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Biomedical subjects

T Shimada

Publications and source records attributed to T Shimada.

At least 577 records · Page 32Linked to original sources
PubMed1994

Interactions of ingested food, beverage, and tobacco components involving human cytochrome P4501A2, 2A6, 2E1, and 3A4 enzymes.

Human cytochrome P450 (P450) enzymes are involved in the oxidation of natural products found in foods, beverages, and tobacco products and their catalytic activities can also be modulated by components of the materials. The microsomal activation of aflatoxin B1 to the exo-8,9-epoxide is stimulated by flavone and 7,8-benzoflavone, and attenuated by the flavonoid naringenin, a major component of grapefruit. P4502E1 has been demonstrated to play a potentially major role in the activation of a number of very low-molecular weight cancer suspects, including ethyl carbamate (urethan), which is present in alcoholic beverages and particularly stone brandies. The enzyme (P4502E1) is also known to be inducible by ethanol. Tobacco contains a large number of potential carcinogens. In human liver microsomes a significant role for P4501A2 can be demonstrated in the activation of cigarette smoke condensate. Some of the genotoxicity may be due to arylamines. P4501A2 is also inhibited by components of crude cigarette smoke condensate. The tobacco-specific nitrosamines are activated by a number of P450 enzymes. Of those known to be present in human liver, P4501A2, 2A6, and 2E1 can activate these nitrosamines to genotoxic products.

Aflatoxin B1↗
PubMed1994

Phasic venous return abnormality in chronic pulmonary diseases: pulsed Doppler echocardiography study.

Features of venous return in chronic pulmonary diseases and factors determining such features were studied by analysis of respiration-related variation in the superior vena cava flow on pulsed Doppler echocardiography. Subjects of this study were 85 patients with chronic pulmonary diseases; 54 healthy subjects served as normal controls. In the healthy subjects, the velocity of the S and D waves increased during inspiration (type I pattern), and the velocity of the A wave increased during expiration. In the patients with pulmonary diseases, the pattern of the superior vena cava flow was either type I or type II (disappearance of the D wave or disappearance of both the D and S waves). The incidence of the type II pattern was significantly higher in the patients showing a reduction of both FEV1.0% and % VC. The respiration-related variation in the superior vena cava flow pattern was found to be determined by the pressure fall between right atrium and subclavian vein. A type II pattern was attributed to the elevation of right atrial pressure caused by positive pleural pressure. The velocity of the A wave increased during expiration, showing a good correlation with pulmonary vascular resistance. Venous return in the presence of chronic pulmonary disease was found to be affected by the type of ventilatory disturbance and intensity of pulmonary vascular resistance.

Adult↗
PubMed1994

A young case with multi-infarct dementia associated with lupus anticoagulant.

A 39-year-old man was admitted because of an abrupt onset of right-side weakness and dysarthria. During the 2 years before admission, he had suffered from insomnia, depressed mood and progressive memory disturbance. Neurological and psychiatric examination revealed severe intellectual impairment in addition to the neurological deficits. Neuroradiological examinations revealed multiple brain infarcts. He had no risk factor for stroke except for lupus anticoagulant. He was diagnosed as having multi-infarct dementia associated with antiphospholipid antibodies. This case suggests that it is necessary to investigate antiphospholipid antibodies in addition to neuroradiological examination when relatively young patients present with unexplained cognitive or behavioral symptoms.

Adult↗
PubMed1994

Reinnervation of allografted pancreatic islets in the rat liver.

Rat pancreatic islets were allografted in the liver and were studied morphologically in order to evaluate possible reinnervation. Islets isolated from rat pancreas were allotransplanted in the liver of streptozocin-induced diabetic rats via the portal vein. Electron microscopy revealed nerve endings with synaptic vesicles in the transplanted islets 100 days after transplantation, whereas axons in the islets appeared to degenerate several hours after isolation and prior to transplantation. These findings suggest that the nerve endings observed in the transplanted islets regenerate from nerves that innervate the recipient's liver. The tissue specimens were also investigated immunohistochemically using antityrosine hydroxylase antibody, and histochemically by the modified Karnovsky and Roots' method for visualizing acetylcholinesterase. Some nerve endings in the transplanted islets reacted positively to antityrosine hydroxylase antibody. Acetylcholinesterase was visualized in other nerves. These results indicate that norepinephrine- and acetylcholinesterase-containing nerves may reinnervate the transplanted islets.

Acetylcholinesterase↗
PubMed1994

New serovars of Plesiomonas shigelloides 1992.

Fourteen new O (O77-O9O) and 4 new H (H42-H45) antigens were described. Seven O and 2 new H antigens were revealed among strains not agglutinating with antisera against 76 O and 41 H officially recognized serovars. The most frequent was serovar O80:H38 which was isolated in 5 countries (Sweden, Czechoslovakia, Bulgaria, Yugoslavia and Canada) from human material and from sewage and surface water.

Antigens, Bacterial↗
PubMed1994

[Two cases of thymic cyst].

Thymic cysts were diagnosed by thoracotomy in two women with leprosy, both 64 years old, within 12 months. Both were asymptomatic and an abnormal mediastinal shadow on an annual screening chest radiograph was a clue to the diagnosis in both cases. According to retrospective studies it took at least six or seven years for the thymic cysts to become large enough to be detected. Real-time echography was effective in the diagnosis of a cystic lesion in one case. Thymic cysts are important cystic lesions rarely found in the anterior mediastinum. A resective operation is thought to be indispensable to differentiate them from thymomas accompanied by large cystic degeneration and from thymic cysts accompanied by malignancies.

Female↗
PubMed1994

Bufuralol hydroxylation by cytochrome P450 2D6 and 1A2 enzymes in human liver microsomes.

Bufuralol 1'-hydroxylation is a prototypical reaction catalyzed by cytochrome P450 (P450) 2D6, an enzyme known to show debrisoquine/sparteine-type genetic polymorphism in humans. In the present study we further examined the roles of several human P450 enzymes, as well as P450 2D6, in the hydroxylation of (+/-)-bufuralol, using liver microsomes from several human samples and human P450 enzymes expressed in human lymphoblastoid cell lines or Escherichia coli. Kinetic analysis of bufuralol 1'-hydroxylation by liver microsomes showed that there were different Km and Vmax values in seven human samples examined; low Km values (approximately 0.05 mM) were observed in four samples (including sample HL-18), high Km values (approximately 0.25 mM) in two samples (including sample HL-67), and an intermediate Km value (approximately 0.1 mM) in one sample. Quinidine and anti-rat P450 2D1 antibody almost completely inhibited bufuralol 1'-hydroxylation in human sample HL-18 at a substrate concentration of 0.4 mM, whereas these effects were not so drastic when liver microsomes from human sample HL-67 were used. In contrast, a very low concentration (< 10 microM) of alpha-naphthoflavone or anti-human P450 1A2 antibody significantly inhibited bufuralol 1'-hydroxylation catalyzed by human sample HL-67, but not HL-18, with 0.4 mM bufuralol. When the relative contents of P450 2D6 and P450 1A2 in 20 human samples were determined, bufuralol 1'-hydroxylation in samples containing large amounts of P450 2D6 tended to be more sensitive to quinidine, whereas the P450 1A2-rich samples were highly susceptible to alpha-naphthoflavone. However, at low substrate concentrations bufuralol 1'-hydroxylation was shown to be catalyzed principally by P450 2D6, based on the inhibitory effects of anti-rat P450 2D1 antibody and quinidine, in both human samples HL-18 and HL-67. At least five other, minor, bufuralol products were formed by human liver microsomes, in addition to 1'-hydroxybufuralol. Two of them were identified as 4- and 6-hydroxybufuralol by 1H NMR spectroscopy and mass spectrometry. The formation of the 4- and 6-hydroxylated products was suggested to be catalyzed by P450 1A2, based on the results of correlation with P450 1A2 contents in 60 human samples and inhibition by anti-P450 1A2 and alpha-naphthoflavone. Purified recombinant P450 1A2 (expressed in E. coli) produced 1'-, 4-, and 6-hydroxybufuralol in a reconstituted system, although P450 2D6 (expressed in human lymphoblast cell lines) was found to catalyze only bufuralol 1'-hydroxylation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Antagonists↗
PubMed1994

[Metabolism under total parenteral nutrition: the influence of different compositions of energy substrate].

Metabolism under total parenteral nutrition according to different compositions of energy substrate was studied using expiratory gas analysis in preoperative and postoperative esophageal cancer patients. The patients were derived from Group G (only glucose was administrated as a non-protein energy source) and group G+F (glucose and fat were administrated as non-protein energy sources). In the preoperative study, there was a significantly positive correlation between non-protein RQ and the energy sufficiency ratio (energy intake/BEE) and non-protein RQ in group G+F was lower than in group G at the same total energy intake. It was revealed that there was a limit to oxidation of exogenous glucose and whether exogenous energy sources are efficiently utilized or not depends on two factors, namely total energy intake and the combination of glucose and fat. In the postoperative study, fat was efficiently utilized in group G+F and glycogen recycling was dominant over fat recycling. Urinary epinephrine, 17-OHCS and 17-KS excretion were significantly high in group G+F. It was clear that energy metabolism and hormonal effect differ with exogenous energy substrate.

Aged↗
PubMed1994

[Present status and future prospects of human gene therapy].

Gene therapy is defined as the treatment of diseases by the transfer of genes into cells. This concept was originally emerged as the definitive therapy for genetic diseases. However, acquired diseases such as cancer and AIDS are now being considered for its potential targets. The first clinical trial of human gene therapy began in 1990 at the NIH for treating a patient with fatal severe combined immunodeficiency caused by adenosine deaminase deficiency. Gene therapy of cancer has also initiated at many research hospitals. Currently, more than 100 patients have already been treated by this innovative therapeutic strategy in the US. In Japan, the Expert Committee on Gene therapy was set up in the council on Science and the Public Health and Welfare in 1991. Recently, the committee released the guidelines of gene therapy. It is thought that the first gene therapy in Japan is not far off.

Forecasting↗
PubMed1994

[A case of resected gastric cancer in which cancer had apparently disappeared by preoperative administration of tegafur].

This paper reports a case of gastric carcinoma in which cancerous tissue was not found in the resected specimen, apparently due to preoperative tegafur administration. The patient was a 56-year-old woman who was diagnosed by initial endoscopic examination including endoscopic biopsy as having an advanced gastric cancer of Borrmann type 2. During the waiting period for operation, she was placed on oral administration of tegafur (Futrafur capsule) 600 mg 3 times a day for 31 days. The second endoscopic examination 14 days later showed reduction of both marginal elevation and central excavation of the lesion, and biopsy at this time was negative for carcinoma. Because of the initial definite diagnosis of cancer, a gastric resection was performed 31 days later, but no cancerous tissue was found in the resected specimen. This case was considered to be a carcinoma especially sensitive to tegafur.

Adenocarcinoma↗
PubMed1994

Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians.

Interindividual variations in the level and activity of cytochrome P-450 enzymes were investigated in the liver microsomes of 30 Japanese and 30 Caucasian patients. The P-450 enzymes used in this study included P-450 1A2, 2A6, 2B6, 2C, 2D6, 2E1 and 3A, and the monooxygenase activities determined were 13 typical P-450 substrates and 9 procarcinogens. Although the total P-450 content was higher in Caucasian (mean, 0.43 nmol/mg of protein) than in Japanese populations (mean, 0.26 nmol/mg of protein), the relative levels (percent of total P-450) of individual forms of P-450 determined immunochemically were not very different except that P-450 2A6 and 2B6 levels were higher in the Caucasians. About 70% of liver P-450 could be accounted for by P-450 1A2, 2A6, 2B6, 2C, 2D6, 2E1 and 3A proteins, and P-450 3A (about 30% of total P-450) and 2C (about 20%) enzymes were found to be the major forms. Considerable levels of P-450 1A2 (about 13%) and 2E1 (about 7%) could be determined, whereas the P-450 2A6 (about 4%), 2D6 (about 2%) and 2B6 (< 1%) were the minor P-450 forms. Differences in some of the P-450 1A2-, 2A6-, 2D6-, 2E1- and 3A4-dependent activities were observed in Japanese and Caucasian populations. No clear sex-related differences in individual P-450 contents and drug- and carcinogen-metabolizing activities were detected in 60 human samples, except that P-450 1A2-dependent activities were found to be higher in mean than in women in the Caucasian population only. A single neonate sample tended to be lower in P-450 1A2-, 2A6- and 2E1-dependent activities. In contrast to rat counterparts, we could not detect apparent developmental changes in P-450 content and activity in humans between 12 and 73 years old. Thus, the results presented in this study provide useful information for the study of drug biotransformation in humans and for the basis of drug toxicities, carcinogenesis and teratogenesis.

Adolescent↗
PubMed1993

O-antigenic lipopolysaccharide of Vibrio cholerae O139 Bengal, a new epidemic strain for recent cholera in the Indian subcontinent.

Lipopolysaccharide (LPS) from Vibrio cholerae O139 Bengal contained colitose (3,6-dideoxy-L-galactose) in addition to glucose, L-glycero-D-manno-heptose, fructose, glucosamine and quinovosamine in its polysaccharide and only glucosamine in lipid A, while perosamine, a characteristic component sugar of V. cholerae O1 LPS, was absent. 3-Hydroxydodecanoic, tetradecanoic and hexadecanoic acids as ester-bound fatty acids and 3-hydroxytetradecanoic acid as amide-bound fatty acid were identified in the lipid A. A very high serological specificity of O139 LPS distinct from that of O1 V. cholerae was demonstrated by passive hemolysis and passive hemolysis inhibition tests by using the LPS either as antigen for sensitizing sheep red blood cells or as inhibitor in the latter test.

Carbohydrates↗