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Biomedical subjects

S Iwamoto

Publications and source records attributed to S Iwamoto.

At least 163 records · Page 9Linked to original sources

A patient with systemic lupus erythematosus presenting both central nervous system lupus and steroid induced psychosis.

We describe a patient with systemic lupus erythematosus (SLE) who presented with both steroid induced psychosis and central nervous system (CNS) SLE at different times. The cerebrospinal fluid (CSF) immunoglobulin indices and electroencephalogram were found to be helpful and reliable for the correct diagnosis of both conditions. There have been no reports of patients with SLE who showed both steroid induced psychosis and CNS SLE, and our patient has provided substantial evidence that both conditions can occur in the same individual.

Adult↗

Intestinal absorption of trichloroethylene in dogs.

In order to examine the intestinal absorption of trichloroethylene (TRI), we developed the intestinal circulation system of dogs and administered TRI solution at three concentrations (0.1, 0.25 and 0.5%) to the three parts of the intestinal tract (jejunum, ileum, and colon) of the operated dogs. We measured TRI and its metabolites, free-trichloroethanol, trichloroacetic acid, and conjugated trichloroethanol, in serum or blood, urine, bile and circulating solutions. The absorption rates of TRI from the intestine were 50-70% of the administered volume of TRI 2 hr after administration in all groups, and all parts of intestine readily absorbed TRI. Moreover, there were no significant differences in the absorption rates of TRI and water between the jejunum and ileum, and ileum and colon, respectively. The excretion rates of TRI and its metabolites in urine and bile were very low (0.1-0.4%) compared with the volume of absorbed TRI from the intestine 2 hr after administration in all groups. The high degree of absorption of TRI should be considered when threshold limits for TRI in the drinking water, the surface water, and the ground water are established.

Animals↗

Induction of umu gene expression by cross-links and other DNA lesions.

The induction of umu gene expression by DNA cross-links was investigated in various strains of E. coli with different DNA-repair capacities. Expression was measured by quantifying enzymatic activity of beta-galactosidase produced under regulation of the umu promoter carried on a plasmid carrying the umuC-lacZ gene fusion. The treatment with MMC induced gene expression more efficiently in a wild-type strain when compared with an excision-repair-deficient strain (uvrA). In contrast, PUVA and cis-Pt treatment induced higher levels of the gene expression in the uvrA strain than in the wild-type strain, as did other DNA-damaging agents including 4NQO, MNNG and MMS. None of these chemicals induced umu expression in either lexA and recA strains. The mechanisms of the induction of umu expression by DNA cross-links in relation to DNA damage and repair are discussed.

DNA Damage↗

The cholecystohepatic circulation of trichloroethylene and its metabolites in dogs.

In order to examine the cholecystohepatic circulation of trichloroethylene (TRI) and its metabolites, we injected the gallbladder with TRI and its metabolites, i.e. chloral hydrate (CH), free-trichloroethanol (F-TCE), trichloroacetic acid (TCA) and conjugated-trichloroethanol (Conj-TCE), using anesthetized dogs. The absorption rates of water from the gallbladder were 25-30% 2 h after administration for all substances. The absorption rates of substances were 65-70% in the CH, F-TCE and TRI groups, and 40-50% in the Conj-TCE and TCA groups 2 h after the administration. Conj-TCE in the blood absorbed from the gallbladder has a tendency to be directly transported to the venous system rather than to be taken into hepatocytes in the liver. All of the administered substances, in particular, F-TCE might be metabolized to other substances in the gallbladder.

Absorption↗

Alteration of chloral hydrate metabolism in rats with carbon tetrachloride-induced liver damage.

The metabolism of chloral hydrate (CH) was investigated in the isolated perfused rat liver system. The experiments were performed on rats that were administered carbon tetrachloride (CCl4) subcutaneously for 15 weeks to induce chronic liver damage and on untreated rats. Clearance of CH from the perfusion system was lower in damaged liver than in control liver. In both groups, 50-70% of the added CH was excreted into perfusate as trichloroethanol (TCE) and trichloroacetic acid (TCA) within 120 min. The TCE/TCA ratio was 1:1.3 in the control group compared to 2:1 in the damaged liver group. The findings suggest that CH metabolism in the liver is affected by chronic damage.

Animals↗

The metabolite ratio as a function of chloral hydrate dose and intracellular redox state in the perfused rat liver.

Chloral hydrate (CH), an intermediate metabolite of trichloroethylene, is reduced to trichloroethanol (TCE) by alcohol dehydrogenase and aldehyde reductase, and is also oxidized to trichloroacetic acid (TCA) by the nicotinamide adenine dinucleotide (NAD)-dependent enzyme, CH dehydrogenase. Alcohol dehydrogenase requires reduced NAD (NADH), aldehyde reductase requires reduced nicotinamide adenine dinucleotide phosphate (NADPH) and CH dehydrogenase requires NAD to complete the reaction. It is unclear which reaction is predominant at the physiological redox level in intact liver cells. To study this question, we perfused the livers of well-fed rats with Krebs-Ringer buffer solution containing 0.1 mM pyruvate/1.0 mM lactate. The levels of TCE and TCA in the effluent were measured by gas chromatography, and the fluorescence of reduced pyridine nucleotides was measured with a surface fluorometer. When a low concentration (below 0.25 mM) of CH was administered, more TCA than TCE was produced. When a high concentration of CH was administered (over 0.5 mM), TCE production was greater. Reduced pyridine nucleotides decreased inversely with the CH concentration. Even at low CH concentrations, pyridine nucleotides were not reduced. When 10 mM lactate was added to the perfusate in order to reduce the pyridine nucleotides in the liver cells, the TCE/TCA ratio increased. On the other hand, the TCE/TCA ratio tended to fall following the addition of 5.0 mM pyruvate. In conclusion, the TCE/TCA ratio was altered according to the concentration of CH, and to the redox level of pyridine nucleotides in the liver.

Animals↗

Extrahepatic metabolism of chloral hydrate, trichloroethanol and trichloroacetic acid in dogs.

To examine the details concerning that part of TRI metabolism which was carried out by the extrahepatic organs, we studied the extrahepatic metabolism of chloral hydrate (CH), free-trichloroethanol (F-TCE) and trichloroacetic acid (TCA) using a method developed in our laboratory. Bypass and non-bypass dogs were given CH, F-TCE and TCA, and we compared the concentrations these substances and their metabolites in the serum and urine of the two groups of animals. In the bypass dogs, F-TCE, TCA and conjugated-trichloroethanol (Conj-TCE) appeared in the blood and urine 30 min. after the CH administration, and TCA and Conj-TCE appeared 30 min. after the F-TCE. All levels of administered substance were higher in bypass dogs than in non-bypass dogs, and the compounds were metabolized in small amounts in the extrahepatic organs compared with the liver. Therefore, administered substances remained at high levels in the serum and were excreted in large amounts in the urine in the form of unchanged substances. The metabolized percentage volumes of CH to TCA in the bypass dogs were 10-20%, and those of F-TCE to TCA were very small, while these percentage values of CH to F-TCE were the same or slightly smaller, respectively. Moreover, trichloroethylene (TRI) acts to decrease the leukocyte count in the blood, but the TRI metabolites described above do not have this function.

Animals↗

The metabolism of trichloroethylene and its metabolites in the perfused liver.

The metabolism of trichloroethylene (TRI) and its metabolites, chloral hydrate (CH), trichloroethanol (free-TCE) and trichloroacetic acid (TCA), were examined in the isolated perfused rat liver, to clarify the role of the liver in the metabolism of TRI. TRI was rapidly converted to TCE and TCA by the perfused liver. TCA was produced from TRI about 2.5 times greater than was total-TCE. CH was metabolized to TCE and TCA immediately. TCA was also a dominant metabolite of CH over total-TCE. TCE(free type) was speedily conjugated by the liver. A portion of TCE was converted to TCA. Less than 10% of these metabolites produced by the liver were excreted into the bile. Most of them appeared in the perfusate.

Animals↗

[Serum concentration of 5-FU and tegafur (FT-207) after administration of tegafur (FT-207) suppository with the colostomy].

Tegafur (FT-207) suppositories were administered at a rate of 750 mg via the artificial anus (ST Group) following surgery of rectal cancer. Comparative studies were conducted of changes in blood concentrations of 5-FU and tegafur at the time of initial administration and following one week of continuous use for the low-anterior resection cases (LA Group) and the rectal administration cases (RE Group). FT-207 concentration at initial administration was low in the ST group compared to those for both LA and RE groups which received anal administration of the drug, but only little changes were noted. Blood concentration one hour after administration was 11.1 micrograms/ml, elevated to 14.3 micrograms/ml at two hours, and remained at 10 micrograms/ml and above for six hours following administration. The ST group 5-FU concentrations at two, four and six hours after administration were significantly lower than those in the RE group but the changes were little. Blood concentrations were 0.015 microgram/ml at one hour after administration, 0.017 micrograms/ml at two hours and maintained virtually the same level thereafter. An effective concentration of 0.012 microgram/ml was maintained even at ten hours following administration. After one week of administration of the suppositories, the ST group showed the lowest concentration among three groups, but it was approximately double compared to the initial concentration; FT-207 showed nearly the same concentration in the LA group and 5-FU blood concentration was 0.025 microgram/ml at one hour after administration, reached to a maximum of 0.030 microgram/ml at two hours and maintained 0.020 microgram/ml and higher at ten hours. 5-FU concentration in the LA and RE groups after one week of continuous administration showed a dual-peaked pattern. No patient with an abnormal artificial anus was involved in this study. The artificial anus is thought to be an adequate and effective administration route of FT-207 suppositories.

Adult↗

[The subrenal capsule assay modified with three-dimensional measurement (volume method) and its higher predictivity].

Subrenal Capsule Assay (SRCA) developed by Bogden et al. is a new in vivo sensitivity test for anticancer agents. However, the presence of host reaction on about day 6 is largest problem for this method, and now many researchers are scrutinizing or introducing several modifications for this assay chiefly by immunosuppressing procedures. As one of the means to measure the actual change of the tumor volume and minimize the misreading of host reactions, we introduced three dimensional measurements of the grafts (volume method) instead of original mean diameter measurement. Using this method, prospective quantitative study was made. The results of 16 assays with 15 cases of miscellaneous malignancies showed 94% evaluability and in 22 treatments predictive accuracy was 77%. Assay/clinical correlation coefficient was 0.38 and coincidence of ranking order of the effectiveness was 6/6, with good contrast to those of 78%, 56%, 0.00 and 1/3, by original method respectively. Clinical responses more than PR were obtained in 9 of 15 cases. Two cases are still in CR for two years by assay directed single agent treatments. Many other minor modifications were also adopted and evaluated by quantitative observation of assay/clinical correlations. SRCA with our modifications seemed to have utilities than original.

Animals↗

Extrahepatic organs metabolism of inhaled trichloroethylene.

An extrahepatic circulation system for dogs was developed using a portal vein to right femoral vein bypass procedure. This system maintained nearly normal biochemical and physiological parameters, i.e. arterial blood pressure, heart rate, electrocardiogram, leukocyte and erythrocyte count, hematocrit, alkaline phosphatase, blood urea nitrogen, ammonia and creatinine, for 2 h. Thus, the system appears to be a valid technique for investigating extrahepatic metabolism. Dogs were exposed for 1 h to 500, 700 and 1500 ppm of trichloroethylene. Free-trichloroethanol, trichloroacetic acid and conjugated-trichloroethanol appeared in the blood and urine after 30 min of exposure. The amounts of metabolite formed by dogs with hepatic bypass were less than by similarly exposed dogs without hepatic bypasses, specifically 50-80%, 10% and 10-20% for free-trichloroethanol, trichloroacetic acid and conjugated-trichloroethanol, respectively. In addition, trichloroethylene exposure produced a smaller decrease in leukocyte counts in the hepatic bypass dogs than in the non-bypass dogs. This observation may indicate that the liver itself played some role in the elimination or increment of leukocyte counts in the blood.

Administration, Inhalation↗

Transcription unit mapping in adenovirus: regions of termination.

Using a series of single-stranded clones of adenovirus DNA, we determined the extent of RNA polymerase II transit early in infection for two rightward-reading transcription units. RNA synthesis beginning at the major late promoter (16.5 on the genomic map) continued until approximately 65 to 70 map units so that differential choices of mRNAs within that region were not based primarily on transcriptional decisions but rather on posttranscriptional decisions. Transcription from the major late promoter beginning at 16.5 map units, however, did greatly decrease before approximately 75 map units, ensuring that no mRNAs were formed with sequences beyond approximately 75 map units. Early transcription from E3 then began just past 75 map units (at a higher rate than transcription from the major late promoter); E3 transcripts terminated at least 2 kilobases downstream from a second and final poly(A) site in this transcription unit. The effectiveness of termination in E3 was greater than 95 to 99%.

Adenoviruses, Human↗

[Trichloroethylene metabolism in chronic liver disorders induced by carbon tetrachloride].

Numerous reports have been published in the field of industrial health on biological monitoring of trichloroethylene exposure, but these studies have been confined to healthy humans. Trichloroethylene metabolism in individuals with chronic liver diseases has not been clarified. This experiment was therefore performed on rats that were administrated carbon tetrachloride subcutaneously for three months to induce chronic liver damage. The metabolism of trichloroethylene and its metabolites, chloral hydrate and trichloroethanol, were investigated using the isolated liver perfusion method. Comparing the changes of these substances in the chronically damaged liver with those in the intact liver, the following results were observed in the chronically damaged liver: The conversion of trichloroethylene to trichloroethanol and trichloroacetic acid decreased. The reduction of chloral hydrate to trichloroethanol increased. The oxidation of chloral hydrate to trichloroacetic acid decreased. The biliary excretion of trichloroethanol and trichloroacetic acid decreased.

Animals↗