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Biomedical subjects

S Iwamoto

Publications and source records attributed to S Iwamoto.

At least 145 records · Page 8Linked to original sources

Induction of resistance to TNF cytotoxicity and mitochondrial superoxide dismutase on U-937 cells by 1,25-dihydroxyvitamin D3.

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) dose-dependently inhibited the cytotoxicity of tumor necrosis factor (TNF) in a human monoblastic leukemic cell line, U-937. Combination of TNF and 1,25(OH)2D3 remarkably increased mitochondrial superoxide dismutase (mSOD) of U-937 cells, TNF alone increased it only slightly and 1,25(OH)2D3 alone did not. The cytosolic SOD (cSOD) activity was not changed by TNF or/and 1,25(OH)2D3. The mSOD activity was not inhibited by 2 mM KCN, suggesting that mSOD should be a manganese SOD (MnSOD). These results suggest that 1,25(OH)2D3 may reduce the susceptibility to TNF cytotoxicity of U-937 cells by enhancing the ability of inducing MnSOD by TNF.

Calcitriol↗

Quantitative determination of IgM-rheumatoid factor by enzyme immunoassay--standardization using a serum from a rheumatoid arthritis patient.

A method to standardize the quantitation of IgM-rheumatoid factor (RF) by enzymeimmunoassay (EIA) is presented. Serially diluted sera from rheumatoid arthritis patients were added to immobilized human IgG, and bound IgM-RF was detected by addition of horseradish peroxidase labeled anti-human IgM (HRPOaM). The concentration of IgM-RF which produced half of the maximal absorbance at 492 nm given by a saturating concentration of IgM-RF in the EIA plate, was defined as 1 U/ml. The IgM-RF values of test samples were measured as the dilution of the sample which provided half-maximal absorbance. The IgM-RF values determined by this method coincided with those determined by referring to a standard curve made from a serum containing known amounts of IgM-RF. Differences in IgM-RF values, which were caused by varying preparations of horseradish peroxidase anti-IgM (HRPOaM) were corrected for the binding capacity of each preparation to various concentrations of human IgM adherent to the plate. The IgM-RF values determined by this method correlated well with the RF values determined by latex photometric immunoassay (r = 0.956, p less than 0.001). IgM-RF values determined by EIA were converted into WHO-units by an empirical formula described. The data observed suggest that the method here reported can standardize IgM-RF values obtained by EIA.

Adolescent↗

Gastric mucosal injury induced by chloral hydrate.

Gastric mucosal injury by chloral hydrate (CH) was investigated in the rat. Rats were injected with CH intraperitoneally or subcutaneously. After the CH injection, gastric ulcers appeared in the glandular stomach at 6 h and the ulcer index peaked in 12 h. The minimum dosage of CH to produce ulcers was 400 mg/kg intraperitoneally and 600 mg/kg subcutaneously.

Animals↗

Combination effects of interferon-gamma and cholera toxin on induction of differentiation of an insensitive U-937 clone.

We examined the combination effect of interferon-gamma (IFN-gamma) and cholera toxin and the role of cAMP in the induction of differentiation of a differentiation-insensitive U-937 clone, in which the reactivity to differentiation-inducers was decreased. IFN-gamma (100 units/ml) or cholera toxin (10(-9) M) alone only marginally induced various differentiation-associated characteristics such as NBT-reducing activity, phagocytic activity, a-naphthyl acetate esterase activity and surface markers. However, when combined with each other, they significantly induced these markers. Other cAMP-inducing agents such as prostaglandin E2, forskolin, epinephrine and isoproterenol did not induce NBT-reducing activity, either alone or in combination with IFN-gamma. However, all these cAMP-inducing agents significantly increased intracellular cAMP levels. Tumor necrosis factor, interleukin 6 or granulocyte/macrophage colony-stimulating factor alone did not induce NBT-reducing activity, but they could induce activity when combined with cholera toxin. These results suggest that enhancement of induction of differentiation by cholera toxin in combination with IFN-gamma or other cytokines may not be merely due to increased cAMP levels. There seems to be a transduction signal other than cAMP coupling with cholera toxin to stimulate induction of differentiation of an insensitive U-937 clone.

Cell Differentiation↗

Mechanism of diethyldithiocarbamate-induced gastric ulcer formation in the rat.

Diethyldithiocarbamate (DDC) was injected subcutaneously in the rat and the mechanism of gastric ulcer formation was investigated. DDC induced gastric ulcers in a dose-dependent manner. DDC significantly suppressed gastric mucosal copper-zinc superoxide dismutase (Cu, Zn-SOD) activity at 2 hr. However, manganese-superoxide dismutase (Mn-SOD) activity was not changed. Gastric mucosal blood flow (GMBF) decreased to 52% of the control level at 2 hr after administration of DDC and gradually increased to reach the control level by 7 hr. A Shay rat preparation (4 hr) was used to study gastric secretion. DDC (200, 400 and 800 mg/kg) inhibited acid secretion to about 80% of the control level. Histopathological examination of the gastric mucosa after administration of DDC revealed mucosal congestive findings from 1 hr to 3 hr. These data suggested that the mechanism of DDC-induced gastric ulcer formation may be attributable to a decreased level of GMBF and O2- production owing to decreased SOD activity.

Animals↗

Some aspects of the communicating branch between the musculocutaneous and median nerves in man.

Fascicular arrangement of the human brachial plexus is examined on 2 common cases and 3 peculiar cases in which a communicating branch was observed between the median and the musculocutaneous nerve. The musculocutaneous nerve consitss of spinal nerves from C.5, 6 and 7. The branch to the coracobrachialis receives its fibers from C.7 before it leaves the musculocutaneous nerve in 3 cases and after it leaves the musculocutaneous nerve in one case. In one case, C.7 does not send a branch to the coracobrachialis. The median nerve arises by two roots, one from the lateral cord, and the other from the medial cord of the brachial plexus. In a case in which a communicating branch was observed from the median nerve to the musculocutaneous, the fibers from C.7 join to the median nerve via the medial cord. Thus the median nerve involved all elements of the spinal nerve from C.5 to T.1. The elements of the median and the musculocutaneous nerves, therefore, are not affected by appearance of the communicating branch. The communicating branch between the median and the musculocutaneous nerves, consists of the fibers arose from C.5 and C.6, in all examined cases.

Brachial Plexus↗

[Possible cytotoxic mechanisms of TNF in vitro].

TNF is a protein originally isolated by its ability to induce hemorrhagic necrosis of some tumors in vivo, and cytotoxic effects against certain tumor cells, but not against normal cells in vitro. Though mechanisms of the cytotoxicity and selectivity of TNF action in vitro are not clear, there is much evidence that free radicals such as superoxide and hydroxyl radicals, mediated by TNF, are correlated with TNF cytotoxicity. Recently, manganous superoxide dismutase (MnSOD) in mitochondria has been demonstrated to be a rescue protein against TNF cytotoxicity and to be induced when the cells are exposed to TNF in the resistant cells. Two steroid hormones, glucocorticoid and 1,25-dihydroxyvitamin D3, block the cytotoxicity of TNF. Glucocorticoid may reduce TNF cytotoxicity by inhibiting phospholipase A2 and 1,25-dihydroxyvitamin D3 by inducing MnSOD in combination with TNF.

Arachidonic Acids↗

Angiography in the diagnosis of liver disease.

Although necessity for angiography has been reduced somewhat because of the development of newer imaging modalities, such as ultrasound and CT, celiac or hepatic arteriography, portography, and hepatic venography often prove useful in the diagnosis of liver disease. They can be utilized for therapeutic purposes as well in certain vascular abnormalities.

Angiography↗

[Angiotensin converting enzyme inhibitory activity of MK-0521 in vivo and antihypertensive effect of its single oral administration on blood pressure and effect on the renin-angiotensin system in 2-kidney Goldblatt hypertensive dogs].

Angiotensin converting enzyme (ACE) inhibitory activity of MK-0521 in dogs and the effects of its single oral administration on blood pressure and the renin-angiotensin system in 2-kidney Goldblatt hypertensive dogs were compared with those of captopril and MK-421. MK-0521 at 0.001-0.1 mg/kg, i.v., or 0.01-1 mg/kg, p.o., attenuated the pressor effect of angiotensin I without affecting that of angiotensin II and augmented the depressor effect of bradykinin. The potency of MK-0521 to reduce the pressor effect of angiotensin I was 9.8 times that of captopril by intravenous administration, and by oral administration, it was 15.9-32.1 times that of captopril and approximately 3 times that of MK-421. When administered orally, the onset of action and the time to peak effectiveness were more rapid than those of MK-421, but slower than those of captopril. Duration of the action of MK-0521 was longer than that of captopril and equal or longer than that of MK-421. The inhibition of ACE was well correlated with serum MK-0521 levels. MK-0521 produced a dose-dependent antihypertensive effect in 2-kidney Goldblatt hypertensive dogs at over 0.3 mg/kg, p.o., without affecting the heart rate. The antihypertensive effect of MK-0521 was persistent and approximately 3 times more potent than that of captopril. MK-0521 inhibited the serum ACE activity and increased the plasma renin activity, while it had a tendency to decrease plasma aldosterone level. These changes were parallel to the time course of the antihypertensive effect. These results suggest that the main mechanism of the antihypertensive effect of MK-0521 is the suppression of angiotensin II production due to the inhibition of the ACE.

Administration, Oral↗

[A case of retroperitoneal neurinoma].

A case of retroperitoneal neurinoma is reported. The patient was a 34-year-old female without symptoms. CT scan showed a large low density mass, a part of which was enhanced. US showed a lobulated cystic mass. Angiography showed avascular mass and portal vein was shown with displacement and stenosis. Pathological diagnosis was benign retroperitoneal neurinoma (Antoni A and Antoni B).

Adult↗

Induction of cytochrome P-450, cytochrome b-5, NADPH-cytochrome c reductase and change of cytochrome P-450 isozymes with long-term trichloroethylene treatment.

Several reports have described the effects of trichloroethylene (TCE) on the microsomal mixed function oxidase system (MFOS). These studies suggest that repeated TCE administration induces MFOS, especially cytochrome P-450 and NADPH-cytochrome c reductase. However, it is uncertain what isozymes are induced by TCE treatment, and it is not clear how microsomal enzymes or cytochrome P-450 isozymes are altered when TCE is administered for a duration longer than 28 days. We investigated the changes of MFOS by long-term TCE treatment. Male Wistar rats were injected with TCE, 1.0 g/kg body weight once a day for 5 continuous days or 2.0 g/kg body weight twice a week for 15 days. The mean body weight of the rats treated with TCE for 15 weeks was slightly, but not significantly, less than that of the control rats. Relative liver weights (liver wt/body wt) of the TCE-treated group were however significantly larger (21%) than those of the control group. The weights of the other organs were not changed by long-term TCE treatment. Trichloroethylene treatments for 5 days and 15 weeks caused significant increases in microsomal protein, cytochrome P-450, cytochrome b-5 and NADPH-cytochrome c reductase. TCE treatments produced an increase in a polypeptide band at 52,000 molecular weight range observed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This increase in similar to, but less pronounced than that induced by phenobarbital (PB) treatment. There were no remarkable changes at 56,000 molecular weight range where a band appeared after the treatment with 3-methylcholanthrene (MC). It is likely that the induction of cytochrome P-450 by TCE is relatively similar to that by PB.

Animals↗

The absorption of trichloroethylene and its metabolites from the urinary bladder of anesthetized dogs.

In order to examine the absorption of trichloroethylene (TRI) and its metabolites from the urinary bladder of dogs, we injected TRI and its metabolites, i.e., chloral hydrate (CH), free trichloroethanol (F-TCE), trichloroacetic acid (TCA) and conjugated trichloroethanol (Conj-TCE), into the urinary bladder of anesthetized dogs, and measured the agents and their respective metabolites in the blood or serum, urine and bile. The percentage of water absorbed from the urinary bladder was 10-20% 2 h after the administration of all substances. The percentage of agents absorbed was 60-70% for the TRI and TCA groups, and 50-60% for the CH, F-TCE and Conj-TCE groups 2 h after administration. The combined urinary and biliary excretion rates of the absorbed materials from the urinary bladder 2 h after administration were 46% for F-TCE, 30% for CH, 6% for Conj-TCE and 0.5-1.0% for TRI and TCA. Urinary re-excretion rates of the total excreted amounts were 65-70% in TRI, CH and F-TCE groups, about 50% in TCA and 99% in Conj-TCE group. It is possible that all of the substances administered, particularly F-TCE, are metabolized to Conj-TCE in the urinary bladder.

Animals↗

Metabolism of chloral hydrate in the anoxic perfused liver.

The metabolism of chloral hydrate (CH) under anoxic conditions was investigated in the non-recirculating, hemoglobin-free liver perfusion system. CH uptake in the anoxic liver decreased to about 80% of that in the oxygen-supplied liver. The reduction of CH to trichloroethanol (TCE) increased and the oxidation of CH to trichloroacetic acid (TCA) decreased. The TCE/TCA ratio increased; however, the total trichloro compounds, that is TCE and TCA, were not significantly altered by anoxia. Though approximate 14% of the CH infused into the oxygen-supplied liver was changed to substances other than TCE or TCA, the unknown part was a very small portion in the anoxic liver. The decrease in CH uptake, by the anoxic liver, is thought to be equivalent to the decrease of the unknown metabolites. The TCE/TCA ratio under anoxia was also altered by pyruvate or lactate infusion.

Animals↗

Intestinal absorption of chloral hydrate, free trichloroethanol and trichloroacetic acid in dogs.

In order to examine the intestinal absorption of chloral hydrate (CH), free trichloroethanol (F-TCE) and trichloroacetic acid (TCA), an intestinal circulation system in dogs was developed using jejunal, ileal and colonic loops, and solutions of CH, F-TCE and TCA were circulated within them. The concentrations of these substances and their metabolites in the serum, urine, bile and circulates were then measured. In all groups, the fraction of water absorbed from the intestine was about 10% of the administered volume two hours after administration. The absorbed fraction of CH was about 50% in the jejunum and ileum, and about 40% in the colon. The absorbed fraction of F-TCE was about 60% in the jejunum, 50-60% in the ileum and about 40% in the colon, while the figures for TCA were about 40-50% in the jejunum and about 30-40% in the ileum and colon. The combined biliary and urinary excretion ratios of the administered substances and their respective metabolites to the total amounts absorbed from the intestine were about 25-30% for F-TCE, 10-15% for CH and 0.1-0.2% for TCA in all parts of the intestine two hours after administration.

Animals↗

[Clinical comparison of 99mTc-diethylenetriaminepentaacetic acid-human serum albumin (99mTc-HSA-D) and 99mTc-human serum albumin (99mTc-HSA) for cardiac blood pool imaging].

99mTc-HSA-D has been developed as a new blood pool scanning agent. Clinical comparison of 99mTc-HSA-D and 99mTc-HSA was made in 16 cases. The activity concentration of 99mTc in blood was measured during 2 hours after the injection in five cases. 99mTc-HSA-D showed higher concentration compared to 99mTc-HSA with the passage of time. Quantitative analysis of contrast between left ventricle and septum was performed on end diastolic frames of gated images 10 minutes after the injection. There was no obvious difference between 99mTc-HSA-D and 99mTc-HSA. The subjective comparison of detectability of lesions between the two agents was performed on three directional gated images. 99mTc-HSA-D was superior to 99mTc-HSA, because the images of the latter deteriorated with the passage of time. On anterior view images 1 hour after the injection, left ventricle/lung and abdominal aorta/background count ratios were greater for 99mTc-HSA-D in many cases. There was no obvious difference in liver/background and kidney/background count ratios between the two agents. Urinary excretion of 99mTc was considerably lesser for 99mTc-HSA-D. The results indicated that 99mTc-HSA-D was superior to 99mTc-HSA for cardiac blood pool imaging.

Aged↗

[A case of colon cancer with pulmonary metastasis treated effectively by uracil futraful].

A 57-year-old female was admitted for advanced ascending colon cancer with a solitary pulmonary metastasis measuring 1.5 cm in diameter. As laparotomy revealed an absolute noncurable tumor of stage V (H0, p2, s2 n1 (+], palliative right hemicolectomy was performed. A pathological diagnosis of well differentiated adenocarcinoma was made postoperatively. A daily dose of 400 mg of UFT was given orally. After 8 months, plain chest film and tomography revealed a reduction in the size of the pulmonary metastasis to 1.0 cm in diameter. The metastatic lung tumor was controlled for a period of 1 year and 9 months. It was suggested that UFT was rather effective for pulmonary metastasis from colon cancer.

Adenocarcinoma↗