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Biomedical subjects

S Tsukamoto

Publications and source records attributed to S Tsukamoto.

At least 109 records · Page 6Linked to original sources

Inhibitory effects of bestrabucil, a conjugate of chlorambucil and estradiol, on the production of androgen-induced growth factor(s) by Shionogi carcinoma 115 cells.

It is known that diffusible trophic factors play an important role in both the normal and cancerous growth regulatory processes of hormone-responsive cells such as are found in the prostate and mammary glands. Consequently, it is important to identify whether the production of such growth factors is affected by administration of therapeutic agents. We examined the effect of bestrabucil, a benzoate of an estradiol-chlorambucil conjugate, on the production of growth factor(s) by Shionogi carcinoma 115 (SC-115) cells, an androgen-responsive cultured cancer cell line. We then investigated whether the inhibitory effect found was specific to bestrabucil, or if it was also produced by a mixture of the 2 compounds, estradiol and chlorambucil. Bioassay employing BALB/3T3 cells demonstrated the presence of two kinds of growth factor in the conditioned medium obtained by culturing SC-115 cells in medium containing 10(-8) M testosterone; these factors could be separated by heparin-sepharose column chromatography using 0.5 M NaCl and 1.1 M NaCl. When the SC-115 cells were cultured in medium containing bestrabucil, at a concentration of 10(-5) M, no growth factor activity was detected in the fraction eluted from the heparin-sepharose column by 1.1 M NaCl. At bestrabucil concentrations of 10(-5)-10(-7) M, concentration-dependent inhibition of growth factor production by SC-115 cells could be demonstrated by 3H-thymidine uptake assay. However, this inhibitory effect could not be demonstrated using only a mixture of estradiol and chlorambucil.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

Simultaneous measurement of alcohols and hydrogen cyanide in biological specimens using headspace gas chromatography.

We attempted to analyze biological specimens simultaneously for alcohols and hydrogen cyanide. A headspace gas chromatographic method with thick film wide bore column (PEG 20M) for the simultaneous determinations of methanol, ethanol, n-propanol and hydrogen cyanide in blood has been developed. This method was applied for the determinations of methanol, ethanol and hydrogen cyanide in a forensic autopsy case and animal experiments.

1-Propanol↗

[Concentrations of ethanol and ethanol metabolites and symptoms of acute alcohol-intoxicated patients].

Five patients who presented to an emergency room and did not have other injury and disease with acute alcohol intoxication were analyzed about blood and urine ethanol, acetaldehyde, acetate and acetone levels. The average concentrations of ethanol, acetaldehyde, acetate and acetone in blood were 37.0 mM (1.7 mg/ml), 18 microM, 1.00 mM and 18 microM, respectively and the concentrations in urine were 50.8 mM (2.3 mg/ml), 37 microM, 0.79 mM and 47 microM, respectively. Clinical symptoms were concerned with both ethanol concentration and concentrations of ethanol metabolites. Their symptoms of acute alcohol-intoxicated patients were caused by the ethanol concentrations which was less than the levels reported in early studies.

Acetaldehyde↗

[Diagnosis of the pancreatic diseases by intraductal ultrasound of the pancreas--with special reference to clinical cases difficult to diagnose differentially pancreatic diseases by the endoscopic retrograde pancreatography].

We examined the usefulness of the intraductal ultrasound (IDUS) examinations by comparing the IDUS images with the endoscopic retrograde (ER) pancreatograms. We inserted an IDUS probe with 30 MHz at frequency transpapillary into the main pancreatic duct (MPD) in 105 cases with pancreatic diseases (30 cancers, 30 mucin-producing tumor, 3 islet cell tumor, 1 pancreatic serous cyst adenoma, 1 pancreatic teratoma, 1 pancreatic solid and cystic tumor and 39 chronic pancreatitis). All 105 cases were performed ER pancreatography. Sixty-four of 105 cases (22 cancers, 20 mucin-producing tumor, 3 islet cell tumor, 1 pancreatic serous cyst adenoma, 1 pancreatic teratoma, 1 pancreatic solid and cystic tumor and 16 chronic pancreatitis) were operated and the IDUS images were compared with the corresponding histopathological sections. The usefulness of the IDUS examinations of the pancreatic diseases were the following cases; differential diagnosis between benign and malignant cases with localized stenosis of the MPD, differential diagnosis of the cases with displacement of the MPD, and the diagnosis of the intraductal extent and of invasion of the tumor in the mucin-producing tumor of the pancreas with the dilation of the MPD. IDUS examinations are performed by the IDUS probe with high frequency, so the indications of the IDUS examinations are to detect the small lesions in the pancreas.

Cholangiopancreatography, Endoscopic Retrograde↗

Synthesis and structure-activity studies of a series of spirooxazolidine-2,4-diones: 4-oxa analogues of the muscarinic agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione.

A series of spirooxazolidine-2,4-dione derivatives related to the putative M1 agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione (RS86; 1) were synthesized. The compounds were evaluated as cholinergic agents in in vitro binding assays and in in vivo pharmacological tests including antiamnesic effects using scopolamine-treated mice, hypothermia, and salivation in mice. Four compounds (5a,c,f and 17a) exhibited affinity for cortical M1 receptors and reversed scopolamine-induced impairment of mouse passive avoidance tasks, as did 1. Among these compounds, only 5a exhibited M1-receptor stimulating activity in pithed rats. Structural requirements for muscarinic activity in this series of spirooxazolidine-2,4-dione derivatives were as strict as those reported for spirosuccinimide derivatives including 1. The antiamnesic dose of 3-ethyl-8-methyl-1-oxa-3,8-diazaspiro[4.5]decane-2,4-dione (5a) was 2 orders of magnitude lower than the doses inducing hypothermia and salivation, in contrast to 1 for which the former dose was only 5-10-fold lower than the latter. These results suggest that the 8-azaspiro[4.5]decane skeleton represents a useful template for designing new muscarinic agonists as antidementia drugs.

Amnesia↗

Changes in free and bound alcohol metabolites in the urine during ethanol oxidation.

Free and bound ethanol, acetaldehyde, acetate, acetone and methanol in urine during alcohol oxidation were analyzed by means of a head space gas chromatography. Four healthy male volunteers drank beer for 20 min with 16 ml/kg for non-flushers (A, B) and 8 ml/kg for flushers (C, D). In the urine, the highest bound ethanol levels were between 0.5-1.1 mM for the non-flushers (NF) and 0.2-0.3 mM for the flushers (F). The urine free ethanol levels were 23-70 times as high as bound ethanol levels. The maximum free acetaldehyde in urine was 11-13 microM for the NF and 26-55 microM for the F. The urine bound acetaldehyde levels were 4-5 microM for the NF and 7-15 microM for the F. Urine acetaldehyde existed in free forms at 2.4-3.6 times as high concentrations as in bound forms during ethanol oxidation. The urine free acetate ranged between 0.3-2.0 mM. The bound acetate varied between 0.7-1.1 mM. The urine free methanol at 70-110 microM before the intake increased to 104-180 microM. The bound methanol reached to 78-126 microM from 48-97 microM before the intake. Ethanol levels in the urine were ethanol dose-dependent, whereas it was thought that free and bound acetaldehyde or acetate reflected individual metabolic abilities and not the amount of ethanol consumed.

Acetaldehyde↗

Effects of seed saponins of Thea sinensis L. (Ryokucha saponin) on alcohol absorption and metabolism.

We evaluated the effects of the seed saponins of Thea sinensis L. on alcohol absorption and metabolism in rats and mice. An ethanolic extract from the seeds of T. sinensis was orally administered to the rats 1 hr before or 0.5 hr after administration of ethanol (2 g/kg), and the blood ethanol assayed 0.5, 1, 2, 3, and 4 hr after ethanol administration. The ethanol level decreased after both pre- and post-administration of the extract. The extract was further purified to obtain a saponin fraction which was orally administered to mice 1 hr before ethanol administration. Blood, liver, and stomach were obtained 0, 1, 3, and 6 hr after ethanol administration, and the ethanol, acetaldehyde, acetate, and acetone concentrations in each specimen were measured by head space gas chromatography. The saponin fraction decreased the ethanol levels in the blood and liver but increased that in the stomach five-fold over the control level, suggesting inhibition of alcohol absorption. The ethanol disappearance time from the blood was shortened, suggesting the promotion of alcohol disappearance. The acetate and acetone levels were unaffected. However, the acetaldehyde level decreased in the blood, liver, and stomach. The decreases in the ethanol and acetaldehyde levels in the liver suggested the protective effects of the seed saponins on the liver. The saponins did not directly inhibit hepatic alcohol dehydrogenase activity. The seed saponins of T. sinensis seem to suppress alcohol absorption by slowing gastric emptying and by inhibiting absorption across the cell membranes of the digestive tract.

Acetaldehyde↗

An analysis of low side molecular weight proteins in human seminal plasma by capillary electrophoresis.

Semen was obtained from 45 healthy males, and its plasma proteins of low side molecular weight obtained by filtration with a Molcut II (Millipore) were analyzed by means of capillary electrophoresis (CE) for an application to forensic medicine, with a phosphoric acid of pH 4.5 and a column of 100 cm x 75 microns ID. There were noted 27 to 36 peaks on the chromatograms, two sections of which showed individual differences in the chromatographic patterns. The chromatographic patterns between 20.0 and 22.0 minutes were classified into 2 groups: I (66.7%) and II (33.3%). The main peak appearing at about 36 minutes was divided between two patterns: A (53.3%) and B (46.7%). The serum, saliva, and vaginal fluid were also analyzed for low-side-molecular-weight proteins by means of capillary electrophoresis, but their levels contained low and their chromatographic patterns different from those of seminal plasma. The patterns of the whole seminal plasma, saliva and serum with pH 7.0 phosphate buffer were different and appeared to be applicable for identifying such samples.

Adult↗

[The partial resection of lung with MULTIFIRE ENDO GIA 30 under the thoracoscopy].

MULTIFIRE ENDO GIA 30 was a newly auto suture developed by US surgical c.o., A 27-year-old man was admitted for right spontaneous pneumothorax in our hospital. We performed the partial resection of lung with this new auto suture under the thoracoscopy. Condition of patient after operation was very good, and he could discharge in short hospitalization. We concluded that this new auto suture was entirely reversible and safety.

Adult↗

[A case report of mediastinal teratoma complicated with cardiac tamponade].

A 10-year-old Japanese boy was admitted to our hospital with complaints of the sudden and severe chest pain having occurred when he caught a ball on his chest. A chest X-ray film and MRI made a diagnosis of cardiac tamponade caused by perforation into the pericardial sac of a mediastinal teratoma and pericardial drainage was carried out. Pericardial effusion showed cloudy yellow and CA 19-9 level in the effusion was 6, 538.2 U/ml. The tumor was extirpated after recovery of his general condition. The tumor was consisted of solid material (5 x 6 x 3 cm) and of cystic part (4 x 6 x 0.8 cm) involving of viscous yellowish fluid. Microscopic sections showed ulcer with bleeding, granulation and pancreatic tissue. Histopathological diagnosis was benign mature teratoma. Including this case, fourteen cases of mediastinal teratomas with cardiac tamponade have been reported and this is the youngest case. Pancreatic tissue were observed histopathologically in most cases and it was thought that autodigestion by digestive enzyme from pancreas was major cause of perforation of the tumor into the pericardial sac.

Cardiac Tamponade↗

[Long-term patency of aorto-coronary saphenous vein grafts].

One hundred eighty-two cases with 814 aorto-coronary saphenous vein grafts were studied according to coronary risk factors (smoking, hypertension, hyperlipidemia, diabetes mellitus, obesity and family history). The patency rates of all cases were as follows, early-term (within one year after operation): 92.3%, mid-term (within 5 years after operation) 80.7%, long-term (more than 5 years after operation): 66.0%. Coronary risk factors have great influence upon the mid- and long-term patency, especially upon the latter. The long-term patency rate of the grafts complicated with hyperlipidemia was 57.4% and that without hyperlipidemia was 81.8% (p less than 0.01). Hyperlipidemia, complicating 55.5% of all cases, was one of the most influential factors on the patency and also the most difficult one to be controlled. In the United States and Europe, many cases were complicated with hyperlipidemia, and it was considered that the poor patency of the saphenous vein grafts in those countries was due to this fact. Pathological studies revealed that hyperplasia of intima and media, characteristics of venosclerosis, appeared frequently in the saphenous vein grafts having more than three risk factors, and that the factors had effect not only upon arteries but also upon veins. So we conclude that saphenous vein grafts are the materials of good long-term patency, and that the control of the risk factors, particularly hyperlipidemia, is the key to improve the patency.

Adolescent↗

[Surgical techniques of ventricular assist device].

Since October 1982 to April 1990, we had 16 ventricular assist device (VAD) cases in our institute. Using this VAD system that was produced by Nippon Zeon company, surgical techniques for cannulation and de-cannulation could be made very easily, and connection between cannulae and pump also could be performed quickly. In this article, the actual surgical techniques and the know-how were illustrated in detail. If this techniques can be more accustomed, the clinical results of VAD cases will be improved.

Cardiac Catheterization↗

Concentrations of blood and urine ethanol, acetaldehyde, acetate and acetone during experimental hangover in volunteers.

Blood and urine samples were analyzed for ethanol, acetaldehyde, acetate and acetone during experimental hangover in 6 healthy male volunteers (A, B, C, D, E, F). They drank freely for some 4 hr. In flushers (A, F) at 9 hr after ingestion (ethanol: 92 g, 1.2 g/kg and 1.3 g/kg), acetaldehyde levels were low in the blood, but high in the urine (37 microM, 45 microM). Heavy drinkers, non-flushers of B (ethanol: 176 g, 2.5 g/kg), C (157 g, 2.4 g/kg) and E (182 g, 2.9 g/kg) had a slightly high [lactate]/[pyruvate] ratio and 3-hydroxybutyrate in the blood at 11 hr after alcohol ingestion. Blood ethanol levels were dose dependent and blood acetaldehyde in B and C had a slightly high 6.3 microM and 8.0 microM 9 hr later, respectively. B, C and E had a high urine acetone concentration (100 microM over) in hangover. In C, in particular, urine acetate and acetone levels were unusually high. The ratio in blood (urine) among alcohol metabolites at 9 hr after drinking was approximately ethanol 1000 (1000): acetaldehyde 0.2-1.0 (0.1-5.9): acetate 36-163 (22-1554): acetone 1-11 (3-47).

Acetaldehyde↗

Pharmacological studies on novel muscarinic agonists, 1-oxa-8-azaspiro[4.5]decane derivatives, YM796 and YM954.

We have investigated the pharmacological profiles of the novel muscarinic agonists, 1-oxa-8-azaspiro[4.5]decane derivatives, YM796 (2,8-dimethyl-3-methylene) and YM954 (2-ethyl-8-methyl-3-oxo). These compounds, like the putative M1 agonists, RS86 and AF102B, inhibited [3H]pirenzepine binding to cerebral cortical membranes in the micromolar range and weakly inhibited [3H]quinuclidinyl benzylate binding to cerebellar membranes. Their (-) isomers had Hill coefficients lower than 1.0. (+/-)-YM796, (+/-)-YM954 and RS86, but not AF102B, stimulated phosphoinositide hydrolysis in hippocampal slices, an effect which is mainly linked to M1 receptors. (+/-)-YM796 (0.031 mg/kg p.o.) and (+/-)-YM954 (0.016 mg/kg p.o.) reversed the cognitive impairment in nucleus basalis magnocellularis-lesioned rats in a passive avoidance task more effectively than did RS86 and AF102B. Similar results were obtained in scopolamine-treated rats. Finally, (+/-)-YM796 was weaker than (+/-)-YM954 and RS86 in the induction of tremor, hypothermia and contraction of isolated ileum, which are mainly mediated by M2 and/or M3 receptors. These results suggest that (+/-)-YM796, (+/-)-YM954 and RS86 have M1 agonistic activity in central nervous system and that (+/-)-YM796 has relatively weak M2 and/or M3 agonistic activity.

Animals↗

[Induction of Cd and Zn-thionein in a clonal osteogenic cell, MC3T3-E1].

Clone MC3T3-E1 cells at various differentiation stages were exposed to 0.44-13.3 microM Cd or 50-175 microM Zn in culture medium. After a 2-h culture period, the amount of Zn accumulated in the cells was shown to be larger than that for Cd, but the production of Zn-thionein was much less compared with that of Cd-thionein. After a 24-h incubation period, the synthesis of Zn-thionein increased markedly at levels of 150 microM Zn or greater, Cd induced metallothionein (MT) synthesis in a dose-dependent manner at 0.44 microM Cd or greater. Since calcified cells differentiated into osteoblastic cells also produced MT, osteoblasts were confirmed to have an ability to induce MT synthesis. Initiation of production of Cd-or Zn-thionein in the cells occurred at an accumulation of about 0.4 nmol Cd and 2.5 nmol Zn/mg cytosol protein. The ratios of thionein-binding Cd/Cd accumulated in the cytosol and thionein-binding Zn/Zn accumulated in the cytosol were 0.11 mol/mol and 0.067 mol/mol, respectively. These results show that the concentration of accumulated Zn necessary for initiating production of MT is about six times that of Cd and one molecule of Cd induces thionein about 1.6 times as effectively as one molecule of Zn does.

Cadmium↗

Effects of amino acids on acute alcohol intoxication in mice--concentrations of ethanol, acetaldehyde, acetate and acetone in blood and tissues.

Condensation reactions between some SH-amino acids (L-and D-cysteine 1%) and acetaldehyde (50 microM) were studied in vitro experiment. In the aqueous solution, free acetaldehyde was reduced to 41.3% by L-cysteine and to 36.4% by D-cysteine. In the reaction with human blood medium, after the medium was deproteinized with perchloric acid reagent, acetaldehyde was reduced to 47.0% by L-cysteine and to 43.8% by D-cysteine. D-Cysteine appears to have great stability of reacting acetaldehyde. In vitro experiment reactability for D-cysteine exhibited 3-8% higher than that for L-cysteine. Next, effects of some amino acids on alcohol metabolism were studied in male ICR mice. The animals were given ethanol through a gastric catheter at a dose of 2 g/kg and they were intraperitoneally injected L-cysteine (300 mg/kg), D-cysteine (300 mg/kg), L-alanine (300 mg/kg) and control (saline), respectively in the period of one hour before the injection of ethanol. Blood and tissues samples were analyzed for ethanol, acetaldehyde, acetate and acetone during alcohol intoxication in mice by head space gas chromatography. In the groups administered D-cysteine and L-cysteine, the mice showed a definitely faster oxidation and disappearance of ethanol. Especially in the D-cysteine group, ethanol levels in blood, liver and brain remained lower than that in the other groups (p less than 0.01). Acetaldehyde levels in blood, liver and brain remained low by L-cysteine. Ethanol metabolites during alcohol oxidation by chemical reactabilities of L- and D-cysteine showed different distribution in the mice, respectively. In the mice received L-alanine, acetate and acetone levels in blood, liver and brain were distinctly reduced (p less than 0.01). L-Alanine is reported to supply an abundance of pyruvic acid that performs the NAD-generating system. NAD produced is introduced to alcohol metabolism and the TCA cycle. It was thus presumed that the L- or/and D-cysteine, and L-alanine was effective in acute alcohol intoxication by heavy drinking.

Acetaldehyde↗