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Biomedical subjects

T Shimada

Publications and source records attributed to T Shimada.

At least 901 records · Page 50Linked to original sources
PubMed1985

Participation of a rat liver cytochrome P-450 induced by pregnenolone 16 alpha-carbonitrile and other compounds in the 4-hydroxylation of mephenytoin.

Mephenytoin 4-hydroxylation, which has been found to be one of the reactions showing genetic polymorphism in humans, has been studied using rat liver microsomes. Pregnenolone 16 alpha-carbonitrile, dexamethasone, troleandomycin, and phenobarbital (but not beta-naphthoflavone) induced the hydroxylation activity to various extents. Mephenytoin itself also increased 4-hydroxylation considerably. Liver microsomes prepared from male rats contained higher mephenytoin hydroxylase activity than preparations isolated from females. These results suggest that a cytochrome P-450 which is inducible by pregnenolone 16 alpha-carbonitrile is involved in the 4-hydroxylation of mephenytoin. We purified cytochrome P-450PCN-E from pregnenolone 16 alpha-carbonitrile-treated rats using modifications of previous methods and compared its 4-hydroxylase activity with other purified rat cytochromes P-450. P-450PCN-E had the highest activity among the 10 purified rat cytochromes P-450 tested and antibodies raised to P-450PCN-E completely inhibited mephenytoin 4-hydroxylase in rat liver microsomes, suggesting the involvement of P-450PCN-E in this reaction. The microsomal concentration of P-450PCN-E, estimated by immunoelectrophoretic blotting analysis, correlated well with the hydroxylase activity in rat liver microsomes (r = 0.906). Mephenytoin induced P-450PCN-E as well as other phenobarbital-inducible cytochromes P-450.

Animals↗
PubMed1984

The Purkinje fiber-myocardial cell region in the goat heart as studied by combined scanning electron microscopy and chemical digestion.

The 3-dimensional architecture of the junctional region between Purkinje fibers and ordinary myocardial cells has been closely studied by combined scanning electron microscopy and chemical digestion in the goat heart. It was revealed that the Purkinje fibers forming the terminal arborization of the atrioventricular bundle are followed by transitional cells which are in contact with ordinary myocardial cells.

Animals↗
PubMed1984

The functional human dihydrofolate reductase gene.

Molecular cloning, mapping, and DNA sequencing techniques have been used to characterize the functional human dihydrofolate reductase (DHFR) gene. The gene is about 30 kilobases in length. Its coding portions are separated into 6 exons, the intron-exon boundaries of which are identical to those of the previously characterized mouse DHFR gene. The 5 introns vary in length from 362 to 12,000 base pairs. The position of the DHFR gene promoter was identified as being shortly upstream from the initiation codon in an in vitro transcription reaction by polymerase II. A DHFR minigene was constructed in a plasmid expression vector by combining a DNA fragment containing exon 1, intron I, and a small part of exon 2 from the functional gene, with a second DNA fragment containing exons 2-6 from a processed intronless gene, the coding sequences of which are identical to those of the normal locus. Transcription initiation from the DHFR promoter was localized to a position 71 +/- 2 base pairs upstream from the initiation codon, both in monkey kidney cells transfected with vectors containing the DHFR minigene, and in human HeLa cells. This single transcription start and the three previously identified polyadenylation sites account for the 800-, 1,000-, and 3,800-nucleotide DHFR mRNA species found in human cells. On comparison of the mouse and human DHFR genes, sequence homology was shown to be limited to the coding regions and 100 base pairs of the 3' untranslated region up to the first polyadenylation site of both genes. In addition, there is fairly extensive homology in the 5' flanking region, although the quadruply repeated 48-base pair sequence found in the mouse genome is represented only once in human DNA.

Base Sequence↗
PubMed1984

[The conversion of thyroxine to triiodothyronine (T3) or to reverse T3 in patients with thyroid dysfunction].

In order to clarify the conversion of thyroxine (T4) to triiodothyronine (T3) or to reverse T3 (rT3), serum concentrations of T4, T3, rT3, thyrotropin (TSH), thyroxine-binding globulin (TBG) and values of T3 uptake (T3 U) were measured in 61 hyperthyroid and 31 hypothyroid patients, 8 patients with subacute thyroiditis, and 40 normal subjects. Then, free T4 index (FT4I), T3/T4, rT3/T4, and rT3/T3 ratio were calculated. The rT3/T3 ratio was high in the hyperthyroid patients and low in the hypothyroid patients compared with that in the normal subjects. The ratio was positively related to serum T4, T3, rT3 levels, and FT4I in the patients and normal subjects. The regression equation was represented by rT3/T3 = 0.015[T4] + 0.083. No influences of serum TBG and age on the rT3/T3 ratio were observed. Our results indicated that thyroid hormones themselves could regulate the conversion of T4 to T3 or rT3 by activating 5-monodeiodinase in hyperthyroidism and by activating 5'-monodeiodinase and suppressing 5-monodeiodinase in hypothyroidism. Serum rT3 level was a more sensitive parameter than serum T4 or T3 for evaluating thyroid dysfunction. During the treatment with methimazole (MMI) or L-thyroxine and the natural course of subacute thyroiditis, serum T4 levels and rT3/T3 ratios changed parallel to the regression line. However, once adverse effects of MMI occurred, those changed out of the line. From these results, we concluded that the relationship between serum T4 level and rT3/T3 ratio should be examined for adequate information concerning the peripheral conversion of thyroid hormones under various thyroid diseases.

Adolescent↗
PubMed1984

Morphological studies of different mitochondrial populations in monkey myocardial cells.

The ultrastructure of mitochondria in monkey myocardial cells was investigated by scanning electron microscopy, thin sections and freeze-fracturing. Mitochondria with well-developed cristae were distributed around the nucleus, between the myofibrils and beneath the sarcolemma. Those clustered near the poles of the nucleus were generally spherical in shape. Interfibrillar mitochondria were arranged in longitudinal rows between the myofibrils, were elongated and usually about the same length as a sarcomere. Subsarcolemmal mitochondria varied in size and shape, being rod-like, spherical, polygonal or horseshoelike. There were usually two profiles of subsarcolemmal mitochondria in each section of sarcomere, although sometimes one or three occurred, and they were typically oriented perpendicularly to the myofibrils. These morphological differences among mitochondria could reflect functional and/or mechanical properties in the various cellular locations.

Animals↗
PubMed1984

Comparative studies on distribution and covalent tissue binding of 2,4,2',4'- and 3,4,3',4'-tetrachlorobiphenyl isomers in the rat.

The 14C-labeled tetrachlorobiphenyl (TCB) isomers 2,4,2',4'-tetrachlorobiphenyl (2,4,2',4'-TCB) and 3,4,3',4'-tetrachlorobiphenyl (3,4,3'4'-TCB) were administered orally to rats, and distribution and covalent binding were measured in several organs. Marked differences in distribution and covalent binding of the two TCBs were observed. The accumulation and retention of 2,4,2',4'-TCB in adipose tissue were much higher than those of 3,4,3',4'-TCB, although the level of radioactivity in the blood was consistently higher in 3,4,3',4'-TCB treated rats. The radioactivity bound in covalent linkages with cellular macromolecules in several tissues was also measured. The data obtained indicated that covalent binding was higher in 3,4,3',4'-TCB treated rats than in those treated with 2,4,2',4'-TCB, particularly in liver and blood components. These results suggest that the two TCB isomers have different pharmacokinetic properties in rats, and the association of covalent binding with 3,4,3',4'-TCB-induced toxicities might be important. In addition, we found that repeated oral dosing with the two TCB isomers caused an increase in in vitro liver microsomal generation of reactive metabolites of TCBs, indicating that the microsomal enzyme system is likely to play an important role in the in vivo covalent binding of TCB.

Animals↗
PubMed1984

Venous occlusive RN plethysmography: comparison with electrical admittance plethysmography.

A venous occlusion plethysmography using radionuclide (RN) was introduced for the measurement of the limb blood flow. This technique, called RN plethysmography, can be carried out in a subject who has been previously administered RN intravenously for the routine angiographic examination. The blood flow is calculated from the initial slope of the RN count rate change (RN accumulation curve) due to venous occlusion. In this study, this method was compared with electrical admittance plethysmography. The blood flow values determined by these two methods correlated well with each other.

Biomedical Engineering↗
PubMed1984

A human dihydrofolate reductase intronless pseudogene with an Alu repetitive sequence: multiple DNA insertions at a single chromosomal site.

A dihydrofolate reductase (DHFR) pseudogene, hDHFR-psi 3 has been isolated from a human genomic DNA fragment library. Sequence analysis of this gene revealed a lack of introns and the presence of a tract of nine adenines, 90 bp downstream from the end of the coding sequence. These features suggest that hDHFR-psi 3 was derived from a processed RNA molecule that has been converted into DNA and inserted into a chromosome, analogous to the origin of three intronless human DHFR genes previously described. An interesting feature of hDHFR-psi 3 is the presence of a member of the Alu moderately repetitive DNA sequence family within the DHFR coding region. This Alu element is flanked by a 16 bp directly repeated DNA segment derived from DHFR coding sequences. The Alu element apparently has been inserted into the intronless DHFR pseudogene and thus, there have been two insertions at a single chromosomal locus. The hDHFR-psi 3 contains only the 3' half of the DHFR coding sequence. Immediately upstream from the directly repeated sequence before the Alu element is an adenine-rich tract. The DNA farther upstream is moderately repetitive and is related to neither DHFR nor Alu DNA sequence. Therefore, it seems possible that a third insertion has occurred at the same site further disrupting the hDHFR coding sequences.

Base Sequence↗
PubMed1984

Chromosomal organization of the human dihydrofolate reductase genes: dispersion, selective amplification, and a novel form of polymorphism.

The human dihydrofolate reductase (DHFR; tetrahydrofolate dehydrogenase; 5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) gene family includes a functional gene (hDHFR) and at least four intronless genes. Three intronless genes (hDHFR-psi 2, hDHFR-psi 3, and hDHFR-psi 4) are identifiable as pseudogenes because of DNA sequence divergence from the functional gene with introns, while one intronless gene (hDHFR-psi 1) is completely homologous to the coding sequences of the functional gene. Analysis of genomic DNA from two panels of somatic human-rodent cell hybrids with specific molecular probes provide insight into the chromosomal organization and assignment of these genes. The five genes are dispersed in that each one is found on a different chromosome. The functional gene hDHFR has been assigned to chromosome 5, and one pseudogene (hDHFR-psi 4), to chromosome 3. In a human cell line (HeLa) that was selected for methotrexate resistance, the functional locus became amplified, while there was no amplification of the four intronless pseudogenes. hDHFR-psi 1 was found to be present in DNA of some individuals and absent from DNA of others, consistent with a recent evolutionary origin of this gene originally suggested by its sequence identity to the coding portions of the functional gene. The presence or absence of this intronless pseudogene represents a previously unreported form of DNA polymorphism.

Animals↗
PubMed1984

Absence of genotoxicity of the carcinogenic sulfated polysaccharides carrageenan and dextran sulfate in mammalian DNA repair and bacterial mutagenicity assays.

The sulfated polysaccharides degraded carrageenan and dextran sulfate sodium were studied for genotoxicity using DNA repair tests employing cultured rat hepatocytes or intestinal mucosal cells. No evidence of unscheduled DNA synthesis was obtained. In addition, both alone and in combination with the comutagen norharman, these substances were nonmutagenic in the Salmonella microsome/mutagenicity test. These findings suggest that the carcinogenicity of the sulfated polysaccharides may be due to nongenotoxic mechanisms.

Animals↗
PubMed1984

Successful treatment of thyrotoxic crisis with plasma exchange.

A 36-yr-old woman with thyroid storm was successfully treated with plasma exchange. After the first plasma exchange, free serum thyroxine (T4) was decreased and serum thyroxine-binding globulin (TBG) was significantly increased. The decrease in the patient's free T4 level after plasma exchange can perhaps be attributed to T4's increased binding capacity. Plasma exchange may be an effective therapy for thyrotoxic crisis and should be performed immediately if conventional therapy fails to improve the patient's condition.

Adult↗
PubMed1984

Ecology of non-O 1 Vibrio cholerae in Toyama Prefecture.

The ecology of non-O 1 Vibrio cholerae and Vibrio mimicus as causes of cholera-like diarrhea or seafood-associated gastroenteritis has been investigated in Toyama Prefecture since 1980. The relationship between biological or serological characteristics of the isolates and their enteropathogenicity is discussed. Overall isolation rates from river water, sea water, and fish were 24.0, 59.5, and 33.7%, respectively, the isolation frequency being, in general, extremely high in the summer season, although the organisms were detected all year around in the case of sea water. Most isolates from river water were unable to grow on plates of TCBS agar to which colistin was added at a concentration of 1 microgram/ml (CL-TCBS). These strains quickly fermented cellobiose. O-51 and O-70 were the two most frequently detected serogroups among them and they did not show enteropathogenicity in the rabbit ileal loop ( RIL ) test. On the other hand, almost all isolates from sea water and fish as well as those from human diarrhea cases were able to grow on CL-TCBS, but were unable to ferment cellobiose quickly. O-36, O-10, O-6, O-8, O-39, and O-26 were the dominant serogroups of these isolates, and some of them showed enteropathogenicity in the RIL test. Six out of 98 isolates from river water, 14 out of 116 from sea water, and 19 out of 112 from fish were classified as Vibrio mimicus . All of these strains were able to grow on CL-TCBS and quickly fermented mannose but not cellobiose. O-41 was the most common serogroup among them and some of these strains showed enteropathogenicity in the RIL test. Production of a cholera-like enterotoxin among the isolates in Toyama Prefecture, if any, seemed to be poor.

Animals↗
PubMed1984

Light and electron microscopic studies on the cytological changes in the rat pancreatic islets induced by sodium diethyl dithiocarbamate (DEDTC) administration.

The effect of sodium diethyl dithiocarbamate ( DEDTC ) administration upon the structure of the pancreatic islet cells has been examined in the rat. In light microscopy, the aldehyde fuchsin stainability of the B cell granules was found to increase notably at 6 h and thereafter following the medication. In electron microscopy, the B cell granules with a porous core were shown to predominate over those with a homogeneous core containing paracrystalline structures between 30 min and 3 h following the medication. Between 6 and 12 h following medication, occasional B cells were seen to be provided with large secretory granules with a porous core. The results of the present study have been discussed with special reference to the chelating action of DEDTC .

Animals↗
PubMed1984

Improvement of pacing induced regional myocardial ischemia by Solcoseryl in conscious dogs with coronary stenosis.

The effects of Solcoseryl on regional myocardial function were studied in 5 conscious dogs with partial coronary constriction, in which temporary ischemia was induced by rapid cardiac pacing. During the coronary artery constriction, the percent shortening of the ischemic segment decreased by 9%. When the heart rate was increased by pacing, the percent shortening of the ischemic segments was further reduced by 57%. On cessation of cardiac pacing, the early potentiation of dP/dt and of control segment shortening became evident and was followed by exponential decay in the subsequent several beats. In the ischemic segment, the percent shortening was significantly improved in the first post-pacing beat but was more severely depressed at five seconds. Thirty minutes after administration of Solcoseryl, the cardiac pacing was repeated in the same manner but the pacing-induced hypokinesia of the ischemic segment were less marked, the percent shortening being at an average of 9.1% during control pacing and 12.7% during the second pacing after Solcoseryl (p less than 0.05). Postpacing deterioration of the ischemic segment shortening was also significantly improved from 9.8 to 11.8% at 5 seconds (p less than 0.05). These findings indicate that Solcoseryl exerts protective effects on the ischemic myocardium by promoting a rapid recovery from ischemia, probably due to the improvement of oxygen utility through activated cellular respiration.

Actihaemyl↗
PubMed1984

Abnormal blood chemistry data in Cushing's syndrome: comparison with those for fatty liver.

It has been reported that fatty liver is not uncommon in Cushing's syndrome. Biochemical data obtained from routine blood chemistry in 10 patients with Cushing's syndrome were compared with those for 15 patients with histologically verified fatty liver. We found an absence of a decreased GOT/GPT ratio, low normal choline esterase and increased lactic dehydrogenase activities together with lowered serum protein and albumin, and increased blood sugar and total cholesterol in Cushing's syndrome when compared with those of fatty liver cases. These data and additional findings in liver histology obtained from one patient with Cushing's syndrome due to adrenocortical carcinoma indicated that fatty changes in the liver were not frequently encountered in Cushing's syndrome. These abnormal biochemical data might be a way of distinguishing Cushing's syndrome from fatty liver.

Adult↗