Search PubMed⌕ Search

Biomedical subjects

H Tagawa

Publications and source records attributed to H Tagawa.

At least 55 records · Page 3Linked to original sources
PubMed1994

Antitumor agents. 7. Synthesis and antitumor activity of novel hexacyclic camptothecin analogues.

Eleven novel hexacyclic and three 7,9-disubstituted pentacyclic derivatives of camptothecin were synthesized and evaluated for in vitro cytotoxic activity against P388, HOC-21, and QG-56 and in vivo antileukemic activity against P388 in mice. Hexacyclic compounds which have an additional 5-, 6-, or 7-membered ring cyclized at positions 7 and 9 of camptothecin were prepared by intramolecular cyclization of pentacyclic camptothecin derivatives or Friedländer condensation of the appropriate bicyclic amino ketone and tricyclic ketone. All of the hexacyclic compounds exhibited compatible or superior activity of 7-ethyl-10-hydroxycamptothecin (SN-38) in in vitro assays without regard to the size or type of the additional ring, and three of six compounds showed more than 300% T/C on in vivo assay. These results suggest that the potency of the hexacyclic ring system is higher than that of the original pentacyclic ring system of camptothecin and that the conformational rigidity of substituents at positions 7 and 9 is favorable for antitumor activity.

Animals↗
PubMed1994

Role of microtubules in contractile dysfunction of hypertrophied cardiocytes.

Cardiac hypertrophy in response to systolic pressure overloading frequently results in contractile dysfunction, the cause for which has been unknown. Since, in contrast, the same degree and duration of hypertrophy in response to systolic volume overloading does not result in contractile dysfunction, we postulated that the contractile dysfunction of pressure hypertrophied myocardium might result from a direct effect of stress as opposed to strain loading on an intracellular structure of the hypertrophied cardiocyte. The specific hypothesis tested here is that the microtubule component of the cytoskeleton is such an intracellular structure, which, forming in excess, impedes sarcomere motion. The feline right ventricle was either pressure overloaded by pulmonary artery banding or volume overloaded by atrial septotomy. The quantity of microtubules was estimated from immunoblots and immunofluorescent micrographs, and their mechanical effects were assessed by measuring sarcomere motion during microtubule depolymerization. We show here that stress loading increases the microtubule component of the cardiac muscle cell cytoskeleton; this apparently is responsible for the entirety of the cellular contractile dysfunction seen in our model of pressure-hypertrophied myocardium. No such effects were seen in right ventricular cardiocytes from normal or volume-overloaded cats or in left ventricular cardiocytes from any group of cats. Importantly, the linked microtubule and contractile abnormalities are persistent and thus may be found to have significance for the deterioration of initially compensatory cardiac hypertrophy into the congestive heart failure state.

Animals↗
PubMed1994

[Property and clinical availability of the noncontact autofocus specular microscope].

Reproducibility of results and possible clinical use of a newly developed noncontact autofocus specular microscope were studied. Morphological parameters of corneal endothelium were analyzed on images taken with the noncontact autofocus specular microscope and the ordinary contact specular microscope simultaneously in 10 eyes of 10 normal subjects. Intraphotographic and interphotographic study by autoanalysis of 5 images each of 10 eyes taken by the noncontact instrument showed small coefficient variation of mean cell area and cell density (less than 5%, individually). These morphological parameters showed about 7% difference between autoanalysis and manual analysis of the images taken by the noncontact instrument. In comparison with the images taken by the contact instrument, the images taken by the noncontact instrument showed about 7% difference in mean cell area and cell density (p < 0.001, individually). In respect of reproducibility, this newly developed noncontact autofocus specular microscope is clinically useful. The differences of morphological parameters between the new and ordinary instruments might be caused the differences in corneal shapes.

Adult↗
PubMed1994

[A case of Crow-Fukase syndrome associated with membranoproliferative glomerulonephritis].

Crow-Fukase syndrome is a rare multiorgan disorder. Although renal disorders, such as proteinuria, and renal impairment, have been observed in half the cases of this syndrome, there have been few reports describing the renal lesions. We report here a case of this syndrome associated with membranoproliferative glomerulonephritis. A 43-year-old woman was referred to our hospital because of hyperglycemia. She had also been suffering from hyperpigmentation, hepatosplenomegaly, lymphadenopathy, polyneuropathy and endocrine dysfunction, including diabetes mellitus and amenorrhea. Serum electrophoresis showed M protein and immunoelectrophoresis revealed IgA (lambda). Bone marrow aspiration showed a slight increase in the number of plasma cells. Urine protein was 30 mg/dl, BUN was 17 mg/dl and creatinine 0.8 mg/dl. Light microscopic examinations showed enlargement of glomeruli with proliferation of mesangial cells and matrix, a lobular pattern of the glomeruli and thickening of the glomerular basement membrane and associated double contour. Electron microscopic examinations showed thickened capillary walls, associated mesangial interposition and subendothelial dense deposits. Moreover, fine granular deposits of IgM, C3, and fibrinogen along the basement membrane were observed on immunofluorescent studies.

Adult↗
PubMed1994

[A case of sporadic acute type A hepatitis associated with acute renal failure].

We report a case of sporadic acute type A hepatitis associated with acute renal failure, due to mesangioproliferative glomerulonephritis and interstitial nephritis. A 42 year-old-man was admitted to Mitsui Memorial Hospital because of jaundice and oliguria with fever in February, 1989. His serum creatinine was 12.2 mg/dl, BUN 87 mg/dl, GOT 57 U/l and GPT 358 U/l. The serum IgM antibody to hepatitis A virus was positive, which indicated recent infection with hepatitis A virus. Hemodialysis and steroidal therapy were started, and the patient's acute renal failure and liver dysfunction ameliorated within one month. Light microscopic examinations showed an increased number of mesangial cells and an increased amount of mesangial matrix, and also showed inflammatory cell invasion in the interstitium. Electron microscopic examinations showed proliferation of mesangial cells and matrix, and a dense deposit along the basement membrane. On immunofluoresent studies, fine granular deposits of IgA and Clq were observed in the mesangium.

Acute Disease↗
PubMed1994

The effects of complete versus incomplete mitral valve repair in experimental mitral regurgitation.

Severe mitral regurgitation (regurgitant fraction 0.75 +/- 0.02) was created in eight dogs by our closed-chest chordal rupture technique. After 3 months of chronic mitral regurgitation all indices of contractile function were depressed. Mitral valve repair was then attempted. Postoperative regurgitant fraction was reduced compared with the preoperative value in all eight dogs. Concomitantly, forward cardiac output increased in all dogs and pulmonary capillary wedge pressure fell in all dogs. However, in some dogs, significant regurgitation persisted despite repair. Postoperative regurgitant fraction ranged from 0% to 60%. Postoperative residual regurgitant fraction was related significantly to postoperative cardiac output (r = 0.99), pulmonary capillary wedge pressure (r = 0.77), ejection fraction (r = 0.75), and two indices of contractile function--the mass-corrected end-systolic stress volume relationship (r = 0.87) and end-systolic stiffness (r = 0.93). In general, these parameters returned to their normal values before mitral regurgitation when postoperative regurgitant fraction was less than 30%. Myocytes isolated from the ventricles at the end of study also demonstrated normal contractile function when regurgitant fraction was less than 30%.

Animals↗
PubMed1994

A multicenter study with once a week or once every two weeks high-dose subcutaneous administration of recombinant human erythropoietin in continuous ambulatory peritoneal dialysis.

OBJECTIVE: To investigate the effectiveness of administering relatively high doses of r-HuEPO subcutaneously once a week or once every 2 weeks in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Multicenter prospective analysis. The trial was divided into two phases: an initial 8-week phase (once a week dosing) followed by a 12-week maintenance phase (once every 2 weeks dosing). A response was defined as a change in hematocrit (Ht) of 3% or more. Results were analyzed using Sheffe's test, Mantel-Haenszel's test, and Dunnett's test. SETTING: Eleven renal units in Japan providing a CAPD program. PATIENTS: Forty-one CAPD patients with a Ht of 28% or less. RESULTS: After the initial 8 weeks, 13 (81.3%) of 16 patients showed a response to 6000 U (106.9 +/- 20.0 U/kg) subcutaneously (sc), once a week. Eleven (84.6%) of 13 in the 9000 U (166.5 +/- 27.7 U/kg) group and all 12 (100%) in the 12,000 U (210.7 +/- 42.1% U/kg) group also showed responses. At the end of both phases, that is, at 20 weeks, 7 (53.8%) of 13 patients in the 6000 U group with once every 2 weeks dosing, 7 (63.6%) of 11 in the 9000 U group, and 10 (90.9%) of 11 in the 12,000 U group maintained responses with the same dosing interval. There were no significant changes in mean blood pressure during the study period, and only 2 patients developed treatable hypertension with mild headache. CONCLUSION: Administration of relatively high doses of r-HuEPO to CAPD patients once a week or once every 2 weeks is safe and potentially an effective regimen for the correction of renal anemia.

Adult↗
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

Electrically stimulated contraction accelerates protein synthesis rates in adult feline cardiocytes.

Cardiocytes were induced to contract via electrical field stimulation with an 8 V/cm electrical square-wave pulse of 5 ms at 0.125-2.0 Hz for up to 6 h. Protein synthesis rates were measured as rate of incorporation of [3H]-phenylalanine into total cell protein. Rates of protein synthesis were accelerated 43 +/- 4%, P < 0.001, by 4 h. The acceleration of total protein synthesis showed a frequency dependence between 0.125 and 0.5 Hz. In addition to accelerating rates of total protein synthesis, electrical stimulation of contraction accelerated fractional rates of synthesis of myosin heavy chain by 42 +/- 8%, P < 0.05. Protein synthesis rates were not accelerated upon electrical stimulation using subthreshold voltages. Addition of 100 ng/ml of actinomycin D had no effect on the ability of electrical stimulation of contraction to accelerate protein synthesis. To uncouple excitation-contraction coupling, 2,3-butanedione monoxime (BDM) was used to block actin-myosin cross-bridge interactions. BDM significantly decreased the ability of electrical stimulation to accelerate protein synthesis rates.

Animals↗
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 chronic mitral regurgitation on diastolic function in isolated cardiocytes.

We have previously shown that chronic mitral regurgitation (MR) increases the rate of left ventricular early diastolic filling. These changes in chamber diastolic function were felt to be secondary to alterations in left ventricular loading conditions. Therefore, cellular diastolic function measured in cardiac muscle cells (cardiocytes) isolated from animals with chronic MR (absent alterations in loading conditions) was expected to be normal. However, chronic MR caused a decrease in sarcomere lengthening rate. The purpose of the current study was to define the mechanisms causing this decreased sarcomere lengthening rate in chronic MR cardiocytes and to explain the apparent dichotomy between chamber and cellular diastolic properties. Accordingly, sarcomere motion was measured using laser diffraction techniques in enzymatically isolated cardiocytes from seven control dogs and 11 dogs with chronic MR (produced by closed-chest transection of the mitral chordae). In the MR cardiocytes, there were abnormalities in cellular systolic function (decreased extent and velocity of shortening) and in cellular diastolic function (decreased velocity of sarcomere lengthening). Because studies in papillary muscles have shown that there is a direct relation between abnormal diastolic function (decreased velocity of muscle lengthening) and abnormal systolic function (decreased extent of muscle shortening), it was unclear whether the changes in cellular relaxation rate observed in chronic MR merely reflected a concomitant decrease in the extent of shortening or instead reflected an impairment in intrinsic relaxation properties. To make this distinction, the relation between relaxation velocity (measured as peak sarcomere lengthening rate) and sarcomere shortening extent was examined in MR cardiocytes and compared with that in control cardiocytes. There was a direct relation between sarcomere relaxation velocity and sarcomere shortening extent in both control and MR cardiocytes. Over a wide range of shortening extent, the slopes and y intercepts of this relation were similar in control and MR cardiocytes (slope, 27.7 sec-1 in control cells versus 28.1 sec-1 in MR cells; y intercept, -1.1 microns/sec in control cells versus -1.7 microns/sec in MR cells; p = NS). At any common shortening extent, relaxation velocity was the same in control and MR cardiocytes. To prove that this relation could detect abnormalities in the intrinsic myocardial relaxation process, interventions known to produce primary alterations in the intrinsic myocardial relaxation process were examined: the effects of hypothermia (30 degrees C) and isoproterenol (10(-6) M) on the relaxation velocity-shortening extent relation were studied in normal and MR cardiocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Safety and accuracy of dipyridamole thallium myocardial scintigraphy in elderly patients.

This study examined mainly the adverse effects of 201Tl myocardial scintigraphy with dipyridamole (D-Tl) in 73 elderly patients over 70 years old in comparison with those in 65 younger patients. Fifty-five of 73 elderly patients (75%) and 49 of 65 younger patients (75%) had a persistent or dipyridamole-induced perfusion defect on D-Tl. The hemodynamic changes induced by dipyridamole as well as the incidence of cardiac and noncardiac adverse effects were similar in both groups and no serious adverse effect occurred in either group. Secondly, we examined the procedure's usefulness for detecting ischemic heart disease in elderly and younger patients. Dipyridamole induced perfusion defect was noted in 21 elderly patients and in 24 younger patients (N.S.). Among the patients in whom coronary angiography was performed, significant coronary artery stenosis was found in 5 of 8 elderly patients and 17 of 20 young patients (N.S.). In patients with one or two-vessel disease, the area with dipyridamole induced ischemia was concordant with the stenotic area seen on coronary angiography in 3 of 3 elderly patients and 12 of 13 younger patients (N.S.). Thus, the safety and usefulness of D-Tl for detecting myocardial ischemia were comparable in elderly and young patients.

Age Factors↗
PubMed1993

[An autopsy case of the sinus of Valsalva aneurysm involved with tuberculous inflammation, leading to complete heart block].

A case is presented of unruptured aneurysm of the non coronary sinus of Valsalva, causing involvement of A-V node and right coronary artery compression. The patient was a 68 year-old woman with a complaint of general fatigue. Electrocardiogram showed complete A-V block. Computed tomography showed an aneurysm of the non coronary sinus of Valsalva. A temporary pacemaker was implanted, but the patient developed respiratory failure and heart failure and died. At autopsy, macroscopically disseminated tuberculosis was noted in both lungs and kidneys. Microscopically a tuberculous inflammatory lesion extending into the A-V node was found. We report this rare case with some consideration of the literature.

Aged↗
PubMed1992

[The usefulness of dipyridamole stress myocardial scintigram as a preoperative test for detecting ischemic heart disease before vascular surgery].

We evaluated the usefulness of dipyridamole 201Tl myocardial scintigraphy (DS) for detecting myocardial ischemia in 18 candidate for vascular surgery. DS indicated significant thallium redistribution in 6 patients. Coronary angiography was performed in 5 of these 6 patients and revealed significant coronary artery disease in all patients. As a result, operation was cancelled in 4 patients with severe coronary artery disease. One of these cases died of acute myocardial infarction after being discharged from hospital. One other patient was operated after percutaneous transluminal coronary angioplasty. Another patient was operated knowing that he had significant but mild coronary artery disease. Subsequently, operations were performed in 14 patients. No serious cardiac event occurred in these 14 patients except one case with T wave inversion without myocardial enzyme elevation. Thus, we concluded that DS was a useful method for detecting ischemic heart disease and prevent cardiac event associated with vascular surgery.

Aged↗
PubMed1992

[Measurement of blood velocity of rabbit iris by laser speckle flowgraphy].

We developed laser speckle flowgraphy which displays the relative velocity of blood microcirculation as a color map in two dimensions. We applied this method to the iris in 10 eyes of 5 normal white rabbits under general anesthesia. The coefficient of variation was small and averaged 5.6. There was no significant difference in the values measured on 3 consecutive days. The blood velocity in the iris increased significantly during experimental ocular hypotony and decreased during ocular hypertension and 2 hours after instillation of timolol (p less than 0.05). These findings indicate that the present method is of value in assessing the relative velocity of iris microcirculation in vivo and that topical instillation of timolol induces decrease of blood flow in the iris and, possibly, in the ciliary body.

Animals↗
PubMed1992

[Retinal blood flow changes in eyes with rhegmatogenous retinal detachment and scleral buckling procedures].

Bidirectional laser Doppler technique and monochromatic photography was used to measure the absolute blood flow rate (F) in the major superior or inferior temporal retinal arteries in 3 patients with rhegmatogenous retinal detachment, in 4 patients following unilateral scleral buckling procedures, and in one patient before and after removal of scleral buckling elements. In 2 of the eyes with retinal detachment, F in arteries supplying the detached portion of the retina was approximately 30% lower than in arteries supplying the attached portion. On average, F measured in the arteries supplying the detached portion of the retina in 2 patients was 8.9 +/- 1.3 microliters/min, 67% lower than normal controls. F measured in the arteries supplying the attached portion of the retina in 3 patients was 15.2 +/- 3.9 microliters/min, on average, 43% lower than in normal controls. In 4 patients who had undergone uncomplicated, unilateral scleral buckling procedures, F in an artery of the affected eye was compared with F in the corresponding artery of the fellow eye. F in the artery of the affected eyes was 8.7 +/- 3.2 microliters/min, on average, 59% lower than that of the fellow eyes (p less than 0.05), and 68% lower than in normal controls (p less than 0.0001). Removal of scleral buckling elements in one patient produced a 79% increase in F in the measured artery. Then, F returned to normal levels after removal of scleral buckling elements.

Adult↗