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Biomedical subjects

K Furuyama

Publications and source records attributed to K Furuyama.

34 records · Page 2Linked to original sources
PubMed1997

Pyridoxine refractory X-linked sideroblastic anemia caused by a point mutation in the erythroid 5-aminolevulinate synthase gene.

To elucidate how pyridoxine-refractory X-linked sideroblastic anemia (XLSA) develops, we analyzed the erythroid-specific 5-aminolevulinate synthase (ALAS-E) gene of a patient with the anemia. The activity and amount of the enzyme in bone marrow cells of the patient were found to be approximately 5% of the normal control. We identified a point mutation, which introduces an amino acid substitution from Asp 190 to Val. In transient transfection analyses using quail fibroblasts, accumulation of aberrantly processed proteins, the sizes of which were larger than that of mature ALAS-E, was found in mitochondria. The proteins were reproducibly detected in assays combining in vitro transcription/translation of ALAS-E precursor and import of the precursor into isolated mouse mitochondria. These results suggest that the mutation causing pyridoxine-refractory XLSA affects the processing of the ALAS-E precursor, thus provoking instability of the ALAS-E protein.

5-Aminolevulinate Synthetase↗
PubMed1997

Polyclonal B-cell lymphocytosis with features resembling hairy cell leukemia-Japanese variant.

Polyclonal B lymphocytosis was found in four patients having clinical and hematologic features resembling those of hairy cell leukemia (HCL). All four patients were women between 37 and 67 years of age. Three patients had splenomegaly. Lymphadenopthy was absent or slight. Persistent lymphocytosis was seen in all the patients, and anemia and/or thrombopenia was observed in three of the patients. Abnormal lymphocytes have long microvilli and prominent membranous ruffles on their surfaces. Bone marrow aspirates and biopsy specimens showed increased numbers of abnormal lymphocytes with round nuclei and abundant pale cytoplasm. Although these findings were similar to those of HCL, studies of Ig gene rearrangements and expression showed the polyclonal proliferation of B cells. We called this new disease hairy B-cell lymphoproliferative disorder (HBLD). All four patients exhibited a polyclonal increase in serum IgG. The morphology of the cells in HBLD was more similar to that of leukemia cells of a variant form of HCL (HCL-Japanese variant) than to typical HCL cells. The surface IgG+, CD5-, CD11c+, CD22+, CD24-, CD25- phenotype and the weak tartrate-resistant acid phosphatase activity in the cells were identical to those of HCL cells of the Japanese variant. Our findings suggest that the B cells in HBLD are the nonmalignant counterpart of leukemic B cells in HCL-Japanese variant.

Adult↗
PubMed1997

5-Aminolevulinate synthase expression and hemoglobin synthesis in a human myelogenous leukemia cell line.

We examined the effect of hemin, TGF-beta1 and cytosine arabinoside (Ara-C) on the levels of mRNAs for the erythroid-specific 5-aminolevulinate synthase (ALAS-E) and gamma-globin in various human myelogenous leukemia cell lines. Detailed analyses were also made using one of them, YN-1, which was isolated and established in culture from a patient with chronic myelogenous leukemia. Our results demonstrate that gamma-globin protein level and the percentage of benzidine-positive cells in the cell line increased markedly (10- to 30-fold) upon treatment with hemin, TGF-beta1, or Ara-C. In contrast, gamma-globin mRNA was already markedly expressed prior to treatment in 4 out of 9 cell lines examined, including YN-1, and the level increased only marginally after treatment with hemin. ALAS-E mRNA levels were increased in YN-1 cells after treatment with TGF-beta1 and Ara-C, while hemin treatment had little effect. These results indicate that heme supply is insufficient in YN-1 cells and suggest that hemin increases hemoglobin synthesis principally at the post-transcriptional level, whereas TGF-beta1 and Ara-C stimulate hemoglobin synthesis by activating efficient endogenous heme supply in the cells.

5-Aminolevulinate Synthetase↗
PubMed1997

Molecular defects of the coproporphyrinogen oxidase gene in hereditary coproporphyria.

Hereditary coproporphyria (HCP) is an acute hepatic porphyria, and is an autosomal dominant disorder but with a variable degree of clinical expression. Molecular cloning, sequencing and expression of the defective gene for coproporphyrinogen oxidase (CPO) in a patient with HCP were carried out. Enzyme assays revealed that CPO activity in EBV-transformed lymphoblastoid cells from the proband and one of her sisters was approximately 50% of normal. Nucleotide sequence analysis of CPO cDNAs isolated from the proband's cells demonstrated 3 base substitutions which accompanied 3 different amino acid substitutions. An A514-->C transition causing an Asn172-->His substitution occurred in one allele, while two other transitions, G265-->A and G580-->A, caused Gly89-->Ser and Val194-->Ile substitutions, respectively, in the other allele. The A514-->C and the G580-->A transitions were shown to be genetic polymorphisms. Transfection of CPO cDNA into E. coli demonstrated that cDNA with the G265-->A transition produced a protein with less than 5% of normal enzyme activity. These findings indicate that the G265-->A transition, involving the highly conserved glycine residue at the 89th position, is responsible for the CPO defect in the patient and accounts for the partial deficiency of CPO activity in this pedigree. This mutation is different from three other mutations reported in patients with HCP. Molecular defects in the porphyrias including HCP are highly heterogeneous.

Cell Line, Transformed↗
PubMed1995

Age-related changes in natural and fast walking.

Age-related changes in the relation between natural and fast walking were investigated for 69 healthy women aged 21 to 88 years. The ratio (fast/natural) of both walking velocity and cadence declined significantly across age groups.

Adult↗
PubMed1995

[Molecular regulation of heme biosynthesis].

It is generally accepted that the major organs producing heme are erythroid cells and the liver. delta-Aminolevulinate synthase (ALAS) plays the key role to regulate heme biosynthesis in the liver as well as in erythroid cells. In the liver, nonspecific (or housekeeping) isozyme of ALAS (ALAS-N) is expressed to be regulated by its end product, heme, in the negative feedback manner. Not only erythroid isozyme of ALAS (ALAS-E) but also ALAS-N is expressed in erythroid tissues, and are regulated by distinctive manners. For example, heme regulates ALAS-N and ALAS-E in the negative and in the positive feedback manner, respectively. In this article, we describe the molecular mechanisms to regulate heme biosynthesis not only in the liver but also in erythroid cells.

5-Aminolevulinate Synthetase↗
PubMed1994

Characterization and expression of cDNA encoding coproporphyrinogen oxidase from a patient with hereditary coproporphyria.

Hereditary coproporphyria (HCP) is an acute hepatic porphyria with autosomal dominant inheritance, but with a variable degree of clinical expression. Molecular cloning, sequencing and expression of the defective gene for coproporphyrinogen oxidase (CPO) in a patient with HCP were carried out. Enzyme assays revealed that CPO activity in EBV-transformed lymphoblastoid cells from the proband and one of her sisters was approximately 50% of normal. Nucleotide sequence analysis of CPO cDNAs isolated from the proband's cells demonstrated three base substitutions, and three accompanying amino acid substitutions. An A514-->C transition causing a Asn172-->His substitution occurred in one allele, while two other transitions, G265-->A and G580-->A, caused Gly89-->Ser and Val194-->Ile substitutions, respectively, in the other allele. The A514-->C and the G580-->A transitions are known genetic polymorphisms. Transfection of CPO cDNA into Escherichia coli demonstrated that cDNA with the G265-->A transition produced a protein with less than 5% of normal enzyme activity. These findings indicate that the G265-->A transition, involving the highly conserved glycine residue at the 89th position, is responsible for the CPO defect in the patient and accounts for the partial deficiency of CPO activity in this pedigree.

Amino Acid Sequence↗
PubMed1993

Two chronic myelogenous leukaemia cell lines which represent different stages of erythroid differentiation.

We established two cell lines, YN-1 and Y-1K, from the peripheral blood of two chronic myelogenous leukaemia patients in blastic crisis. Characterization of the YN-1 and Y-1K cells revealed that these cells expressed erythroid lineage markers. However, there was a marked difference in the level of gamma-globin mRNA and haemoglobin in YN-1 and Y-1K cells. YN-1 contained approximately 1-5% benzidine-positive staining cells, whereas no benzidine-positive cells were observed in Y-1K cells. Haemoglobin production in YN-1 cells was markedly increased with various chemical inducers of erythroid differentiation, but was not in Y-1K cells. In contrast, Y-1K cells expressed CD34 stem cell antigen and CD41 megakaryocyte-specific antigen. These observations suggested that, although both cell lines were committed to the erythroid lineage, each cell line represented a distinct differentiation stage in the erythroid differentiation programme. Y-1K seemed to correspond to an early stage of cells in erythroid lineage, whereas YN-1 represented a more advanced stage in human erythropoiesis.

Adult↗
PubMed1992

[Effect of pH on preferential antibacterial-activity of ethylenediaminetetraacetic acid (EDTA)].

Ethylenediaminetetraacetic acid (EDTA), a chelating agent, was examined for the antibacterial activity against 15 species of bacteria by treating with a 10mM solution at pH adjusted to 5.0, 7.0 or 9.0. All bacterial species tested were classified into three groups; tentatively named the pH5 EDTA-sensitive group comprising Vibrio cholerae and Staphylococcus aureus, the pH9 EDTA-sensitive group comprising Escherichia coli and Pseudomonas aeruginosa and the EDTA-nonsensitive group comprising Proteus mirabilis. The EDTA-sensitivity grouping may be used as a tool for preferential decontamination of certain bacteria in live edible fishes, although further experiments are needed to characterize more strains and also species of bacteria.

Bacteria↗
PubMed1992

[A case of monoblastic crisis of CML beginning with extramedullary tumor formation in a rib].

A patient with CML showed monoblastic crisis which started with extramedullary tumor formation in a rib before medullary involvement. She was diagnosed as having CML in 1984 at the age of 57. In February 1990, she was admitted to Furukawa City Hospital because of extramedullary blastic crisis beginning at the right 5th rib. At that time, the bone marrow revealed 4.6% blasts. On March 5, after one course of chemotherapy, she was transferred to our hospital for radiotherapy. Hematological findings were WBC 10,100/microliter with 10% blasts, Hb 10.9 g/dl, platelet 3.7 x 10(4)/microliters. Bone marrow aspiration was unsuccessful. The blasts in the peripheral blood were negative for peroxidase and chloroacetate esterase; but positive for naphtylbutyrate esterase. The leukemic cells were positive for CD13, CD33, and had phagocytic activity. Chromosomal analysis revealed 46XX with Ph1 chromosome and some additional anomalies. Southern blot analysis of tumor cells shows BCR rearrangement. These findings suggest that the blasts were immature monocytic cells, and we conclude that this is a rare case of extramedullary monoblastic crisis of CML.

Bone Neoplasms↗
PubMed1992

[Differentiating effect of oral administration of retinol palmitate (Chocola-A) for an aged AML (M3) with severe complications].

A 74 year-old woman, who had been diagnosed as AML (M3) in poor condition, was treated with Retinol Palmitate (Chocola-A, 150,000 unit/m2 per os, after informed consent. An increase of white blood cells (neutrophil) counts was observed after 7 days. After 4 weeks, WBC counts were increased to 20,700/microliters (neutrophil counts 6,400/microliters) Maturation tendency of leukemic cells was also proved in the bone marrow. In vitro studies showed that morphological differentiation was recognizable in cultured leukemic cells treated with 10(-6)M all-trans retinoic acid after 6 days, but not in controls. Responses in the NBT reduction test were slightly less than in the clinical study. The administration of Retinol Palmitate may be a new regimen to treat AML (M3) in aged patients in poor condition.

Administration, Oral↗