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Biomedical subjects

K Sakaguchi

Publications and source records attributed to K Sakaguchi.

At least 343 records · Page 19Linked to original sources
PubMed1988

Reocclusion of the infarcted vessel during acute interventions in myocardial infarction.

Acute reocclusion of the recanalized infarcted vessel was observed during thrombolytic therapy in 28 or 138 patients, and during angioplasty following thrombolysis in 5 of 70 patients. The occluded vessel reopened again in 20 of 28 patients by additional administration in nitroglycerin and urokinase and in 3 of 5 patients by repeated angioplasty. There was no significant difference in success rate of thrombolysis or angioplasty between patients with acute reocclusion and those without. However, reinfarction after acute intervention tended to be more common in the former patients than the latters.

Aged↗
PubMed1988

Platelet-activating factor and anti-platelet-aggregating factor in acute reduction of blood pressure following percutaneous transluminal renal angioplasty in patients with renovascular hypertension.

The mechanism of the acute fall of BP following percutaneous transluminal renal angioplasty (PTRA) was studied in four patients with renovascular hypertension caused by fibromuscular dysplasia. One hour after PTRA, systemic blood pressure and plasma renin activity in the ipsilateral renal venous blood decreased significantly (P less than 0.05), but the plasma noradrenaline level in ipsilateral renal venous blood increased significantly (P less than 0.05). At the same time, a platelet-activating factor (PAF) and an unidentified factor that inhibited the aggregation of rabbit platelets induced by PAF, arachidonic acid or ADP were detected in the ipsilateral renal venous blood, but were not found in the contralateral renal venous blood. Plasma noradrenaline level in cubital venous blood decreased significantly (P less than 0.05) after 24 hours as compared with that before PTRA and BP also maintained the normal level. These results suggest that the reduction in plasma renin activity is associated with the acute reduction in BP following PTRA. PAF and an unidentified factor blocking the aggregation of platelets may be involved in ipsilateral renal venous blood following PTRA in patients with renovascular hypertension. The reduction in plasma noradrenaline level is an additional mechanism involved in maintaining normal BP following PTRA in the late stage.

Adult↗
PubMed1988

Changes in plasma lipids and uric acid with sodium loading and sodium depletion in patients with essential hypertension.

The short-term effects of manipulating dietary salt intake on plasma levels of cholesterol, lipoproteins and uric acid were studied in two groups of patient with essential hypertension. With dietary salt restriction in 8 patients (10 g to 2 g salt/day for five days), plasma total cholesterol, esterified cholesterol, beta-lipoprotein, low density lipoprotein and uric acid rose significantly. With salt repletion (2 g salt/day to 20 g/day for five days) in 17 patients, plasma total cholesterol, esterified cholesterol, beta-lipoprotein, low density lipoprotein and uric acid fell significantly. Total/HDL cholesterol ratio increased significantly with salt restriction and decreased significantly with repletion. However, very low density lipoprotein, HDL-cholesterol, triglyceride, phospholipid, chylomicron and non-esterified fatty acid were not influenced by the changes in salt intake. These results indicate that the severe restriction of dietary salt raises plasma cholesterol and uric acid levels in patients with essential hypertension in the short term.

Blood Pressure↗
PubMed1988

Normalization of high plasma level of ouabain-like immunoreactivity in primary aldosteronism after removal of adenoma.

Plasma ouabain-like immunoreactivity, which has been supposed to be associated with hypertension, was significantly higher in five patients with primary aldosteronism than in age-matched normotensive subjects. High plasma levels of ouabain-like immunoreactivity decreased to normal after removal of adenoma. Extracts of adenoma tissue did not contain any apparent ouabain-like immunoreactivity. Anti-ouabain antibody used in this study did not cross-react with aldosterone, cortisol, corticosterone, arachidonic acid or lysophosphatidylcholine. Hypertension, hypokalemia, a high plasma aldosterone level and low plasma renin activity were also normalized after surgery. These results indicate that hyperaldosteronism induces the high plasma level of ouabain-like immunoreactivity and this is associated in part with high blood pressure (BP) in primary aldosteronism.

Adenoma↗
PubMed1987

[4,4'-(Z)-dehydrophenylalanine]gramicidin S with stabilized bioactive conformation and strong antimicrobial activity.

Dehydrophenylalanine (delta Phe) was incorporated into an antibiotic peptide gramicidin S (GS) in place of D-Phe4,4' to prepare an unsaturated analog. Conformational analysis with 1H-NMR indicated that the unsaturated analog has much the same backbone conformation as that of natural gramicidin S as shown by NOE experiments. Studies on temperature dependences and on the chemical shift differences showed that the hydrogen bonds between Val-NH and Leu-CO in the unsaturated analog are strengthened by the incorporation of delta Phe4,4'. This resulted in the reinforcement of the beta-sheet structure which is the most important structural element for GS bioactivity. [delta Phe4,4']gramicidin S exhibited indeed very strong antimicrobial activities against Gram-positive bacteria as well as the natural peptide.

Circular Dichroism↗
PubMed1987

Immunochemical and functional analysis of HLA class II antigens induced by recombinant immune interferon on normal epidermal melanocytes.

The effect of recombinant immune interferon (IFN-gamma) on the expression and shedding of HLA antigens and of melanoma-associated antigens (MAA) by epidermal melanocytes was investigated by using serologic and immunochemical techniques. IFN-gamma enhances the expression and/or shedding of HLA class I antigens and of the cytoplasmic MAA defined by monoclonal antibody (MoAb) 465.12S and induces a slight reduction in the expression of the high m.w. melanoma-associated antigen (HMW-MAA). In agreement with the data in the literature, melanocytes incubated with IFN-gamma acquire HLA-DR, -DQ, and -DP antigens. Contrary to previous information in the literature, the effect is not restricted to HLA class II antigens, since IFN-gamma also induces the expression of the 96-kDa MAA recognized by MoAb CL203. The effect of IFN-gamma on HLA class II antigens and 96-kDa MAA is dose and time dependent and is specific, because recombinant leukocyte interferon affects the expression of neither type of antigen. In spite of the expression of HLA class II antigens, IFN-gamma-treated melanocytes do not acquire the ability to stimulate the proliferation of allogeneic lymphocytes. HLA-DR antigens are more susceptible to induction by IFN-gamma than HLA-DQ and -DP antigens, since the percentage of melanocytes acquiring HLA-DQ and -DP antigens is lower than that acquiring HLA-DR antigens. Furthermore, the dose of IFN-gamma is higher and the time of incubation is longer to induce HLA-DQ and -DP antigens than to induce HLA-DR antigens. The differential susceptibility of HLA-DR, -DQ, and -DP antigens as well as of melanocytes from various donors to the modulating effect of IFN-gamma may provide an explanation for the more frequent detection of HLA-DR than of HLA-DQ and -DP antigens in melanoma lesions and for the expression of HLA class II antigens by some, but not all, melanoma lesions.

Animals↗
PubMed1987

Synthetic parathyroid hormone fragments shortened at the amino terminus stimulate glucose-6-phosphate dehydrogenase activity in the distal renal tubule.

The cytochemical bioassay, using glucose-6-phosphate dehydrogenase (G6PD) activity in the distal convoluted tubule of a guniea pig as an index, is specific and the most sensitive method of evaluating the biological activity of parathyroid hormone (PTH). Using this method, biological activities of the amino- or carboxyl-terminal PTH fragments and analogues, human (h) PTH-(3-34), [Tyr34]hPTH-(7-34)amide(NH2), [Tyr34]hPTH-(13-34)NH2, hPTH-(39-84), hPTH-(51-84), hPTH-(69-84), were tested over a concentration range of 10(-16) to 10(-13) M. In addition, the combined effect of these hormones with human or bovine PTH-(1-84) and the effect of dibutyryl (Bu)2) cAMP were also evaluated. In the 14-min time-course study, amino-terminal PTH fragments and analogues induced cyclic changes of G6PD activity with shorter cycle lengths in higher concentrations and with constant peak heights regardless of the concentrations. Human and bovine PTH-(1-84) showed the same activity on G6PD activation at 6 min. hPTH-(3-34), [Tyr34]hPTH-(7-34)NH2, and [Tyr34]hPTH-(13-34)NH2 were equipotent with PTH-(1-84) on a molar basis, and none of these analogues inhibited PTH-(1-84) even with doses up to 240 times that of PTH-(1-84). Carboxyl-terminal PTH showed no effect. (Bu)2cAMP mimicked the effect of PTH-(1-84) on G6PD activation in time course and dose response. We conclude that the amino terminus is not essential for the biological activity of PTH in the cytochemical bioassay.

Animals↗
PubMed1987

Functional epithelial cell line cloned from rat parathyroid glands.

Primary cultures of rat parathyroid cells were developed in medium containing 5% calf serum, 1% Nutridoma-SP (a serum-free medium supplement from Boehringer Mannheim), and 0.7 mM calcium. The PT-r strain was purified by successive colony isolations and maintained differentiated characteristics (secretion of bioactive and radioimmunoactive parathyroid hormone into the culture medium, sensitivity to calcium regulation, and modulation by secretin) for 7 months in continuous culture. These cultured cells are epithelioid, display diploid chromosome numbers, and do not show a transformed phenotype. There has been no decrease in the rate of cell division or decline in parathyroid hormone secretion since the cell line was established. This clonal cell line provides an important system for further studies on the biology of the parathyroid cell.

Animals↗
PubMed1987

Thromboxane A2 analogue induced coronary artery vasoconstriction in the rabbit.

Diffuse coronary artery vasoconstriction was provoked in the rabbit by a stable thromboxane A2 analogue, STA2 (9,11-epithio-11,12-methano thromboxane A2). Injection of 25 micrograms.kg-1 STA2 into the left main trunk caused complete occlusion of the left anterior descending artery and narrowing of the left circumflex artery. Two minutes after injection, however, the diameter of the coronary artery returned to the control value (n = 10). The right coronary artery was also temporarily occluded by an injection of 25 micrograms.kg-1 STA2. Left ventricular end diastolic pressure increased significantly, and ST segment elevation of the electrocardiogram occurred during vasoconstriction. The angiographic findings showed that the vasoconstriction in the coronary artery induced by STA2 was similar to the diffuse vasoconstriction seen clinically. Induction of the vasoconstriction by STA2 was prevented by the preadministration of 25 micrograms.kg-1 of either a calcium antagonist, diltiazem, or a thromboxane A2 receptor antagonist, ONO 3708 (n = 10). The relation of the calcium movement to this vasoconstriction was studied in vitro using the isolated left circumflex artery in the rabbit. STA2 (50 micrograms.litre-1 to 0.5 mg.litre-1) produced a concentration dependent contraction of helical strips of left circumflex artery. Diltiazem (50-100 g.litre-1) suppressed this contraction dose dependently. ONO 3708 (10 micrograms.litre-1 to 1 mg.litre-1) caused a significant rightward and downward shift of the dose-response curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Blockade of angiotensin converting enzyme in circumventricular organs of the brain after oral lisinopril administration demonstrated by quantitative in vitro autoradiography.

1. To elucidate the central effect of lisinopril, a new angiotensin converting enzyme (ACE) inhibitor, ACE localization and levels were followed in the brain of Sprague-Dawley rats by quantitative in vitro autoradiography after administration of the drug. 2. Following acute lisinopril (10 mg/kg p.o.) treatment, serum ACE activity was acutely reduced, but returned to normal by 24 h. 3. Levels of ACE in most parts of the brain, including the basal ganglia and choroid plexus of all ventricles were not affected by lisinopril. Lisinopril inhibited brain ACE in the subfornical organ and organum vasculosum of the lamina terminalis, circumventricular organs, where the blood brain barrier is deficient. These regions are rich in ACE and angiotensin II receptors, and are known targets for angiotensin II-induced effects on fluid, electrolyte and blood pressure homeostasis. 4. These observations indicate that quantitative in vitro autoradiography is a powerful method to study the access of drugs to the central nervous system. 5. This study shows that blood brain barrier plays an important role in limiting the penetration of lisinopril into the central nervous system. The circumventricular organs may be important targets for ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Pharmacokinetics of angiotensin converting enzyme inhibition in tissues following oral lisinopril: studies in the rat using quantitative radioinhibitor binding.

1. The pharmacokinetics of angiotensin converting enzyme (ACE) inhibition in plasma and tissues were measured in the rat following 10 mg/kg lisinopril given by oral gavage. 2. Specific binding of 125I-351A to ACE was measured in plasma, and homogenates of lung, aorta, kidney, testis, epididymis and brain, and used as an index of ACE activity. 3. Plasma ACE binding of 125I-351A was reduced to 5% of that in untreated rats 2 h after treatment, and returned to normal by 48 h. Kidney ACE showed a similar time course. Angiotensin converting enzyme from lung, aorta and brain was inhibited at a slower rate, and to a lesser degree. No significant inhibition of ACE was detected in epididymis or testis. 4. Individual tissues in the rat had differences in time course and degree of ACE inhibition after a single dose of lisinopril.

Administration, Oral↗
PubMed1987

Age-dependent changes in phenytoin tissue distribution in rats.

Age-dependent changes of phenytoin disposition in rats were studied following intravenous administration of 5,5-[4-14C]-diphenylhydantoin to 1-d, 1-, 3- and 8-week-old rats. The distribution volumes changed similarly to those of warfarin in the growth process of rats. The lower clearances in infant and young rats were considered to be caused by the undeveloped liver function to metabolize phenytoin. The changes of distribution volumes in the growth process of rats were assumed to be based upon not only the changes in blood free fractions but also other factors. In any aged rats, the muscle largely contributed to the distribution of phenytoin in the body and the Kp values in the muscle decreased in the growth process of rats. This change of phenytoin transfer to the muscle affected the decrease of distribution volumes of phenytoin in 8-week-old rats and the distribution volumes of brain, lung and liver in infants and young rats were greater than those in adult rats. The Kp value in the lung in 8-week-old rats was smaller than the values in 1-d, 1- and 3-week-old rats and there was no significant difference in the Kp values in the liver among the 4 ages. These results were different from those in warfarin reported previously and suggested that warfarin and phenytoin bind different macromolecules in the liver and the lung.

Aging↗
PubMed1987

Age-dependent change in warfarin distribution volume in rats: effect of change in extracellular water volume.

The pharmacokinetics of insulin was studied following intravenous administration of 14C-inulin to 1-d, 1-, 3- and 8-week-old rats. The distribution volume of inulin varied 2-fold, from 689 ml/kg in 1-d-old rats to 340 ml/kg in 8-week-old rats in the growth process of rats. This result was similar to that of warfarin and there was a statistically significant correlation between the distribution volume of warfarin and inulin (r = 0.984, p less than 0.02). In the growth process of rats, the Kp values of warfarin in muscle, which play an important role in the distribution kinetics of warfarin changed in parallel with those of inulin. These results and pharmacokinetic considerations indicated that in warfarin, which is highly bound to serum protein and shows a small distribution volume, the change in the distribution volume in the growth process of rats following administration of a pharmacologically realistic dose (1 mg/kg) is led by the change in the extracellular volume of tissues and that the change in serum protein binding of warfarin might play a minor role in the change in the distribution volume in the growth process.

Aging↗
PubMed1987

Age-dependent changes in phenytoin tissue bindings in rats: comparison between in vivo and in vitro tissue-to-blood partition coefficients (Kp values) of phenytoin.

Age-dependent changes in phenytoin tissue bindings in rats were investigated by equilibrium dialysis using serum and 10% tissue (brain, lung, liver, kidney and muscle) homogenates. All percentages of phenytoin bound to serum and tissue homogenates were independent of the initial phenytoin concentration (2 to 25 micrograms/ml) in 1-d, 1-, 3- and 8-week-old rats. The percentages bound to serum, brain, liver, kidney and muscle in newborn rats (1-d-old rats) were lower than those in 8-week-old rats and the percentages bound increased gradually in the growth process. However, those in lungs were constant in all ages of rats. It was assumed that the age-dependent changes in phenytoin tissue binding were caused by the changes in the quantities of tissue constituents to which phenytoin bound in the growth process. Tissue-to-blood partition coefficients (Kp values) were calculated from in vitro tissue binding data and the pH-difference across the cell membrane. These Kp values were in good agreement with the in vivo Kp values reported previously. It was concluded that the age-dependent changes in phenytoin tissue distribution were caused by the age-dependent changes in phenytoin binding to blood constituents and tissues but that the change of phenytoin blood binding contributed to the age-dependent changes in Kp values of phenytoin more than to phenytoin tissue binding and consequently the Kp values of phenytoin decreased as rats grew.

Aging↗