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Biomedical subjects

T Kuga

Publications and source records attributed to T Kuga.

At least 91 records · Page 5Linked to original sources
PubMed1995

Adherent leukocytes to the aortic wall promotes atherosclerosis in the Watanabe heritable hyperlipidemic rabbits.

It is well known that leukocytes adherence to the endothelium of arterial wall occurs in diet-induced hypercholesterolemic animals. We examined the relationship between leukocytes adherence and atherosclerosis in the thoratic aorta of the Watanabe heritable hyperlipidemic rabbits (WHHL rabbits). Five of 2 or 3 months old WHHL rabbits were sacrificed and after perfusion fixation with 2.5% gulutaraldehyde, thoratic aorta was taken out carefully and divided into the 4 portions: Portion 1; cranial side of aortic arch, Portion 2; caudal side of aortic arch, Portion 3; upper side of thoratic aorta except aortic arch, Portion 4; lower side of thoratic aorta except aortic arch. Three to 6 samples from each portion except branching sites were examined using electron microscopy, and the counts of adherent leukocytes (LC) in each portion were calculated. Seven of 6 to 12 months old WHHL rabbits were sacrificed and the internal side of thoratic aorta was cut opened from the ventral side and the atherosclerotic lesions were copied. From these copies, the % area of atherosclerotic plaques (%AT) in each 4 portions as described was calculated using microcomputer. LC in Portion 1 to 4 was 265 +/- 62, 234 +/- 46, 53 +/- 8 and 41 +/- 13/mm2 respectively. LC in Portion 1 or 2 was significantly larger than that in Portion 3 or 4 (p < 0.05). The endothelium to which leukocytes adhered was intact. %AT in Portion 1 to 4 was 68 +/- 8, 63 +/- 8, 40 +/- 8 and 34 +/- 8% respectively. %AT in Portion 1 or 2 was significantly larger than that in Portion 3 or 4 (p < 0.05). It is concluded that leukocytes adherence to the intact endothelium of the arterial wall was one of the geneses and promoters of atherosclerosis in WHHL rabbits.

Animals↗
PubMed1994

Actions of a new Ca2+ channel antagonist, CD832, on two types of Ca2+ channels in smooth muscle.

The purpose of this study was to determine the characteristics of blockade of L- and T-type Ca2+ channels by a new Ca2+ channel antagonist, 3-(2-nicotinoylamino)ethyl 5-(3-nitrooxypropyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride (CD832), in comparison with those of nifedipine, in rat aortic smooth muscle cells in primary culture. In a whole-cell configuration under voltage-clamp, CD832 and nifedipine dose dependently blocked both L- and T-type Ca2+ currents (L- and T-type ICa) without shifting the axis of the current-voltage relations. The 50% inhibition concentration (IC50) of CD832 was 310 nM for L-type and 1.1 microM for T-type ICa. The IC50 of nifedipine was 36 nM for L-type and 2.7 microM for T-type ICa. CD832 blocked both types of ICa from the first step pulses after drug application, shifted their steady-state inactivation curves to the left, and did not significantly accelerate the current decay. The effect of CD832 reached its maximum within 6 min and was hardly washed out, while that of nifedipine reached a maximum within 30 s and could be washed out within 3 min. These results suggest that (1) CD832 blocks L-type ICa less potently than does nifedipine, (2) CD832 blocks T-type ICa more potently than does nifedipine, (3) CD832 blocks not only the resting state but, more preferentially, the inactivated state of L- and T-type Ca2+ channels, and (4) CD832 has a slow and long-acting activity in blocking both types of ICa as compared with nifedipine.

Animals↗
PubMed1994

Effects of intracoronary infusion of atrial natriuretic peptide on pacing-induced myocardial ischemia in patients with effort angina pectoris.

BACKGROUND: Atrial natriuretic peptide (ANP) has been shown to dilate the coronary artery. The aim of this study was to determine whether, in patients with effort angina pectoris, intracoronary infusion of ANP attenuates pacing-induced myocardial ischemia either by dilating the stenotic lesion in a large coronary artery or by dilating collateral vessels. METHODS: We studied six patients who had total or subtotal occlusion in one coronary artery and well-developed, angiographically visible collateral vessels (group A) and five patients who had a significant stenosis in a large coronary artery with no visible collateral vessels (group B). Their heart rate was increased by atrial pacing both before and after intracoronary infusion of ANP (0.03 microgram/kg/min for 15 min) into the donor artery of collateral vessels in group A or into the stenotic artery in group B. RESULTS: Before ANP infusion, all patients of both groups developed an ischemic ST-segment depression (> or = 0.1 mV) and angina-like chest pain from pacing tachycardia. After ANP infusion, significant ST-segment depression was induced by rapid pacing in only one out of six patients of group A, whereas it was noted in all patients of group B (P < 0.01). After ANP infusion, chest pain developed in one out of six patients in group A, whereas it appeared in four out of five patients in group B (P < 0.05). ANP significantly dilated the angiographically normal segment of the epicardial coronary artery, but it did not significantly change the severity of the stenotic lesion in either group. ANP did not change the basal arterial pressure or heart rate, nor did it change their response to pacing tachycardia. CONCLUSION: Infusing ANP into the donor artery of collateral vessels, but not into the artery with culprit stenotic lesion, attenuated pacing-induced myocardial ischemia. Therefore, the beneficial effects of ANP in reducing pacing-induced myocardial ischemia may result from the increase in myocardial perfusion to the ischemic area caused by dilating the collateral vessels.

Aged↗
PubMed1994

Improved recovery of myelosuppression following chemotherapy in mice by combined administration of PSK and various cytokines.

Granulocyte-colony-stimulating factor (G-CSF), granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) were used in combination with PSK, a protein-bound polysaccharide extracted from mycelium of Coriolus versicolor (strain CM101), in myelosuppressed mice. The myelosuppression model consisted of BDF1 mice who received 150 mg/kg 5-fluorouracil (5-FU) intravenously. The peripheral blood leukocyte count during the recovery stage was significantly increased when these cytokines were administered with PSK compared to when the cytokines were used individually. In vitro colony assay revealed that the combination of PSK and any of GM-CSF, IL-3 or stem cell factor (SCF) showed a greater increase in colony numbers than when these materials were administered individually, although G-CSF did not show a synergistic effect with PSK. When bone marrow cells were obtained from mice which had been given PSK or IL-3, the colony assays were made in the presence of PSK or IL-3 in vitro. The greatest increase in the numbers was observed in colonies of the cultured group in the presence of IL-3 after the PSK priming. However, the colony formation potential of PSK was not inhibited by addition of anti-SCF antibody. The above results indicate that the combined administration of PSK with G-CSF, GM-CSF or IL-3 increased the hematological recovery of myelosuppressed mice. Moreover, the phase at which PSK has effects on hematopoietic cells seems to be at a more immature level than with IL-3. The combined administration of PSK and the above cytokines may improve myelosuppression after chemotherapy in patients with malignancy.

Animals↗
PubMed1994

[Ehlers-Danlos syndrome with impending ruptured thoracic descending aortic aneurysm in a young adult--a case report].

We here report on a rare case of Ehlers-Danlos syndrome type IV with impending ruptured thoracic aortic aneurysm in a young adult. A 38-year-old man complained of severe back pain and transient paralysis in both legs. He was diagnosed as having an impending ruptured thoracic descending aortic aneurysm. Emergency operation which was aneurysmectomy and reconstruction of the descending aorta was performed. The fact that the aneurysm (11 cm) in a patient was so large for his age and the abnormal subcutaneous fatty tissue suggested the existence of systemic metabolic disease. An analysis of collagen extracted from the patient revealed the absence of type III collagen. Furthermore, an electron microscopic analysis finding that the collagen fibrils was of non-uniform size lead to the diagnosis of Ehlers-Danlos syndrome, Type IV (arterial type). Postoperatively the patient suffered paralysis in both legs due to ischemia of the spinal cord. However, his general condition was stable. He was transferred to another hospital for rehabilitation of both legs 60 days after the operation. Although the physical signs usually associated with Ehlers-Danlos syndrome were absent in this case, diagnosis followed electrophoresis of collagen extracted from the patient. As a result of the above observation, we recommended analysis of collagen in cases where the size of the aneurysm or the age of the patient appear unusual even though physical signs of Ehlers-Danlos syndrome are absent.

Adult↗
PubMed1993

Sequential bypass for multisegmental occlusive disease.

We evaluated the effectiveness of a sequential bypass for multisegmental occlusive disease. Forty-seven multiple bypass grafts were performed on 43 patients ranging in age from 55 to 83 years (mean: 70 years). The indications for operation included incapacitating claudication in 20 limbs, resting pain in 15, and nonhealing ulcers in 12. An anatomical arterial bypass was performed on 36 limbs, consisting of an aorto-femoro-popliteal bypass in 21 limbs, a femoro-popliteal-posterior tibial bypass in 8, an ilio-femoro-popliteal bypass in 4, an ilio-femoro-posterior tibial bypass in 2, and a femoro-popliteal-plantar bypass in 1. Similarly, an extra-anatomical arterial bypass was performed on 11 limbs, consisting of an axillo-femoro-popliteal bypass in 6, a crossover femoro-femoro-popliteal bypass in 3, an axillo-femoro-posterior tibial bypass in 1, and a crossover femoro-femoro-anterior tibial bypass in 1. The follow-up period ranged from 3 to 77 months (mean: 23 months). Twelve graft failures occurred, and 2 of them required major amputations. The cumulative graft patency rate was 85% at one year and 65% at 3 years. Arterial Doppler examination revealed a mean preoperative ankle-brachial index of 0.29 +/- 0.25. The early and late mean postoperative ankle-brachial indices, however, increased to 0.97 +/- 0.19 and 0.84 +/- 0.25, respectively. Midterm results have indicated that such multiple sequential bypass grafts are effective.

Aged↗
PubMed1993

Effects of a new calcium antagonist, CD-832, on experimental coronary artery spasm in miniature pigs.

The effects of a new calcium antagonist, CD-832, on experimental coronary artery spasms were studied in Göttingen miniature pigs. Pigs underwent endothelial denudation at the left anterior descending coronary artery using a balloon catheter. Changes in the diameter of the denuded and nondenuded site in response to an intracoronary administration of serotonin (10 micrograms/kg) or histamine (10 micrograms/kg) were assessed quantitatively by selective coronary arteriography 1 week after endothelial denudation. Percent reductions of the coronary artery diameter induced by serotonin or histamine in the denuded site were significantly greater than those in the nondenuded site (p < 0.01). Coronary artery spasm induced by serotonin or histamine in the denuded site was attenuated in a dose-dependent manner by intravenous infusion of CD-832 (10 and 30 micrograms/kg/min) or nifedipine (1 and 3 micrograms/kg/min). The degrees of inhibition of coronary artery spasm by CD-832 were similar to those produced by nifedipine. CD-832 and nifedipine at the high dose caused comparable increases in the basal coronary artery diameter. These results suggest that CD-832 may be a useful drug for the treatment of coronary artery spasm.

Animals↗
PubMed1993

Correlation of basal coronary artery tone with constrictive response to ergonovine in patients with variant angina.

OBJECTIVES: This study was conducted to examine whether basal coronary artery tone is elevated at the spastic site in patients with variant angina and to determine the significance of basal artery tone in predicting provocation of coronary artery spasm. BACKGROUND: Previous data have been conflicting on whether basal coronary artery tone is elevated in patients with variant angina. METHODS: We assessed basal coronary artery tone by obtaining the percent increase in coronary artery diameter induced by nitroglycerin in 20 patients with variant angina and 24 control subjects. We also examined the correlation between basal coronary artery tone and the constrictive response to ergonovine. RESULTS: In the patients with variant angina in whom spasm was provoked by the lower doses (1 or 5 micrograms) of ergonovine, basal coronary artery tone was greater (p < 0.05) at the spastic site (54 +/- 15% or 36 +/- 16%, respectively) than at the nonspastic site (40 +/- 25% or 25 +/- 15%, respectively). Basal coronary tone at the nonspastic site in these patients was greater (p < 0.01) than that in control subjects (15 +/- 6%). In the patients with variant angina in whom spasm was provoked only by the higher doses (15 or 50 micrograms) of ergonovine, basal coronary artery tone was comparable at the spastic and nonspastic sites and was not different from that in control subjects. The diagnostic sensitivity and specificity of elevated basal coronary artery tone (> or = 40%) in predicting provocation of spasm were 26% and 98%, respectively. CONCLUSIONS: These results indicate that elevated basal coronary artery tone may be useful in predicting provocation of coronary spasm, but the normal level of basal coronary artery tone does not exclude such provocation.

Adult↗
PubMed1993

Inhibitory effects of heparin, aspirin and ketanserin on coronary artery vasoconstriction after arterial balloon injury in hypercholesterolemic miniature pigs.

OBJECTIVES: The present study aimed to clarify the effects of heparin, aspirin and ketanserin on coronary artery vasoconstriction after arterial balloon injury. BACKGROUND: The mechanisms of coronary artery vasoconstriction after coronary angioplasty are not well understood. METHODS: After being fed a cholesterol-rich diet for 1 month, 71 Göttingen miniature pigs were randomly allotted to five groups: 16 pigs with no pretreatment (group A); 21 pigs pretreated with heparin, 3,000 U (group B); 13 pigs pretreated with aspirin, 50 mg/day orally for 2 days (group C); 11 pigs pretreated with ketanserin, 1 mg/kg body weight (group D); 10 pigs pretreated with aspirin, 50 mg/day for 2 days, heparin, 6,000 U and ketanserin, 1 mg/kg (group E). After this pretreatment, the left anterior descending or the left circumflex coronary artery, or both, was denuded by a 2F balloon catheter. RESULTS: The coronary vasoconstriction at the injured sites reached a peak level 6 min after the arterial injury and subsided within 30 min. The coronary vasoconstriction at the injured site 6 min after arterial injury was 56 +/- 5% in group A, which was significantly greater than that in group B (28 +/- 6%, p < 0.01), group C (25 +/- 5%, p < 0.01), group D (26 +/- 7%, p < 0.01) or group E (24 +/- 5%, p < 0.01), whereas there was no significant difference in the coronary vasoconstriction among the latter four groups. CONCLUSION: These results suggest that serotonin released from aggregating platelets plays a major part in the platelet-dependent coronary artery vasoconstriction after arterial injury.

Angioplasty, Balloon, Coronary↗
PubMed1993

Hyperreactivity of aortic smooth muscle to serotonin is related to the presence of atheroma in Watanabe heritable hyperlipidaemic rabbits.

OBJECTIVE: The aim was to elucidate the contribution of atheromatous plaque to alterations of smooth muscle contraction to vasoconstrictive agents, by examining vasoreactivity of vascular smooth muscle from the thoracic aorta of 10-13 month old Watanabe heritable hyperlipidaemic rabbits. METHODS: From the same vascular ring of the lower thoracic aorta, a pair of small medial smooth muscle strips was prepared from the sites beneath the atheroma (atherosclerotic medial muscle strip) and from those beneath the plaque-free intima (normal medial muscle strip), and isometric tension was measured. RESULTS: Contractions to 118 mM KCl, histamine (30 nM to 10 microM), and noradrenaline (3 nM to 0.3 microM) were similar between atherosclerotic and the normal medial muscle strip. The ED50 to serotonin was 49(SD 28) and 116(66) nM (p < 0.05, n = 7) and the maximum tension to serotonin was 125(29)% and 82(29)% of that induced by 118 mM KCl (p < 0.01, n = 7) in atherosclerotic and normal medial muscle strip, respectively. Serotonin specific hyperreactivity of the atherosclerotic strip disappeared in Ca(2+)-free solution or in the presence of 10 microM H-7, an inhibitor of protein kinase C. After incubation with 0.1 microM phorbol 12,13-dibutyrate, an activator of protein kinase C, the isometric contractions induced by Ca2+ were significantly greater in atherosclerotic than in normal medial muscle strip. CONCLUSIONS: These results indicate that medial smooth muscle located beneath the atheroma is specifically hyperreactive to serotonin and that altered protein kinase C activity may explain in part the augmented response to serotonin.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Role of coronary artery spasm in progression of organic coronary stenosis and acute myocardial infarction in a swine model. Importance of mode of onset and duration of coronary artery spasm.

BACKGROUND: Coronary spasm may play an important role in progression of organic coronary stenosis and myocardial infarction, but the mechanisms responsible for these complications are not known. This study aimed to examine whether the mode of onset and the duration of coronary spasm influenced progression of organic coronary stenosis and acute myocardial infarction in a swine model of coronary spasm. METHODS AND RESULTS: Göttingen miniature pigs were subjected to cholesterol feeding, balloon-induced coronary arterial denudation, and x-ray irradiation. Five months later, coronary spasm was induced by intracoronary injection of serotonin. In 10 pigs, coronary spasm was provoked abruptly and maintained for 25 minutes by five repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes (group A, abrupt onset and short duration). In group B, coronary spasm was provoked gradually by intracoronary injections of serotonin at graded doses of 0.1, 0.3, and 0.6 microgram/kg every 5 minutes and was then maintained for 25 minutes in four pigs (group B1, gradual onset and short duration) and for 120 minutes in six pigs (group B2, gradual onset and long duration) by repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes. Intramural hemorrhage was noted histologically at the spastic site more frequently in group A with abrupt onset (nine of 10 pigs) than in group B with gradual onset (two of 10 pigs) (p < 0.01). Progression of organic coronary stenosis due to intramural hemorrhage was noted in seven pigs (six pigs in group A and one pig in group B), including three cases of total coronary occlusion. Evidence for the evolution of acute myocardial infarction (serial ECG findings, left ventriculograms, and histological findings) was noted in one pig (7%) of group A or B1 with short duration and in five of six pigs (83%) in group B2 with long duration (p < 0.01 versus group A and B1). CONCLUSIONS: These results indicate that: 1) intramural hemorrhage was frequently induced by coronary spasm of abrupt but not of gradual onset, 2) intramural hemorrhage resulted in acute progression of coronary stenosis and sometimes resulted in persistent total coronary occlusion leading to acute myocardial infarction, and 3) prolonged coronary spasm resulted in acute myocardial infarction without progression of organic coronary stenosis.

Animals↗
PubMed1993

Effects of age on endothelium-dependent vasodilation of resistance coronary artery by acetylcholine in humans.

BACKGROUND: It has been suggested that endothelium-related vasomotion is important in the control of coronary circulation. Our goal was to determine if endothelium-dependent dilation of the coronary vasculature was altered with aging in 18 patients with atypical chest pain (age, 23-70 years) who had angiographically normal coronary arteries and no coronary risk factors. METHODS AND RESULTS: We infused an endothelium-dependent vasodilator acetylcholine (1, 3, 10, and 30 micrograms/min) and an endothelium-independent vasodilator papaverine (10 mg) into the left coronary artery. The large coronary diameter was assessed by arteriography, and the increase in coronary blood flow was measured using the intracoronary Doppler catheter technique. Acetylcholine increased coronary blood flow in a dose-dependent manner with no changes in arterial pressure and heart rate. The maximum increase in coronary blood flow evoked by acetylcholine varied widely among patients (increase in coronary blood flow ranged from 200% to 560%) and was correlated significantly with aging (r = -.86, P < .001), whereas the peak coronary blood flow response to papaverine was affected slightly by aging (r = -.44, P = .07). The percent increase in blood flow response to acetylcholine to the response to papaverine correlated with aging (r = -.87, P < .001). The slope of the coronary blood flow response to acetylcholine also correlated significantly with aging. The large epicardial coronary artery response to the low doses of acetylcholine (< or = 10 micrograms/min) correlated inversely with aging. CONCLUSIONS: The results of this study suggest that endothelium-dependent dilation of coronary arteries evoked by acetylcholine may be decreased with aging in humans.

Acetylcholine↗
PubMed1993

Arterial reconstruction in elderly patients.

The surgical results of primary peripheral arterial reconstruction for arteriosclerosis obliterans during a 16-year period were examined as a function of age. Data in group 1 were of 121 procedures performed on 95 patients aged > or = 70 years and those in group 2 of 215 procedures performed on 148 patients aged < or = 69 years. There was no significant difference between the operative mortality rate of 4% (four of 95) in group 1 and 3.4% (five of 148) in group 2. The long-term mortality rate was 33% (31 of 95) in group 1, significantly higher (P < 0.05) than 18.9% (28 of 148) in group 2. The most common cause of death in both groups was cardiac failure. Cumulative 5-year survival rates in groups 1 and 2 were 56.3 and 78.3% respectively (P < 0.0001). The cumulative primary 5-year patency rates of suprainguinal bypass grafts in the two groups were 94.2 and 90.4%, respectively, while those of infrainguinal reconstruction were 67.7 and 55.0% respectively. The 5-year cumulative limb salvage rate was 93.1% in group 1 and 92.7% in group 2. None of these differences was significant. The results support an active approach to surgery in elderly patients with peripheral arterial obstruction caused by arteriosclerosis obliterans.

Adult↗
PubMed1993

[Intensive 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) and cryopreserved autologous bone marrow transplantation].

High-dose ACNU followed by autologous bone marrow transplantation was administered alone or together with other agents such as cyclophosphamide, dacarbazine, carboquone or/and VP-16. The starting dose of ACNU was 200 mg/m2, with gradual escalation up to 400 mg/m2. Median duration of granulocytes of less than 100/mm3 and platelets of less than 30,000/mm3 was 4.5 days (range; 0-9) and 10.5 days (range; 0-43), respectively. Bacteremia occurred in 4 cases, but no case of pneumonia was encountered. Heart failure possibly due to the cyclophosphamide was noted in one case with arrhythmia. Out of 13 cases with measurable diseases, three patients with Hodgkin's disease, two patients with diffuse lymphoma, and one patient with follicular lymphoma attained a complete response. Partial response was obtained in two patients with non-Hodgkin's lymphoma. Two patients with melanoma and one with acute nonlymphocytic leukemia without measurable disease still remain disease-free.

Adult↗
PubMed1992

[Cystic disease of right popliteal artery with spontaneous resolution].

The case was 50-year-old man. He was admitted to our hospital suffering from intermittent claudication. DSA and CT showed stenosis of the right popliteal artery due to compression by the tumor like lesion. The adventitial cystic disease was suggested. Three weeks later he had no symptom. DSA and CT revealed no reappearance of the adventitial cystic disease. The popliteal adventitial cyst spontaneously decreased in size. It is a very rare case.

Angiography, Digital Subtraction↗