Biomedical subjects

S Kojima

Publications and source records attributed to S Kojima.

At least 667 records · Page 37Linked to original sources

PubMed1991

Comparative effects of N,N-disubstituted dithiocarbamates on excretion and distribution of cadmium in mice.

Sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), sodium N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD) and sodium N-p-methoxybenzyl-D-glucamine dithiocarbamate (MeOBGD) were evaluated for their efficacy in the distribution and excretion of cadmium in mice exposed to cadmium. Mice were injected i.p. with 109CdCl2 (1 mg Cd/kg and 74 kBq of 109Cd/animal) and 30 min or 24 h later, they were injected with chelating agents (400 mumol/kg). At 30 min after treatment with cadmium, these chelating agents all significantly enhanced the biliary excretion of cadmium, and HBGD and CBGD significantly increased the urinary excretion of the metal. At 24 h after cadmium injection, BGD, HBGD, and MeOBGD significantly increased the biliary excretion of cadmium and HBGD was the most effective on the biliary excretion of the metal. These chelating agents were effective in mobilizing cadmium from the liver at 30 min after cadmium treatment. At 24 h after cadmium treatment, HBGD and MeOBGD effectively depressed cadmium content in the liver and only HBGD among these chelating agents significantly reduced the cadmium content in the kidney. In another experiment, mice were injected i.p. with 109CdCl2 and three days later, they were injected with chelating agents every other day for 2 weeks. HBGD was the most effective on the fecal and urinary excretions of cadmium. The hepatic cadmium content was decreased after HBGD or MeOBGD injection. The injection of HBGD caused a much greater decrease in renal cadmium content than did BGD, CBGD, or MeOBGD. The results of this study indicated that the injection of HBGD to mice pretreated with cadmium can remove cadmium from the body, mainly through fecal excretion, without redistribution of cadmium to other tissues such as the brain, testes, and heart, more effectively than that of BGD, CBGD, or MeOBGD.

Animals↗

PubMed1991

Protective effects of dextran sulfate and polyvinyl sulfate against acute toxicity of paraquat in mice.

The protective effects of sodium dextran sulfate (SDS) and potassium polyvinyl sulfate (PPS) against the acute toxicity of paraquat (PQ) in mice were studied. The survival rates of mice treated with SDS (2000 mg/kg) or PPS (2000 mg/kg) immediately after PQ ingestion (200 mg/kg) were 100% or 100%, respectively. When treated with SDS (2000 mg/kg) or PPS (2000 mg/kg) 15 or 30 min after PQ ingestion (200 mg/kg), the survival rates were 83% or 67% for SDS-treated groups and 67% or 33% for PPS-treated groups, respectively. Treatment with SDS (2000 mg/kg) or PPS (2000 mg/kg) immediately after oral administration of PQ (200 mg/kg) increased the fecal excretion of PQ, decreased the urinary excretion of PQ and decreased the contents of PQ in the lung, liver and kidney. Such effects of SDS and PPS were reduced in the treatment with these drugs at 15 min after PQ. The in situ small intestinal absorption of PQ was significantly reduced in the presence of SDS or PPS. The binding of PQ to SDS or PPS was determined by an ultrafiltration method. These results indicate that SDS and PPS inhibit the gastrointestinal absorption of PQ on the basis of the increased intestinal transit of PQ and the binding of PQ to the drugs resulting in the protective effectiveness of SDS and PPS on the acute toxicity of PQ.

Animals↗

PubMed1991

Comparative renal toxicity of metallothioneins with different cadmium/zinc ratios in rats.

The comparative renal toxicity of rats after injection of cadmium (Cd) and zinc (Zn)-metallothioneins (MTs) with different Cd/Zn ratios at the same dose of 200 micrograms MT-bound Cd/kg was studied. From determination of the urinary excretion of protein, aspartate aminotransferase (AST) and glucose, which are indices of Cd-induced renal damage, the extent of the renal toxicity of the MTs used here was in the order (1 Cd/0Zn)-MT = (2Cd/1Zn)-MT greater than (1Cd/2Zn)-MT greater than (1Cd/6Zn)-MT. The characterization of Cd, Zn and Cu in the urine after injection of MTs was examined using a Sephadex G-75 column. (1Cd/0Zn)-MT injection showed that Cd was present mainly in lower-molecular-weight fractions, with only small amounts of Cd in the MT fraction. Upon injection of other MTs, Cd was present mainly in the MT fraction and increased with decreasing Cd/Zn ratio. Zn was present mainly in lower-molecular-weight fractions and Cu mainly in the MT fraction, indicating the replacement of MT-bound Zn by Cu. The cumulative urinary excretion of Cd during 12 days after injection of MTs decreased with increasing Cd/Zn ratio. The Cd content of the kidney and liver increased with increasing Cd/Zn ratio. The results of this study indicate that in rats injected with MTs with different Cd/Zn ratios, the renal uptake of Cd increases with increasing Cd/Zn ratio, resulting in more severe renal damage.

Animals↗

PubMed1991

Sequential enzymatic synthesis and biodistribution of radiolabelled inositol and inositol analogs.

The desired radiolabelled inositol (Ins) and inositol-1-phosphate (IP) were obtained from radiolabelled glucose by sequential enzyme reactions in a short time. Rapid separation and fractionation of enzymes and labelled products from the reaction mixture was achieved by HPLC with a gel-permeation chromatography column. Examination of the biodistribution of radiolabelled Ins, IP and their acetylated analogs suggested that intact Ins labelled with 11C would be more effective than 11C-labelled acetylated Ins as a brain diagnostic agent for positron emission tomographic studies of the metabolism of phosphatidylinositol and its role as a second messenger in the brain.

Acetylation↗

PubMed1991

Radioimmunodetection of human colon cancer in nude mice by a new monoclonal antibody A7 against human colorectal cancer.

The in vivo localization of a monoclonal antibody A7 against a human colorectal cancer was studied in nude mice bearing human solid carcinomas, to evaluate potential applications of this antibody for radioimmunodetection of cancer. The tissue distribution of 125I-labeled A7 MoAb at 3 days after i.v. injection into mice bearing five different kinds of human solid tumors revealed a high uptake ratio by colon cancer, mammary cancer, and glioblastoma. In contrast, the uptake ratio by murine colorectal cancer (Colon-38) was extremely low. In immunoscintigraphic studies, HCT-15, one of the human colon cancer, was clearly visualized with 111In-DTPA-A7 MoAb. Glioblastoma was also imaged with the same extent. These results suggest that A7 MoAb would be applicable to the in vivo radioimmunodetection of colon- and mammary-cancer, and of glioblastoma.

Adenocarcinoma↗

PubMed1991

Effect of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics in essential hypertension.

The effects of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics were studied in essential hypertension. A 4-week study was performed in eight patients with essential hypertension who were given a regular sodium diet in the first and third weeks, and a sodium-restricted diet in the second and fourth weeks. Nicardipine, 60 mg/d, was administered in the third and fourth weeks. The urinary sodium excretion rate (UNaV) was plotted on the y-axis against the mean arterial pressure (MAP) on the x-axis before and after the administration of nicardipine. Assuming the difference between MAP and the x-intercept of this renal function curve represents the effective filtration pressure across the glomerular capillaries, the intrarenal hemodynamics such as afferent arteriolar resistance (RA) and efferent arteriolar resistances (RE), glomerular pressure (PG), and gross filtration coefficient (KFG) were calculated. Although the MAP on regular salt diet was lowered from 125 +/- 3 to 109 +/- 2 mm Hg by nicardipine, neither the renal blood flow rate (RBF) (670 +/- 40 mL/min) nor the glomerular filtration rate (GFR) (79 +/- 2 mL/min) was altered. The RA was estimated to be reduced from 9,300 +/- 900 to 7,400 +/- 700 dyne.s.cm-5 (P less than 0.01), while no changes were noted in RE (4,900 +/- 400 dyne.s.cm-5), PG (50 +/- 1 mm Hg), or KFG (0.180 +/- 0.041 [mL/s]/mm Hg). Essential hypertension has been characterized by a prominent increase in RA, resulting in maintenance of normal PG. This Ca-entry blocker worked to normalize intrarenal hemodynamics in essential hypertension by dilating afferent arterioles alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Diet, Sodium-Restricted↗

PubMed1991

Lipoprotein (a) inhibits the generation of transforming growth factor beta: an endogenous inhibitor of smooth muscle cell migration.

Conditioned medium (CM) derived from co-cultures of bovine aortic endothelial cells (BAECs) and bovine smooth muscle cells (BSMCs) contains transforming growth factor-beta (TGF-beta) formed via a plasmin-dependent activation of latent TGF-beta (LTGF beta), which occurs in heterotypic but not in homotypic cultures (Sato, Y., and D. B. Rifkin. 1989. J. Cell Biol. 107: 1199-1205). The TGF-beta formed is able to block the migration of BSMCs or BAECs. We have found that the simultaneous addition to heterotypic culture medium of plasminogen and the atherogenic lipoprotein, lipoprotein (a) (Lp(a)), which contains plasminogen-like kringles, inhibits the activation of LTGF-beta in a dose-dependent manner. The inclusion of LDL in the culture medium did not show such an effect. Control experiments indicated that Lp(a) does not interfere with the basal level of cell migration, the activity of exogenous added TGF-beta, the release of LTGF-beta from cells, the activation of LTGF-beta either by plasmin or by transient acidification, or the activity of plasminogen activator. The addition of Lp(a) to the culture medium decreased the amount of plasmin found in BAECs/BSMCs cultures. Similar results were obtained using CM derived from cocultures of human umbilical vein endothelial cells and human foreskin fibroblasts. These results suggest that Lp(a) can inhibit the activation of LTGF-beta by competing with the binding of plasminogen to cell or matrix surfaces. Therefore, high plasma levels of Lp(a) might enhance smooth muscle cell migration by decreasing the levels of the migration inhibitor TGF-beta thus contributing to generation of the atheromatous lesions.

Animals↗

PubMed1991

Aspirin test for differentiation of unilateral renovascular hypertension from hyperreninemic essential hypertension.

Responses of renin release and blood pressure to aspirin DL-lysine (ASP) were examined to find out if the responses could help in the differentiation between unilateral renovascular hypertension (RVH) and hyperreninemic essential hypertension (EHT). The two studies involved ten patients with unilateral RVH, eight with hyperreninemic EHT, and five with hyporeninemic EHT. In a radiological study, before and 30 min after an intravenous injection of ASP (18 mg/kg), renal venous and abdominal aortic plasma was sampled and assayed for prostaglandin (PG) E2 and plasma renin activity (PRA). Systemic blood pressure was measured serially. The reproducibility of the responses to ASP was confirmed in a bedside study. In unilateral RVH, ASP suppressed renin release from the stenotic kidney and reduced the renal vein PRA ratio to less than 1.5 via the inhibition of PG synthesis, which is accelerated in that kidney. The mean suppression of aortic PRA at this dose of ASP was 35% in these patients, and their blood pressure decreased in proportion to the suppression of PRA. However, in the two EHT groups, ASP elevated the mean blood pressure. The renal synthesis of PGE2 was inhibited by ASP in all patients, but the suppression of PRA, while small, was significant (19% in the aorta) in the patients with hyperreninemic EHT, and not significant in patients with hyporeninemic EHT. The different responses of blood pressure and PRA to ASP between RVH and EHT were reproducible in the bedside study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Inhibition of subtilisin BPN' by reaction site P1 mutants of Streptomyces subtilisin inhibitor.

It has been shown that the P1 site (the center of the reactive site) of protease inhibitors corresponds to the specificity of the cognate protease, and consequently specificity of Streptomyces subtilisin inhibitor (SSI) can be altered by substitution of a single amino acid at the P1 site. In this paper, to investigate whether similar correlation between inhibitory activity of mutated SSI and substrate preference of protease is observed for subtilisin BPN', which has broad substrate specificity, a complete set of mutants of SSI at the reaction site P1 (position 73) was constructed by cassette and site-directed mutagenesis and their inhibitory activities toward subtilisin BPN' were measured. Mutated SSIs which have a polar (Ser, Thr, Gln, Asn), basic (Lys, Arg), or aromatic amino acid (Tyr, Phe, Trp, His), or Ala or Leu, at the P1 site showed almost the same strong inhibitory activity toward subtilisin as the wild type (Met) SSI. However, the inhibitory activity of SSI variants with an acidic (Glu, Asp), or a beta-branched aliphatic amino acid (Val, Ile), or Gly or Pro, at P1 was decreased. The values of the inhibitor constant (Ki) of mutated SSIs toward subtilisin BPN' were consistent with the substrate preference of subtilisin BPN'. A linear correlation was observed between log(1/Ki) of mutated SSIs and log(1/Km) of synthetic substrates. These results demonstrate that the inhibitory activities of P1 site mutants of SSI are linearly related to the substrate preference of subtilisin BPN', and indicate that the binding mode of the inhibitors with the protease may be similar to that of substrates, as in the case of trypsin and chymotrypsin.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1991

Molecular recognition at the active site of subtilisin BPN': crystallographic studies using genetically engineered proteinaceous inhibitor SSI (Streptomyces subtilisin inhibitor).

Unlike trypsin-like serine proteases having only one conspicuous binding pocket in the active site, subtilisin BPN' has two such pockets, the S1 and S4 pockets, which accommodate the P1 and P4 residues of ligands (after Schechter and Berger notation) respectively. Using computer graphics, the geometrical nature of the two pockets was carefully examined and strategies for site-directed mutagenesis studies were set up against a protein SSI (Streptomyces subtilisin inhibitor), which is a strong proteinaceous inhibitor (or a substrate analogue) of subtilisin BPN'. It was decided to convert the P1 residue, methionine 73, into lysine (M73K) with or without additional conversion of the P4 residue, methionine 70, into glycine (M70G). The crystal structures of the two complexes of subtilisin BPN', one with the single mutant SSI (M73K) and the other with the double mutant SSI (M73K, M70G) were solved showing that (i) small 'electrostatic induced-fit movement' occurs in the S1 pocket upon introducing the terminal plus charge of the lysine side chain, and (ii) large 'mechanical induced-fit movement' occurs in the S4 pocket upon reducing the size of the P4 side chain from methionine to glycine. In both (i) and (ii), the induced-fit movement occurred in a concerted fashion involving both the enzyme and 'substrate' amino acid residues. The term 'substrate-assisted stabilization' was coined to stress the cooperative nature of the induced-fit movements.

Bacterial Proteins↗

PubMed1991

Allergic contact dermatitis from para-tertiary-butylphenol-formaldehyde resin (PTBP-FR) in athletic tape and leather adhesive.

4 girls with severe allergic contact dermatitis from a brand of athletic tape and a cobbler with allergic contact dermatitis from leather adhesive are presented. Alkylphenol resin with unknown chemical structure had been compounded in both products. One of the girls developed foot dermatitis later from the adhesive used on the inside of new sneakers. By patch testing and chemical analysis of alkylphenol resin and the products, the 5 patients were given a specific diagnosis of allergic contact dermatitis from PTBP-FR.

Adhesives↗

PubMed1991

Dominance of blood pressure in natriuresis associated with supraventricular tachycardia.

Supraventricular tachycardia was induced in 10 patients by programmed cardiac stimulation through esophageal lead. Blood pressure, heart rate, renal function, and hormonal factors were measured before, during, and after tachycardia. The patients were divided into two groups, depending on whether antinatriuresis occurred during tachycardia; one group (n = 5) with antinatriuresis during tachycardia associated with a decrease in blood pressure and the other group (n = 5) with neither antinatriuresis nor changes in blood pressure. The urinary sodium excretion tended to increase after tachycardia only in the latter group. On the other hand, urine volume and free water clearance increased during or after tachycardia in both groups. Plasma levels of atrial natriuretic peptide significantly increased and the urinary vasopressin excretion significantly decreased during tachycardia in both groups. During tachycardia, natriuresis due to atrial natriuretic peptide secretion seems to be hampered by hypotension, but polyuria is preserved despite the fall in blood pressure probably related to suppression of vasopressin release.

Adult↗

PubMed1991

Intrarenal hemodynamics in patients with essential hypertension.

Intrarenal hemodynamics were estimated clinically in essential hypertension. Two-week studies were performed in 30 patients with essential hypertension who were given a regular sodium diet in the first week and a sodium-restricted diet in the second week. Intrarenal hemodynamic parameters such as afferent arteriolar (preglomerular) resistance, efferent arteriolar resistance, and glomerular hydrostatic pressure were calculated from renal clearances and plasma total protein concentration measured on the last day of the regular sodium diet. Calculations were based on Gomez's equations with the assumption that the gross filtration coefficient of glomerular capillaries was normal. The increase in afferent arteriolar resistance (8,100 +/- 500 dyne.sec.cm-5) was significantly correlated with an elevation in mean arterial pressure (120 +/- 2 mm Hg), whereas glomerular pressure (56 +/- 1 mm Hg) and efferent arteriolar resistance (2,500 +/- 100 dyne.sec.cm-5) remained normal. The renal function curve (pressure-natriuresis relation) was drawn by plotting urinary sodium excretion on the y axis as a function of mean arterial pressure on the x axis, both of which were measured on the last 3 days of each week. The extrapolated x intercept (107 +/- 2 mm Hg) of the renal function curve was strongly correlated in a 1:1 fashion with the sum of the arterial pressure drop from the aorta to the renal glomeruli plus the opposing pressures against glomerular filtration at glomeruli (r = 0.7, p less than 0.001) on the regular sodium diet, suggesting that the difference between mean arterial pressure on the regular sodium diet and the extrapolated x intercept represented the effective filtration pressure across the glomerular capillaries on the regular sodium diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Mobilization of renal and hepatic cadmium by dithiocarbamates in rats.

Sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), sodium N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD), and sodium N-p-methoxybenzyl-D-glucamine dithiocarbamate (MeOBGD) were evaluated for their efficacy in the distribution and excretion of cadmium in rats exposed to cadmium. Rats were injected intraperitoneally with 109CdCl2 (1 mg Cd/kg and 74 kBq of 109Cd/one animal) and 30 min or 24 h later, they were injected with chelating agents (400 mumol/kg). At both 30 min and 24 h after treatment with cadmium, these chelating agents all significantly enhanced the biliary excretion of cadmium. At 24 h after cadmium injection, BGD and MeOBGD were the most effective on the biliary excretion of the metal. These chelating agents were effective in mobilizing cadmium from the liver at 30 min after cadmium treatment. At 24 h after cadmium treatment, BGD and MeOBGD significantly depressed cadmium content in the liver. In another experiment, rats were injected intraperitoneally with 109CdCl2 and 3 d later, they were injected with BGD, HBGD, or MeOBGD every other day for 2 weeks. The fecal excretion of cadmium was significantly increased by these chelating agents and MeOBGD was the most effective. The hepatic and renal cadmium contents were significantly decreased after BGD, HBGD or MeOBGD injection. The injection of MeOBGD to rats pretreated with cadmium was more effective than that of BGD, HBGD, or CBGD in removing cadmium from the liver. HBGD injection was more effective in decreasing the cadmium content in the kidney. The treatment with these chelating agents did not cause the redistribution of cadmium to brain, testes, and heart.

Animals↗

PubMed1991

Effect of molecular weight in amphipathic polyethyleneglycol on prolonging the circulation time of large unilamellar liposomes.

The effect in mice of the molecular weight of polyethyleneglycol on prolonging the circulation time of large unilamellar liposomes (LUVs) was examined using four different distearoyl N-(monomethoxy polyethyleneglycol succinyl) phosphatidylethanolamines (DSPE-PEGs). The molecular weights tested were 1000, 2000, 5000 and 12000. Incorporation of 6 mol% of DSPE-PEG in LUV composed of distearoylphosphatidylcholine (DSPC) / cholesterol (CH) (1:1 in molar ratio) increased the blood circulation half-life significantly more than those without DSPE-PEG derivatives. DSPE-PEGs with molecular weights of 1000 and 2000 prolonged the circulation time of liposomes more than other DSPE-PEGs with higher molecular weights, such as 5000 and 12000. Their effects are also higher than ganglioside GM1, a well described glycolipid with this effect. DSPC/CH LUV-incorporated DSPE-PEG with a molecular weight of 2000 displayed a high concentration in the blood, approximately 40% of the dose, 6 h after the injection.

Animals↗

PubMed1991

Metallothionein concentrations and organ retention of mercury in the liver and kidney of the neonatal guinea pig after exposure to mercury vapor.

Neonatal guinea pigs were exposed to mercury vapor on the day of birth, and the following mercury distribution and concentrations of metallothioneins (MTs) in the liver and kidney were observed. In the liver, two hours after exposure, an appreciable amount of mercury accumulated and a substantial portion of this was associated with MTs. During postnatal development, the mercury concentration increased, whereas the hepatic concentration of MTs decreased. The mercury in the soluble fraction of the liver shifted from the region of MTs to the high-molecular-weight region and, finally, the mercury peak in the MT region was not detected. The kidney mercury concentration was high even 2 hr after the exposure and on days 3 and 7 postpartum. The peak concentration was observed on day 3 postpartum. The mean renal concentration of MTs in the mercury-exposed neonates was significantly higher than that of the control at all times observed. The changes in both the mercury level and the concentration of MTs were strongly correlated. Furthermore, most mercury in the soluble fraction was associated with MTs on day 7. These findings indicated enhanced synthesis of MTs in the kidney, but not in the liver, after mercury vapor exposure in the neonatal period, with corresponding elevated copper and zinc concentrations in the kidney.

Administration, Inhalation↗

PubMed1991

Auditory evoked potentials in the Japanese monkey.

Auditory sensitivity based on auditory brain stem response (ABR), whole nerve action potential (AP), and cochlear microphonics (CM) to tone bursts of 0.5-8 kHz were compared with behavioral audiometry in the Japanese monkeys. Although sensitivity loss at 4-6 kHz was observed in these potentials, an increase in sensitivity at 8 kHz was obtained only in the ABR. Thus the sensitivity loss at 4-6 kHz originates at the peripheral system and the increased sensitivity at 8 kHz originates at the central.

Action Potentials↗

PubMed1991

[A five-year follow-up study on blood pressure and serum cholesterol in junior high school children].

Blood pressure and serum cholesterol changes over a five-year period were studied in 299 junior high school children (127 males and 172 females) examined during 1980-1984 in Akita Prefecture, Japan. The six factors studied were height, weight, body mass index (by Minowa's method), systolic blood pressure, diastolic blood pressure and serum cholesterol. Mean values for systolic and diastolic blood pressure increased more than 10 mmHg during the five years in both sexes. Significant positive correlations between initial and follow-up blood pressure ('tracking') were observed. The correlation coefficients for systolic blood pressure in males and in females were 0.33 and 0.28 respectively, and those for diastolic blood pressure were 0.36 in males and 0.19 in females. While there were no significant differences in serum cholesterol levels between the two periods in either sex, the correlation coefficients, which were higher than those for blood pressure, were 0.55 in males and 0.45 in females. Among the six factors at each period, significant positive correlations were observed between height and systolic blood pressure at the initial period, and between obesity and systolic blood pressure at both periods in males and females. A significant positive relationship between obesity and serum cholesterol was seen at the follow-up period in both sexes. These data suggest that a moderate degree of 'tracking' occurs in blood pressure and serum cholesterol during childhood, and that obesity is an important factor related to blood pressure and serum cholesterol.

Adolescent↗