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Biomedical subjects

K Sakaguchi

Publications and source records attributed to K Sakaguchi.

At least 361 records · Page 20Linked to original sources

Heparin requirement in tissue-type plasminogen activator-induced experimental coronary thrombolysis: comparison with urokinase-induced coronary thrombolysis.

The requirement of heparin in experimental coronary thrombolysis induced by tissue-type plasminogen activator (t-PA) was studied in closed-chest dogs with one hour old coronary thrombi and compared with that in urokinase (UK)-induced coronary thrombolysis. Animals were divided into 5 treatment groups as follows: group 1 received intracoronary t-PA alone (1,000 IU/kg/min; n = 5), and if thrombolysis was not induced within 40 to 50 min, dogs then received an intravenous injection of heparin (300 U/kg) plus intracoronary t-PA; group 2 received intravenous heparin at first, and if thrombolysis was not induced within 10 min, dogs subsequently received intracoronary t-PA (n = 5); group 3 also received intravenous heparin at first, and if thrombolysis was not induced within 10 min, dogs subsequently received t-PA but intravenously, as compared with the groups administered by the intracoronary route (n = 6); group 4 received intracoronary UK alone (1,000 IU/kg/min; n = 6); group 5 received intravenous heparin at first, and if thrombolysis was not induced within 10 min, dogs subsequently received intracoronary UK (n = 5). Thrombolysis was confirmed angiographically. In group I, coronary thrombolysis could not be induced within 44 +/- 4 min by intracoronary t-PA alone, but it occurred in 8 +/- 4 min when administered in combination with heparin in all dogs. Heparin alone failed to elicit reperfusion within 10 min in group 2, 3 and 5. t-PA, however, induced successful reperfusion in 16 +/- 5 min (group 2) and in 23 +/- 6 min (group 3), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hemodynamic effect of oral TA-064 after dobutamine in congestive heart failure.

The hemodynamic effect of oral TA-064 (20 mg), a newly synthesized inotropic agent, was compared with that of intravenous dobutamine (5 micrograms/kg/min) in eight patients with congestive heart failure who had been treated with intravenous dobutamine, digitalis, diuretics, and prazosin. Hemodynamics was measured using a Swan-Ganz catheter during the pre-dobutamine control period, during dobutamine infusion period, during the pre-TA-064 control period and at 90 minutes after oral administration of TA-064. Stroke work index was increased and mean pulmonary capillary wedge pressure was decreased with TA-064 or dobutamine. Cardiac index and stroke index was increased by each drug, and pulmonary and systemic vascular resistances were decreased. Mean systemic arterial pressure, heart rate and pressure-rate product did not significantly change in comparison with the control level. In conclusion, TA-064 has a hemodynamic effect similar to that of dobutamine and may be useful as an oral substitute for dobutamine in patients with congestive heart failure after temporary management with dobutamine.

Administration, Oral↗

Effect of paraquat on plasma fibronectin, serum free hydroxyproline, serum ceruloplasmin and lung collagen content in monkeys.

The purpose of this study was to characterize paraquat toxicity in monkeys and to determine the feasibility of using the monkey as an animal model for the study of paraquat-induced pulmonary fibrosis in humans. Sixteen Japanese monkeys (Macaca fuscata), more than 3.5 years of age, with bodyweight ranging from 3.2 kg to 10.2 kg, were randomly divided into two groups. They were administered paraquat dichloride (PQ) by injection (s.c.) at a dose of 2.0 mg/kg bodyweight (12 monkeys) or s.c. saline, at a dose of 0.2 ml/kg bodyweight (control group, 4 monkeys), every two days for a period of four to five times. Eight monkeys (66.7%) from the PQ treatment groups expired due to subchronic PQ toxicity from days 11 to 35. Four monkeys (33.3%) from the PQ treatment group and all four monkeys from the control group survived the observation period of 66 days. On day 66, all of the surviving monkeys were sacrificed and examined for possible histopathological changes and the lung hydroxyproline content was determined. Our results indicate that the concentration of free hydroxyproline and plasma fibronectin did not vary significantly. The serum ceruloplasmin for the monkeys of the PQ treatment groups was significantly increased from day 14 to 21, compared to the control group. Also the total lung collagen of both the expired and surviving monkeys in the PQ treatment groups was elevated significantly, compared to the control group. The monkeys can provide extensive opportunities for research on the mechanism and the treatment of PQ poisoning in man.

Animals↗

Angiotensin converting enzyme inhibition in plasma and tissues.

Angiotensin converting enzyme (ACE) and the ACE inhibitor lisinopril were measured in patients with renal impairment, by both radioinhibitor 125I MK351A binding studies, and by radioimmunoassay. Plasma concentration of lisinopril estimated by radioinhibitor binding displacement correlated closely with that measured by radioimmunoassay. Plateau lisinopril concentration in 8 patients with varying degrees of renal failure treated with 5 mg lisinopril per day for 1 week, was inversely related to renal function. Plasma lisinopril concentrations of 30-70 ng/ml were required for 50% inhibition of plasma ACE activity in vivo. Acute studies in the rat showed inhibition of ACE in different tissues had different time courses. These observations suggest that 125I MK351A binding studies in tissues will be useful in establishing the pharmacokinetic and pharmacodynamic profiles of newer ACE inhibitors, and may help delineate the contribution of ACE in different tissues to cardiovascular homeostasis.

Angiotensin-Converting Enzyme Inhibitors↗

Calcium-dependent activation of glucose-6-phosphate dehydrogenase by 1,25-dihydroxycholecalciferol in the guinea pig distal convoluted tubule.

The effect of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) on glucose-6-phosphate dehydrogenase (G6PD) activity in the distal convoluted tubule of a vitamin D-depleted guinea pig was determined using quantitative cytochemistry. When kidney segments were incubated with 1,25(OH)2D3 (0, 0.15, 0.30, 1.5 or 3.0 nM) during the initial 5 h maintenance culture, G6PD activity at each steroid concentration decreased gradually to reach its stable basal level, which was higher in proportion to the increasing concentration of 1,25(OH)2D3. 1,25(OH)2D3-induced activity of this enzyme was completely abolished by cycloheximide (35 microM). In the presence of 1.5 nM 1,25(OH)2D3, at 0.15 mM calcium, increasing concentrations of EGTA from 0.1 to 2.0 mM caused a dose-dependent reduction in the enzyme activity and abolished it to the cycloheximide-treated level at 2 mM, whereas in the absence of 1,25(OH)2D3, the enzyme activity remained unchanged regardless of the concentration of calcium. These results indicate that G6PD is activated by 1,25(OH)2D3 via new protein synthesis, and that the extracellular calcium plays a crucial role in the regulation of this enzyme activity.

Animals↗

A sandwich assay to detect and characterize syngeneic anti-idiotypic antibodies to murine anti-HLA and tumor associated antigen monoclonal antibodies.

The parameters of a sandwich assay to analyze syngeneic polyclonal and monoclonal anti-idiotypic antibodies to murine anti-HLA and anti-human melanoma associated antigen monoclonal antibodies have been characterized. Furthermore, the sensitivity of the sandwich assay has been compared with that of assays widely used to characterize anti-idiotypic antibodies, i.e., the binding assay to F(ab')2 fragments of monoclonal antibodies and the radioimmunoassay. The latter is more sensitive than the sandwich assay when monoclonal anti-idiotypic antibodies are tested, but less sensitive when anti-idiotypic antisera are analyzed. Both assays are less sensitive than the binding assay to F(ab')2 fragments of monoclonal antibodies.

Animals↗

Vasodilator therapy with a new stable prostacyclin analog, OP-41483, for congestive heart failure due to coronary artery disease and comparison of hemodynamic effects and platelet aggregation with nitroprusside.

A new stable prostacyclin analog, OP-41483, was used in patients with severe congestive heart failure (CHF) due to coronary artery disease and compared with nitroprusside. During infusion of both drugs, mean brachial arterial pressure, total pulmonary resistance, pulmonary artery wedge pressure and systemic vascular resistance decreased significantly. Cardiac index and stroke index also increased significantly. Platelet aggregation did not change significantly during nitroprusside but decreased significantly with OP-41483 infusion. Thus, this analog may be useful for treatment of patients with CHF due to coronary artery disease.

Aged↗

Characteristics of parathyroid hormone-specific cyclic changes of glucose-6-phosphate dehydrogenase activity in the distal convoluted tubule of the guinea pig.

The effect of parathyroid hormone (PTH) on the time course of glucose-6-phosphate dehydrogenase (G6PD) activity in the distal convoluted tubule of a vitamin D-depleted guinea pig was determined using quantitative cytochemistry. G6PD activity decreased to the stable basal level 5 hrs after the initiation of the kidney segment maintenance cultures. The exposure of the tissues to 1 pg/ml of bovine PTH-(1-84) induced a cyclic change of G6PD activity, whereas neither carboxyl-terminal PTH nor other hormones tested showed such activity. After a 16-min exposure to bovine PTH-(1-84), the peak height of each cycle began to decrease until it disappeared at 34 min. The second exposure to this hormone at 46 min reinduced a similar cyclic change with a similar peak, indicating full viability of the cells. When bovine PTH-(1-84) was incubated with an excess amount of anti-bovine PTH antibody, the PTH-induced G6PD activity was completely abolished. Throughout a 14-min exposure to either human PTH-(1-84), human PTH-(1-34) or bovine PTH-(1-84), similar cyclic changes were observed with the constant peak height regardless of the dose (10(-16)-10(-12) M), although the cycle length shortened progressively as the dose was increased. They were equipotent on a molar basis between the concentrations of 10(-16) and 10(-13) M at 6 min of hormone exposure. The present data demonstrate that the cytochemical bioassay of PTH in a vitamin D-depleted animal is based on a dose-dependent difference in the time course of G6PD activity.

Animals↗

The influence of a protein synthesis inhibitor on sister-chromatid exchange in the plant Vicia faba.

Cycloheximide strongly antagonizes the induction of sister-chromatid exchange by mitomycin C in Vicia faba root tips. This behavior is analogous to that previously observed in mammalian cells (Sono and Sakaguchi, 1981) and suggests that newly synthesized protein is also required for recombination between sister DNA molecules in plants. Conversely hydroxyurea is shown to increase the frequency of both spontaneous and induced sister-chromatid exchange. Based on these results, possible mechanisms underlying sister-chromatid exchange formation in plants are discussed with special emphasis on the absence of DNA polymerase beta in somatic tissues.

Chromosome Aberrations↗

Altered platelet alpha 2 adrenoreceptor in acute myocardial infarction and its relation to plasma catecholamine concentrations.

Changes in platelet alpha 2 adrenoreceptors and their relation to plasma catecholamine concentrations were studied in 11 patients with acute transmural myocardial infarction. A radiolabelled alpha 2 adrenoreceptor antagonist, [3H]-yohimbine, was used to assay alpha 2 adrenoreceptors on platelet membranes, and plasma catecholamine concentrations were measured by high performance liquid chromatography. The number of platelet alpha 2 adrenoreceptors, the dissociation constant, and plasma noradrenaline and adrenaline concentrations were studied 6.6 (3.3) (mean (SD)) hours after the onset of acute myocardial infarction and one month later. The mean (SD) number of adrenoreceptors increased significantly from 94.5 (50.5) fmol/mg protein immediately after infarction to 157.0 (65.7) fmol/mg protein one month later. The dissociation constant, however, did not change significantly (4.33 (1.40) nmol/l vs 4.37 (1.22) nmol/l). Raised noradrenaline (5.60 (4.37) nmol/l) and adrenaline (0.28 (0.14) nmol/l) concentrations had fallen significantly to normal values (1.21 (0.67) and 0.09 (0.05) nmol/l respectively) a month after infarction. The decrease in the number of alpha 2 adrenoreceptors soon after infarction may be beneficial because such a change will reduce the strength of various reactions to catecholamines, such as vasoconstriction.

Aged↗

Age-dependent changes in warfarin tissue distribution.

Whole blood levels, serum protein binding and tissue concentration following intravenous administration of warfarin were investigated in 1-d-old, 1-, 3- and 8-week-old rats to determine the drug disposition in the growth process. It was shown that the clearance of warfarin in 1-d-old or 1-week-old rats was considerably lower than that in 3- or 8-week-old rats. The decrease in clearance in infant and young rats was considered to be caused by the immaturity of the physiological function of the liver to remove exogenous compounds. The distribution volume in 1-d-old or 1-week-old rats was larger than that in 3- or 8-old rats. The percentages of serum free warfarin in 1-d-old and 1-week-old rats were about twice those in 3- and 8-week-old rats. The increased distribution volume in infant rats was considered to be caused by a lower serum protein binding in these rats.

Aging↗

Study of nasal surface basophilic cells in patients with nasal polyp.

Surface basophilic cells in samples obtained from the inferior concha of nasal polyp patients were examined microscopically. Although the cells were believed to be specific to nasal allergy patients, we were also able to observe them in nasal polyp patients without nasal allergy. These cells were found in 5% of normal controls, in 14% of patients with chronic sinusitis without nasal polyp, in 65% with nasal polyp and in 91% with nasal allergy. In patients with unilateral nasal polyp the surface basophilic cells increased on the side with nasal polyp but not on the side without nasal polyp. As the nasal polyp grew in size, so the number of cells grew. After the polyp was removed, the cells decreased appreciably in number. With regard to other nasal diseases, surface basophilic cells were observed in 80% of tracheotomized patients, in 88% of laryngectomized patients due to laryngeal cancer, in 100% of patients with a tumor in nasal cavity, in 100% of patients with irradiation treatment of the nasal cavity and in 90% of patients with atrophic rhinitis. The surface basophilic cells seem to increase in number through some mechanism induced by a blockage of nasal airway by nasal polyp.

Basophils↗