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Biomedical subjects

K Hayashida

Publications and source records attributed to K Hayashida.

At least 19 recordsLinked to original sources

Monoclonal antibody against the common beta subunit (beta c) of the human interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor receptors shows upregulation of beta c by IL-1 and tumor necrosis factor-alpha.

High-affinity receptors for human granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 are composed of two distinct subunits, alpha and beta. Each receptor has its own ligand-specific alpha subunit, and the three receptors share the common beta subunit, beta c. Using a transfectant of NIH3T3 cells expressing the high-affinity human GM-CSF receptor, monoclonal antibodies (MoAbs) against beta c were generated. These MoAbs specifically bound to cells bearing beta c and immunoprecipitated the beta c protein of 120 Kd. Using these MoAbs, expression of beta c was examined. It is known that IL-1 augments the proliferative response of a human factor-dependent hematopoietic cell line TF-1 to either GM-CSF, IL-3, or IL-5, and that it upregulates the high-affinity receptors for GM-CSF, IL-3, and IL-5. Antibody binding and immunoprecipitation demonstrated that IL-1 increased cell surface expression of beta c. This enhancement by IL-1 was accompanied by an increased level of beta c mRNA. In addition, we found that tumor necrosis factor-alpha (TNF-alpha) also increased the expression of beta c, although it did not augment the proliferative response of TF-1 to GM-CSF, IL-3, and IL-5.

3T3 Cells

[Detectability of diagonal branch disease by 201TlCl exercised myocardial scintigraphy].

The detectability of diagonal branch disease in 10 patients (five with angina pectoris, five with myocardial infarction) with isolated diagonal branch lesions (more than 75% luminal stenosis in coronary angiography) was reviewed. In exercised 201TlCl myocardial scintigraphy, chest pain occurred in four of 10 patients, electrocardiographic change indicating myocardial ischemia was seen in four, and diagonal branch lesion was detected in only four patients by planar images. In contrast, diagonal branch lesions were detected in 10 of 10 patients by SPECT (single photon emission computed tomography). In planar images, perfusion defects appeared high in the anterolateral, posterolateral, and anterior walls of the left ventricle. In SPECT images they appeared high in the anterior to anterolateral wall. The extent of diagonal branch lesions could be quantitatively evaluated by coronary territory maps developed from unfolded maps of exercised SPECT. The mean ratio of the extent of diagonal branch lesion to left anterior descending branch territory was 24.7%, and the extent of myocardial infarction was significantly larger than that of angina pectoris (p < 0.05). In conclusion, SPECT is useful for detecting diagonal branch lesions and can quantitatively show the extent of these lesions by coronary territory map.

Aged

[Raise up 99mTc-HMPAO brain SPECT for detecting the changes in cerebral perfusion pressure].

99mTc-HMPAO crossed the blood brain barrier instantly in proportional to cerebral blood flow. Raise up stress and supine resting 99mTc-HMPAO with brain SPECT was devised for detecting abnormal response in the changes of cerebral perfusion pressure. Asymmetric ratio in the middle cerebral artery area in patients with internal carotid artery occlusion (n = 5) was changed significantly from 0.82 +/- 0.06 to 0.90 +/- 0.06 and that of normal (n = 5) was not changed from 0.94 +/- 0.03 to 0.95 +/- 0.01. Raise up 99mTc-HMPAO brain SPECT enhanced the detectability in abnormality of regional cerebral blood flow and visualized the dys-autoregulated area during blood pressure falls.

Blood Pressure

Bone marrow changes in adjuvant-induced and collagen-induced arthritis. Interleukin-1 and interleukin-6 activity and abnormal myelopoiesis.

OBJECTIVE: To investigate the role of bone marrow in arthritis. METHODS: Bone marrow changes over time were investigated in rats with adjuvant-induced and collagen-induced arthritis, using bioassay techniques and histologic analysis. RESULTS: In both animal models, bone marrow interleukin-1 and interleukin-6 activity began to rise before the onset of arthritis and increased in relation to the progression of arthritis. Enhanced myelopoiesis in the bone marrow was noted in conjunction with the increased cytokine activity. CONCLUSION: Bone marrow changes such as those demonstrated in this study may be common to various models of induced arthritis and may have an important role in the pathogenesis of this disease.

Animals

Visualization of posture-dependent cerebral blood flow in a patient with Takayasu's disease by means of 99mTc-HMPAO brain single photon emission tomography.

A case of Takayasu's disease in a 22-year-old woman who complained of severe fainting attacks is presented. Bilateral obstruction of the cervical arteries was confirmed by digital subtraction angiography. Preoperative technetium-99m hexamethylpropylene amine oxime brain SPET in the sitting position showed bilateral hypoactivity in the temporoparietal areas. Subtraction brain SPET showed slightly increased activity in the lying position. The patient has had no fainting attacks since bypass surgery. Postoperative 99mTc-HMPAO brain SPET in the sitting position showed normal activity except in the right temporoparietal area. This area was filled in the lying position. 99mTc-HMPAO brain SPET is the only technique that can visualize the cerebral blood flow in any position, this capability deriving on the fact that the distribution of 99mTc-HMPAO in the brain is fixed in the first 2-3 min following injection. The use of both sitting and lying 99mTc-HMPAO brain SPET is very useful for detecting an abnormality (i.e. an inhomogeneous response due to the fall in perfusion pressure) that could not be seen if the cerebral blood flow were to be assessed only in the lying position.

Adult

Coronary arterial involvement in aortitis syndrome: assessment by exercise thallium scintigraphy.

It is important in patient management to evaluate coronary arterial involvement in aortitis syndrome. Twenty-one cases of aortitis syndrome who experienced chest pain were examined using exercise thallium scintigraphy. The patients were divided into 4 groups according to the angiographic findings. There were five patients with left main coronary arterial involvement (group A), four with left or right coronary arterial involvement (group B), nine with aortic regurgitation (group C), and three with pulmonary arterial involvement (group D). In groups A and B, all patients had positive ECGs and thallium perfusion defects. Group A patients showed extensive anterolateral perfusion defects, which were compatible with left main coronary arterial involvement. Groups C and D patients, who had normal coronary arteries, showed no remarkable perfusion defects although five had positive ECG findings. Thus, the sensitivity and specificity of exercise scintigraphy for detection of myocardial ischemia were 9/9 and 12/12, while those of stress ECG were 9/9 and 7/12 (58%), respectively. it is recommended that exercise thallium scintigraphy be used for detecting clinically occult but significant coronary arterial involvement in aortitis syndrome with chest pain.

Adult

Favorable biodistribution of 99mTc-ECD for brain SPECT comparing with 123I-IMP using alternative body scan.

In order to evaluate the lung and brain uptake of 99mTc ethyl cysteinate dimer (99mTc-ECD) and N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP), alternative body scans were carried out in 15 cases of cerebrovascular disease. The biodistribution of 99mTc-ECD was 5.5 +/- 0.7%, 3.8 +/- 0.7% in the brain; 13.1 +/- 3.7%, 2.2 +/- 1.2%, in the lung at 15 min and at 4 hours, respectively, whereas that of 123I-IMP was 3.9 +/- 1.4%, 5.0 +/- 1.0% in the brain; 32.2 +/- 7.6%, 12.7 +/- 3.3%, in the lung at 15 min and at 4 hours, respectively. 99mTc-ECD accumulated in comparatively high amounts in the brain but remained low in the lung in the early image compared to 123I-IMP. However there was a high inverse correlation between brain and lung uptake of 123I-IMP (r = -0.82), but not of 99mTc-ECD (r = -0.18). We concluded that 99mTc-ECD had a better biodistribution in terms of low lung accumulation than 123I-IMP in brain SPECT.

Aged

Mechanical matching of the left ventricle with the arterial system in exercising dogs.

We investigated how changes in ventricular contractility and arterial properties associated with exercise influence the energy transmission from the left ventricle to the arterial system. On six chronically instrumented dogs preconditioned to run on a treadmill, we imposed exercise loads of various degrees by altering the speed and slope of the treadmill (up to 7 km/hr and 20% slope). We evaluated ventricular contractility by end-systolic elastance (Ees) and arterial properties in terms of the effective arterial elastance (Ea). Ea was estimated by the ratio of mean aortic pressure to stroke volume. With exercise, Ees significantly increased from 7.6 +/- 1.7 to 10.9 +/- 2.6 mm Hg/ml (p less than 0.005), and Ea tended to increase from 4.9 +/- 1.4 to 6.7 +/- 1.8 mm Hg/ml (p = 0.068), whereas the ratio of Ea to Ees remained fairly constant (from 0.69 +/- 0.26 to 0.63 +/- 0.21, NS). The mechanical optimality index, defined as the ratio of stroke work to its theoretically derived maximal value, was 0.93 +/- 0.07 at rest and 0.92 +/- 0.08 at peak exercise. Similarly, the metabolic optimality index, defined as the ratio of cardiac oxygen consumption to stroke work conversion efficiency and its theoretical maximal value, was 0.98 +/- 0.02 at rest and 0.99 +/- 0.01 at peak exercise (NS). We conclude that external work of the left ventricle of these dogs was at a near maximal level for a given preload during exercise as well as at rest without compromising the conversion efficiency of metabolic energy to stroke work.

Animals

[Hepatic protein synthesis and cytokines in obstructive jaundice].

UNLABELLED: To clarify the mechanism of the increase of hepatic protein synthesis observed in the obstructive jaundiced rats, hepatocellular protein synthesis (HPS) and secretory protein synthesis (SPS) were estimated in the rats with obstructive jaundice and the contents of the following in the peripheral blood were determined in 21 patients with obstructive jaundice before and two weeks after percutaneous transhepatic biliary drainage (PTBD): interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), endotoxin (Et), acute-phase protein (APP) and negative acute-phase protein (NAPP). THE RESULTS: (1) HPS and SPS were markedly increased by obstructive jaundice; (2) IL-1 beta and IL-6 were significantly high and were reduced after PTBD; (3) neither TNF alpha nor Et was detected; (4) APP were significantly high and failed to decline after PTBD; (5) NAPP were significantly low and the contents were restored to the normal levels after PTBD. These results suggest that increased hepatic protein synthesis observed in the rats with obstructive jaundice correspond to the increased hepatic production of APP in patients with obstructive jaundice.

Acute-Phase Proteins

[Function, molecular structure and gene expression of granulocyte-macrophage colony stimulating factor].

Granulocyte-macrophage colony stimulating factor (GM-CSF), a 22 kDa glycoprotein secreted from activated T cells and stroma cells, plays an important role, both in the constructive and inducible hemopoiesis, by stimulating a wide range of hemopoietic cells. After the cloning of receptor genes, the high affinity GM-CSF receptor was reconstituted by the combination of cloned 80 kDa molecule (alpha chain) and 120 kDa molecule (beta chain). This human GM-CSF receptor beta chain also works as a beta chain of IL-3 or IL-5 high affinity receptor. The fact that the alpha chains of GM-CSF, IL-3 and IL-5 share the same beta chain may define a biological interaction among these three cytokines.

Gene Expression Regulation

[Dipyridamole-thallium myocardial imaging in patients unable to exercise adequately: comparison with arm and bicycle ergometer].

We assessed the usefulness of dipyridamole-thallium myocardial imaging in patients unable to exercise adequately, compared with arm-ergometer and standard (bicycle) ergometer. Fifty-six patients with arteriosclerosis obliterans, aortic aneurysm, aortic dissection and so on, who were revealed normal imaging, were studied. Only one of 13 cases with arm-ergometer and two of 14 with bicycle ergometer reached target heart rate. Lung thallium uptake in the cases with arm-ergometer (37 +/- 9%) is higher than that with dipyridamole (29 +/- 5%). This elevation may be confused with pectoralis muscle uptake. Washout rate is 45 +/- 9% with dipyridamole and 46 +/- 12% with bicycle ergometer, respectively, though there was no significant differences. Myocardial/background counts ratio with dipyridamole (4.6 +/- 0.8%) is significantly higher than that with arm and bicycle ergometer (arm-ergometer; 3.5 +/- 0.7, bicycle ergometer; 4.2 +/- 0.9). Then, myocardial image with dipyridamole have superior quality. We concluded that dipyridamole-thallium myocardial imaging is very useful in the patients who have suboptimal exercise efforts.

Aged

[Influence of hypertensive left ventricular hypertrophy on detection of ischemic area with exercise thallium-201 myocardial scintigraphy].

Sixty-four patients with single left anterior descending artery disease having effort angina (group A: 40 patients without hypertension, group B: 10 patients with hypertrophic hypertension, group C: 14 patients with non-hypertrophic hypertension) were assessed the influence of hypertensive left ventricular (LV) hypertrophy on detection of ischemic area. The criterion of hypertrophy by two-dimensional echocardiography was > 12 mm in the wall thickness of interventricular septal or posterior wall. Population in Group B might show low detectability in ischemic area by 201Tl myocardial scintigraphy (positive thallium rate 60%, defect score 2.7 +/- 3.6), and high lung thallium uptake and high frequence of ECG positive among three groups. In semiquantitative analysis, the washout rate of the posterolateral wall and %RD (delayed %uptake-initial %uptake) of the septal wall in patients with Group B were lowest among three groups. However, the washout rate in the septal wall against the posterior wall, and the initial %uptake and the delayed %uptake of the septal wall were not significantly different among three groups. We could conclude that the decreased washout rate in nonischemic area with hypertensive LV hypertrophy might make the ischemic area masked.

Aged

[Diagnostic accuracy of coronary artery lesion by 99mTc-MIBI exercise myocardial scintigraphy--containing the utility of simultaneous assessment of left ventricular function].

To determine whether technetium-99m hexakis-2-methoxy isobutyl isonitrile (99mTc-MIBI) myocardial scintigraphy is a superior method in the detection of coronary artery disease, exercise and rest 99mTc-MIBI planar and SPECT scintigraphy were performed on 27 patients with coronary artery disease. When 99mTc-MIBI (555 MBq (15 mCi)) was injected, first-pass radionuclide angiography (FPRNA) was simultaneously performed by a new mobile multicrystal gamma camera (SIM-400), and LV function (LVEF) was evaluated quantitatively. Visual semiquantitative detection of coronary lesions using 99mTc-MIBI images showed superior accuracy to that obtained using 201TlCl images. 99mTc-MIBI SPECT images were particularly useful in diagnosing LCX and RCA lesions. Moreover, the simultaneous assessment of perfusion and left ventricular function by 99mTc-MIBI FPRNA proved to be useful in the diagnosis of multi-vessel disease. In summary, 99mTc-MIBI SPECT scintigraphy with simultaneous assessment of left ventricular function showed better diagnostic accuracy than 201TlCl myocardial scintigraphy.

Aged

[Thallium-201 scintigraphy after dipyridamole infusion in patients with ischemic heart disease--comparison with maximal exercise].

Myocardial images after dipyridamole infusion (DIP-Tl) were compared with maximal thallium-201 images (Ex-Tl) to determine the utility for detecting coronary artery disease and the ischemic level in ischemic regions. Ex-Tl was performed in 36 patients of angina pectoris (Group 1), and DIP-Tl was performed in 22 patients of angina pectoris (Group 2), who were divided into two groups (Group 2a: 15 patients with low level exercise, Group 2b: 7 patients without low level exercise). Each group had normal controls (41, 27 and 31 people). The detectability of coronary artery by DIP-Tl was almost same with Ex-Tl (sensitivity 85% vs. 86%, specificity 80% vs. 95%). In the case of normal controls, the mean washout rate of group 2b was 44.4%, which was less than other two groups (50.6% for group 1, 48.8% for group 2a). And the mean myocardial/background (M/B) ratio of group 2b was 4.3 less than other two groups (4.7 for group 1, 4.9 for group 2a). In the case of the patients of angina pectoris, washout rate, M/B ratio, initial % uptake and delayed % uptake in the ischemic region were almost same among the 3 groups. This study demonstrates that DIP-Tl is as effective as Ex-Tl, and the ischemic level in the ischemic region is almost same among the 3 groups. But the thallium accumulation in the background of the group 2b is slightly higher than other two groups in the normal controls, so it is suggested that the image after only dipyridamole infusion becomes slightly unclear.

Coronary Disease

[Diagnostic utility of myocardial imaging using 123I-labeled beta-methyl-iodophenyl pentadecanoic acid in ischemic heart disease].

We evaluated the myocardial metabolism in the acute and subacute phases of myocardial infarction or unstable angina using 123I-labeled beta-methyl-iodophenyl pentadecanoic acid (BMIPP). We then compared those findings with (1) myocardial perfusion images obtained with 201TlCl and (2) the regional and global left ventricular function determined by left ventriculography. Thirty-one patients were examined, consisting of 16 with acute myocardial infarction (6.8 +/- 2.6 days after onset), 8 with subacute myocardial infarction (35 +/- 3.0 days after onset) and 7 with unstable angina. The BMIPP images showed a larger uptake-defect than 201TlCl images in the patients in the acute or subacute phase of myocardial infarction. This finding was especially remarkable in the acute phase after successful coronary revascularization therapy. Moreover, in such cases, the myocardial BMIPP uptake improved to the same degree as 201TlCl one month later. The decrease in myocardial uptake of BMIPP agreed well with the decrease in regional wall motion in the acute and subacute phases of myocardial infarction. In contrast, the myocardial perfusion of 201TlCl did not always agree with the regional wall motion in stunned or hibernating myocardium, where BMIPP showed an uptake-defect in the acute phase but improved in the subacute phase. Thus, BMIPP is surmised to be able to depict fatty acid metabolism in in vivo myocardial imaging.

Adult

[Usefulness of 201Tl myocardial scintigraphy after dipyridamole infusion in patients with atherosclerotic vascular disease].

To determine the utility for detecting ischemic heart disease (IHD), Dipyridamole thallium myocardial images (DIP-Tl) have been performed in the 103 patients with atherosclerotic vascular disease who can't exercise fully. Of 103 patients, there were 36 patients with arteriosclerosis obliterans (ASO), 31 patients with aneurysm of the abdominal aorta (AAA), 24 patients with aneurysm of the thoracic aorta (TAA) and 12 patients with dissecting aortic aneurysm (DAA). Clinical evidence of IHD was found in 20 patients with ASO, 10 with AAA, 7 with TAA and 4 with DAA respectively. Positive evidence of DIP-Tl was identified in 66% of 41 patients who had clinical evidence of IHD, and particularly in the patients with AAA (80%) and ASO (65%). On the other hand, in the patients without clinical evidence of IHD, positive evidence of DIP-Tl was identified in 19% of 62 patients and particularly in the patients with AAA (39%). In all patients, the percentage of the positive DIP-Tl ratio was 38%. And, when the 38% patients of the positive DIP-Tl were added to the patients of the negative DIP-Tl who had clinical evidence of IHD, almost half patients (51%) were considered to be complicated with IHD. This study suggests that the atherosclerotic vascular disease is highly complicated with IHD and DIP-Tl is useful to detect IHD.

Aged

Diagnostic value of technetium-99m radionuclide angiography for detecting thrombosis in left atrial appendage.

In mitral valve disease, it is important to know whether thrombi are present in the left atrium when deciding upon a course of treatment. The left atrial thrombus usually locates in the left atrial appendage. In most cases of mitral valve disease, the left atrial appendage is clearly demonstrated by radionuclide angiography using 99mTc-labeled red blood cells and it can be speculated that the cases in which left atrial appendage are not demonstrated by RNA have left atrial thrombi. On the basis of this hypothesis, the diagnostic accuracy of radionuclide angiography to detect left atrial thrombi was evaluated retrospectively in 60 patients with mitral valve disease who had undergone surgery. The sensitivity of first-pass and equilibrium radionuclide angiography to detect left atrial thrombi was 83% and 67%, the specificity 79% and 54%, and the accuracy 80% and 57%, respectively. Although there were two false-negative cases in which the left atrial thrombi did not locate in the appendage and 10 false-positive cases in which left atrial appendages were not dilated, the negative predictive value was so high that a clearly demonstrated left atrial appendage can be translated into the absence of left atrial thrombi.

Adult

Reconstitution of functional receptors for human granulocyte/macrophage colony-stimulating factor (GM-CSF): evidence that the protein encoded by the AIC2B cDNA is a subunit of the murine GM-CSF receptor.

The high-affinity receptor for human granulocyte/macrophage colony-stimulating factor (hGM-CSF) is composed of two subunits, alpha and beta. The alpha subunit binds GM-CSF with low affinity, whereas the beta subunit does not bind GM-CSF by itself. The alpha and beta subunits together form the high-affinity GM-CSF receptor. The beta subunit has extensive sequence homology with the mouse interleukin 3 (IL-3) receptor (AIC2A) and its homologue (AIC2B) that does not bind IL-3 or other cytokines including GM-CSF. To examine the function of these receptor components, we expressed the alpha subunit of the hGM-CSF receptor with the human beta subunit or the mouse AIC2A or AIC2B in a mouse IL-3-dependent pro-B-cell line, Ba/F3, and in a mouse IL-2-dependent T-cell line, CTLL2. Coexpression of the alpha and beta subunits in Ba/F3 and CTLL2 cells resulted in high-affinity hGM-CSF binding and growth response to low concentrations of hGM-CSF. Whereas Ba/F3 cells expressing the alpha subunit alone proliferated in response to high concentrations of hGM-CSF, CTLL2 cells expressing the alpha subunit alone did not respond to hGM-CSF at all. Since Ba/F3 cells express endogenous AIC2A and AIC2B whereas CTLL2 expresses neither of them, we examined the possibility that either AIC2A or AIC2B is involved in the formation of a functional GM-CSF receptor. The expression of the human alpha subunit with AIC2B, but not with AIC2A, in CTLL2 cells conferred a growth response to hGM-CSF. These results indicate that the beta subunit of the GM-CSF receptor is required for generation of growth signals and that AIC2B is likely the beta subunit of the mouse GM-CSF receptor.

Animals