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Biomedical subjects

K Nagata

Publications and source records attributed to K Nagata.

At least 649 records · Page 36Linked to original sources
PubMed1992

Cerebral blood flow and glucose metabolism measurements in a patient surviving one year after carbon monoxide intoxication.

A 29-yr-old woman was studied for 1 yr after acute carbon monoxide intoxication following an attempted suicide by inhalation of automobile exhaust fumes. The patient demonstrated impaired responsiveness to stimuli without any specific neurological deficits for 1 yr after carbon monoxide intoxication. Repeated brain magnetic resonance imaging consistently displayed only bilateral globus pallidus lesions, but no lesions in either deep white matter or cerebral cortex. Position emission tomography measurements of regional cerebral blood flow, and glucose utilization rate were made in this patient at 6 mo and 1 yr following carbon monoxide intoxication. Impairment of both blood flow and glucose metabolism were found not only in the basal ganglia but also in morphologically normal frontal cortex. The decrease in glucose utilization in the frontal cortex was greater than that in the basal ganglia. During the period of 6 mo to 1 yr, blood flow and glucose metabolism in the basal ganglia recovered to the normal range. In the frontal cortex, however, blood flow and glucose metabolism remained approximately 20% lower than the normal mean values. This prolonged dysfunction in the frontal cortex may therefore be responsible for the impaired responsiveness of the subject.

Adult↗
PubMed1992

[Adult T-cell leukemia with cervical bone tumor showing immunophenotypic change].

A 60-year-old man born in Miyazaki prefecture was admitted to our hospital complaining of skin rash in December 1989. On hematological examinations, leukocyte count was 14,200/microliters with 49% of abnormal lymphocytes showing lobulated nuclei. The surface marker study revealed their phenotype as CD4+8-. Anti human T cell leukemia virus type I (HTLV-I) antibody and monoclonal integration of proviral DNA were positive. From the above results, he was diagnosed as adult T-cell leukemia (ATL). Abnormal lymphocytes gradually decreased without treatment after the first admission. In January, 1990, he began to complain of neck pain. Two months later he was readmitted because of paresis of extremities and disturbance of urination. Vertebral bone mass and a compressed spinal cord in the 4th cervic level were confirmed by MR imaging. He received a resection of tumor and an anterior fusion of vertebrae. The bone tumor was histologically diagnosed as malignant lymphoma, diffuse medium-size cell type and the infiltrating cells had their phenotype as CD4+8+. He was postoperatively treated with combination chemotherapies, but neurological abnormalities did not improve. He died of pneumonia on 35 days after the operation. A postmortem examination revealed extradural tumor formation with ATL cells. This case is considered to be rare in respect of both the disappearance of most peripheral abnormal lymphocytes without any treatments and the cervical bone tumor showing immunophenotypic change.

CD4 Antigens↗
PubMed1992

Constitutive expression of leukemia inhibitory factor (LIF) mRNA and production of LIF by a cloned murine thymic stromal cell line.

We have found that normal mouse thymus expressed mRNA for leukemia inhibitory factor (LIF), suggesting the presence of cell component(s) in the thymus that produces this cytokine. High levels of mRNA for LIF were observed to be constitutively expressed in the murine thymic stromal cell clone, MRL104.8a. This stromal cell clone produced potent magnitudes of LIF activity in its culture supernatant. These observations imply that LIF may also exert its growth/differentiation-regulating effect in the thymus. Thus, this thymic stromal cell clone provides a tool for investigating potential roles of LIF in the intrathymic T cell development.

Animals↗
PubMed1992

[The hemodynamics of intracranial aneurysm by transcranial Doppler arteriography].

The use of an ultrasonic transcranial Doppler arteriography (TCDA) technique for noninvasive diagnosis of cerebral aneurysm is described. Twenty one patients with intracranial aneurysm previously diagnosed by conventional angiography were evaluated with Trans-Scan (EME). Mapping image was used as a guide to identify parent artery and aneurysm. In four patients, we could not record aneurysmal blood flow because of their poor or non existent acoustic window. Good images were recorded in 17 patients. The location of aneurysms were A-com (1 case), Distal ACA (2 cases), IC (7 cases), MCA (3 cases), Basilar (1 case) and IC fusiform (3 cases). Two types of Doppler spectra were obtained from the aneurysmal blood flow. One was characterized by a high density zone along the base line and the other was characterized by a homogeneous high density zone. In both types, Doppler sound was characterized by low frequency sound. The low frequency sound reflects the turbulent flow in the aneurysm. The pattern of Doppler spectra obtained from ordinary arteries was characterized by a high density zone along the descending limb of the envelope. Doppler sound is characterized by high frequency sound. A homogeneous spectral pattern was obtained in both aneurysms and ordinary arteries. But it was possible to differentiate them by Doppler sound. Consequently to be able to hear Doppler sound is very important. We were able to detect fourteen of seventeen aneurysms (A-com 1/1, Distal ACA 1/2, IC 7/7, MCA 2/3, Basilar 1/1, and IC fusiform 2/3). The rate of detection was 82 percent. Aneurysm size ranged from 5mm x 4mm to 16mm x 18mm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Role of GTP-binding proteins in phospholipid metabolism in human platelets].

Phosphoinositide-specific phospholipase C (PLC) catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DG), which act as second messengers. Substantial evidence has strongly suggested that a putative G-protein (s), Gp, regulates PLC activity in human platelets. Recently, the molecular mechanism of PLC activity regulation was clarified as to two types of enzymes, PLC-gamma and PLC-beta. In this chapter, the regulatory mechanisms of the PLCs via a Gp or tyrosine kinase is summarized, and the involvement of some G-protein in the regulation of other phospholipases, phosphatidylcholine-specific PLC, phospholipase A2 and phospholipase D, is also discussed.

Blood Platelets↗
PubMed1992

The in vitro growth patterns and drug sensitivities of leukemic blast progenitors among the subtypes of acute myelocytic leukemia.

The in vitro growth activities and drug sensitivities of leukemic blast progenitors were compared among the subgroups of acute myelocytic leukemia (AML) classified according to the French-American-British (FAB) cooperative group. Leukemic cells separated from the peripheral bloods of AML patients were cultured in methylcellulose media, and the plating efficiencies of primary colonies (PE1) and secondary colonies after replating (PE2) were determined. PE1 and PE2 have been considered to reflect the capacities of terminal divisions and self-renewal of leukemic blast progenitors, respectively. PE1 and PE2 were variable among AML patients; these findings suggest that AML is a heterogeneous disease in terms of the proliferative activities of leukemic cells. No significant correlation was noted between PE1 or PE2 and the AML subtype. The sensitivities to cytosine arabinoside (Ara-C) of leukemic blast progenitors were studied in methylcellulose and suspension cultures. Ara-C sensitivity was not significantly correlated with the AML subtype, either. In contrast, there was statistically significant correlation between PE2 and the remission outcome of the patients, whereas PE1 was not significantly associated with the clinical outcome. The results in the present study indicate that the proliferative activity, especially self-renewal capacity, of leukemic blast progenitors is highly predictive of the prognosis of AML patients but is not significantly correlated with the AML subtype classified by the blast morphology.

Adolescent↗
PubMed1992

[Lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) therapy that improved lymphadenopathy in a patient with B cell non-Hodgkin's lymphoma].

A 70-year-old man was admitted to our hospital on March 9, 1989 because of fever, superficial generalized lymphadenopathy, upper abdominal mass and right pleural effusion. The diagnosis of non-Hodgkin's lymphoma (follicular medium sized cell type, B cell) was made by a biopsy of the neck lymph node. Peripheral blood mononuclear cells were obtained from the patient by cytopheresis. The cells were cultured for 8 days with interleukin-2 (IL-2) to generate Lymphokine-activated killer (LAK) cells. The patient received a total of 7.7 x 10(9) LAK cells intravenously over a period of 3 weeks. He also received continuous intravenous infusion of IL-2 for 17 days, starting 2 days before the first infusion of LAK cells. After this therapy, although his superficial generalized lymphadenopathy disappeared or decreased in size, the size of the upper abdominal mass did not decrease. Therefore, it is suggested that adoptive immunotherapy is a beneficial treatments for B cell lymphoma. However, LAK cells should be generated in much larger quantities for a more successful therapeutic result.

Aged↗
PubMed1991

Identification of rat cDNA encoding hck tyrosine kinase from megakaryocytes.

A rat homologue of hck tyrosine kinase cDNA from a rat megakaryocyte library contains 1911 nucleotides with an open reading frame encoding 503 amino acids. The rat hck had distinct amino acid residues from the mouse homologue exhibiting 97.6% identity. The sequence contains the SH2 and SH3 regions that interact with cytoplasmic signaling proteins, the kinase domain including the nucleotide binding site and the autophosphorylation site, and the C-terminal Tyr-499 known as a negative regulator.

Amino Acid Sequence↗
PubMed1991

Mouse pulmonary cytochrome P-450 naphthalene hydroxylase: cDNA cloning, sequence, and expression in Saccharomyces cerevisiae.

We have isolated a cDNA clone, Nah-2, encoding the cytochrome P-450Nah (naphthalene hydroxylase) from a mouse lung lambda ZAP cDNA library using anti-cytochrome P-450Nah IgG as a probe. This same antibody selectively blocked [Nagata, K., Martin, B.M., Gillette, J.R., & Sasame, H.A. (1990) Drug Metab. Dispos. 18, 557-564] the cytochrome P-450 in mouse lung microsomes that catalyzed the conversion of naphthalene to (1R,2S)-naphthalene 1,2-oxide, which has been postulated as a causative agent in the naphthalene-induced tissue-specific necrosis of Clara cells in mouse lung. The toxic effect is seen in mouse and not in rat. The cDNA encodes a polypeptide of 491 amino acids with a molecular mass of 50 kDa. Northern blot analysis with an Nah-2-specific probe revealed that the mRNA is expressed in a species- and tissue-specific manner, present only in mouse lung and liver and not in that of rat. The mRNA encoding Nah-2 is constitutively expressed and is not induced by either phenobarbital, pyrazole, pregnenolone 16 alpha-carbonitrile, or 3-methylcholanthrene. Comparative amino acid sequence analyses with other documented members of the P-450 gene superfamily revealed that this encoded protein is in the IIF subfamily. To analyze its substrate specificity, the cDNA was inserted into the vector, pAAH5, and expressed in the Saccharomyces cerevisiae strain, AH22. The presence of cytochrome P-450Nah in the microsomes isolated from transformed cells and analyzed by Western blot was confirmed by immunocomplexing product with anti-cytochrome P450Nah IgG. Furthermore, activity toward naphthalene in the microsomes from the transformed cells established that this clone encodes a naphthalene hydroxylase.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Interferon-inducible mouse Mx1 protein that confers resistance to influenza virus is GTPase.

The murine Mx1 protein is an interferon-inducible nuclear protein and confers resistance to influenza virus infection even though the resistance mechanism is yet unclear. The Mx1 protein contains a tripartite GTP-binding domain consisting of GXXXXGKS, DXXG, and T/NKXD motifs. In the GTPase gene superfamily such as p21ras protein, signal-transducing G protein, and translation elongation factor, the GTPase activity plays a key role in each protein function. Here we show that GTPase activity is indeed associated with the intact Mx1 protein purified from Escherichia coli expressing Mx1 cDNA. Amino acid substitution within the GTP-binding motif led to significant reduction in the GTPase activity. Yeast vacuolar protein sorting (VPS1) protein and the rat microtubule-associated mechanochemical enzyme dynamin were found to be homologous to Mx1 not only in the tripartite GTP-binding motif, but also in the amino-terminal region of approximately 300 amino acids in length. The function of Mx1 is discussed in comparison with these proteins.

Amino Acid Sequence↗
PubMed1991

Efficient Ca2+ mobilization induced by neurokinin A in rat vas deferens.

Although both neurokinin A (NKA) and norepinephrine (NE) induced similar maximal contractions in the epididymal and the prostatic site of vas deferens, NKA affected sensitivity more potently than did NE in both sites. The NKA-induced contractions were more strongly inhibited by nicardipine, a dihydropyridine Ca2+ entry blocker, or by elimination of extracellular Ca2+ (Cao2+) in both sites. However, ryanodine, which interferes with the release of intracellular Ca2+ (Cai2+), abolished the contractions caused by NKA in the prostatic site whereas it had no effect in the epididymal site. These results suggest that NKA-induced contraction utilizes both Cai2+ and Cao2+ in the prostatic site but mobilizes only Cao2+ in the epididymal site. Cai2+ concentration [( Ca2+]i) was measured directly with a Ca(2+)-sensitive fluorescent dye, fura-2. In the epididymal site NKA induced contractions with smaller increase in [Ca2+]i compared to that necessary for NE-induced contractions. These results suggest that NKA utilizes Ca2+ more efficiently than does NE and plays a role as a neuromodulator in rat vas deferens.

Animals↗
PubMed1991

Atherogenic risk factors in cerebrotendinous xanthomatosis.

In a study of coronary artery disease in patients with cerebrotendinous xanthomatosis (CTX), we documented the presence or absence of atherogenic risk factors and performed detailed analyses of serum lipid and lipoprotein profiles. Four of the seven patients examined had coronary arterial narrowing and/or obstruction, but multiple atherogenic risk factors were not found in any of these patients. Total cholesterol (T.ch) levels and low density lipoprotein-cholesterol (LDL-ch) levels were lower, and high density lipoprotein2-cholesterol (HDL2-ch) levels were higher in CTX patients than in controls. Triglyceride and very low density lipoprotein (VLDL) levels were significantly lower in the former. Indices correlating with the risk of atherosclerosis, such as the atherogenic index, and the ratios of apolipoprotein B/apolipoprotein AI, HDL2-ch/LDL-ch, HDL2-ch/HDL3-ch, indicated that CTX serum was, in fact, 'anti-atherogenic'. However, coronary artery disease is frequently seen in patients with CTX. This discrepancy suggests the existence of a unique mechanism by which atherosclerosis is induced in patients with CTX. We discuss a mechanism of disturbed lipoprotein metabolism which might be responsible for the deposition of sterols in the tissues of patients with CTX.

Adult↗
PubMed1991

Antiproliferative and differentiative effects of recombinant interleukin-4 on a granulocyte colony-stimulating factor-dependent myeloblastic leukemic cell line.

The effect of recombinant human interleukin-4 (IL-4) on a granulocyte colony-stimulating factor (G-CSF)-dependent human myeloblastic leukemic cell line, OCI-AML1a, was investigated. IL-4 suppressed the clonogenic cell growth in methylcellulose culture, inhibited the uptake of 3H thymidine in a dose-dependent manner at 5 to 100 U/mL, and consequently suppressed the growth of clonogenic cells in short- and long-term suspension cultures. In addition, IL-4 markedly increased the number of adherent cells. These adherent cells were alpha-naphthyl-butyrate (alpha-NB) esterase-positive and showed macrophage-like appearance, increased expression of CD14, CD11b, CD23, and Ia, and significantly decreased clonogenicity. On the other hand, nonadherent cells growing in suspension showed only slight increase in proportion of alpha-NB esterase-positive or monocyte/macrophage-like cells and increased CD23 expression by an addition of IL-4. The clonogenicity of the nonadherent cells was not significantly influenced by IL-4. By addition of the media conditioned by OCI-AML1a cells in the presence of IL-4, the clonogenic cells growth of OCIAML1a cells was suppressed and adherent cells were markedly increased. The suppressive and differentiative effects on OCI/AML1a cells of the conditioned media and IL-4 itself were almost completely abolished by anti-IL-4 antibody. Furthermore, the neutralizing antibodies against transforming growth factor-beta 2 (TGF-beta 2), tumor necrosis factor-alpha (TNF-alpha), or IL-6 did not influence the effect of recombinant IL-4. Taken together, IL-4 was shown to suppress the growth and induce differentiation toward adherent macrophage-like cells of the G-CSF-dependent myeloblastic cell line. The effect of IL-4 may be direct, and not secondary via inducing production of other cytokines such as TGF-beta, TNF-alpha, or IL-6 by leukemic cells.

Cell Adhesion↗
PubMed1991

In vivo analysis of the promoter structure of the influenza virus RNA genome using a transfection system with an engineered RNA.

A system for the expression of a foreign gene derived from negative polarity RNA was developed using influenza virus, a negative-stranded RNA virus. From cDNA for the influenza virus RNA genome segment 8, the region coding for the nonstructural protein was deleted and replaced by the chloramphenicol acetyltransferase (CAT) gene. The resulting DNA sequence was placed under the control of the promoter of T7 RNA polymerase such that the antisense RNA to CAT mRNA was produced when transcribed by T7 RNA polymerase. Transfection of HeLa cells with this antisense CAT RNA in the presence of the helper ribonucleoprotein cores led to no significant production of the CAT. In contrast, when the RNA was covered with purified nucleoprotein prior to transfection, the CAT gene was efficiently expressed. This indicated that the viral RNA polymerase transcribed the RNA transfected as the RNA-nucleoprotein complexes. In addition, this system was used for analysis of the cis-acting region in transcription and the promoter structure of the viral RNA genome.

Base Sequence↗
PubMed1991

A gene structure of testosterone 6 beta-hydroxylase (P450IIIA).

Genomic clones of a rat testosterone 6 beta-hydroxylase have been isolated and characterized as the first gene (P450/6 beta A) among P450IIIA subfamily. This gene spans about 25Kb and consists of 13 exons, which is the largest number of exons among cytochrome P-450 genes reported previously. The nucleotide sequence of the exon region showed high similarity to those of P450PCN2 and P450PCN1 cDNA (Gonzalez, F.J. et al. (1987) Mol. Cell. Biol. 2969-2974), but several replacements and deletions of nucleotide were found between the P450/6 beta A gene and both cDNAs, indicating the existence of multiple P450IIIA genes in rats.

Animals↗
PubMed1991

Phosphorylation of the stress protein hsp27 is an early event in murine myelomonocytic leukemic cell differentiation induced by leukemia inhibitory factor/D-factor.

Leukemia inhibitory factor/D-factor, a potent differentiation-inducing glycoprotein for murine myelomonocytic leukemic M1 cells, rapidly stimulated the phosphorylation of a 27 kDa protein with an isoelectric point of 5.6 in a LIF-sensitive M1-T22 cell line but not in a LIF-resistant M1-D(-) cell line. The increase in phosphorylation was detectable 5 min after LIF treatment and was maximal at 10 min. Heat shock treatment at 44.5 degrees C for 30 min also induced the phosphorylation of the same 27 kDa protein. Although this 27 kDa protein did not become labeled with [35S]-methionine, metabolic labeling experiments using [35S]-cysteine or [3H]-leucine clearly demonstrated that the synthesis of this protein was enhanced after heat shock. These results suggest that the phosphorylated 27 kDa protein is a low molecular weight stress protein and that the protein may play a role at an early stage in the LIF signaling pathway probably linked to macrophagic differentiation.

Animals↗
PubMed1991

Purification and characterization of human platelet phospholipase A2 which preferentially hydrolyzes an arachidonoyl residue.

A phospholipase A2 with an arachidonoyl residue preference was purified about 11,700-fold from human platelet soluble fraction to near homogeneity. The purified phospholipase A2 exhibited a molecular mass of about 90 kDa on SDS polyacrylamide gel electrophoresis and hydrolyzed phospholipids with an arachidonoyl residue more effectively than those with a linoleoyl residue. The catalytic activity of the purified enzyme detected with phosphatidylcholine as a substrate increased sharply between 3 x 10(-7) and 10(-6) M free calcium ion. Thus, the 90-kDa phospholipase A2 is considered to be a novel enzyme, distinct from the 14-kDa one previously purified from human platelets. The 90-kDa phospholipase A2 may participate mainly in arachidonate metabolism of platelets.

Arachidonic Acid↗