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Biomedical subjects

K Hayashida

Publications and source records attributed to K Hayashida.

At least 253 records · Page 14Linked to original sources

Right ventricular thallium-201 visualization in hypertrophic cardiomyopathy.

Fifty-six patients with hypertrophic cardiomyopathy who had echocardiography and cardiac catheterization were studied. Eleven (18%) of 56 patients had right ventricular (RV) thallium-201 visualization at resting scan. RV thallium-201 visualization was observed in the apex or lower half of the RV free wall, which was quite different from that with RV pressure or volume overload. There was no significant correlation between RV thallium-201 visualization and interventricular septal thickness or haemodynamic data. RV systolic pressure and RV dimension were within normal limits whether RV visualization was observed or not. Thus, an abnormal increase of RV mass in hypertrophic cardiomyopathy may lead to RV thallium-201 visualization without RV pressure or volume overload.

Adult↗

Quantitative assessment of thallium myocardial washout rate: importance of peak heart rate and lung thallium uptake in defining normal values.

Traditionally, the results of exercise thallium scintigraphy were interpreted by transient defect analysis using initial and delayed images. Recently, washout rate analysis has been used for the relative quantification of exercise thallium scintigraphy. A diffuse slow washout from all myocardial regions has been defined as the indicator of extensive coronary artery disease. However, slow washout has occasionally been observed in normal cases and in healthy myocardial segments which are not supplied by a stenosed artery in patients with single or double vessel disease. We evaluate the factors influencing washout rate in 100 normal patients and 63 patients with angina pectoris (33 cases of single vessel disease and 30 cases of double vessel disease). The washout rates were calculated using circumferential profile analysis. In normal patients, washout rate was closely related to peak heart rate (r = 0.72) and inversely related to lung thallium uptake (r = -0.56). A diffuse slow washout was observed in seven (7%) of 100 normal patients, six (18%) of 33 cases of single vessel disease and eight (24%) of 30 cases of double vessel disease. The patients with diffuse slow washout showed significantly higher lung thallium uptake values and lower peak heart rates than those without diffuse slow washout (P less than 0.01). Thus, this false positive slow washout should be considered in the interpretation of quantitative exercise thallium scintigraphy.

Adult↗

Clinical significance of 201Tl reverse redistribution in patients with aorto-coronary bypass surgery.

Detection of myocardial ischemia by the stress thallium scan has traditionally been performed using transient defect analysis on exercise, followed by redistribution studies. Worsening of the 201Tl myocardial image from exercise to redistribution is referred to as reverse redistribution. In this study, we found reverse redistribution in 10 (21%) of 48 angina pectoris patients who had undergone aortocoronary bypass surgery. The clinical significance of this phenomenon in these patients was investigated in relation to angiographic and surgical findings. Reverse redistribution was found to occur in regions which were supplied by bypass grafts. These areas showed increased coronary blood flow and rapid thallium washout. Our results indicate that a perfusion defect in the bypass region of the redistribution image might be caused by relatively rapid washout in the bypass graft region compared to the adjacent normal myocardium. These results should be considered in the clinical interpretation of stress thallium scans.

Adult↗

Cor pulmonale due to embolization of metastatic chondrosarcoma.

A 25-year-old woman with acute dyspnea was found to have nodular shadows in a chest X-ray film. Multiple defects in a perfusion scan indicated pulmonary embolization. The cause of acute cor pulmonale was extensive metastatic embolization from chondrosarcoma of the calf. Embolization by metastasis as a rare occurrence resulting in acute cor pulmonale should be considered in patients with a malignant tumor.

Adult↗

Scintigraphic assessment of double-chambered right ventricle.

A double-chambered right ventricle is often clinically misdiagnosed and may be missed even during cardiac catheterization. We encountered a 56-year-old male who had abnormal right ventricular thallium-201 uptake and a photon deficient area in the right ventricle by radionuclide cardioangiography. These findings strongly suggested the existence of anomalous muscle band in the right ventricle. It was demonstrated by contrast angiography that the right ventricle was divided into two chambers by a hypertrophic muscular band; the pressure gradient in the right ventricle was 98 mmHg.

Heart Ventricles↗

Sequence analysis of the putative regulatory region of rat alpha 2-macroglobulin gene.

Rat alpha 2-macroglobulin (alpha 2M) is an acute-phase reactant, concentration of which in serum increases more than 100-fold in the course of inflammation. Glucocorticoid and some protein factors such as interleukin 1 (IL-1) have been known to be involved in the regulation of this plasma protein synthesis. To understand the regulatory mechanism of alpha 2M production at the molecular level, we isolated genomic DNA clones of rat alpha 2M gene and characterized the promoter region of the gene by comparing the nucleotide sequence with those of other acute-phase reactant genes. Several possible regulatory signals were identified. Particularly, a sequence (T/A)T(C/G)TGGGA(A/T) was found about at 170 bp upstream from a putative capping site, which was also found in the 5'flanking region of various acute-phase reactant genes.

Animals↗

Kupffer cell stimulation of alpha 2-macroglobulin synthesis in rat hepatocytes and the role of glucocorticoid.

When stimulated with lipopolysaccharide (LPS), primary cultures of Kupffer cells from the rat secreted a hepatocyte-stimulating factor (Kupffer factor) which induced the synthesis of alpha 2-macroglobulin (a2M) by hepatocytes. The effect of this Kupffer factor was found only when dexamethasone was present in the hepatocyte culture medium. Dexamethasone alone stimulated the a2M synthesis, to some extent, in a dose-dependent manner. When both Dex and the Kupffer factor were added to the medium, cultured hepatocytes synthesized 100-fold a2M, quantitative evidence that explains the in vivo phenomenon in which the serum a2M concentration increases more than 100-fold in the acute phase. A co-culture study with hepatocytes and Kupffer cells indicated that the latter cells have a major function in the induction of a2M synthesis in vivo. A hybridization study with rat a2M cDNA showed that the concentration of mRNA increased in cultured hepatocytes in the presence of the Kupffer factor, but only when dexamethasone was present. From these results we concluded that Kupffer cells secrete a hepatocyte-stimulating factor when stimulated by LPS and that glucocorticoid is essential for the induction of a2M in rat hepatocytes. The effect of the Kupffer factor and glucocorticoid appears to be regulated in the pretranslational, probably the transcriptional, phase.

Animals↗

Pharmacokinetic studies on 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077). I. Blood and tissue concentrations of a new nitrosourea antitumor agent TA-077 and its metabolite TA-G after intravenous injection of TA-077 in various experimental animals.

1-(2-Chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077) is a new masked antitumor agent, which is hydrolyzed by maltase to give rise to a more cell-permeable and, hence, more cytotoxic metabolite, TA-G. TA-077 was intravenously administered to mice, rats, guinea pigs, rabbits and dogs and the time-courses of blood concentrations of TA-077 and TA-G were followed. The time-course patterns of blood TA-077 in these animals were markedly different from one another depending on the level of plasma maltase, while those of blood TA-G were all similar except in the early stage after the injection; i.e., the blood concentration of TA-G reached a peak shortly after the injection and decreased rapidly with a half-life of 6 to 15 min, and the higher the level of plasma maltase, the earlier the time of peak appearance. Tissue concentrations of TA-077 and TA-G in major organs were also measured at various times after intravenous injection of TA-077 to guinea pigs and VX-2 tumor-bearing rabbits. In both species, tissue concentrations of TA-077 did not exceed the blood concentration and rapidly decreased to insignificant levels by 30 to 45 min. The tissue level of TA-G in the kidney, a maltase-rich organ, was always the highest among the organs examined in both species. The concentration of TA-G in the VX-2 tumor was relatively high. Possible significance of tissue maltase to the cellular uptake and antitumor effect of TA-077 is also discussed.

Animals↗

Pharmacokinetic studies on 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077). II. Hydrolysis by tissue homogenates and drug uptake by tumor cells in vitro.

1-(2-Chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077) was hydrolyzed to its glucosyl metabolite TA-G by homogenates of guinea pig organs, rabbit VX-2 carcinoma and rat Yoshida sarcoma. The rate of TA-G formation by the kidney was the highest among the tissues examined and that by the diluted blood was undetectably low, reflecting their maltase activities. TA-077 was also hydrolyzed by suspensions of Yoshida sarcoma, AH130 hepatoma, L1210 leukemia, P388 leukemia and DBLA-10/C leukemia cells. The rate of TA-G formation was increased 10 fold by homogenizing the tumor cells. TA-G was taken up by the tumor cells much more efficiently than TA-077, explaining the higher sensitivities of the cultured tumor cells to TA-G than to TA-077. However, neither the maltase activity nor the membrane permeability to the drugs was a factor influential enough to explain the differences in drug sensitivity among the tumor cell lines.

Animals↗

Pharmacokinetic studies on 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077). III. Pharmacokinetics of a new nitrosourea antitumor agent TA-077 in humans (a phase I study).

A new nitrosourea antitumor agent TA-077, 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea, was intravenously administered to 15 cancer patients at doses ranging from 7 to 100 N (1 N = 30 mg/m2) in a phase I clinical trial. Time courses of blood concentrations of TA-077 and its active metabolite TA-G, 3-beta-D-glucopyranosyl analog of TA-077, were followed. The TA-G concentration reached a maximum at 7.0 +/- 2.3 min, and decreased thereafter with a half-life of 12.9 +/- 2.8 min. The time-course patterns and various pharmacokinetic parameters of TA-077 and TA-G were similar to those in the guinea pig, which, like humans, lacks plasma maltase activity. The 2 h-urinary excretion rate of TA-G in the above patients ranged from 0.15 to 7.7% of the dose. The areas under the concentration-time curve and maximal concentration values were both linearly correlated to the dose with correlation coefficients of 0.78 and 0.82, respectively. Repeated administration of TA-077 (29 to 40 N) for 5 or 6 consecutive days did not affect the pharmacokinetic parameters of TA-077 and TA-G in 7 cancer patients except for slight increases in the half-life and area under the curve of blood TA-G.

Adult↗

Differentiation of myocardial ischemia and left ventricular aneurysm in the genesis of exercise-induced ST-T changes in previous anterior myocardial infarction.

We attempted to differentiate between myocardial ischemia and left ventricular asynergy as the underlying mechanisms of exercise-induced ST-segment elevation in patients with previous myocardial infarction (MI). Sixty patients with previous anterior MI, who underwent stress myocardial scintigraphy (SMS) and coronary angiography (CAG), which revealed a single vessel disease of the left anterior descending artery, were entered in this study. SMS and CAG were performed within 3 months of MI onset, and SMS and ECG were quantitatively analyzed. T wave changes to a complete upright position with concomitant ST-segment elevation (T-dominant ST-elevation) was seen in 56% of the patients with post-MI angina pectoris (N = 16) and in 50% of those with significant redistribution in SMS (n = 20). On the other hand, ST-segment elevation without T wave reversion (ST-dominant ST-elevation) was seen in 43% of patients with severe LV asynergy (akinesis and dyskinesis, n = 39) and in 50% of those with severe scintigraphic defect in delayed images (relative thallium uptake less than or equal to 40%, n = 10). When these findings were combined, T-dominant ST-elevation had sensitivity and specificity of 54% and 78%, respectively, for the diagnosis of myocardial ischemia, while the corresponding values for ST-dominant ST-elevation were 44% and 100%, for the diagnosis of severe ventricular asynergy. We conclude that the two underlying mechanisms, ischemia and asynergy, may produce different changes in ST-T shape in patients with previous myocardial infarction.

Adult↗