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T Shimada

Publications and source records attributed to T Shimada.

At least 469 records · Page 26Linked to original sources
PubMed1996

Characterization of microsomal cytochrome P450 enzymes involved in the oxidation of xenobiotic chemicals in human fetal liver and adult lungs.

Levels and catalytic activities of cytochrome P450 (P450) enzymes involved in the oxidation of drugs and carcinogens were determined in human adult lungs and fetal livers and compared with those in microsomes from adult livers. P450s immunoreactive with anti-human P4501A1 and anti-human P4503A antibodies were detected in fetal liver microsomes by immunoblotting analysis, and P450s related P4501A1, 2A6, 2C9, 2E1, and 3A4 were determined in adult lung microsomes; all of these P450 enzymes were detected in much higher amounts in adult liver microsomes except that P4501A2 was only the 1A subfamily of P450 found in adult livers. Drug oxidation activities with the substrates ethoxyresorufin, coumarin, 7-ethoxycoumarin, bufuralol, and testosterone were determined in these microsomes, and we found that none of the activities were higher in microsomes of adult lungs and fetal livers than in adult livers. Activation of procarcinogens to reactive metabolites that induce umu gene expression in Salmonella typhimurium TA1535/pSK1002 or NM2009 was also examined and it was found that activities with (+)- and (-)-enantiomers of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene were higher in fetal liver microsomes than adult lung or liver microsomes. The adult liver and lung activities for these two procarcinogens were similar on the basis of microsomal protein contents despite the fact that p450 contents are higher in liver than lung microsomes. alpha-Naphthoflavone, a known inhibitor of P4501A-related activities, did not affect these procarcinogen activation in fetal liver microsomes. Fetal liver microsomes catalyzed activation of aflatoxin B1 and sterigmatocystin, two procarcinogens known to be activated by P4503A4/7 in humans, although activation of carcinogenic arylamines that are good substrates for P4501A2 was much lower in microsomes of fetal livers and adult lungs than in adult livers. These results suggest that in human fetal livers at least two P450 enzymes, a form of P450 that is immunoreactive P4501A1 and P4503A7, are actually expressed and these enzymes are suggested as being involved in the activation of the (+)- and (-)-enantiomers of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene and the carcinogenic mycotoxins, respectively. The exact nature of the former enzyme in fetal livers is unknown. In adult human lungs, several P450 enzymes are expressed, although the precise roles of these enzymes in the oxidation of xenobiotics were not determined due to the low level of expression of these P450s.

Antibodies↗
PubMed1996

[Primary carcinosarcoma of TE lung--a report of two cases].

Carcinosarcoma is a rare lung tumor and accounts for less than 0.3% of primary lung malignancies. Since the first description by Kika in 1908, only 36 cases with this kind of tumor have been appeared in the Japanese literatures by 1993. This report presents our surgical experiences of two cases with carcinosarcoma of the lung confirmed by pathological examination. Case 1: 64-year-old male underwent left lower lobectomy with lymph node resection. The patient has been well 27 months after the operation without tumor recurrence. Case 2: was a 75-year-old male, who underwent left upper lobectomy, partial resection of left lower lobe (S6) with lymph node resection. This patient died of aspiration pneumonia 90 days after successful resection of the tumor. In both patients, resected lung tumors were diagnosed to be true carcinosarcoma by histopathological examinations. True carcinosarcoma is defined to contain both cancelous and sarcomatous elements. Sarcomatous elements may differentiate into rhabdomyosarcoma, osteosarcoma and so on, or they may have non-epithelial elements demonstrated by electron microscopy or immunohistochemical studies. We reviewed the 36 cases with carcinosarcoma of the lung reported in Japanese literatures with special consideration of their histopathological findings. The prognosis of the patients with this rare tumor is also discussed according to the TMN stages.

Aged↗
PubMed1996

[Pulmonary sarcoidosis presenting with many cotton-like unilateral shadows].

A 22-year-old woman came to our hospital for a thorough examination of nodular lesions fund in the right lung field on a chest roentgenogram. A CT scan revealed typical cotton-like infiltrates: fluffy margins and granular interiors. Pulmonary sarcoidosis was diagnosed from examination of biopsy specimens from the lesions. The lesions disappeared in 6 months without therapy. Pulmonary sarcoidosis presenting only with many cotton-like unilateral shadows is rare. A cotton-like infiltrate seen on a CT scan is a valuable finding for the diagnosis of pulmonary sarcoidosis.

Adult↗
PubMed1996

[Heart conduction system and accessory pathways].

The morphology of atrioventricular (AV) junctions in the heart has been investigated using comparative anatomical analyses. For scanning electron microscopy, tissue blocks are treated with HCl to digest connective tissue elements. In fishes, amphibians and reptiles, there is a muscular system connecting the atrial muscle to the ventricular myocardium. These muscle fibers completely surround the inner surface of the atrioventricular ring and termed "ring muscular tissue", the cells of which are slender and small and vertically oriented. They contain small-sized mitochondria, relatively few myofibrils and variable amounts of glycogen. In mammalian hearts, the AV node and bundle system is the only functional myocardial connection between the atria and ventricles. Architecture and ultrastructure of AV nodal cells are similar to those of AV ring muscular tissue seen in the lower vertebrates. In human hearts, however, the muscle bundles which directly connect the atrium with the ventricle, i.e., accessory conduction pathways, are scarcely encountered. From the developmental- and comparative-anatomical points of view, it is likely that the accessory pathways in man are the remnants of the ring muscular tissue seen in lower vertebrates.

Animals↗
PubMed1996

In vivo and in vitro characterization of CYP2E1 activity in Japanese and Caucasians.

Chlorzoxazone's disposition after oral administration was determined in 20 young healthy Caucasian men and a similar group of Japanese men. The drug's plasma concentrations were significantly higher and its rate of elimination slower in Japanese compared to Caucasian men. Accordingly, chlorzoxazone's oral clearance was smaller (40%) in Japanese men and a similar difference (30%) was still apparent after normalizing for body weight (3.74 +/- 1.23 versus 5.05 +/- 1.41 ml.min-1.kg-1, P < .05). This slower elimination was associated with a reduced (fractional) clearance by 6-hydroxylation (2.34 +/- 1.04 ml.min-1.kg-1 versus 3.23 +/- 1.10, P < .05). Because such metabolism is mediated by cytochrome P4502E1 (CYP2E1), these findings suggest a lower level of the enzyme's catalytic activity in Japanese men. This was confirmed by in vitro studies with microsomes prepared from livers of individuals representative of the two racial groups. CYP2E1 levels were lower (61% P < .002) and CYP2E1-mediated chlorzoxazone 6-hydroxylase (22%, P < .001) and aniline 4-hydroylase (35%, P < .0001) activities were reduced in Japanese preparations compared to those from Caucasians. No relationships were found between measures of CYP2E1 activity, both in vivo and in vitro, and genomic polymorphisms in the CYP2E1 gene identified by Rsal/Pstl and Dral restriction fragment length polymorphisms. Collectively, these data show an interracial difference in CYP2E1 activity. Because this enzyme is importantly involved in the activation of environmental procarcinogens, such a difference may account, in part, for the lower rate of some cancers, e.g., lung cancer, in Japanese compared to Caucasians men.

Adolescent↗
PubMed1996

Sucralfate and Helicobacter pylori.

Sucralfate enhances the eradication rate of Helicobacter pylori when administered with antibiotics. Sucralfate acts on H. pylori through mucus gel. Whether sucralfate exerts its anti-ulcer action through the eradication of H. pylori is still controversial. As sucralfate itself is an effective, well-tolerated and cost-effective anti-ulcer agent, its mechanisms of action should be investigated further.

Anti-Bacterial Agents↗
PubMed1996

Retinopathy in diabetic (KKA gamma) mice: diabetic microvascular changes to the retina in KKA gamma mice revealed by light and electron microscopy.

Pericytic changes in the retinal vessels of diabetic (KKA gamma) and control (C57BL) mice were studied by light and electron microscopy. An improved histochemical technique for alkaline phosphatase was used in the light microscopic study. In the control mice, a continuous pathway was identified extending from the retinal arterioles, via the superficial and deep retinal capillaries, to the retinal venules. The deep retinal capillaries formed networks and were localized within the deeper retinal layers; the retinal arterioles, superficial capillaries, and venules were present in the nerve fiber layer. Examination of KKA gamma mice, aged 16 to 28 weeks, revealed engorgement of the arterioles, hypertrophy of the pericytes (which contained numerous actin filaments) within the superficial retinal capillaries, and narrowing of the deep retinal capillaries. These microvascular changes indicate retinal hyperperfusion, local hypertension of the superficial retinal capillaries, adaptive hyperfunctional changes in the pericytes of these capillaries, and ischemia of the deep retinal capillaries. The pericytic changes observed in the diabetic capillaries contrasted sharply with previous reports; an explanation for this variance is suggested.

Alkaline Phosphatase↗
PubMed1996

[Erythropoietin improved anemia in a case of multicentric Castleman's disease].

Severe anemia A 37 year-old male with therapy resistant multicentric Castleman's disease (MCD) anemia was treated by subcutaneous injection of erythropoietin. Although immunoglobulin and CRP concentration increased, anemia obviously improved with hemoglobin levels increasing from 4.8 g/dl to 8.5 g/dl without any side effects. Colony assay revealed that the bone marrow mononuclear cells responded to erythropoietin in a dose dependent manner. The mechanism of anemia of MCD is not clearly understood, and treatment is sometimes very difficult. There is no other previous report concerning erythropoietin as a treatment for anemia in MCD.

Adult↗
PubMed1996

Factors affecting appearance patterns of hip-flexion contractures and their effects on postural and gait abnormalities.

Hip flexion contractures accompanying various orthopedic and neurologic conditions not only limits the physical activities of the patients but also distorts their postures and gait patterns. The purposes of this study were to characterize the appearance patterns of flexion contracture at the hip joints and to elucidate how this disability affects their postural and gait abnormalities. Seventy-eight patients (mean age of 68.1 +/- 10.5 years) with hemiplegia, femoral neck fractures, osteoarthritis of the hip and other conditions causing hip flexion contractures were studied. The presence and degree of hip flexion contracture were estimated in the supine position using the Thomas maneuver with a goniometer. Relationship between appearance patterns and 12-survey variables was also analyzed statistically. As a result, it was revealed that whether lack of mobility caused by hip flexion contracture was compensated for by pelvic tilt an an increase of lumbar lordosis or not was affected by four factors. It was also revealed that whether it appeared unilaterally or bilaterally was affected by five factors. In addition, some postural and gait abnormalities caused by hip flexion contracture were observed in many patients. These results suggest that clinical pictures of the patient's posture and gait abnormality depend on his ability to regulate the position of the trunk and knees as well as the mobility of his spine.

Adolescent↗
PubMed1996

Characterization of Aeromonas hydrophila: a comparative study of strains isolated from diarrheal feces and the environment.

Thirty-five strains of Aeromonas hydrophila isolated from feces of diarrheal patients and from the environments were collected from Thailand and Japan. The physiological, biochemical, and serological characteristics, antibiotic resistance patterns and cell surface-related properties were compared. The diarrheal and environmental isolates of A hydrophila were found to be remarkably consistent in general culture and biochemical characteristics, with the exception of the reaction to D-arabinose in which the diarrheal strains were positive and environmental strains were negative. The plasmid patterns and cell surface-related properties of the environmental and diarrheal isolates were different. All strains produced Vero cell cytotoxin, hemolysin and lecithinase at 37 degrees, 30 degrees and 15 degrees C. In contrast, 83% of the environmental strains produced these virulence factors even at 4 degrees C. All strains indicated almost uniform susceptibility to the 16 antibiotics tested. Variations were found in the plasmid profile, toxin production in relation to the differences of temperature and cell surface-related properties of the strains. These variations between the clinical and environmental isolates could have potential as epidemiological markers for the sources of strains.

Aeromonas hydrophila↗
PubMed1996

[Pericardial cyst].

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed1995

Loss of expression of the human MSH3 gene in hematological malignancies.

Human MSH3 (hMSH3), previously named human mismatch repair protein 1 (MRP1), is one of the human homologs of the bacterial DNA mismatch repair protein MutS. The hMSH3 gene is expressed at low level in most types of cells. Using the RT-PCR technique, we examined the expression of the hMSH3 gene in bone marrow cells from 40 patients with various hematological malignancies. The hMSH3 mRNA was not detectable in 7 cases including 3 of chronic myelogenous leukemia, 2 of acute myelogenous leukemia, and 1 of acute lymphocytic leukemia, and 1 of myelodysplastic syndrome. In addition, 17 cases showed significantly reduced expression of the hMSH3 gene. Southern blot analysis of genomic DNA demonstrated no remarkable changes in the structure and the copy number of the hMSH3 gene in all cases. These results suggest that inactivation of the hMSH3 gene may be involved in the development of hematological malignancies.

Base Sequence↗
PubMed1995

Mutagenic activation of 3-methoxy-4-aminoazobenzene by mouse renal cytochrome P450 CYP4B1: cloning and characterization of mouse CYP4B1.

A new P450 responsible for mutagenic activation of 3-methoxy-4-aminoazobenzene (3-MeO-AAB) which is a potent procarcinogen was purified from renal microsomes of male mice using an index of umu gene expression. The purified P450 had high bioactivation toward 3-MeO-AAB and also 2-aminofluorene and 2-aminoanthracene. The antibody against this P450 completely inhibited mutagenic activation of 3-MeO-AAB of mouse renal microsomes. With immunoblotting, this form was present abundantly in renal microsomes of male mice but not in those of female mice. This P450 was also present in pulmonary microsomes of male and female mice but not in hepatic microsomes. The NH2-terminal amino acid sequence analysis indicated that this form belonged to the CYP4B subfamily. Thus, mouse kidney cDNA library was screened with rat CYP4B1 probe. The cDNA-deduced amino acid sequence of isolated cDNA consisted of 511 amino acids and bore 90, 86, and 84% similarities to rat, rabbit, and human CYP4B1, respectively. The NH2-terminal amino acid sequence of the purified renal P450 and amino acid sequence of BrCN-digested peptides from the purified P450 agreed with the cDNA-deduced amino acid sequence. These results suggest that CYP4B1 is a major form in renal microsomes of male mice and plays a major role in mutagenic activation of 3-MeO-AAB. In extrahepatic tissue, CYP4B1 may contribute to chemical carcinogenesis.

Amino Acid Sequence↗
PubMed1995

Roles of divalent metal ions in oxidations catalyzed by recombinant cytochrome P450 3A4 and replacement of NADPH--cytochrome P450 reductase with other flavoproteins, ferredoxin, and oxygen surrogates.

Recombinant cytochrome P450 (P450) 3A4 was most active in nifedipine and testosterone oxidation in a system including NADPH-P450 reductase, cytochrome b5 (b5), a semisynthetic phospholipid mixture plus cholate, glutathione, and MgCl2. The MgCl2 effect could be seen with high concentrations of Ca2+ or Sr2+ but not readily when these cations were replaced with monovalent cations. The divalent cation effect was also seen in liver microsomes. Part of the basis of this effect appears to be enhanced rates of b5 reduction, as judged from studies on deletions of reconstitution components and analysis of steady-state spectral studies. Rapid reduction of ferric P450 3A4 to ferrous was dependent upon the presence of substrate, either testosterone or ethylmorphine. When testosterone was present, reduction was also highly dependent upon the presence of b5 and Mg2+. In the case of the substrate ethylmorphine, the need to add b5 and Mg2+ to obtain optimal reduction rates was less pronounced. These patterns are consistent with the dramatic dependence of testosterone 6 beta-hydroxylation on b5 and the lack of dependence of ethylmorphine N-demethylation on b5. Our interpretation is that divalent cations stimulate electron transfer from NADPH-P450 reductase to several acceptors and that substrates and b5 can bind to P450 3A4 to influence its rate of reduction by the reductase. P450 3A4 catalyzed testosterone 6 beta-hydroxylation within Escherichia coli cells. The reactions could be supported by E. coli cytosol or by purified E. coli flavodoxin and NADPH-flavodoxin reductase. Spinach ferredoxin and NADPH-ferredoxin reductase also supported catalytic activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Diversity of DNA sequences among Vibrio cholerae O139 Bengal detected by PCR-based DNA fingerprinting.

Vibrio cholerae O139, a causative agent of a large epidemic of cholera-like illness, has suddenly emerged and spread widely over several months. To investigate the characteristics unique to O139, traditional typing techniques for V. cholerae, such as biochemical characteristics, antibiotic susceptibility and detection of toxin production, were performed, with the result that 145 O139 strains, except for two O139 strains isolated from Argentina and Germany, were indistinguishable from O1 strains. Thus, in order to clarify the genetical relatedness among O139 strains, and between O139 and O1 strains, the RAPD (random amplified polymorphic DNA) DNA fingerprinting method was undertaken. Although the RAPD arrays in five O139 isolates from Vellore with one arbitrary primer were slightly different from the other O139 strains, the RAPD patterns of the 145 forty-five O139 strains except for two O139 strains from Argentina and Germany were quite similar to each other, but were different from those of O1 strains, indicating that those O139 epidemic strains are closely related to each other regardless of their place of isolation. Furthermore, the RAPD patterns of the O139 strains resembled those of E1 Tor strains rather than classical strain, and a small change in the RAPD pattern of O139 strains occurred during subculture for 200 generations. These results taken together suggested that O139 V. cholerae have emerged from a common origin associated with the E1 Tor strain.

Base Sequence↗