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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 721 records · Page 40Linked to original sources

Heavy-chain isoforms of non-muscle myosin in human tissues.

The heavy-chain isoforms of myosin in human non-muscle and smooth muscle tissues were analyzed by means of SDS/PAGE and using three distinct newly developed monoclonal anti-(human cerebrum myosin) Ig (HBM-1, HBM-3 and HBM-4). Purified cerebrum myosin contained three electrophoretic variants of non-muscle myosin heavy chain (NM1, NM2 and NM3, with apparent molecular masses of about 200, 198 and 196 kDa, respectively). Both NM1 and NM2 were recognizable by the brain-specific antibody HBM-1, while NM3 was recognizable by HBM-3. Each of the variants reacted with HBM-4 to a similar extent. Purified cerebellum myosin gave three electrophoretic variants of the heavy chain which were indistinguishable electrophoretically or immunologically from those of cerebrum myosin. Aortic myosin contained four electrophoretic variants, including the two smooth muscle myosin heavy chain isoforms and NM2-like and NM3-like heavy chains. Liver, platelet and kidney myosins contained a heavy chain very similar to NM3. Kidney myosin also contained a small fraction of an NM2-like electrophoretic variant. In addition, cerebrum, kidney, liver and platelet myosins appeared to contain minor, 194-kDa myosin heavy-chain-like polypeptide(s) (NM4). NM1, as well as NM2 and NM3, thus appear to be the brain-type and non-brain-type non-muscle myosin heavy-chain isoforms, respectively, and additional minor heavy-chain isoforms are also likely to be present in human tissues.

Animals↗

Retinoic acid inhibits DNA and albumin synthesis stimulated by growth factor in adult rat hepatocytes in primary culture.

Retinoic acid inhibits proliferation as a result of inducing differentiation in various cells. Isolated hepatocytes have quiescent cell function and seldom proliferate in culture. It is of interest whether such function changes in proliferation induced by growth factors and the proliferation is inhibited by retinoic acid. In adult rat hepatocytes in primary culture, retinoic acid reduced DNA synthesis stimulated by epidermal growth factor or hepatocyte growth factor in a dose-related manner. Albumin synthesis was increased with EGF stimulation. Retinoic acid attenuated this increase, but affected neither albumin synthesis in the absence of EGF nor EGF binding to the cells. Adult rat hepatocytes in primary culture may proliferate with quiescent cell function. Retinoic acid inhibits such proliferation and cell function.

Albumins↗

Cyclic flow variations in a conscious dog model of coronary artery stenosis and endothelial injury correlate with acute ischemic heart disease syndromes in humans.

OBJECTIVES: The purpose of this study was to test the hypothesis that episodes of cyclic flow variations (CFVs) in conscious dogs with coronary stenoses and endothelial injury correlate with acute ischemic heart disease syndromes in humans. BACKGROUND: Although the canine model with CFVs has proved to be a useful model of coronary thrombosis, whether CFVs progress to these syndromes has not been clearly described. METHODS: Cyclic flow variations were produced by an external constrictor placed at the site of the left anterior descending coronary artery with injured endothelium. Blood flow in this artery and 24-h Holter electrocardiogram (ECG) were recorded during the 1st 5 postoperative days. RESULTS: Of 41 dogs that underwent the initial operative procedure successfully, 29 developed an episode of CFVs. In five dogs in which CFVs persisted throughout the monitoring period, the left anterior descending coronary artery flow decreased until day 3 and thereafter increased through day 5. Transient coronary occlusion during CFVs induced ST segment changes that returned to baseline after reflow. In 12 dogs, CFVs progressed to persistent coronary occlusion, and histologic examination revealed thrombus formation at the stenotic site and evidence of myocardial infarction. Four of these 12 dogs died suddenly of ventricular arrhythmias during persistent coronary occlusion; another 5 dogs died of reperfusion arrhythmias during CFVs with no evidence of myocardial infarction. CONCLUSIONS: Conscious dogs with CFVs closely correlated with clinical acute ischemic heart disease syndromes, suggesting them to be a useful model for investigating the complex mechanisms of cellular interactions in the pathogenesis of these syndromes.

Animals↗

Functional expression of interleukin 2 receptor in a human factor-dependent megakaryoblastic leukemia cell line: evidence that granulocyte-macrophage colony-stimulating factor inhibits interleukin 2 binding to its receptor.

Human interleukin 2 (IL-2) is a member of the class of crucial regulators of lymphocyte proliferation. The action of IL-2 is known to be mediated through binding to a specific IL-2 receptor (IL-2R) which comprises at least two distinct proteins: IL-2R alpha (p55) and IL-2R beta (p70-75). However, the expression and function of IL-2R are largely unknown in acute myeloblastic leukemia cells. In a human granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, or stem cell factor-dependent myeloid leukemia cell line (M07E), IL-2 was found to stimulate proliferation in a dose-dependent manner and to augment GM-CSF- and stem cell factor-induced proliferation of M07E cells. The expression of IL-2R beta on M07E cells was detectable with 125I-IL-2 binding and affinity cross-linking analyses and with a monoclonal antibody against IL-2R beta, Mik-beta 1. Although the expression of IL-2R beta was not down-regulated but somewhat up-regulated by treatment with GM-CSF in both mRNA and protein levels, GM-CSF was found to compete (75%) with radiolabeled IL-2 for binding to IL-2R on M07E cells, whereas no competition of GM-CSF binding was observed with IL-2 even at a 400-fold molar excess. These results suggest that IL-2R may be functionally expressed in some cases of acute myeloblastic leukemia cells and raise the possibility that IL-2 may have some effects on human myelopoiesis.

Binding, Competitive↗

Effects of sodium bicarbonate and ammonium chloride on the incidence of furosemide-induced fetal skeletal anomaly, wavy rib, in rats.

Furosemide produces fetal wavy ribs when administered to pregnant rats during late gestation. The compound is also known to produce metabolic alkalosis in laboratory animals and man. In order to evaluate the effect of furosemide on maternal blood pH, Crj:CD(SD) female rats received an oral administration of 150 or 200 mg/kg of furosemide by gavage on day 16 of gestation and were bled at 4 hr post-dose. Compared to an average pH of 7.39 in control females, there was a significant elevation in blood pH in these furosemide-treated females (average pH of 7.44 to 7.48). When 2% sodium bicarbonate was provided in the drinking water for females treated with 150 mg/kg of furosemide, there was a further rise in maternal blood pH (7.52) compared to females treated with furosemide alone. Associated with this elevation in maternal blood pH was a marked increase in the incidence of fetal wavy ribs (87.6% compared to 27.6%). When females treated with 200 mg/kg of furosemide were provided with 0.5% ammonium chloride, furosemide-induced maternal alkalosis was corrected (pH decreased to 7.35) and there was a reduction in the incidence of fetal wavy ribs (7.0% compared to 37.2%). In addition, maternal blood pH among individual females was positively correlated with the incidence of fetal wavy ribs (r = 0.714). These results suggest that maternal metabolic alkalosis is involved in the pathogenesis of furosemide-induced wavy ribs.

Alkalosis↗

Human erythrocyte band 3 (EPB3) polymorphism: analysis of blood and bloodstains by an immunodetection method and frequency of the EPB3* Memphis variant.

The erythrocyte band 3 (EPB3) variant, band 3 Memphis (EPB3*Memphis), was detected by immunoblotting with a monoclonal antibody to the 41 kDa cytoplasmic N-terminal domain of band 3 without protease treatment of erythrocytes. EPB3*Memphis was also detected by immunoblotting from 3-month-old bloodstains subjected to alpha-chymotrypsin treatment. A population genetic study using this method indicated that the EPB3 variant would be useful for forensic work in Japan, since the frequency of this variant in Japanese (Wakayama prefecture) is relatively high (0.159).

Anion Exchange Protein 1, Erythrocyte↗

The molecular defect in propionic acidemia: exon skipping caused by an 8-bp deletion from an intron in the PCCB allele.

Propionic acidemia is an autosomal recessive metabolic disease resulting from a deficiency of propionyl CoA carboxylase (PCC) activity. To investigate the genetic basis of propionic acidemia, we isolated a cDNA encoding the precursor of the beta subunit of human PCC (beta PCC). The cloned cDNA sequence was 1,832 bp long and the open reading frame of 1,617 nucleotides encoded a polypeptide of 539 amino acids with a molecular mass of 58,202 Da. The human beta PCC sequence shared a high degree of homology (91%) with the full-length cDNA of rat beta PCC at the amino acid level; there were only 47 differences among 539 amino acid residues compared. Polymerase chain reaction amplification and sequencing of cDNA from a beta subunit-deficient Japanese patient revealed a deletion of 101 nucleotides consisting of one exon from mature mRNA. This deletion resulted in a frameshift and a stop codon in the new frame. Analysis of the genomic DNA revealed a homozygous 8-bp deletion from bp3 to bp10 of the intron just downstream of the deleted exon. This deletion disrupted the consensus 5' splice signal and led to exon skipping.

Alleles↗

ABO blood grouping of bloodstains by sandwich ELISA using monoclonal antibody specific for human red cell band 3.

ABO blood grouping of human bloodstains was performed by a sandwich ELISA using a species-specific monoclonal antibody to the amino-terminal cytoplasmic domain of human red cell membrane band 3. In a blind trial, all A, B and O bloodstains (a 1 cm long thread) and AB bloodstains (a 1.5 cm long thread) were accurately typed by this method. Even when bloodstains were contaminated by other body fluids (e.g., semen and saliva), only the ABO blood group epitopes on band 3 of the red cell membrane were detected. Thus, identification of human blood and ABO blood grouping of bloodstains which were contaminated by other body fluids could be simultaneously performed by this method.

ABO Blood-Group System↗

A case of schizophrenia with a dicentric Y chromosome.

A case of DSM-III-R schizophrenia with a dicentric Y chromosome (46,X,dic(Y)(q11)) is reported. Structural chromosome abnormalities such as this case may provide clues to finding regions of the genome etiologically involved in schizophrenia.

Chromosome Banding↗

Clinical significance of low or negative titer of antibody to hepatitis B core antigen during the course of chronic hepatitis B virus infection in adolescents.

Antibody to hepatitis B core antigen (anti-HBc) was measured by radioimmunoassay in 127 asymptomatic hepatitis B surface antigen (HBsAg) carriers (ASC; mean age 19) who had normal serum alanine aminotransferase (ALT) levels and 16 patients with chronic hepatitis B (CH; 19). All 16 CH patients, who were positive for hepatitis B e antigen (HBeAg) and 5 ASC cases who were negative for both HBeAg and its antibody (anti-HBe), had high anti-HBc titers. Anti-HBc titers in 27 (56.3%) of the 48 HBeAg-positive ASC and 18 (24.3%) of the 74 anti-HBe-positive ASC were relatively low. Two of the ASC were HBeAg-positive/anti-HBc-negative. In a follow-up study of the 19 HBeAg-positive ASC with low or negative anti-HBc titers, 5 had abnormal serum ALT levels and increased anti-HBc titers. In contrast, in the other 14 of these subjects, serum ALT levels remained normal and the low anti-HBc titers remained unchanged and/or decreased. The serological profile of HBsAg-positive/low or negative anti-HBc titer and increased anti-HBc titer with abnormal serum ALT levels are not necessarily exceptional in HBeAg-positive adolescent ASC. It is suggested that anti-HBc is associated with the liver damage that occurs before adolescence in chronic hepatitis B virus infection.

Adolescent↗

Consequences of transient retinal hypoxia on rod input to horizontal cells in the rat retina.

The effects of hypoxia on horizontal cells were studied by intracellular recording in the superfused rat retina. Hypoxic challenge from the photoreceptor surface resulted in horizontal cell depolarization, associated with a reduction of the light-evoked hyperpolarization (S-potential). This depolarization, though not the reduction in S-potential, was reversed by non-NMDA receptor antagonists, but not by NMDA related antagonists. Horizontal cells were also depolarized during hypoxia when calcium-dependent synaptic transmitter release was blocked by Co2+. Diazoxide, an activator of ATP-sensitive K+ channels (K+ATP), had no effect on normal cells but blocked the depolarization and the reduction in S-potential. We conclude that retinal hypoxia results in increased activation of the non-NMDA receptors of horizontal cells, whilst the activation of K+ATP channels may be protective in retinal hypoxia.

Animals↗

Primary lymphoma of the brain developing in a boy after a 5-year history of encephalitis: polymerase chain reaction and in situ hybridization analyses for Epstein-Barr virus.

A 7-year-old boy presented with headache, vomiting, fever, epileptic seizure, and a left hemiparesis. Computed tomography revealed low-density areas in the left frontal lobe and right occipital lobe. Incisional biopsy of the right occipital lesion showed a diffuse and laminar destruction accompanied by microglial reaction in the cortex. An encephalitis of unknown etiology was suspected without data on viral titers in the serum and cerebrospinal fluid. Two months later right hemiparesis and ataxia appeared that were alleviated by prednisolone. Thereafter, similar symptoms repeatedly appeared, but disappeared after treatment with prednisolone. Approximately 5 years later, hemiparesis recurred: computed tomography revealed an 8 x 5 cm mass in the right lobe. A brain biopsy revealed non-Hodgkin's lymphoma of diffuse large, predominantly non-cleaved cell type of B-cell nature. The patient died 1 week after the surgery. The first biopsy specimen (taken at 7 years of age) did not contain Epstein-Barr virus genomes even when examined by polymerase chain reaction. The polymerase chain reaction and in situ hybridization techniques on the second biopsy specimens (taken at 12 years of age) revealed the Epstein-Barr virus sequences in the nuclei of diffuse large cell lymphoma. These findings suggested that the Epstein-Barr virus infection occurring between the first and second biopsies played an etiologic role in the pathogenesis of the brain lymphoma.

Brain Neoplasms↗

Clinical aspects of primary thyroid lymphoma: diagnosis and treatment based on our experience of 119 cases.

We describe the clinical aspects of primary thyroid lymphoma, particularly diagnostic procedures and successful therapy based on our observation of 119 patients with primary thyroid lymphoma. Thyroid lymphoma occurred exclusively in the thyroid gland of patients with Hashimoto's thyroiditis as a rapidly growing mass in the thyroid gland. Therefore, progressively enlarging goiter and compression symptoms were the most common clinical manifestations. A significant number of patients in our series had subclinical hypothyroidism (14%) or overt hypothyroidism (27%) because of the coexistence of Hashimoto's thyroiditis. Whenever thyroid lymphoma is suspected, we recommend an ultrasound scan of the thyroid gland and fine needle aspiration biopsy as initial diagnostic procedures. Thyroid ultrasound showed characteristic asymmetrical pseudocystic pattern in 43 of the 46 patients (93%), and thyroid cytologic examination showed abundant monomorphic infiltration of lymphoid cells. Among 83 patients who underwent fine needle aspiration biopsy, 65 patients (78.3%) were diagnosed correctly and 10 patients (12%) had borderline cytologic results. Thus, 90% of patients with thyroid lymphoma were diagnosed or the diagnosis suspected based on fine needle aspiration biopsy. To confirm the diagnosis of lymphoma histologically and to determine the degree of malignancy, open biopsy taking 2-3 g tissue should be done for all cases. Treatment of thyroid lymphoma does not require resection of all lymphoma tissue or total thyroidectomy. Our successful treatment is radiation therapy combined with six courses of CHOP chemotherapy (cyclophosphamide, adriamycin, vincristine, prednisolone). This mode of therapy improved the 8-year survival rate to nearly 100% regardless of the histological type of malignancy.

Adult↗

Effects of uvsX, uvsY and DNA topoisomerase on the formation of tandem duplications of the rII gene in bacteriophage T4.

We have characterized tandem duplications in the rII regions of phage T4. The rII deletion r1589 blocks only the function of the rIIA cistron, although it extends into the B cistron. Another rII deletion, r1236, blocks the function of the rIIB cistron and overlaps r1589. When a cross is made between r1589 and r1236, true rII+ progeny cannot form. Instead, anomalous phenotypically rII+ phages are detected carrying an rII region from each parent. Analyses of nucleotide sequences of the recombination junctions indicate that recombination takes place between short regions of homology (from 2 to 10 bp). Open reading frames of the recombinants deduced from the nucleotide sequences reveal that they contain a normal rIIA cistron and one of a variety of fused, duplicated rIIB cistrons. The T4 uvsX and uvsY genes, which participate in homologous recombination, are involved in this duplication formation. T4 DNA topoisomerase is encoded by genes 39, 52 and 60. Mutations in 52 and 60 reduced the frequency of such duplications, but mutations in gene 39 and some in gene 52 did not. Hence, the effects of topoisomerase mutations are allele-specific. Models are proposed in which these proteins are involved in tandem duplication.

Adenosine Triphosphatases↗

Treatment of indolent non-Hodgkin's lymphoma localized in the head and neck.

A total of 25 patients with indolent non-Hodgkin's lymphoma localized in the head and neck region was analyzed. Of these, 21 patients were classified as clinical Stage I, and 4 as Stage II. In 22 patients the extranodal site was involved, and it was a remarkable characteristic of this series of patients. Overall treatment results were as follows: survival rate 100% at 5 years, and relapse-free survival rate 81% at 2 and 5 years. There was only 1 death at 6 years and 2 months after treatment, and 4 relapses occurred by 2 years after treatment. Relapse was observed in 3 of 8 patients with follicular mixed/follicular medium type, which was in contrast to the other indolent histologies (SL, DSCl, ILL) with very few relapses.

Adult↗

Brefeldin A blocks the cytotoxicity of T cell receptor alpha/beta and gamma/delta cytotoxic T lymphocyte clones reacting against human autologous cancer cells.

We studied the effector mechanism of T cell receptor (TCR) alpha/beta- and gamma/delta-type cytotoxic T lymphocyte (CTL) clones that react with human autologous tumor cells. Treatment of tumor cells with a fungal antibacterial reagent, brefeldin A (BFA), resulted in the inhibition of cytotoxicity of an autologous tumor (HST-2)-specific CD8+ TCR alpha/beta-type CTL, TcHST-2. Other anti-metabolites such as chloroquine, cycloheximide and colchicine did not affect the cytotoxicity. The cell-surface antigen expression, including MHC class I molecules, was not influenced by BFA treatment. Furthermore, BFA did not influence the cytotoxicity of lymphokine-activated killer cells and natural killer cells. Since BFA blocks the transport of peptides from endoplasmic reticulum to the Golgi apparatus, the above data suggest that BFA could affect washing out of the peptide fragments from the MHC class I groove. Consequently, target tumor cells were protected from killing by CTL. Moreover, we obtained a CD4-, 8-, TCR gamma/delta-type (V delta 1+) CTL clone, TcHOT, that reacts against an autologous ovarial carcinoma, HOT. BFA could also inhibit this cytotoxicity, and it is likely that different presenting molecules other than MHC class I proteins participate in the cytotoxicity of this TCR gamma/delta-type CTL. These studies suggest that both TCR alpha/beta- and gamma/delta-type CTL may require antigenic peptides that are most likely derived from the BFA-sensitive, intracellular endogenous target proteins.

Brefeldin A↗

Predictive value of screening tests for persistent hepatitis C virus infection evidenced by viraemia. Japanese experience.

In November 1989, Japanese Red Cross Blood Centres started screening for hepatitis C virus (HCV) with enzyme-linked immunosorbent assay (Elisa) for the C100-3 viral peptide as the first such nationwide programme in the world. Thereafter post-transfusion non-A non-B hepatitis (PTNANBH) was reduced by 61-80%, but this was not as complete a success as our programme to prevent post-transfusion hepatitis B by screening for high titer hepatitis B core antibody, which we began in the same period. In order to acquire more effective control of PTNANBH, the HCV core-related antigen (GOR, N14) and second-generation Elisa (Ortho2, Abbott2) and second-generation antigen agglutination (PA, PHA) tests have been employed. Among 16,500 donors in 11 blood centers, 365 were serologically positive by at least one of these tests. Among these, HCV RNA was detected in 138 units and the remaining 227 were HCV RNA negatives. The effectiveness of these serological tests to detect HCV RNA-positive status were analyzed. Passive haemagglutination and particle agglutination (PHA and PA) tests were highly effective to predict HCV viraemia among blood donors. Also, these tests can easily determine antibody titre. By either PHA or PA, all units with > or = 2(12) agglutination titre (120 and 122 units) were HCV RNA positive and all agglutination-positive units with serum alanine aminotransferase level higher than 35 Karmen units were HCV RNA positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗