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Biomedical subjects

H Sugihara

Publications and source records attributed to H Sugihara.

At least 289 records · Page 16Linked to original sources

1,5-Benzoxathiepin derivatives. III. Optical resolution of methyl (+/-)-cis-3-hydroxy-4-[3-(4-phenyl-1-piperazinyl)propyl]-3,4-dihydro- 2H-1,5-benzoxathiepin-4-carboxylate hydrochloride ((+/-)-CV-5197) with selective 5-hydroxytryptamine2(5-HT2)-antagonistic activity.

The selective 5-HT2-receptor antagonist, methyl (+/-)-cis-3-hydroxy-4-[3-(4-phenyl-1-piperazinyl)propyl]-3,4-dihydro-2H- 1,5-benzoxathiepin-4-carboxylate hydrochloride ((+/-)-CV-5197) was resolved in high optical purity using (R)-(-)- and (S)-(+)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphates ((R)-(-)- and (S)-(+)-BNP). The absolute configuration of (+)-CV-5197 was determined to be 3S,4R by X-ray crystallographic analysis. In the binding assay, it was demonstrated that (+)-CV-5197 was a more active isomer (IC50 = 23 nM +/- 6.3) for 5-HT2 receptor binding than the (-)-enantiomer (IC50 = 1600 nM +/- 82). (+)-CV-5197 completely inhibited the 5-HT-induced contraction of the isolated pig coronary artery at a concentration of 3 x 10(-7) M, whereas (-)-CV-5197 showed little antagonistic activity, even at 3 x 10(-4) M. Thus, the agreement between the results of the binding assays and the biological activities for the 3S,4R enantiomer of CV-5197 suggests that its physiological activity is probably exerted through 5-HT2-receptor antagonism.

Animals↗

Effect of cardiac sympathetic nerve stimulation on acutely ischemic myocardium--a comparison with the response to exogenous noradrenaline.

To assess the integrity of an adrenergic nervous function in acute myocardial ischemia, the contractile response of the ischemic region to cardiac sympathetic nervous stimulation (CSNS) was measured in comparison that with to exogenous noradrenaline (NA) infusion. In 13 anesthetized open chest mongrel dogs, haemodynamic changes, segmental wall motion, and the concentration of NA in the efferent coronary vein were measured. CSNS was performed by electrically stimulating the left ansa subclavia. Data concerning baseline values, values during CSNS, and those obtained during NA infusion both before and up to 5 h after coronary occlusion were compared. Regional myocardial blood flow of the ischemic region was also measured using the H+ clearance method. Systolic expansion with coronary occlusion was not changed or augmented by CSNS. However, improvement was observed in all experiments when NA infusion was used. The percent change of systolic shortening, indicating the response of segmental wall motion to CSNS, decreased soon after occlusion, recovered temporarily within 30 min after occlusion, but did not improve throughout the period after 60 min. The decrease of NA overflow into the efferent vein by CSNS showed a biphasic pattern; reduction occurring immediately after occlusion and again 3-5h after occlusion. Throughout these experimental studies it was considered that the preserved responses to the exogenous injected NA represented the contribution of presynaptic factor.

Animals↗

A pathologic study on the inhibitory effects of a herbal medicine against the glomerular lesion induced by Agkistrodon venom in mice.

The inhibitory effects of a prescription of herbal medicine, tentatively named P-3, were studied pathologically in an experimental model of the glomerular lesion induced by purified snake Agkistrodon acutus venom proteinase (Ac1-P) in mice. Ac1-P was intravenously inoculated at a single LD50 dose. In the treated group, mice were intraperitoneally injected with an extract of P-3 at a designated time once every two days from 2 days before to 1 week after Ac1-P inoculation. The control group mice were injected with saline instead of P-3. In the control group, the main pathologic changes within 48 hrs after inoculation were pulmonary and gastrointestinal tract hemorrhage and renal petechiae with hematuria. The kidney microscopically showed cystic transformation of the glomerular capillary tufts. followed by occlusive thrombosis. One week after inoculation, the glomerular lesions were mostly replaced by proliferative or proliferative-sclerosing changes with occasional crescent formation. Early signs of tubular atrophy accompanying the glomerular changes were observed. In the P-3 treated mice surviving 48 hrs and 1 week, the changes observed in the controls were markedly inhibited, although P-3 treated mice dying earlier than 30 hrs exhibited hemorrhagic changes similar to controls. This indicated that the herbal medicine had efficacy against the tissue injuries induced by Ac1-P as a proteolytic enzyme.

Angiography↗

Growth hormone secretion in stalk-sectioned rats.

Idiopathic pituitary GH deficiency appears to result from neonatal disruption of hypophyseal portal vessels in the majority of patients. To examine the mechanism of GH deficiency associated with the disease, the effect of pituitary stalk section on GH secretion was studied in rats. Adult male rats were subjected to stalk section without inserting an impermeable membrane between the cut ends. They were studied 3 to 4 weeks after surgery. In stalk-sectioned rats, pituitary weight, body weight and hypothalamic SRIH content were significantly reduced as compared with sham-operated rats. Hypothalamic GHRH content, plasma T3, T4, corticosterone and testosterone levels, and weights of testes remove and adrenal glands were comparable in the two groups. Plasma GH profiles of sham-operated rats showed characteristic periodic pulses occurring at 2.5-3 h intervals with intervening trough period. In stalk-sectioned rats, plasma GH levels were low small fluctuations, but GH levels were significantly higher than trough levels of sham-operated rats. The amount of GH secreted during a 6-h period as measured by planimetry was significantly reduced. To ascertain the regeneration of hypophyseal portal vessels, post SRIH rebound in GH secretion, which requires the presence of endogenous GHRH, was examined. Withdrawal of exogenous SRIH infusion triggered a large rebound GH secretion whose magnitude did not differ between groups. In stalk-sectioned rats, GH response to met-enkephalin analogue, FK 33-824, was not observed, whereas prolactin response to the secretagogue was observed in the majority of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of extracellular matrix on the proliferation and differentiation of glioma cells in culture.

The influence of extracellular matrix on the proliferation and differentiation of glioma cells in vitro was investigated by culturing glioma cells in collagen gel and on collagen and laminin films. Rat C-6 glioma cells extended thin cytoplasmic processes, proliferated, and differentiated in collagen gel and on collagen film. The cells were stellate with multiple thin processes like the astrocyte in vivo. The intracellular content of cyclic adenosine-monophosphate in rat C-6 glioma cells on collagen film increased approximately four fold over the control level. In laminin film culture, rat C-6 glioma cells extended thin cytoplasmic processes with many knotty structures and proliferated. These findings confirm that extracellular matrix induces the differentiation of glioma cells.

Animals↗

[Impairment of left ventricular diastolic function during the asymptomatic period in vasospastic angina patients without significant coronary stenosis].

We examined whether recurrent transient ischemia may effect left ventricular systolic and diastolic function or not. Left ventricular systolic and diastolic function during the asymptomatic period was studied by gated radionuclide ventriculography (RNV) in 25 patients with vasospastic angina (VA) who had no significant coronary stenosis, in 25 patients with effort angina (EA), and in 20 controls (C). There was no significant difference among patients in all three groups in regards to systolic indices (Ejection Fraction, Peak Ejection Rate). But diastolic indices (Peak Filling Rate, Time to Peak Filling Rate, 1/3 Mean Filling Rate, 1/3 Filling Fraction) were impaired not only in patients with EA but also in patients with VA. The treatment with nitrates and/or Ca antagonist for 6-24 months did not bring about any changes in these data concerning systolic and diastolic function in patients with VA. Thus, it is suggested that the diastolic function is impaired in patients with VA even during the asymptomatic period, though systolic function remains normal. Recurrent transient ischemia may cause irreversible myocardial injury.

Adult↗

[Effect of age on visualization of right atrium by thallium-201 myocardial scintigraphy].

With Thallium-201 (Tl) myocardial scintigraphy, right atrial (RA) myocardium has been visible in the disease involving the right side of the heart. We have found RA visualization in the elderly patients without the evidence of right heart disease. Therefore, we studied the relation of age to the RA visualization with Tl myocardial scintigraphy performed at rest. Planar images of 291 patients without valvular or congenital heart disease were read by two observers and classified into the three by the degree of RA visualization; RA 0 = not visualized, RA 1+ = moderately visualized, RA 2+ = intensely visualized. The results were as follows: 93.1% of under 50 y.o., 77.8% of fifties, 86.7% of sixties, 50.5% of seventies and 36.7% of over 80 y.o. showed RA 0. 6.9% of under 50 y.o., 22.2% of fifties, 8.3% of sixties, 46.5% of seventies and 36.7% of over 80 y.o. showed RA 1+. None of under 60 y.o., 5.0% of sixties, 3.0% of seventies, and 26.6% of over 80 y.o. showed RA 2+. In conclusion, RA visualization in Tl myocardial scintigraphy, suggesting right heart overload, may increase with aging.

Aged↗

[The clinical significance of reverse redistribution of Tl-201 SPECT at rest in the 1st month after the onset of acute myocardial infarction].

The pattern of Thallium-201 reverse redistribution (r-RD) at rest has been reported in some patients with acute myocardial infarction (AMI) in the acute phase. But there is no report of this pattern in the later phase. To investigate the significance of Thallium-201 reverse redistribution in the subacute phase, 37 patients with AMI underwent Thallium-201 SPECT at rest a month after the onset. The patients were classified into three groups visually and 19 of 37 patients (51%) showed the persistent defect pattern (Group PD), and the remaining 18 patients (49%) had the reverse redistribution pattern (Group r-RD). None of them had the redistribution pattern. Coronary reflow was earlier and the incidence of the scintigraphic overlap on Dual SPECT image of 99mTc-PYP/201TlCl in the acute phase was more frequent in Group r-RD than in Group PD. A decrease in thallium defect size of patients with r-RD from the acute phase to one month after the onset represented improvement more significantly than that with PD. Initial %Tl uptake of the infarcted region of Group r-RD was greater than that of Group PD. The degree of stenosis of the infarct-related coronary artery in Group r-RD was less severe than that in Group PD. And corresponding regional wall motion of Group r-RD was less impaired. The Thallium-201 washout in the infarcted region with r-RD was significantly faster than that in the normal region. It is concluded that the r-RD pattern at rest in the 1st month after the onset of AMI may be a sign of viable myocardium.

Aged↗

[Apical sequestration in hypertrophic cardiomyopathy: its clinical features and pathophysiology].

The clinical and pathophysiological significance of apical sequestration, in which an apical cavity was sequestered from the remainder of the left ventricle by cavity obliteration was investigated in patients with hypertrophic cardiomyopathy (HCM). Among 196 consecutive patients, 24 with apical sequestration and 70 control subjects proven to have no sequestration with left ventriculography were selected for this study using echocardiography combined with Doppler color flow imaging. Various cardiac disorders occurred significantly more frequently in patients with apical sequestration than in the 70 controls: NYHA > or = II, 83% vs 51%; thromboembolism, 17% vs 3%; ventricular tachycardia, 47% vs 11%; and apical asynergy, 75% vs 4%. Continuous Doppler ultrasound revealed that all 24 patients with sequestration had a high systolic blood flow velocity across the obliterated cavity (2.7 +/- 0.9 m/s). During isovolumic relaxation or early diastolic filling or both, 21 of them had paradoxical jet flow directed toward the basal cavity away from the apex, with the peak flow velocity ranging from 1.0 m/s to 3.5 m/s (mean 1.9 +/- 0.7). The maximal diastolic pressure gradient across the obliterated cavity ranged between 4 mmHg and 49 mmHg using the simple Bernoulli's equation, which suggested a significantly higher pressure in the sequestered apical chamber during early diastole. Patients with sequestration were classified into 2 groups; 17 with (group A) and 7 without (group B) apical hypertrophy. The time interval from the closing of the aortic valve to the onset of filling into the sequestered cavity was longer in group A than in group B (401 +/- 191 vs 131 +/- 145 ms, p < 0.01) as assessed by the pulsed Doppler technique. Angiographic asynergy of the apex was more frequent in group A than in group B (100 vs 29%, p < 0.01). In group B, the midventricular cavity was incompletely obliterated throughout the cardiac cycle; whereas, in group A, it was obliterated completely in systole and partially in diastole. Apical sequestration is not uncommon in HCM; it is accompanied by abnormal segmental wall motion, which may be related to ventricular arrhythmias and thromboembolism. Prolonged cavity obliteration with a higher systolic apical pressure and a persistent diastolic intraventricular gradient may play a pathogenic role in apical aneurysmal formation in the absence of fixed coronary artery disease, particularly in patients with apical hypertrophy.

Adolescent↗

Quantitative measurements of balloon-to-artery ratios in coronary angioplasty.

To determine the optimal balloon-to-artery ratio in percutaneous transluminal coronary angioplasty (PTCA), the effects of balloon size on the extent of residual stenosis, the incidence of coronary dissection, and the percentage of cases requiring repeat PTCA for restenosis were examined retrospectively. Fifty consecutive patients who underwent elective PTCA for simple and discrete lesion localized in the left anterior descending coronary artery were selected for this study. To measure the absolute cross-sectional area of the adjacent control segment of the artery, we developed a new method of quantitative coronary angiography, a hybrid of cinevideodensitometry and the edge detection method. The balloon-to-artery ratio was calculated as the cross-sectional area ratio between the control segment adjacent to the stenosis and the balloon which was visually selected by the operator during PTCA. Residual stenosis was determined as the percent area of stenosis by our hybrid method using cinevideodensitometry. The balloon-to-artery ratio ranged from 0.4 to 2.4, and a weak but significant inverse correlation (r = -0.51) was observed between the balloon-to-artery ratio and the extent of residual stenosis. In 23 patients whose balloon-to-artery ratios were less than 1.0, residual stenosis was greater (59.9 +/- 11.9% vs 46.0 +/- 19.6%, p < 0.05), and the percentage of repeat PTCA was higher (26% vs 4%, p < 0.05) than in the group of 27 patients whose balloon-to-artery ratios were higher than 1.0. The incidence of coronary dissection was similar in the 2 groups (9% vs 15%, ns). The percent area of stenosis before PTCA, the number of inflations, the inflation pressures, and the inflation times were also similar between these 2 groups. We concluded that the optimal balloon size is slightly more than the control segment dimensions of simple and discrete isolated stenoses of the left anterior descending artery treated at lower inflation pressures, and that an accurate measurement method of the coronary arterial dimensions is necessary to determine this optimal balloon size.

Angioplasty, Balloon, Coronary↗

[A case of hypertrophic cardiomyopathy with progressive cavity dilatation--a review of serial 201Tl myocardial imaging].

We reviewed 201Tl images of a 32 year old man with dilated hypertrophic cardiomyopathy (DHCM). At 22 years of age, when he was diagnosed as having nonobstructive hypertrophic cardiomyopathy (HCM)IVST; 20mm, Dd; 44mm, EF; 62%), 201Tl images showed only a small defect in the anteroseptal segment. At 27 years of age, when he had the first cardiac symptom as palpitation on exertion, his perfusion defect of 201Tl became wider. At 32 years age, he was hospitalized because of deterioration of congestive heart failure. Echocardiography revealed left ventricular wall thinning(IVST; 6mm), left ventricular cavity enlargement (Dd; 63mm) with a large mural thrombus and reduced left ventricular ejection fraction (EF; 32%). Thus 201Tl images may provide useful information on the process of DHCM from HCM.

Adult↗

[A prominent retrograde flow in coronary artery in patients with hypertrophic cardiomyopathy].

Pathophysiology and clinical significance of a systolic backward flow in the epicardial coronary artery have not been elucidated. Using a 20 MHz Doppler catheter, we assessed coronary flow velocity waveforms in the left anterior descending coronary artery in 19 patients with hypertrophic cardiomyopathy (HCM) and 11 patients without apparent cardiac abnormalities as control subjects. Systolic flow fraction was smaller in HCM than in controls. Only 4 patients with HCM showed a prominent retrograde flow persisting during almost the entire systole. All the 4 had marked cavity obliteration and two of them had systolic intraventricular pressure gradients of 80 and 110 mmHg respectively. Exercise thallium-201 ECT revealed that myocardial hypoperfusion was more frequent in those 4 patients. Through these observations, it is concluded that a high intramyocardial systolic pressure combined with a relatively low coronary perfusing pressure may result in a large systolic retrograde flow in the left epicardial coronary artery, and that it may be related to myocardial ischemia in patients with HCM.

Adult↗

[Evaluation of coronary arterial stenosis before and after PTCA: visual estimation versus computer-assisted analysis].

Coronary arteriogram of 34 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) were evaluated visually and by computer-assisted analysis, that employed an edge detection method and cine-videodensitometry. The results of visual estimation were in general agreement with those of computer-assisted analysis for determination of percent area of stenosis in severe stenosis, and percent diameter of stenosis in slightly stenotic lesions. Before PTCA, the findings obtained by densitometry agreed with those using the edge detection method. However, after PTCA, the results were significantly different. This discrepancy may have been due to asymmetric morphologic changes in the luminal cross sectional area immediately after PTCA, which could not be assessed by the edge detection method in a single-plane view. Through these studies it was concluded that the densitometry is most useful for evaluating the effects of PTCA.

Absorptiometry, Photon↗

Drosophila choline acetyltransferase uses a non-AUG initiation codon and full length RNA is inefficiently translated.

RNA from a partial cDNA clone containing the entire protein coding sequence of Drosophila melanogaster acetyl-CoA:choline O-acetyltransferase (EC 2.3.1.6; choline acetyltransferase) can be translated into active enzyme. This is unusual since this partial cDNA clone contains no appropriate ATG (AUG) initiation codon. In this study we use in vitro deletion and point mutants to identify GTG as the starting codon for protein translation. We also report the sequence of a full length Drosophila choline acetyltransferase cDNA and demonstrate that RNA produced by this clone is translated into active choline acetyltransferase but at a significantly reduced efficiency when compared to the partial cDNA clone. These results indicate that translational control may be an important regulatory step in production of Drosophila choline acetyltransferase.

Amino Acid Sequence↗

Effect of intermittent infusions of somatostatin on growth hormone secretion in unrestrained male rats with hypothalamic deafferentation.

The effect of intermittent infusions of somatostatin (SS) on growth hormone (GH) secretion was studied in unrestrained adult male rats deprived largely of SS influence on the medial basal hypothalamus by anterolateral deafferentation (AL-cut). In addition, the influence of hypothalamic surgery on the plasma GH response to beta-endorphin (beta-END) was observed. In sham-operated rats, high-amplitude GH pulses separated by low baseline levels occurred at 185 min intervals. In rats with AL-cut, GH pulses were difficult to identify upon visual appraisal and baseline plasma GH levels became significantly higher than those of sham-operated rats. When AL-cut was performed unilaterally (half-AL-cut), low amplitude GH pulses separated by elevated baseline GH levels occurred at frequent intervals. The amount of GH secreted during 6 h was significantly reduced in rats with AL-cut or half-AL-cut as compared to that of sham-operated rats. The plasma GH response to intracerebroventricular injection of beta-END (4 micrograms) was abolished in AL-cut rats, and the response was significantly reduced in half-AL-cut rats as compared to that of sham-operated rats. When AL-cut rats were subjected to repeated infusions of SS (30 micrograms/kg b. wt./h, 150 min) separated by 30 min control periods, a large rebound of GH secretion was observed after removal and the amount of GH secreted during 6 h became comparable to that of sham-operated rats. The results suggest that SS plays important roles in the dynamic secretion of GH.

Animals↗

Regional ploidy variations in signet ring cell carcinomas of the stomach.

Regional ploidy variations within individual tumors were analyzed by in-situ cytofluorometry of metaphase cells in Feulgen-stained paraffin sections, using 45 resected stomachs with early and advanced signet ring cell carcinomas. Aneuploid cells were found in one of 30 early cancers and in eight of 15 advanced cancers, and were almost always accompanied by diploid cancer cells in the mucosal part of the cancers. The diploid and the aneuploid cells were generally found to be distributed in different territories in the mucosa, and aneuploid foci were often included in the diploid area. These findings suggest the diploid origin of signet ring cell carcinomas and the occurrence of aneuploidy during the tumor development. Moreover, the aneuploid cells appeared to infiltrate beyond the mucosa more readily than the diploid cells; most of the aneuploid populations already invaded the extramucosal tissue, and the cancer cells infiltrating in the extramucosal tissue were predominantly aneuploid in six of the nine cancers with aneuploidy. Thus, it appears that the occurrence of aneuploid clones may accelerate the progression of signet ring cell carcinomas from early to advanced stages.

Adenocarcinoma, Mucinous↗

Correlation of heart rate and radionuclide index of left ventricular contraction and relaxation.

Since the cardiac function indices derived from radionuclide ventriculography (RNV) are considered to depend on the heart rate, we studied the relationship between systolic or diastolic indices and heart rates in patients with normal RNV and devised a method of correcting these indices according to the heart rate. For the systolic indices, the heart rate showed significant correlation with ET (r = -0.640), PER (r = 0.791) and TPE (r = -0.401) but not with EF, 1/3 EF, MNSER or 1/3 MNSER. For the diastolic indices, the heart rate correlated with FT (r = -0.938), RFT (r = -0.736), SFT (r = -0.803), 1/3 FF (r = -0.758), PFR (r = 0.759), 1/3 PFR (r = 0.742) and TPF (r = -0.389) but not with AFT, 1/3 MNDFR or AFF. These results indicate that many systolic and diastolic indices derived from RNV are affected by the heart rate. So when cardiac function is evaluated with the use of radionuclide indices, those which are independent of the heart rate should be used, or they should be corrected for the heart rate. As a method of correction, we proposed a rotating method obtained by manipulation of the regression equation of heart rates and indices. This new method is certain and easier to use when the correcting equations are set into a computer program.

Adult↗