Proportional hazards modeling showed that 5-year intervals of age (relative risk of 2.95, 95% CI 1.62 - 5.37), 10 nmol/ml intervals of tHcy levels (relative risk of 2.31, 95% CI 1.31 - 4.08), and presence of diabetes mellitus (relative risk of 6.62, 95% CI 1.07 +/- 40.8) were independent predictors of future AVD events, and tHcy levels (relative risk of 2.67, 95% CI 1.29 - 5.52) and age (relative risk of 2.10, 95% CI 1.15 - 3.83) were those of AVD mortality. We also found a significant association between carotid plaque prevalence and AVD events (X(2) = 11.6, p = 0.001). CONCLUSION: Hyperhomocysteinemia, diabetes mellitus, and carotid atherosclerosis appeared to contribute independently to increase the risk of AVD outcome in Japanese patients with ESRD.

Adult↗

Inhibition of liver metastases and tumor cell invasion in spontaneous liver metastasis model (LMFS) by sodium D-glucaro-delta-lactam (ND2001).

We examined the inhibitory effect of sodium D-glucaro-delta-lactam (sodium 5-amino-5-deoxy-D-glucosaccharic acid-delta-lactam: ND2001) upon liver metastases of the LMFS tumor. A permanent cell line, LMFS, was established from a spontaneously occurring murine retroperitoneal tumor of BALB/c mouse origin, and after a subcutaneous injection, the LMFS cells proliferated at the inoculation site (100% take) with liver metastases. ND2001 had little effect on the cell growth, cell cycle and phagokinesis of the LMFS cells in vitro. However, when the invasive activity was measured by the Boydem chamber method, the number of LMFS cells was reduced, with inhibition rates of 98.0%. After the LMFS cells treated with ND2001 in vitro, the numbers of hepatic metastases of subcutaneous inoculation of treated cells were reduced dose-dependently, and those of intravenous inoculation were not found by microscopical study. When the LMFS tumor-bearing mice were treated with ND2001 (0, 30, 100 mg/kg/d) from day 1, ND2001 (30 mg/kg) inhibited the liver metastases with a rate of 56.4%, and when given from day 15, ND2001 (100 mg/kg) inhibited with a rate of 47.5%. But ND2001 showed neither cytocidal nor anti-tumor activity. Combination therapy of primary tumor resection and ND2001 administration revealed that preoperative use of ND2001 was more effective in preventing liver metastases. These results suggested that ND2001 might have a potential use as an anti-metastatic agent for operative patients without metastasis.

Animals↗

Residual cardiomyocytes and scintigraphic findings in advanced coronary artery disease: correlation with technetium-99m-tetrofosmin and thallium-201 single photon emission computed tomography.

A 68-year-old man suffering from chronic heart failure due to coronary artery disease (CAD) underwent rest technetium-99m (99mTc)-tetrofosmin and thallium-201 (201Tl) with reinjection studies, but died thereafter. The heart was removed and sectioned into short-axis slices and examined by gross and microscopic pathologic methods. A close correlation between the amount of residual cardiomyocytes and the level of regional tracer activity in the left ventricular wall was obtained for redistribution 201Tl, reinjection 201Tl and rest 99mTc tetrofosmin images. The correlation coefficients were r=0.901 for the 201Tl redistribution images, r=0.913 for the 201Tl reinjection images and r=0.917 for the rest 99mTc-tetrofosmin images. This case report provides further evidence of the validity of SPECT tetrofosmin imaging for the determination of myocardial viability in CAD.

Aged↗

[Effects of HCFU and TNP 470 on liver metastasis of BALB/c retroperitoneal sarcoma (LMFS)].

Combination therapy using HCFU and TNP 470, which inhibits angiogenesis, was examined for effectiveness against the footpad injection model of LMFS tumor. This LMFS, a retroperitoneal sarcoma of BALB/c mice, proliferated at the inoculation site (100% take) and all mice operated on after day 15 had spontaneous metastatic nodules in the liver. Mice with the LMFS tumor were given HCFU and 5-FU (5 days/week), and/or TNP 470 (3 days/week) from day 3 for 3 weeks and sacrified at day 28 under anesthesia. Seven of 10 mice receiving 5-FU and TNP 470 died from the side effects of the drugs. Mean tumor weight and liver metastatic nodules were determined and compared with a control group. The results were as follows: HCFU group: 94.6%, 11.8%, 5 FU group: 73.9%, 28.8%, TNP 470 group: 67.6%, 44%, HCFU and TNP 470 group: 33.3%, 6.4%. Mice with LMFS were given HCFU and/or TNP 470 from day 3 for 4 weeks. The foot on the injected side was amputated on day 15, and the animals were sacrified on day 35. Liver metastatic nodules compared with those of the operation (OP) group as follows: OP + HCFU group: 14.4%, OP + TNP group: 39.1%, and OP + HCFU + TNP 470 group: 5.4%. Histologically, 5 of 5 mice of the OP group, 3 of 5 of the OP + HCFU group, 4 of 5 of the OP + TNP 470 group and 1 of 5 of the OP + HCFU + TNP 470 group had liver metastases. These results show that while either HCFU or TNP 470 is effective by itself, a combination of these drugs is more effective against liver metastasis.

Angiogenesis Inhibitors↗

Quantitative rest technetium-99m tetrofosmin imaging in predicting functional recovery after revascularization: comparison with rest-redistribution thallium-201.

OBJECTIVES: This study was undertaken to 1) compare the regional myocardial tracer distributions between rest technetium (Tc)-99m tetrofosmin and rest-redistribution thallium (Tl)-201 images in patients with coronary artery disease and left ventricular dysfunction; and 2) assess the comparative values of these agents for predicting functional recovery after revascularization. BACKGROUND: Tc-99m tetrofosmin is a new myocardial perfusion imaging agent, but its role for detecting viable myocardium is still unclear. METHODS: Thirty-six patients with coronary artery disease and left ventricular dysfunction underwent rest Tc-99m tetrofosmin, rest-redistribution Tl-201 and gated blood pool scintigraphy. In 21 patients with successful revascularization confirmed by follow-up angiography, gated blood pool scintigraphy was repeated after revascularization. Optimal threshold cutoffs to separate reversible from irreversible dysfunction were determined by receive operating characteristic analysis. RESULTS: Regional Tc-99m tetrofosimin activity highly correlated with redistribution Tl-201 activity (r = 0.93). The diagnostic performance for predicting functional recovery, as measured by the area under the receiver operating characteristic curves, measured 0.66 +/- 0.07 (mean +/- SD) for Tc-99m tetrofosmin and 0.67 +/- 0.07 for Tl-201 (p = 0.60, 96.7% power to detect difference in area of 0.10). The optimal threshold cutoffs for viability were considered to be 50% of peak activity for Tc-99m tetrofosmin and 55% of peak activity for Tl-201. The positive and negative predictive values for reversible dysfunction were, respectively, 69% and 82% for Tc-99m tetrofosmin and 69% (p = 0.99 vs. Tc-99m tetrofosmin) and 71% (p = 0.66 vs. Tc-99m tetrofosmin) by Tl-201. CONCLUSIONS: The diagnostic performance of quantitative rest Tc-99m tetrofosmin imaging in predicting functional recovery after revascularization is comparable to that of rest-redistribution Tl-201.

Aged↗

Significance of late redistribution thallium-201 imaging after rest injection for detection of viable myocardium.

UNLABELLED: The aim of this study was to determine whether late redistribution imaging after rest injection of 201Tl would provide further information on myocardial viability over conventional rest-early redistribution 201Tl imaging. METHODS: Twenty-nine patients with coronary artery disease and left ventricular dysfunction underwent rest, early (3-4 hr) and late (20-24 hr) redistribution 201Tl and gated blood pool studies. In 14 patients with successful revascularization, gated blood pool study was repeated after the coronary intervention. RESULTS: Nine of 29 patients showed early redistribution, and six additional patients showed further redistribution on the late images. Of 136 segments with initial 201Tl defects, 18 showed early redistribution, and 10 showed late redistribution. When a threshold of 60% of peak activity was used as an index of myocardial viability, only a small fraction (3%) of the initial 201Tl defects were additionally considered viable by the late images. In 14 patients who underwent revascularization, the positive (69%) and negative (87%) predictive values of the early redistribution images for functional recovery were similar to those obtained by the late images (68% and 86%, respectively). CONCLUSION: Although late redistribution after rest injection of 201Tl occasionally occurs, most of the clinically relevant information on myocardial viability may be obtained by conventional rest-early redistribution 201Tl imaging when the defect severity is considered an index of tissue viability.

Aged↗

Comparison of defect size between thallium-201 and technetium-99m tetrofosmin myocardial single-photon emission computed tomography in patients with single-vessel coronary artery disease.

Defect size on exercise-rest technetium (Tc)-99m tetrofosmin myocardial perfusion imaging was compared with that on exercise-reinjection thallium-201 imaging with 20 patients with 1-vessel coronary artery disease. In each patient, exercise-reinjection thallium-201 single-photon emission computed tomography (SPECT) and exercise-rest Tc-99m tetrofosmin SPECT imaging were performed. For visual analysis of the obtained SPECT images, the left ventricular myocardium was divided into 20 segments based on 3 short-axis slices from the apical, middle, and basal ventricular levels. For quantitative analysis, a square region of interest was placed on the center of each segment which was used for visual analysis, and relative regional activity to the normal reference region was calculated for each segment. By visual interpretation of the images, exercise Tc-99m tetrofosmin imaging showed a smaller defect size than exercise thallium-201 imaging (6.9 +/- 3.9 vs 8.8 +/- 3.0 segments, p <0.01). In contrast, rest Tc-99m tetrofosmin imaging showed a defect size similar to that on reinjection thallium-201 imaging (5.9 +/- 3.6 vs 5.6 +/- 3.9 segments, p = NS). Similarly, the mean defect sizes during exercise determined by quantitative analysis were smaller on Tc-99m tetrofosmin SPECT than those on thallium-201 SPECT at all tested threshold cutoff points ranging from 50% to 70%, whereas there were no significant differences in defect sizes between rest Tc-99m tetrofosmin and reinjection thallium-201 imaging. These data indicate that exercise Tc-99m tetrofosmin SPECT defect size determined either by visual analysis or by quantitative analysis may be smaller than on exercise thallium-201 SPECT.

Aged↗

Impaired fatty acid uptake in ischemic but viable myocardium identified by thallium-201 reinjection.

Iodine 123-labeled 15-iodophenyl-3-methyl-pentadecanoic acid (BMIPP) has been proposed as a potential myocardial fatty acid probe. We studied BMIPP uptake in ischemic myocardium identified by thallium reinjection. Fifty-five patients with coronary artery disease who had persistent defects on standard exercise-redistribution thallium imaging were investigated. Patients underwent exercise-redistribution-reinjection thallium and resting BMIPP imaging. BMIPP uptake less than that seen with thallium on reinjection imaging was observed in 105 (82%) of 128 myocardial segments with new fill-in after thallium reinjection and 87 (37%) of 238 segments with reversible thallium defects. In contrast, only 32 (19%) of 166 segments with no fill-in showed discordantly decreased BMIPP uptake. Quantitative analysis showed reduction in BMIPP activity compared with differential uptake of thallium, an index of resting myocardial perfusion, especially in the area of fill-in (53.5% +/- 15.0% vs 76% +/- 12.1% of peak; p<0.01). These observations are consistent with impaired fatty acid uptake in ischemic myocardium, particularly in the area of fill-in after thallium reinjection.

Adult↗

[Surgical treatment for ascending aortic aneurysm using a transthoracic left ventricular venting].

Three patients with ascending aortic aneurysms underwent graft replacement using deep hypothermic circulatory arrest with continuous retrograde cerebral perfusion. In all three cases, preoperative radiographic examination revealed that the aneurysm was large, thin, and adherent to the back of the sternum. For this reason, left ventricular venting was performed through a left thoracotomy before median sternotomy, to decrease both the risk of rupture of the aneurysm and the difficulty of cannulation. This new method, called transthoracic left ventricular venting, was very useful for performing a median sternotomy under hypotensive and hypothermic conditions adequate to reduce the risk of rupture and to manage any rupture immediately through deep hypothermic circulatory arrest.

Aged↗

Identification of two novel Dictyostelium discoideum cysteine proteinases that carry N-acetylglucosamine-1-P-modification.

Dictyostelium discoideum makes multiple developmentally regulated lysosomal cysteine proteinases. One of these, a lysosomal enzyme called proteinase I, contains a cluster of GlcNAc-alpha-1-P-Ser residues. We call this phosphoglycosylation. To study its function, a cDNA library from vegetative cells was screened, and two novel cysteine proteinase clones were characterized (cprD and cprE). Each of them has highly conserved regions expected for cysteine proteinases, but unlike any other, each has a serine-rich domain containing three distinct motifs, poly-S, SGSQ, and SGSG. cprD and cprE cDNAs were overexpressed in Dictyostelium and the active enzymes identified. cprD codes for a protein of approximately 36 kDa (CP4), which is recognized by monoclonal antibodies against GlcNAc-1-P and fucose. cprE corresponds to a 29-kDa protein, which is recognized by antibodies against GlcNAc-1-P. mRNA for both enzymes is present in the vegetative phase and increases during growth on bacteria but decreases throughout development. When the formation of the fruiting body is complete the mRNA for both messages is detected again but in very low levels. Having cloned cDNAs for proteins that carry GlcNAc-1-P should allow us to probe the function of the carbohydrate in these putative lysosomal enzymes.

Acetylglucosamine↗

Clinical use of low porosity woven ultrafine polyester fiber grafts.

A woven fabric graft made of ultrafine polyester fibers (UFPF) (Toray Graft, water porosity: 100 ml/min/cm2:120 mm Hg H2O) was clinically applied in 81 cases (28 thoracic aortic aneurysms, 6 thoracoabdominal aortic aneurysms, 42 abdominal aortic aneurysms, and 5 atherosclerotic obstructions of the peripheral arteries). Eight patients died after surgery due to causes unrelated to the graft. The other 73 patients were in good condition after surgery. For operations requiring extracorporeal circulation, the graft was presealed with human albumin. For the abdominal aortic aneurysms, the graft was preclotted in situ with nonheparinized autoblood after the completion of the proximal anastomosis. It took about 2 min to complete the preclotting. A nonsealed graft was used for the reconstruction of peripheral arteries for the intraaortic balloon pumping procedure. The graft was easy to handle. There was no cut edge fraying problem with the graft in any direction of cutting. Even after presealing, the graft was soft and pliable enough to enable easy adaptation and anastomosis. Just after implantation, bleeding was minimal from the graft wall, anastomotic sites, and suture pores, and it stopped spontaneously. These clinical data showed that the woven UFPF graft exhibited both easy handling despite in spite of low porosity and safe application in the reconstruction of arterial systems even under totally heparinized conditions during extracorporeal circulation.

Aortic Aneurysm↗

Myocardial viability assessment with technetium-99m-tetrofosmin and thallium-201 reinjection in coronary artery disease.

UNLABELLED: Exercise-rest 99mTc-tetrofosmin myocardial perfusion images with a 2-day protocol was compared to exercise-redistribution-reinjection 201Tl images to assess the ability of 99mTc-tetrofosmin to detect viable myocardium. METHODS: We studied 25 patients with coronary artery disease and regional or global left ventricular dysfunction. Myocardial SPECT images with 99mTc-tetrofosmin were obtained 10 min after injection during exercise and 1 and 3 hr after rest injection. Within 1 wk of the 99mTc-tetrofosmin study, exercise-redistribution-reinjection 201Tl SPECT imaging was performed. RESULTS: Visual analysis demonstrated concordance between 201Tl and 99mTc-tetrofosmin imaging for defect reversibility in 126 of 209 segments (60%), with initial defects on both exercise 201Tl and 99mTc-tetrofosmin images. In the remaining discordant 83 segments (40%), 73 (88%) appeared nonreversible on 99mTc-tetrofosmin imaging but were reversible on 201Tl imaging. CONCLUSION: On the basis of defect reversibility by visual analysis, exercise-rest 99mTc-tetrofosmin imaging underestimates myocardial viability compared to 201Tl reinjection imaging. The identification of viable myocardium with both 99mTc-tetrofosmin and 201Tl can be greatly enhanced to a similar degree if the severity of reduction in activity within nonreversible defects is considered. These two agents may provide comparable information about myocardial viability by quantitative analysis of defect severity.

Coronary Disease↗

Improved myocardial fatty acid utilization after percutaneous transluminal coronary angioplasty.

Exercise-reinjection 201Tl imaging and resting 20-min and 3-hr BMIPP imaging were performed before and 4 mo after percutaneous transluminal coronary angioplasty (PTCA) in a patient with effort angina. Before PTCA, exercise 201Tl imaging showed decreased 201Tl activity in the septal wall, with significant fill-in on the reinjection 201Tl image. The resting 20-min BMIPP image showed decreased activity in the septal wall, with a slight redistribution on the 3-hr BMIPP image. The 201Tl and BMIPP images 4 mo after PTCA showed significant improvement in the 201Tl pattern and BMIPP uptake in the septal wall with no abnormally decreased activities.

Aged↗

Kinetics of iodine-123-BMIPP in patients with prior myocardial infarction: assessment with dynamic rest and stress images compared with stress thallium-201 SPECT.

UNLABELLED: Myocardial kinetics of 123I-labeled 15-(p-iodophenyl)3R, S-methylpentadecanoic acid (BMIPP) were evaluated with dynamic SPECT, and stress and rest BMIPP images were directly compared in conjunction with stress 201Tl. METHODS: We studied 26 patients with prior myocardial infarction. Two minutes after injection of BMIPP, dynamic data acquisition with a three-headed SPECT was started and continued for 12 min. Conventional SPECT images were obtained at 20 min and 3 hr after injection. On a separate day, exercise, stress 201Tl SPECT was performed at 10 min and 3 hr after injection. Exercise stress-BMIPP imaging was performed in 15 of the patients, and static SPECT images were obtained. RESULTS: With dynamic SPECT, early clearance of BMIPP from the myocardium was observed in the segments with reversible 201Tl defects, suggesting enhanced contribution of backdiffusion from BMIPP. In myocardial segments with reversible 201Tl defects, 20-min BMIPP images showed a higher frequency of reduced uptake when compared to 3-hr 201Tl (90/163) imaging. CONCLUSION: With BMIPP dynamic SPECT, an enhanced contribution of backdiffusion in the early phase from ischemic myocardium was suggested. When exercise stress BMIPP images were obtained, a more severe defect was observed than on rest BMIPP and stress 201Tl imaging, possibly due to decreased coronary blood flow and impaired fatty acid uptake induced by ischemia during exercise.

Exercise Test↗

The pharmacokinetics and pharmacodynamics of furosemide in the anaesthetized dog.

The correlation between pharmacokinetics and dynamics of furosemide was investigated in anaesthetized dogs. After intravenous administration (i.v.) of furosemide (5 mg/kg), the plasma concentration declined rapidly with bioexponential decay. The half-life (t1/2 beta) of the late phase of elimination was 0.931 +/- 0.187 h and the apparent volume of distribution at steady state was 0.25 +/- 0.043 l/Kg. The total clearance (Cltot) was 0.435 +/- 0.031 l/h/kg, in which the renal clearance was 0.260 +/- 0.020 (about 60% of Cltot). The change in rate of urinary excretion of furosemide was similar to the plasma concentration decay curve. The diuretic effect of furosemide was accompanied by an extreme increase in the excretion rate of sodium and chloride, but not potassium. The relationships between the diuretic response and the plasma concentration or the urinary excretion rate of furosemide was depicted by sigmoidal dose-response curves in both cases. The half-maximum effect was obtained at 1.5 micrograms/ml of plasma concentration or at 80 micrograms/min of excretion rate of furosemide.

Anesthesia, Intravenous↗

Effects of metabolic control on ventricular function in type 2 diabetic patients.

The effects of the metabolic changes of type 2 diabetic patients on ventricular function, especially diastolic ventricular function were investigated. An examination was performed before and after treatment of 18 diabetic patients divided into 3 groups: insulin therapy, oral hypoglycemic drugs and diet therapy (6 patients each). The results indicated that both systolic and diastolic ventricular dysfunctions observed were improved by the correction of hyperglycemia. Therefore it is necessary to treat diabetes mellitus as early as possible for the prevention of both cardiac dysfunction and microangiopathy.

Adult↗

Different rates of acceptance of health examination among the people under 2 separate health insurance programs in Japan.

The entire population in Japan is covered by either workplace-based health insurance program or region-based health insurance program. While both programs were originally for curative medical care, only the former program has recently extended its financial support to preventive health examination. The attitude of the people toward health examination was studied in Miyagi prefecture in north-east Japan by questionnaires with more than 32,000 respondents to examine whether the difference in health insurance reflect on the rates of acceptance of 4 health examination items (i.e., blood pressure measurement, chest x-ray taking, and 2 screening tests for stomach and cervical cancer). Throughout the 4 items, the rate of acceptance was higher among those who were covered by workplace-based health insurance than among those covered by regional health insurance. The difference is large for the insured and less so for the family dependents of the insured. Further analysis for the preferred opportunities for health examination such as personal examination at clinics in contrast to region-based mass examination showed that the weight of clinics was quite large for the insured of national health insurance and their family dependents (i.e., 50% or even larger) but it was less so for the people covered by workplace-based insurance.

Blood Pressure Determination↗

[The correlation between pulse wave velocity and diabetic angiopathy].

Pulse wave velocity (PWV) of the aorta was measured in 40 patients with diabetes mellitus, in order to study the relation between PWV and diabetic angiopathy. The PWV was significantly faster in diabetic patients on oral hypoglycemic agents than in those on diet alone or on insulin. The PWV correlated significantly and positively with age, systolic blood pressure and urinary albumin index. The PWV significantly faster in diabetics with microalbuminuria than in those without this findings. It was concluded that PWV in addition to known risk factors such as elevated blood pressure, atherogenic abnormalities of plasma lipids and lipoproteins, and elevated blood glucose, may be a reliable index of diabetic micro- and macroangiopathy.

Aged↗