PubMed Health⌕ Search

Biomedical subjects

J Nishida

Publications and source records attributed to J Nishida.

At least 91 records · Page 5Linked to original sources
PubMed1992

Therapeutic effects of arotinolol, a beta-adrenergic blocker, on tremor in MPTP-induced parkinsonian monkeys.

The effect of arotinolol, a peripherally acting beta-adrenergic-blocking agent, on postural or kinetic tremor was studied in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Male cynomolgus monkeys (Macaca fascicularis) were treated with three injections of MPTP hydrochloride (0.3 mg/kg, i.v.) at an interval of 3-4 days, followed by several injections of the same dose every 7 days. Four monkeys with persistent parkinsonian symptoms manifested for greater than 1 year were used. The animals developed mild to moderate degrees of postural or kinetic tremor, and their motor activity was reduced. Arotinolol (20-30 mg/kg, s.c.) significantly suppressed postural tremor in a dose-dependent manner. Propranolol (20-30 mg/kg) was also effective in suppressing the tremor. However, the application of propranolol induced emesis, whereas arotinolol had no adverse effects. These results suggest that arotinolol is a useful adjunct to dopaminergic therapy for tremor in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Definition of a GC-rich motif as regulatory sequence of the human IL-3 gene: coordinate regulation of the IL-3 gene by CLE2/GC box of the GM-CSF gene in T cell activation.

The human IL-3 gene, located on chromosome 5, contains several cis-acting DNA sequences, i.e. CLE (conserved lymphokine element) and a GC-rich region, similar to the GM-CSF gene. To investigate the role of these elements, the 5' flanking region of the IL-3 gene was attached to a bacterial chloramphenicol acetyltransferase (CAT) gene. The fusion plasmids were analyzed by an in vitro transcription system using Jurkat cell nuclear extract prepared from cells stimulated with phorbol-12-myristate-13-acetate and calcium ionophore (PMA/A23187), introduced into Jurkat cells, expressed transiently, and stimulated by co-transfection of human T cell leukemia virus type I (HTLV-I) encoded transactivator, p40tax. The GC-rich region enhanced TATA-dependent transcription in the in vitro transcription system and also strongly responded to p40tax stimulation in the in vivo cotransfection assay. Using this GC-rich region as a probe, we identified a constitutive DNA-protein complex, alpha, whose binding specificity correlates with transcription activity. However, this element is not sufficient for the expression of the IL-3 gene in response to T cell activation signals (PMA/A23187) and no sequence was found within the IL-3 gene which mediates the response to PMA/A23187. The enhancer sequence which responds to T cell activation signals may be located outside the IL-3 gene and may be shared by other lymphokines, possibly by GM-CSF. We propose that the GM-CSF enhancer (CLE2/GC box) which mediates the response to T cell activation signals may stimulate the expression of the IL-3 gene.

Base Composition↗
PubMed1990

[Coordinate regulation of immune and inflammatory responses by cytokines].

In response to antigenic stimulation, T cells and macrophages secrete a set of glycoproteins termed lymphokines and monokines such as IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, GM-CSF, G-CSF, IFN-alpha, IFN-gamma, TNF-alpha, and lymphotoxin. These glycoproteins mediate immune and inflammatory responses by regulating proliferation, differentiation and maturation of lymphocytes, hemopoietic cells and endothelial cells. Along with factors such as M-CSF, IL-7, LIF, IFN-beta and TGF-beta produced by stromal cells, all these molecules are collectively called cytokines. Most cytokines are pleiotropic and have multiple biological activities. Accordingly, regulatory network is formed between lymphoid cells, hemopoietic cells and endothelial cells. All or a part of this network can be activated in different ways by unique combinations of cytokines. IL-3, IL-4 and IL-5 produced by TH2 cells enhance whereas IFN-gamma produced by TH1 cells suppresses IgE mediated allergic response. Through production of a spectrum of cytokines, T cells and macrophages play a vital role in coordinating the function of different body compartments in immune and inflammatory responses. The activation of cytokines genes in T cells and macrophages is transient. Therefore, an inflammatory response that involves proliferation and maturation of hemopoietic progenitor cells may be restricted to the site of cytokine production. The inducible nature of the hemopoiesis associated with inflammatory response is in contrast to the constitutive, steady state hemopoiesis that occurs in the bone marrow microenvironment in the absence of immunological stimuli.

Animals↗
PubMed1990

A novel protein-tyrosine kinase, tec, is preferentially expressed in liver.

To identify protein-tyrosine kinases which play an important role in the process of hepatocarcinogenesis, we have screened a murine liver cDNA library with v-fps kinase domain as a probe. Using low stringency screening, we could isolate cDNAs of a putative protein-tyrosine kinase, tec (tyrosine kinase expressed in hepatocellular carcinoma). Nucleotide sequences of the cDNAs show that the C-terminal domain of its predicted protein has significant homology with that of the members of the src family. The tec gene is expressed mainly in liver and faintly in heart, kidney and ovary. Northern analysis further shows that in 2 out of 4 cell lines of human hepatocellular carcinoma (HCC) the tec gene is highly expressed compared to normal human liver. This is the first report showing a protein-tyrosine kinase which may be specifically involved in the cell growth of hepatocytes or in the step of hepatocarcinogenesis.

Amino Acid Sequence↗
PubMed1989

Microcirculatory disturbances of oral mucosa and periodontal disease in patients with liver cirrhosis.

This study showed: (1) The bone score in cirrhotic patients was significantly lower than that in the control group. (2) In liver cirrhosis, capillaries were decreased in number and they were dilated compared to that in the control. In particular, the capillaries in cirrhotic patients with ascites or oesophageal varices were dilated compared to those without. (3) Blood flow of the mucogingival junction was significantly decreased in patients with liver cirrhosis in comparison with the control group. These results suggest that microcirculatory disturbances of oral mucosa are important in the progress of periodontal disease in patients with liver cirrhosis.

Female↗
PubMed1988

Activation of T cell-derived lymphokine genes in T cells and fibroblasts: effects of human T cell leukemia virus type I p40x protein and bovine papilloma virus encoded E2 protein.

The effects of p40x, a product of an human T cell leukemia virus type I, on the activation of lymphokine genes were examined. The mouse GM-CSF and IL-3 genes were activated by cotransfection with a pX containing plasmid both in Jurkat and CV1 cells. Mouse GM-CSF gene was also activated by phytohaemagglutinin A (PHA)/phorbol myristate acetate (PMA) or PMA/calcium ionophore A23187 stimulation. The 5'-flanking region of the mouse GM-CSF gene which is required for activation by pX or mitogen was mapped within 226 bp upstream from the transcription initiation site. Action of pX was not restricted to T cells. pX activated exogenously added GM-CSF, IL-2, IL-3 and IL-4 genes in fibroblasts. Activation of the GM-CSF gene in fibroblasts appears to require the same regulatory region as in T cells. Similar results were obtained using bovine papilloma virus encoded E2 protein. We propose that pX or E2 protein, both in T cells and fibroblasts, activates cellular component(s) in the signal transduction pathway which results in the activation of lymphokine genes in the absence of extracellular stimuli.

Adenovirus Early Proteins↗
PubMed1988

Relationship between an activated N-ras oncogene and chromosomal abnormality during leukemic progression from myelodysplastic syndrome.

The relationship between chromosomal abnormality and oncogene activation was investigated during leukemic progression in two patients with myelodysplastic syndrome (MDS). Both patients had partial or complete deletion of chromosome 5 in metaphase cells obtained throughout the progression to leukemia. Analysis with specific oligonucleotide probes revealed that bone marrow cells containing an activated N-ras oncogene proliferated in a dominant manner during the process of leukemic conversion in both patients. These observations suggest that the chromosomal abnormality may precede activation of the N-ras gene in these patients, and that both the chromosomal abnormality and the activated N-ras oncogene contribute to the development of leukemia.

Acute Disease↗
PubMed1987

A novel putative tyrosine kinase receptor encoded by the eph gene.

Growth factors and their receptors are involved in the regulation of cell proliferation and also play a key role in oncogenesis. In this study, a novel putative kinase receptor gene, termed eph, has been identified and characterized by molecular cloning. Its primary structure is similar to that of tyrosine kinase receptors thus far cloned and includes a cysteine-rich region in the extracellular domain. However, other features of the sequence distinguish the eph gene product from known receptors with tyrosine kinase activity. Thus the eph protein may define a new class of these molecules. The eph gene is overexpressed in several human carcinomas, suggesting that this gene may be involved in the neoplastic process of some tumors.

Amino Acid Sequence↗
PubMed1987

Activation mechanism of the N-ras oncogene in human leukemias detected by synthetic oligonucleotide probes.

The synthetic oligonucleotide probes were used for the analysis of N-ras oncogenes detected in human acute leukemias. The mutations of N-ras genes were observed to occur randomly among the subtypes of myeloid leukemias, whereas the N-ras mutations at codon 12 are more likely to occur in lymphoid leukemias than other mutations. The mutations at codon 13 of the N-ras gene were not detected in acute leukemias although they were found in myelodysplastic syndrome that is considered to be a preleukemic state.

Animals↗
PubMed1987

Highly frequent detection of transforming genes in acute leukemias by transfection using in vivo selection assays.

DNAs from nine out of ten acute leukemia cases that were negative by in vitro focus forming assays exhibited transforming activity tested by in vivo selection assays in nude mice using transfected NIH3T3 cells. Of the nine cases, six cases contained activated N-ras genes, and one case exhibited activation of the c-K-ras gene. None of the ras gene family showed homology with the transforming genes derived from the other two cases. Our observations indicate that in vivo selection assays detect transforming genes including ras oncogenes at high frequency, and that activated N-ras genes are frequently detected in human acute leukemias.

Animals↗
PubMed1987

A point mutation at codon 13 of the N-ras oncogene in a human stomach cancer.

A surgically removed human stomach cancer with the histological diagnosis of poorly differentiated adenocarcinoma contained an activated N-ras oncogene detected by an in vivo selection assay in nude mice using transfected NIH3T3 cells. Analysis using synthetic 20-mer oligonucleotide probes revealed a point mutation from G to C at the first letter of codon 13 of the N-ras gene resulting in the substitution of arginine for glycine. This is the first observation of an activated N-ras oncogene in human stomach cancers.

Adenocarcinoma↗
PubMed1987

Molecular cloning of the closed circular provirus of human T cell leukaemia virus type I: a new open reading frame in the gag-pol region.

A DNA clone of human T cell leukaemia virus type I (HTLV-I) was isolated from extrachromosomal closed circular copies in chronically infected promyelocytic leukaemia HL60 cells. The new HTLV-I isolate had an intact reading frame in the gag-pol region which could encode protein of 234 amino acids. This open reading frame has not been observed in previous HTLV-I isolates, although similar open reading frames have been reported in the corresponding locations in the related bovine leukaemia virus and HTLV type II. We consider that this open reading frame codes for the virus-encoded protease, on the basis of the homology of the predicted amino acid sequence with those of previously identified retrovirus proteases.

Amino Acid Sequence↗
PubMed1987

Constitutive expression of the granulocyte-macrophage colony-stimulating factor gene in human solid tumors.

We detected constitutive expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene in 3 human solid tumors by Northern blot analysis. Two of them were also found to secrete the GM-CSF protein by colony forming unit-culture assay. Southern blot analysis of each tumor DNA showed no gross rearrangement of the GM-CSF gene. This is the first report that demonstrates expression of the GM-CSF gene in solid tumors at the mRNA level.

Colony-Forming Units Assay↗