[Original diseases causing chronic kidney failure and selection of their treatment].
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Glomerulonephritis↗
Biomedical subjects
T Shimada
Publications and source records attributed to T Shimada.
Characterization of human lung microsomal cytochrome P-450 1A1 and its role in the oxidation of chemical carcinogens.
Rat and human lung microsomal cytochrome P-450 (P-450) enzymes have been characterized with regard to their catalytic activities towards several xenobiotic chemicals, including procarcinogens, in different microsomal preparations. Rat lung microsomal P-450s were more active than the human P-450s in catalyzing most of the monooxygenation reactions. Human lung microsomal P-450 was solubilized and purified. Human lung microsomes contain approximately 10 pmol of P-450/mg of protein, on the basis of Fe2+.CO versus Fe2+ difference spectra of the eluates obtained from an octylamino-agarose column. The partially purified P-450 preparations from two human lung microsomal samples showed high activities for the conversion of both (+)- and (-)-isomers of 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene to genotoxic products. After DEAE-cellulose column chromatography, a partially purified P-450 fraction containing polypeptides of Mr 52,000 and 58,000 was obtained from the early fraction of the octylamino-agarose column eluate, and an electrophoretically homogeneous protein having a molecular weight of approximately 52,000 was recovered from a latter fraction. The amino-terminal amino acid sequences of the two peptides in the earlier fraction were determined; neither polypeptide appears to resemble any known P-450 protein. The protein from the latter octylamino-agarose fraction was immunoreactive with anti-rat P-450 1A2 and anti-human P-450 1A2 but not with antibodies raised against other P-450 enzymes or autoimmune antibodies that specifically recognize human P-450 1A2. A tryptic peptide was isolated from the preparation, and the amino acid sequence matched that of human P-450 1A1 perfectly (residues 31-48) but not that of human P-450 1A2. All of nine human lung microsomal samples examined contained proteins that were immunoreactive with rabbit anti-rat P-450 1A2 and catalyzed the activation of 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene. The activities could be inhibited by rabbit anti-rat P-450 1A2 and, to a lesser extent, by anti-rat P-450 1A1. The addition of 7,8-benzoflavone caused inhibition or stimulation, depending upon the particular human lung microsomal preparation. Thus, this work clearly shows that human lung microsomes contain at least two major P-450 enzymes; human P-450 1A1 is present in lungs and can actually catalyze the activation of environmental procarcinogens, including polycyclic aromatic hydrocarbons.
Animals↗
[Successful low-dose etoposide therapy for a case of myelofibrosis with chronic myelogenous leukemia megakaryocytic predominance type].
A 38-year-old woman presented with ear pain and vertigo. No hepatosplenomegaly or lymphadenopathy were found, but her platelet counts markedly rose to 414 x 10(4)/microliters with an increase of megakaryocytes in the bone marrow (859/microliters). Cytogenetic assay revealed positive Ph1 chromosome and rearrangement of the break point cluster region (bcr). Although platelet counts remained under 100 x 10(4)/microliters after the administration of carboquone, a high fever and pancytopenia appeared 31 months later. Bone marrow biopsy showed marked myelofibrosis which was improved by low dose etoposide. This case was thought to be Ph1 positive ET, but it was more compatible with CML megakaryocytic predominance type according to the newly proposed "Hannover criteria for myeloproliferative disorders" and cytogenetic assay.
Adult↗
Oxidation and conjugation of aflatoxins by humans and experimental animals.
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Aflatoxins↗
Molecular defect in familial lecithin:cholesterol acyltransferase (LCAT) deficiency: a single nucleotide insertion in LCAT gene causes a complete deficient type of the disease.
Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a hereditary disorder with clinical manifestations including corneal opacity, premature atherosclerosis and renal failure. In this study, we analyzed the molecular base underlying a case of Japanese LCAT deficiency, in which both LCAT mass and activity of the proband were nearly absent. DNA blot hybridization analysis showed no gross rearrangement in the LCAT gene of the proband. The nucleotide sequence analysis of the cloned LCAT gene demonstrated only an extra nucleotide "C" insertion at the first exon, when compared to the sequence of wild type. This single base insertion caused a shift of the following reading frame, probably resulting in a truncated abnormal LCAT polypeptide that consist of only 16 amino acids. The direct sequence analysis of PCR-amplified DNA showed only the same insertion, indicating that the LCAT-deficient proband is a homozygote for the mutant allele. These results indicate that the clinical and biochemical feature of the patient is mainly caused by a complete deficiency of the enzyme based on a homozygous abnormality of LCAT gene.
Adult↗
Superior vena cava flow and tricuspid anular motion after cardioversion of atrial fibrillation, and role of right atrial relaxation on systolic venous return.
To determine whether atrial relaxation or systolic descent of the tricuspid anulus is the predominant factor determining systolic venous return, 22 patients with atrial fibrillation were studied. Venous return (i.e., superior vena cava (SVC) flow) was measured using pulsed Doppler echocardiography. Systolic descent of the tricuspid anulus (i.e., total excursion of tricuspid anulus during systole) was also measured using echocardiography. Serial examinations were performed before and after cardioversion of atrial fibrillation in 15 patients. In 11 patients, both the total excursion of the tricuspid anulus and SVC flow were examined in relation to the ratio of the preceding to the pre-preceding RR interval (R2/R1). Systolic forward flow of SVC increased as the ratio of late diastolic to total excursion of the tricuspid anulus (i.e., right atrial systolic function) increased. It correlated significantly with the ratio of late diastolic to total excursion of the tricuspid anulus but not with total excursion. Total excursion of the tricuspid anulus correlated significantly with R2/R1, but systolic forward flow of SVC did not. These results indicate that atrial relaxation rather than systolic descent of the tricuspid anulus was the predominant factor determining systolic forward flow in the SVC.
Atrial Fibrillation↗
Autocrinological role of basic fibroblast growth factor on tube formation of vascular endothelial cells in vitro.
When bovine capillary endothelial (BCE) cells plated on type I collagen gel were covered with a second layer of collage gel, BCE cells reorganized into a network of capillary-like structures. In the presence of affinity purified anti-basic fibroblast growth factor (bFGF) antibody, this reorganization was inhibited. By using a computerized image analyzer, the formation of network structures and the effect of anti-bFGF antibody was quantitated. The inhibitory effect of anti-FGF antibody was dose-dependent and maximal inhibition was observed at 2.0 micrograms/ml of antibody. Exogenously added bFGF potentiated network formation of BCE cells and coadministration of bFGF abrogated the inhibitory effect of anti-bFGF antibody. Platelet factor 4, which blocks the binding of bFGF to its receptor, inhibited network formation. These results indicate that bFGF produced by endothelial cells regulates angiogenesis as an autocrine factor.
Adrenal Glands↗
Sequence of 5.8S ribosomal RNA in the mosquito, Culex tritaeniorhynchus.
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Animals↗
Activation of amino-alpha-carboline, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and a copper phthalocyanine cellulose extract of cigarette smoke condensate by cytochrome P-450 enzymes in rat and human liver microsomes.
The ability of cigarette smoke condensate to induce a genotoxic response has been measured in liver microsomal and reconstituted monooxygenase systems containing rat and human cytochrome P-450 (P-450) enzymes, as determined by umu gene expression in Salmonella typhimurium TA1535/pSK1002. The reactivities of amino-alpha-carboline and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), two compounds known to be present at considerable levels in cigarette smoke condensate, were also determined and compared with regard to genotoxicity. Amino-alpha-carboline and PhIP are activated principally by P-450 1A2 enzymes in human and rat liver microsomes: (a) activation of both compounds was catalyzed efficiently by liver microsomes prepared from rats treated with 5,6-benzoflavone, isosafrole, or the commercial polychlorinated biphenyl mixture Aroclor 1254, and the activities could be considerably inhibited by antibodies raised against P-450 1A1 or 1A2; (b) the rates of activation of these compounds were correlated with the amount of human P-450 1A2 and of phenacetin O-deethylation activity in different human liver microsomal preparations, and these activities were inhibited by anti-P-450 1A2; (c) reconstituted enzyme systems containing P-450 1A enzymes isolated from rats and humans showed the highest rates of activation of amino-alpha-carboline and PhIP. In rat liver microsomes PhIP may also be activated by P-450 3A enzymes; activity was induced in rats treated with pregnenolone 16 alpha-carbonitrile and was inhibited by anti-human P-450 3A4. However, in humans the contribution of P-450 3A enzymes could be excluded as judged by the very low effects of anti-P-450 3A4 on the microsomal activities and poor correlation with P-450 3A4-catalyzed activities in various liver samples. Cigarette smoke condensate strongly inhibited the activation of several potent procarcinogens by human liver microsomes, particularly the reactions catalyzed by P-450 1A2, but was not so inhibitory of the activation reactions catalyzed by P-450 3A4 and of P-450 2D6-catalyzed bufuralol 1'-hydroxylation. Genotoxic components of the cigarette smoke condensate were extracted by using copper phthalocyanine cellulose (blue cotton). Genotoxicity of this extract was observed only after activation by P-450, and the inhibition of P-450 1A2 activities by these extracts was slight.(ABSTRACT TRUNCATED AT 400 WORDS)
Aflatoxin B1↗
Beta-angonists modulate ACh-inhibition of a K current in intestinal smooth muscle cells.
ACh causes a long-lasting inhibition of STOCs via G proteins in intestinal smooth muscle cells. We examined the effects of isoproterenol (Iso) on the ACh-induced inhibition of STOCs in isolated ileal smooth muscle cells using the G omega-seal whole cell clamp technique. In control, ACh (1 microM) completely suppressed STOCs, which did not desensitize over a period lasting 20 minutes. When Iso (10 microM) was added to the bath in the presence of ACh, the ACh-induced inhibition of STOCs was gradually removed. This effect of Iso was prevented by propranolol (10 microM). Application of Db-cAMP (500 microM) mimicked the Iso effects. Intracellulary applied GTP-gamma S (100 microM) gradually suppressed STOCs in the absence of ACh, which could not be removed by either Iso or Db-cAMP. These results suggest that beta-adrenergic stimulation causes a removal of the muscarinic inhibition of STOCs via a cAMP-dependent process.
Acetylcholine↗
Self-assembled B19 parvovirus capsids, produced in a baculovirus system, are antigenically and immunogenically similar to native virions.
B19 parvovirus is pathogenic in humans, causing fifth disease, transient aplastic crisis, some cases of hydrops fetalis, and acquired pure red cell aplasia. Efforts to develop serologic assays and vaccine development have been hampered by the virus's extreme tropism for human bone marrow and the absence of a convenient culture system. We constructed recombinants containing either the major (VP2) or minor (VP1) structural proteins of B19 in a baculovirus-based plasmid, from which the polyhedrin gene had been deleted; these recombinant plasmids were used to generate recombinant infectious baculovirus. Subsequent infection of insect cells in vitro resulted in high-level expression of either B19VP1 or VP2. Parvovirus capsids were obtained by self-assembly in cell cultures coinfected with either VP1- and VP2-containing baculoviruses or, surprisingly, VP2-containing baculoviruses alone. Empty B19 capsids composed of VP1 and VP2 could replace serum virus as a source of antigen in a conventional immunoassay for detection of either IgG or IgM antiparvovirus antibodies in human serum. Immunization of rabbits with capsids composed of VP1 and VP2 resulted in production of antisera that recognized serum parvovirus on immunoblot and neutralized parvovirus infectivity for human erythroid progenitor cells. Baculovirus-derived parvovirus antigen can substitute for scarce viral antigen in immunoassays and should be suitable as a human vaccine.
Amino Acid Sequence↗
Correction of ornithine transcarbamylase (OTC) deficiency in spf-ash mice by introduction of rat OTC gene.
We introduced rat ornithine transcarbamylase (OTC) gene into OTC-deficient spf-ash mice by mating spf-ash heterozygotes with transgenic mice which carried recombinant DNA composed of 1.3 kb of the 5' flanking region of the gene fused onto rat OTC cDNA. The liver OTC activity of hemizygous spf-ash mice which carried the transgene was about twice that of nontransgenic spf-ash mice, and the small intestinal OTC activity was 6 times higher; the values being 12% and 27% of the control levels, respectively. The transgenic spf-ash mice showed normal hair growth without sparse fur, nearly normalized urinary orotic acid excretion and normalized serum citrulline concentration.
Animals↗
Detection of IgA binding site by flow cytometry with fluorescent microspheres.
To establish a sensitive method to detect IgA Fc receptors (Fc alpha R) on human and murine lymphoid cells, fluorescent microspheres (FMS) were used in a flow cytometric assay. The following three assays with FMS were tested and compared with a conventional indirect Fc alpha R assay using FITC-labeled anti-IgA: (1) direct cell binding assay with murine myeloma IgA(MOPC315)-coated FMS(IgA-FMS assay), (2) indirect assay with TNP-BSA-coated FMS which bind to cells preincubated with MOPC315 IgA bearing anti-TNP activity (TNP-BSA-FMS assay), and (3) indirect assay with anti-IgA coated FMS after preincubation of the cells with IgA(anti-IgA-FMS assay). In these three assays for Fc alpha R using FMS, the binding of IgA to the cells was not affected by purified IgM or IgG preparations. In both indirect assays using TNP-BSA-FMS and anti-IgA-FMS, sharp and dose dependent IgA binding was obtained at lower IgA concentrations ranging from 4 to 125 micrograms/ml as compared with the conventional indirect assay. The background MFI levels in all these FMS assays remained as low as those in the conventional assay. These findings suggest that FMS coupled with TNP-BSA or anti-IgA antibodies is suitable for the detection of Fc alpha R on both murine and human T cells.
Animals↗
Angina pectoris due to possible vasospasm of small coronary arteries.
Recently, the presence of vasospasm in small coronary arteries is speculated in animals and humans. A 40-year-old female patient complained of chest pain at rest. Left ventriculogram showed normal wall motions. Left and right coronary arteries were also normal. After methylergometrine maleate was selectively administered to a right coronary artery, she complained of chest pain, and ST-segment elevation was detected in leads II, III, and aVF of ECG. Right coronary arteriography was performed immediately, but no coronary stenosis was found. The next day, methylergometrine maleate was again administered intravenously and the patient complained of chest pain, but no ischemic changes were observed in ECG. Thallium-201 myocardial scintigraphy followed immediately. Apical perfusion defect was detected in stress image. In the delayed image, it showed complete redistribution. Three days later, catheterization and scintigraphy were performed at the same time. When methylergometrine maleate was administered to the left coronary artery, she complained of chest pain within a few minutes of the injection; however, ECG remained unchanged. 201Tl myocardial scintigraphy was performed immediately. In the stress image, it showed apical perfusion defect as shown in the intravenous methylergometrine maleate injection study. It also showed complete redistribution in the delayed image. Apical perfusion defect can be attributed to myocardial ischemia of left coronary artery, which are too small to be detected by conventional coronary arteriography. Vasospasm in small coronary arteries may be involved in this phenomenon.
Adult↗
The detection of myocardial ischemia by thallium-201 myocardial scintigraphy in patients with multiple coronary arterioventricular connections.
The question of whether myocardial ischemia could be induced in 5 patients with multiple coronary arterioventricular connections by thallium-201 (201Tl) exercise stress myocardial scintigraphy was investigated. Both ST-T changes on ECG and transient myocardial perfusion defects in myocardial scintigrams were observed in 2 patients (40%). In previous reports, all multiple coronary arterioventricular connections, which were shown in angiograms, have been regarded as either Thebesian veins or embryonic sinusoids. However, it is unlikely that Thebesian veins cause myocardial ischemia judging from anatomy. If the vessels cause myocardial ischemia, they should be regarded as multiple coronary arterioventricular fistula. Angiography itself cannot differentiate multiple coronary arterioventricular fistula from Thebesian veins or remnants of embryonic sinusoids. Exercise stress myocardial scintigraphy has a high potential to detect myocardial ischemia due to intracoronary steal. Exercise stress myocardial scintigraphy was used to demonstrate myocardial ischemia in multiple coronary arterioventricular connections. It is concluded that exercise stress myocardial scintigraphy is a reliable test to differentiate multiple coronary arterioventricular fistula from Thebesian veins or remnants of embryonic sinusoids in clinical practice.
Aged↗
Cytochrome P-450 oxidations and the generation of biologically reactive intermediates.
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Biotransformation↗
Effect of platelet-activating factor on cortisol and corticosterone secretion by perfused dog adrenal.
Administration of platelet-activating factor (PAF) to perfused adrenal increased cortisol and corticosterone secretion. With hexadecyl PAF (C16PAF; 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine), the increase was significant at 1 nM and maximal at 10 nM. The responses to 10 nM octadecyl PAF (C18PAF; 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine) were one fourth of those to 10 nM C16PAF. The addition of C16PAF to dispersed adrenal cells significantly increased cortisol and corticosterone production at 0.1 nM and 10 nM, respectively. C16PAF was about 1000 times more potent than histamine on a molar basis in respect to cortisol response in both perfused adrenal and dispersed adrenal cells. The results suggest that PAF induces cortisol release from dog adrenal.
Adrenal Cortex↗
Characterization of a newly established cell line (JR-St) derived from human gastric signet ring cell cancer, producing tumor markers.
Despite the importance of in vitro study of gastric cancer, there are very few established cell lines derived from human gastric carcinoma. We have recently established a new cell line derived from human gastric cancer which has the ability to produce tumor markers. This cell line has been designated JR-St. This cell line was derived from the cerebrospinal fluid of a 37-yr-old female patient who had metastatic brain tumor of signet ring cell gastric adenocarcinoma. This cell line has been maintained for more than 24 months through 80 passages with stable growth. PAS staining showed intracellular mucin granules. Transmission and scanning electron microscopy revealed cells with numerous microvilli and fine projections as well as intracellular granules, indicating mucin. This cell line had the ability to produce high concentrations of tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. Thus Thus this cell line should provide a very useful tool for the investigation of gastric cancer such as analysis of tumor markers as well as effects of anti-cancer drugs or growth factors.
Adenocarcinoma, Mucinous↗