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Biomedical subjects

T Sakamoto

Publications and source records attributed to T Sakamoto.

At least 901 records · Page 50Linked to original sources

Effects of gammalinolenic acid on plasma lipoproteins and apolipoproteins.

Nineteen hypercholesterolemic patients (10 without and 9 with hypertriglyceridemia) were given evening primrose oil rich in gammalinolenic acid (GLA, 18: 3n - 6), in a placebo controlled cross-over design, over 16 weeks (8 + 8 weeks), with safflower oil as the placebo. During supplementation with evening primrose oil, dihomogammalinolenic acid (20: 3n - 6) increased in plasma lipids and red blood cells, and in subjects without hypertriglyceridemia there was a significant decrease in low density lipoprotein-cholesterol and plasma apolipoprotein B compared with the levels observed during safflower oil administration. Our results confirmed that evening primrose oil is effective in lowering low density lipoprotein in hypercholesterolemic patients.

Adult↗

Genomic DNA with transformation-related activity and melanoma antigen expression.

We have analyzed the mouse melanoma antigen with monoclonal antibodies established by syngeneic immunization. To further understand the structure of this antigen at a molecular level, we have cloned the genomic DNA controlling the expression of melanoma antigen by cosmid library transfection and a monoclonal antibody. In the process of analyzing this DNA fragment we found that it contained a gene related with transformation, which was proved by tumor formation in nude mice inoculated with NIH/3T3 transfectants of this DNA fragment. We discuss the structure of the gene product based on the deduced amino acid sequence of cDNA, which maps the genome bearing transformation-related activity.

Animals↗

Aortic regurgitation associated with hypertrophic cardiomyopathy: a colour Doppler echocardiographic study.

The frequency, severity, and cause of aortic regurgitation were assessed by colour Doppler and cross sectional echocardiography in 87 patients (mean SD) age 57 (12) years) with hypertrophic cardiomyopathy, and 48 age matched controls (57 (8) years). Aortic regurgitant murmurs were recorded in only three of 87 patients and in none of the controls. Colour Doppler echocardiography showed an aortic regurgitant signal in 20 (23%) of the patients and three (6%) of the 48 controls. The colour Doppler signals typical of aortic regurgitation were limited to the left ventricular outflow tract. There were no significant differences between patients with hypertrophic cardiomyopathy with and without aortic regurgitation in terms of age (59 years v 56 years), blood pressure (140/84 mm Hg v 136/80 mm Hg), aortic diameter (34 mm v 33 mm), or frequency of calcification of the aortic valve (15% v 10%) and of systolic anterior motion of the mitral valve with mitral-septal contact (25% v 16%). On cross sectional echocardiograms, the degree of septal protrusion into the left ventricular outflow tract during systole was significantly more prominent (15 v 10 mm), and the portion of the basal septum that protruded most deeply into the left ventricular outflow tract was significantly closer to the aortic annulus in patients with aortic regurgitation than in those without it (11 v 14 mm). Mild aortic regurgitation was found in almost a quarter of patients with hypertrophic cardiomyopathy. The regurgitation was related to the morphological abnormality of the left ventricular outflow tract.

Adolescent↗

Regional blood flow in the brain and spinal cord of hypothermic rats.

[14C]butanol tissue uptake was used to measure simultaneously regional blood flow in three regions of the brain (cerebral and cerebellar hemispheres and brain stem) and in five levels of the spinal cord in 10 normothermic rats (group A) and in 10 rats in which rectal temperature had been lowered to 27.7 +/- 0.3 degrees C by applying ice to the torso (group B). Pentobarbital sodium anesthesia was used. Mean arterial blood pressure varied minimally between groups as did arterial pH, PO2, and PCO2. In group A, regional spinal cord blood flow (rSCBF) varied from 49.7 +/- 1.6 to 62.6 +/- 2.1 ml.min-1.100 g-1; in brain, regional blood flow (rBBF) averaged 74.4 +/- 2.3 ml.min-1.100 g-1 in the whole brain and was highest in the brain stem. rSCBF in group B was elevated in all levels of the cord by 21-34% (P less than 0.05). rBBF, however, was lowered by 21% in the cerebral hemispheres (P less than 0.001) and by 14% in the brain as a whole (P less than 0.05). The changes in calculated vascular resistance tended to be inversely related to blood flow in all tissues. We conclude that rBBF is depressed in acutely hypothermic pentobarbital sodium-anesthetized rats, as has been noted before, but that rSCBF rises under these experimental conditions. The elevation of rSCBF in hypothermic rats confirms our previous observations.

Animals↗

Studies on the osmophilic fungus Wallemia sebi as an allergen evaluated by skin prick test and radioallergosorbent test.

Recently, Wallemia sebi, a species of osmophilic fungi, has been abundantly detected in house dust using low water activity media. In this study, allergenic activity of W. sebi was assessed by skin prick test and radioallergosorbent test (RAST) in 74 asthmatic patients ranging from 6 to 32 years of age. Aspergillus fumigatus and house dust were used for comparison. In skin prick test, W. sebi extract, A. fumigatus extract and house dust extract elicited positive reactions in 4 (5.4%), 4 (5.4%) and 51 (68.9%) patients, respectively. RAST showed positive results in 14 subjects (18.9%) for W. sebi extract, in 8 (10.8%) for A. fumigatus extract and in 59 (79.7%) for house dust extract. These results indicated that some asthmatic individuals showed immediate-type hypersensitivity to W. sebi, and which means this fungal species may be of importance to atopic diseases as a causative agent.

Adolescent↗

Biological properties of an initial degradation product of insulin by insulin-degrading enzyme.

We previously reported on the degradation of monocomponent porcine insulin by affinity-purified pig skeletal muscle insulin-degrading enzyme (IDE) and on the detection and HPLC separation of the initial degradation product (peak VI). Using relatively high concentration of insulin, peak VI appeared rapidly at 30 sec of incubation, whereas other peaks were not detected within 5 min of incubation. Performate oxidation studies suggested that peak VI is composed of a cleaved A-chain and an intact B-chain. To assess whether the initial degradation product of insulin generated by IDE preserves biological properties, we analyzed several insulin-like activities of peak VI. It had a hypoglycemic effect on rats. In vitro, it bound to the insulin receptors of rat adipocytes and stimulated glucose oxidation there. It also strengthened insulin receptor kinase activity in insulin receptors from rat liver and human placenta. Its biological potency, however, was 1/40th to 1/160th that of insulin itself. This is probably due to reduced affinity for the insulin receptor, since it had 2.5% of insulin's ability to both bind to the receptor and stimulate glucose oxidation. Moreover, peak VI had all of insulin's agonistic effect on glucose oxidation when used at a higher concentration. On the other hand, cross-linking analysis suggested that peak VI preserves almost the same affinity for IDE as does insulin. These results suggest that pig skeletal muscle IDE may cleave peptide bonds within the A-chain early in insulin degradation, generating peak VI; this then serves as the next substrate of IDE while exerting reduced insulin-like activity, and peak VI is converted to several relatively low mol wt products.

Adipose Tissue↗

Pharmacological study of phospholipase A2-induced histamine release from rat peritoneal mast cells.

The effect of some drugs on phospholipase A2 (PLA2)-induced histamine release from rat peritoneal mast cells was investigated. 1. PLA2 (Naja naja) caused the release of histamine from rat peritoneal mast cells in a dose related fashion. 2. The release of histamine by PLA2 was decreased by the removal of each of calcium and glucose from the reaction medium (Tyrode's solution). 3. p-Bromophenacyl bromide and mepacrine, PLA2 inhibitors, inhibited the release of histamine caused by PLA2. 4. Cinnarizine and nifedipine, calcium channel blockers, and oxatomide, KC-404, tranilast and disodium cromoglycate, anti-allergic agents, also inhibited the PLA2-induced histamine release. 5. When prednisolone (0.5 mg/kg) was administered i.p. 2, 3 and 4 h prior to the harvest of the mast cells, the amount of histamine released by PLA2 ex vivo was significantly decreased. Hydrocortisone, prednisolone and dexamethasone clearly inhibited the release of histamine from mast cells when they were administered 4 h prior to harvest of the cells.

Acetophenones↗

A novel heterocyclic compound. Synthesis and reactivities of an oxazolo[3,2-a]thieno[3,2-d]-pyrimidine derivative.

A practical preparation of 2,3-dihydro-5H-oxazolo[3,2-a]thieno[3,2-d]pyrimidin-5-one (2) from methyl 3-aminothiophene-2-carboxylate in two steps was developed. The addition reactions of various nucleophiles to 2 were investigated and oxazole-ring-opened compounds were produced (5, 6, 12, 13 and 14). Desulfurization reaction of 2 with Raney Ni gave an oxazolo[3,2-a]pyrimidine derivative (15). It was found that 2 showed potent anti-gastric secretion activity.

Animals↗

Condensed thienopyrimidines. I. Synthesis and gastric antisecretory activity of 2,3-dihydro-5H-oxazolothienopyrimidin-5-one derivatives.

A practical preparation of various 2,3-dihydro-5H-oxazolo[3,2-a]thieno[3,2-d]-, [3,4-d]-, and [2,3-d]pyrimidin-5-one derivatives was developed starting from the corresponding aminothiopheneesters in two steps, and their chloro-substituted derivatives were prepared. These compounds were evaluated for gastric antisecretory activity in pylorus-ligated rats, compared to the anti-ulcer standard, cimetidine, and their structure-activity relationships are discussed.

Animals↗

Condensed thienopyrimidines. II. Synthesis and gastric antisecretory activity of thiazole and polymethylene condensed thienopyrimidine derivatives.

Thiazolo[3,2-a]thieno[3,2-d]-, [3,4-d]- and [2,3-d]pyrimidin-5-one derivatives (6, 11 and 16), and polymethylene condensed thieno[3,2-d]-, [3,4-d]- and [2,3-d]pyrimidin-5-one derivatives (19-21), in which the oxygen atom of the oxazolidine moiety in 3 was replaced by a sulfur atom or methylene groups, were synthesized and evaluated for gastric antisecretory activity in pylorus-ligated rats. The structure-activity relationships of these compounds are discussed.

Animals↗

[Behavior of chlorpheniramine in vivo after administration of d- and l-chlorpheniramine maleate].

A high performance liquid chromatographic (HPLC) method was developed for the determination of chlorpheniramine (I) in the plasma. By this method, 1 ng of I could be measured. Plasma levels of I were determined by the HPLC method after oral administration of d-chlorpheniramine maleate (II) or l-chlorpheniramine maleate (III) to healthy subjects and dogs. Plasma levels of I brought about by oral administration of II were evidently higher than those by III both in humans and dogs. On the other hand, there was no difference in plasma levels of I when II or III was injected intravenously into dogs. Therefore, it was considered that the discrepancy in plasma levels of I after oral administration of II and III to dogs was neither due to a difference in elimination rate nor a distribution volume but rather in first-pass effect in absorption process. The result observed in the human study could be also explained in the same way as that in dogs.

Administration, Oral↗

[Non-crystallinity determination by thermal analysis of freeze-dried cephalothin sodium].

Cephalothin sodium (CET-Na) prepared according to the conventional freeze-drying methods is known to easily develop color during storage. Since amorphous CET-Na has been reported to be markedly unstable, the color development is thought to be due to the presence of traces of CET-Na in an amorphous state observed with scanning electron microscopy. Quantitation by use of the powder X-ray diffractometry of such traces of amorphous CET-Na has proved to be of little use. Thermogravimetry (TG) and differential scanning calorimetry (DSC) have demonstrated that the freeze-dried CET-Na by the conventional methods contains three types of CET-Na: amorphous (unstable phase), quasi-crystalline (metastable phase) and crystalline (stable phase). Pyrolysis initiation temperatures of these three types of CET-Na have been demonstrated to become higher in this order. A new parameter for the evaluation of non-crystallinity of CET-Na has been introduced, in which the ratio is calculated from the data of the total weight loss observed through the pyrolysis of both amorphous and quasi-crystalline CET-Na against the total weight loss of all components during the pyrolysis of sample specimen. The ratio thus calculated is defined as "non-crystallinity". This new parameter has successfully been introduced to establish a good correlation to the degree of increasing color intensity with aging of freeze-dried CET-Na.

Calorimetry, Differential Scanning↗

[Crystallization and subsequent freeze-drying of cephalothin sodium by seeding method].

Cephalothin sodium (CET-Na) in crystals can be obtained by freezing the aqueous solution and subsequent warming at a fixed temperature for facilitating crystallization prior to vacuum application for drying. The product has, however, been found to unavoidably contain traces of the amorphous CET-Na, which causes a rapid color development during storage. By using thermal analysis, differential scanning calorimetry (DSC), electric conductometry, and polarized light cryomicrographic techniques, the solubilities in water, freezing point, eutectic point, and melting behavior of CET-Na in aqueous solution were investigated. The investigation demonstrated that CET-Na in supersaturated aqueous solution is very stable, and that seeding with microcrystalline CET-Na to the supersaturated solution and subsequent cooling of the mixture till its freezing point gives neither any evidence for crystallization nor for growth of the seed crystals. The freeze-drying of CET-Na in the supersaturated solution after seeding has been demonstrated to give crystalline CET-Na containing neither of amorphous nor of quasi-crystalline form.

Cephalothin↗

[Topical chemotherapy of chronic periodontitis using controlled-release insert containing ofloxacin (PT-01) without root planing].

Topical chemotherapy of periodontal disease using several drug delivery systems (DDS) is currently being attempted. PT-01 is a DDS which consists of fast- and sustained- release parts containing ofloxacin as an antibacterial agent. Since PT-01 was found to sustain the antibacterial effect for 7 days in a periodontal pocket, it was used tor periodontal patients without root planing or scaling in this study. PT-01 and a placebo were applied to two separate and opposite pockets of 46 patients, once a week from the first visit (week 0) to week 3. The clinical parameters (plaque index, gingival index, tooth mobility, bleeding on probing, pus discharge, and probing depth) were evaluated from weeks 0 to 4. At the end of the test (week 4), global improvement at the two sites was assessed. The clinical parameters and the global improvement of the PT-01 and placebo-treated sites were compared statistically. All parameters at the PT-01 sites except for tooth mobility showed much greater improvement than at the placebo sites. The global improvement of PT-01 sites was also significantly greater than that of the placebo sites. No side effects could be seen in patients treated with PT-01. These results indicate that topical chemotherapy using PT-01 could be effective and safe for periodontal therapy.

Chronic Disease↗

Attenuated renal production of dopamine in patients with low renin essential hypertension.

Our previous studies have shown that a suppressed pressure natriuresis may contribute to the hypertensive mechanism in patients with essential hypertension (EHT), particularly in low renin patients (LRH). In this study, in order to clarify the role of renal dopaminergic activity in the blunted natriuresis of LRH, the conversion of 1-dopa (DOPA) to dopamine (DA) in the kidneys was investigated in 9 normotensive subjects (NT) and 20 EHT, including 15 normal renin EHT (NRH) and 5 LRH. All subjects were hospitalized and received a constant diet (Na:120mEq, K:75mEq daily). Plasma DOPA concentration (p-DOPA:HPLC-ECD), creatinine clearance (Ccr), urinary excretion of sodium (UNaV) and DA (UDA), as well as fractional excretion of sodium (FENa) were measured before and after the single oral administration of 1-DOPA (400mg). DOPA administration caused a significant increase of p-DOPA, UDA and FENa with undetectable DOPA levels in the urine in EHT. In addition, under the basal condition, UDA correlated positively with p-DOPA or the product of p-DOPA x Ccr, which might reflect the DOPA delivery at the renal proximal tubule. No significant difference was found in p-DOPA and the product of p-DOPA x Ccr among NT, NRH and LRH. However, the ratio of UDA/(p-DOPA x Ccr), which may indicate the conversion from DOPA to DA in the kidneys, was lower in EHT, especially in LRH, than that in NT. These results suggest that a reduced renal conversion from DOPA to DA may contribute to the attenuated natriuresis as well as renal dopaminergic activity in LRH.

Adolescent↗

The effect of hypothermia on regional spinal cord blood flow in rats.

Spinal cord ischemia may accompany surgical procedures on the aorta or vertebral column. Regional spinal cord blood flow (SCBF) was measured at five vertebral levels in the spinal cords of pentobarbital-anesthetized rats based on the distribution of intravenously injected carbon-14-labeled butanol. In seven normal rats, mean SCBF (+/- standard error of the mean) ranged from 52.7 +/- 5.4 to 68.5 +/- 4.9 ml.min-1.100 gm-1 (depending on the level, being lowest at the thoracic levels) and mean arterial blood pressure (MABP) was 126 mm Hg. Corporal hypothermia (mean rectal temperature 28.1 degrees +/- 0.6 degrees C) was induced by cold exposure in seven other rats, and SCBF, measured immediately thereafter, was significantly elevated at all five levels by 52% to 69% compared to the normal group. However, MABP was elevated in the hypothermic group to 165 +/- 4 mm Hg (p less than 0.0001). Therefore, in seven additional hypothermic rats, MABP was maintained at the control level by withdrawal of arterial blood as necessary. In these animals, SCBF at all levels was still significantly elevated compared with the normal group and the values were nearly identical to those measured in the hypertensive hypothermic rats. It was concluded that hemodynamic autoregulation of SCBF is impaired in the presence of moderate systemic hypothermia in pentobarbital-anesthetized rats.

Animals↗

[Antiarrhythmic action of beta-blocking agent in patients with mitral valve prolapse having premature ventricular contractions].

To investigate the origin and evaluate the effect of one of the most potent beta blocker, carteolol, on premature ventricular contractions (PVCs) in patients with mitral valve prolapse (MVP), 21 patients (35 +/- 12 years; mean +/- SD) including 10 with PVCs were studied by simultaneous electrocardiography and echocardiography before and after intravenous injection of carteolol. In all 21 MVP patients including 10 MVP patients with PVCs, carteolol (6 micrograms/kg/2 min, i.v.) caused significant decrease in systolic and diastolic blood pressures and in heart rate. Carteolol markedly (25% or more) reduced frequency of PVCs in four of the 10 patients, but no significant changes in five, and PVCs were increased in frequency in the remaining one. However, in all 21 MVP patients, carteolol did not change left ventricular end-diastolic and end-systolic dimensions, and the degree of MVP nor mitral regurgitant areas evaluated by color Doppler echocardiography. These results were exactly the same as those of the patients with PVCs. In conclusion, intravenous injection of beta-blocker, carteolol, reduced PVCs in 40% of the MVP patients with PVCs, but this antiarrhythmic action is not related to the degree of mitral valve prolapse, or mitral regurgitation evaluated by Doppler method.

Adolescent↗