Estimation of factors causing fluctuations and scattering in the interocclusal rest space.
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Adult↗
Biomedical subjects
T Shimada
Publications and source records attributed to T Shimada.
[Coronary reserve of the hypertensive heart: relationship to left ventricular hypertrophy].
We investigated the relationship between electrocardiographic left ventricular hypertrophy with ST-changes, and coronary circulation and myocardial metabolism in 25 patients with essential hypertension (systolic blood pressure greater than or equal to 160 mmHg, diastolic blood pressure greater than or equal to 95 mmHg). No patients had abnormal coronary arteriograms. They were categorized in two groups: non-hypertrophy group; cases with no hypertrophy on echocardiograms (interventricular septum and posterior wall thickness less than or equal to 11 mm), and hypertrophy group; cases with hypertrophy (wall thickness greater than or equal to 12 mm). Supine bicycle ergometry (50 watts, 50 rpm, 15 min) was performed during coronary sinus catheterization and electrocardiography. For cardiac hemodynamics, the coronary circulation and myocardial metabolism were observed at rest and during exercise. There was no significant difference in unit coronary blood flow (coronary blood flow per 100 gm) before exercise between the two groups. Unit coronary blood flow was significantly greater in the non-hypertrophy group after exercise. However, total coronary blood flow (coronary blood flow per 100 gm x left ventricular mass) showed no significant difference between the two groups. Coronary vascular resistance per 100 gm was higher in the hypertrophy group during exercise, though there was no significant difference at rest. Myocardial oxygen extraction O2 (A-C) was not different between the two groups at rest and during exercise, but unit myocardial oxygen consumption (MVO2) during exercise was higher in the non-hypertrophy group than in the hypertrophy group. The lactate extraction ratio tended to decrease in the hypertrophy group during exercise, and tended to increase in the non-hypertrophy group. Myocardial potassium flux tended to increase in the hypertrophy group during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Activation of mutagens by human cytochrome P-450 enzymes.
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Alkylation↗
[Kinetics and clinical application of 99mTc-technegas].
Biological characteristics and clinical utilization of 99mTc-technegas were evaluated in three normal volunteers and 10 patients with various pulmonary diseases. 99mTc-pertechnetate (296 MBq (8 mCi] was injected in the crusible of 99mTc-technegas generator, and about 37 MBq (1 mCi) of 99mTc-technegas was inhaled in the lung by three times of deep inspiration. Blood activity was appeared immediately after inhalation of 99mTc-technegas and it was 0.2% of the inhaled dose/liter of blood after 2 hours. Urine activity was also increased after inhalation and cumulative dose was 4.96% of the inhaled dose after 24 hours. The tracer dose to distribution to the lung was about 95% of the total dose in whole body. Biological half time of 99mTc-technegas in the lung was 135 hours and pulmonary image was stable even after 24 hours. Radiation dose to the lung was 0.004 Gy/37 MBq (1 mCi). In patients with pulmonary disease, distribution of 99mTc-technegas was similar to that of 81mKr gas, although defect on 99mTc-technegas image was larger in severe obstructive disease. 99mTc-technegas study was superior over 133Xe gas study to identify the areas of ventilation abnormality more clearly, although quantitative evaluation was difficult in 99mTc-technegas study. On comparative study with 99mTc-aerosol, 99mTc-technegas distributed in more peripheral sites and both methods were cooperative for evaluation of ventilatory disturbance. These results suggest that 99mTc-technegas inhalation study is safe and useful method for ventilation study.
Administration, Inhalation↗
Lidocaine metabolism by human cytochrome P-450s purified from hepatic microsomes: comparison of those with rat hepatic cytochrome P-450s.
The metabolism of lidocaine by human hepatic microsomes and purified human cytochrome P-450s, P-450NF (P450IIIA4), P-450MP (a P450IIC form) and P-450PA (P450IA2) was examined and their metabolism was compared with that by rat hepatic cytochrome P-450s. Human hepatic microsomes produced monoethylglycinexylidide (MEGX) and 3-hydroxylidocaine (3-OH-LID) from lidocaine. In a reconstituted system with dilauroylphosphatidylcholine, P-450NF efficiently produced MEGX. P-450PA was not efficient in lidocaine N-deethylation (formation of MEGX) but produced 3-OH-LID. P-450NF and P-450MP did not produce 3-OH-LID. Lidocaine N-deethylation activity of P-450NF was enhanced in a modified reconstituted system with a phospholipid mixture and sodium cholate. P-450NF appears to be an ortholog to rat P450 PB-1 (P450IIIA2). Anti-P450 PB-1 antibody cross-reacted with P-450NF and efficiently inhibited lidocaine N-deethylation in human hepatic microsomes. The correlation of lidocaine N-deethylation activity with the concentration of P-450NF determined immunochemically with anti-P450 PB-1 antibody was good (r = 0.81). In addition, correlation between P-450NF content estimated with anti-P450 PB-1 and anti-P-450NF preparations was good (r = 0.96). These results suggest that rat P450 PB-1 and human P-450NF have closely related properties and P-450NF is the major enzyme involved in lidocaine N-deethylation in human hepatic microsomes.
Adult↗
[Skin peripheral perfusion pressure (SPPP) in the leg using a technique of 133Xe clearance method].
We developed a new technique for measuring skin peripheral perfusion pressure (SPPP) in the leg by 133Xe clearance method and studied the SPPP in 50 normal volunteers and 86 diabetic patients, including 16 diabetics with gangrene. The SPPP in normal subjects, diabetics without gangrene and diabetics with gangrene were 41.9 +/- 8.6 cmH2O, 30.2 +/- 12.7 cmH2O and 19.4 +/- 10.3 cmH2O, respectively. Our result revealed that the SPPP in diabetics with gangrene was significantly lowest in three groups. The decrease of the SPPP in the diabetics may be due to the steal phenomenon of the blood flow through the abnormally dilated arteriovenous shunt vessels caused by the diabetic neuropathy. The measurement of the SPPP is very useful to assess the impairment of peripheral circulation.
Adult↗
[Fulminant hepatic failure induced by intermediate dose methotrexate in a case of non-Hodgkin's lymphoma].
Methotrexate (MTX) is frequently used as an antifolics agent in many malignant neoplasms such as leukemia, lymphoma and osteosarcoma. The major side effects of MTX are liver and renal damages, bone marrow suppression and so on. But careful management and citrovorum factor rescue could decrease the incidence and degree of these side effects. In this report, we described a patient with non-Hodgkin's lymphoma who developed and died of fulminant hepatic failure soon after the administration of intermediate dose MTX. Serological tests for HB virus were not changed throughout, and lymphocyte stimulation test for MTX was strongly positive. His autopsy revealed no inflammatory cell infiltration into the liver, but marked biliary congestion which is a distinctive feature of drug induced hepatitis. From above results, it was suggested that nature of this fulminant hepatic failure was an allergic reaction to MTX. There is no previous report which is concerning about MTX and fetal drug related hepatic failure.
Adult↗
[A comparative study of myocardial scintigraphy with 99mTc-SQ-30,217 and 201Tl in cases with myocardial infarction].
A comparative study of myocardial scintigraphy with 99mTc-SQ-30217 (SQ) and 201Tl was performed in 6 patients having ischemic heart diseases which were confirmed by the coronary angiography. The SQ study was done 1 week after the 201Tl study. Both studies were performed in exercise and resting state. Degree of perfusion defect was compared between SQ and 201Tl SPECT by means of scoring 0-2 (0: no defect, 1: equivocal, 2: definite defect) by five doctors (two physicians and three radiologists). Ability of this agent to detect the ischemic lesions was similar to that of 201Tl except for two regions. Effect of the liver image on the evaluation of the inferior wall of the left ventricle was small on this study, although the hepatic accumulation of the tracer was prominent. This agent is a promising tracer for the evaluation of myocardial perfusion in the cases with myocardial infarction.
Heart↗
[The role and clinical value of thallium-201 myocardial scintigraphy in ischemic heart disease].
To define the role and clinical value of thallium-201 myocardial scintigraphy in ischemic heart disease, 967 consecutive patients referred to our laboratory since 1985 were studied. The purpose of scintigraphy has changed from diagnosing myocardial ischemia to assessing myocardial viability with the progress of coronary angioplasty. At present, thallium-201 myocardial scintigraphy has become an indispensable noninvasive method for the management of patients with ischemic heart disease.
Adolescent↗
[Clinical evaluation of Kr-81m inhalation study through a dead space].
A new inhalation technique of 81mKr gas was applied to evaluate the pathophysiological abnormality of ventilation. 81mKr gas (370 MBq) was continuously supplied into a mouth piece directly (without dead space), VE, or through a dead space of 500 ml, VL, in 110 subjects with various lung diseases. Subjects were divided in four groups by a combination of distribution patterns of 81mKr gas obtained by these two inhalation techniques. Group 1: No ventilatory defect in both techniques. Group 2: Defects larger in VE than VL. Group 3: Defects larger in VL than VE. Group 4: No remarkable difference in defects in both techniques. Cases of group 1 were normal in pulmonary function test and chest X-ray. Finding of group 2 reflects early airway closure. This group consisted of cases in remission of bronchial asthma, small air way disease and pulmonary congestion. In group 3, restrictive disease and obstructive disease, especially emphysema, were included. Patients with severe obstructive disease and organized change of pulmonary parenchyma were belonged in group 4. In ventilation study with 81mKr gas, a combined study of inhalation technique through a dead space and by direct infusion may be useful to evaluate a pathophysiological change of various pulmonary diseases.
Administration, Inhalation↗
[Pulmonary clearance of 99mTc-HMPAO aerosol].
The clearance rate of inhaled aerosols of a lipophilic substance, 99mTc-HMPAO (Hexamethyl propylene amine oxime) was studied and compared to that of hydrophilic substances in 6 normal volunteers and 18 patients with lung diseases. The subject in sitting position inhaled a single deep breath of 99mTc-HMPAO aerosols, and held his breath about 30 sec. Then he continued to breath aerosols again for about 3 min. Radioactivity rapidly falls down during breath holding, to about 60% of the peak value (fast phase), with T 1/2 of 3.75 +/- 2.22 sec in 6 normal volunteers. This rapid phase was not appeared in hydrophilic aerosols with 99mTc-DTPA and 99mTc-pertechnetate and in lipophilic aerosol with 123I-IMP aerosol. The clearance of residual activity of 99mTc-HMPAO was slow with T 1/2 of 17.4 +/- 4.0 min. The T 1/2 of 99mTc-DTPA, 99mTc-pertechnetate and 123I-IMP were 50.2 +/- 20.9 min, 11.4 +/- 4.3, and 62.5 +/- 20.8 min respectively. 99mTc-HMPAO may cross transcellularly using the whole alveolar surface. The clearance of aerosols in the fast phase is rapid and depend on the regional perfusion. On the other hand, hydrophilic aerosol pass by an intercellular pathway and the clearance will be diffusion limited. As conclusion, inhalation study of 99mTc-HMPAO might be a new method to evaluate perfusion following ventilation study.
Administration, Inhalation↗
A 165-base pair sequence between the dihydrofolate reductase gene and the divergently transcribed upstream gene is sufficient for bidirectional transcriptional activity.
The dihydrofolate reductase gene encodes a key enzyme of one-carbon metabolism and is constitutively expressed in all cells. Recently, transcripts initiated at 89 base pairs upstream from the transcriptional initiation site of the dihydrofolate reductase gene and transcribed from the opposite strand have been identified and shown to encode for a protein with homology to a bacterial DNA mismatch repair enzyme (Fujii, H., and Shimada, T. (1989) J. Biol. Chem. 264, 10057-10064). Therefore, the two genes are organized in a head-to-head configuration separated by an 89-base pair segment. The promoter activities of this short spacer sequence were studied in a transient assay using the chloramphenicol acetyltransferase and the guanine phosphoribosyltransferase genes as reporters. A 165-base pair fragment from -111 to +54 relative to the dihydrofolate reductase initiation site was shown to be sufficient for transcriptional activity in either direction, suggesting that expression of the two divergent genes is regulated by a bidirectional promoter that may use common regulatory elements.
Animals↗
Roles of individual human cytochrome P-450 enzymes in the bioactivation of benzo(a)pyrene, 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, and other dihydrodiol derivatives of polycyclic aromatic hydrocarbons.
Human liver microsomes oxidized 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene [B(a)P-7,8-diol] to products that yield DNA adduct formation and umu gene expression in the tester system Salmonella typhimurium TA1535/pSK1002. The umu response is correlated to levels of microsomal cytochrome P-450NF (P-450NF) and nifedipine oxidation in different human liver samples used for activation, and both the (+)- and (-)-enantiomers of B(a)P-7,8-diol gave similar results in these and other assays. The microsomal umu response was inhibited by antibodies raised against P-450NF. 7,8-Benzoflavone stimulated the B(a)P-7,8-diol-dependent umu response observed with purified P-450NF and human liver and lung microsomes. Thus, P-450NF appears to be the major enzyme involved in the activation of B(a)P-7,8-diol in human liver and possibly lung. Similar results were obtained for the activation of trans-9,10-dihydroxy-9,10-dihydrobenzo(b)fluoranthene and trans-3,4-dihydroxy-3,4-dihydro-7,12-dimethylbenz(a)anthracene, compounds that are known to form highly tumorigenic diol-epoxides. The major product of the oxidation of (+)-B(a)P-7,8-diol was the cis-syn isomer of benzo(a)pyrene-7,8,9,10-tetraol[7 beta, 8 alpha, 9 beta, 10 beta-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene]. Studies on the nature of the human liver enzymes involved in the formation of B(a)P-7,8-diol [from benzo(a)pyrene] indicate that neither P-450NF, P-450PA, P-450j, P-450DB, nor P-450MP is involved. The correlation of 7,8-diol formation with phenacetin O-deethylation in a set of liver samples and the partial inhibition of the reaction by 7,8-benzoflavone and anti-rat P-450 beta NF-B suggest that the enzyme involved may be P1-450, the human ortholog of rat P-450 beta NF-B, which catalyzes both the formation of B(a)P-7,8-diol and its subsequent oxidation in tissues of polycyclic hydrocarbon-treated rats. The differential effects of inhibitors indicate that benzo(a)pyrene 3-hydroxylation, 4,5-epoxidation, and 9,10-epoxidation are catalyzed by an enzyme(s) distinct from that which forms the 7,8-epoxide. The roles of the human P-450 enzymes differ from the rodent orthologs in the paradigm for bioactivation of polycyclic hydrocarbons; further, flavones appear to have opposing effects on diol formation and further epoxidation in both human liver and lung.
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
A frequent DHFR polymorphism detected by an intron fragment.
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Chromosomes, Human, Pair 5↗
Human liver microsomal cytochrome P-450 enzymes involved in the bioactivation of procarcinogens detected by umu gene response in Salmonella typhimurium TA 1535/pSK1002.
A total of 57 procarcinogens was examined for induction of umu gene response in the chimeric plasmid pSK1002, carried in Salmonella typhimurium TA 1535, after incubation with a series of human liver microsomal preparations which had been selected on the basis of characteristic levels of individual cytochrome P-450 (P-450) enzymes. The 18 most active compounds were selected and further analyzed using the umu gene response and correlative studies with a larger number of microsomal preparations, enzyme reconstitution studies involving purified enzymes, immunochemical inhibition, and patterns of stimulation and inhibition of catalytic activity by 7,8-benzoflavone. The results collectively indicate that 16 of these 18 most potent genotoxins examined are activated primarily either by P-450NF (the nifedipine oxidase) or P-450PA (the phenacetin O-deethylase). P-450NF appears to be the major enzyme involved in the bioactivation of aflatoxin B1, aflatoxin G1, sterigmatocystin, trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, 6-aminochrysene, and tris-(2,3-dibromopropyl)phosphate in human liver. P-450PA appears to be the major enzyme involved in the bioactivation of 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3,5-dimethylimidazo[4, 5-f]quinoline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-aminoanthracene, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole, 2-aminofluorene, 2-acetylaminofluorene, 4-aminobiphenyl, 3-amino-1-methyl-5H-pyrido[4,3-b] indole, and 2-aminodipyrido[1,2-a:3',2'-d]imidazole. More than one enzyme appears to contribute significantly to the bioactivation of the other two compounds examined, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b] indole and 6-nitrochrysene. The literature suggests that the two human liver P-450s involved in activation of these 16 procarcinogens are highly inducible by barbiturates, macrolide antibodies, and certain steroids (P-450NF) and by smoking and ingestion of charcoal-containing food (P-450PA); noninvasive assays are available to monitor the function of both P-450NF and P-450PA.
Animals↗
Isolation and characterization of cDNA clones derived from the divergently transcribed gene in the region upstream from the human dihydrofolate reductase gene.
Transcripts initiated in the region immediately upstream from the human dihydrofolate reductase gene but transcribed from the opposite strand have been identified in human cells. These divergent upstream transcripts are polyadenylated, start at 89 base pairs upstream from the dihydrofolate reductase major initiation site, and are composed of two species of 5.0 and 3.8 kilobases in length. We have isolated complementary DNA clones derived from the divergent transcripts and identified a 3.5-kilobase open reading frame in one of these clones. Computer-assisted sequence analyses have shown that there is no significant sequence homology between the putative amino acid sequence and known protein sequences. This arrangement of two divergent transcriptional units suggests that the expression of these two genes may be regulated by a bidirectional promoter with common sequence elements.
Amino Acid Sequence↗
Effect of adenosine and adenosine analogs on [14C]aminopyrine accumulation by rabbit parietal cells.
Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate cyclase. We investigated the effect of adenosine and its analogs on [14C]aminopyrine accumulation by rabbit parietal cells. Rabbit gastric mucosal cells were isolated by enzyme digestion. Parietal cells were enriched by nonlinear percoll gradients. [14C]Aminopyrine accumulation was used as an indicator of acid secretion. The effect of 2-chloroadenosine on histamine-stimulated [14C]aminopyrine accumulation was studied. The effects of N-ethylcarboxamideadenosine, 2-chloroadenosine, stable analogs of adenosine, and adenosine on [14C]aminopyrine accumulation were assessed. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and carbachol, known secretagogues, stimulated [14C]aminopyrine accumulation. 2-Chloroadenosine did not suppress histamine-stimulated [14C]aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine dose dependently increased [14C]aminopyrine accumulation. The order of potency was N-ethylcarboxamideadenosine greater than 2-chloroadenosine greater than adenosine. 8-Phenyltheophylline and theophylline, adenosine-receptor antagonists, or cimetidine did not have significant effects on the increase of AP uptake induced by 2-chloroadenosine. Coadministration of dipyridamole, and adenosine uptake inhibitor, augmented the effect of adenosine on [14C]aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine each induced a significant increase in cellular cyclic AMP. We conclude that there may be adenosine A2 receptors on rabbit parietal cells which modulate gastric acid secretion.
2-Chloroadenosine↗
Splenic ablation by percutaneous injection of ethanolamine oleate in dogs: a possible therapy for hypersplenism.
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Administration, Cutaneous↗