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Biomedical subjects

N Arai

Publications and source records attributed to N Arai.

At least 217 records · Page 12Linked to original sources
PubMed1991

[Thrombotic thrombocytopenic purpura associated with myasthenia gravis].

A case of thrombotic thrombocytopenic purpura (TTP) associated with myasthenia gravis (MG) is reported. A 56-year-old woman was admitted to our hospital on April 27, 1988, because of easy fatigue and double vision. She was diagnosed as having myasthenia gravis from her neurological and laboratory findings. On the 14th hospital day, she developed fever, jaundice, hematuria, purpura and consciousness disturbance. Hematological examination revealed marked anemia, thrombocytopenia, fragmented red blood cells, elevated bilirubin and LDH level. Coagulation studies were almost normal. She was diagnosed as having TTP and treated with corticosteroid, antiplatelet agents and plasma exchange. Clinical condition and laboratory findings improved by the 23rd hospital day. It has been reported that TTP is associated with various autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome or idiopathic thrombocytopenic purpura. However TTP associated with MG appears the first report. This case may suggest that one of pathogenesis of TTP is autoimmune mechanism.

Autoimmunity↗
PubMed1990

Evaluation of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black mouse model for parkinsonism.

We evaluated neurochemically, behaviorally, and neuropathologically the availability of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black (BL) mice as a model for Parkinson's disease. The dopamine and 3,4-dihydroxyphenyl acetic acid content in the striatum, measured by high-performance liquid chromatography with an electrochemical detector, decreased by 70% at 10 and 20 days after the withdrawal of MPTP (30 mg/kg, i.p. twice daily for 5 days). During these days, the mice showed a decrease in locomotor activity and exhibited akinesia in both pole and traction tests. Light microscopically, 44% of the MPTP-treated mice showed neuronal degeneration in the substantia nigra 1 month after the withdrawal (damaged group), and 56% showed no change (undamaged group). Morphometric analysis revealed that the number of neurons in the substantia nigra decreased by 33% on the average in both groups. Electron microscopically, an electron-dense degeneration of most neurons was seen in the substantia nigra of the damaged group, and even in the undamaged group, loss of rough endoplasmic reticulum and mitochondrial deformity were seen in 50-70% of the neurons. Electron-dense bodies were seen in the striatum of both groups. These results show the validity of the MPTP-treated C57 BL mice as a suitable model for parkinsonism, including Parkinson's disease.

Animals↗
PubMed1990

Inducible and non-inducible factors co-operatively activate the GM-CSF promoter by interacting with two adjacent DNA motifs.

The upstream region of the mouse granulocyte macrophage colony stimulating factor (GM-CSF) gene between positions -95 and -73 is required for phorbol-12-myristate-13-acetate (PMA)- and calcium ionophore (A23187)-inducible transcriptional activity in vivo. To study the mechanism of GM-CSF gene activation in T cells, nuclear extracts from non-stimulated and PMA/A23187-stimulated Jurkat cells were used in DNA binding assays. DNA mobility shift assays with wild type and mutant oligonucleotides revealed that this region contains at least two DNA binding motifs. One is the binding sequence GGTAGTTCCCC (positions -91 to -81), recognized by NF-GM2 (nuclear factor of GM-CSF 2), and the other is a GC-rich sequence (GC-box). NF-GM2, induced in Jurkat cells by PMA/A23187 stimulation, effectively competed with DNA containing the NF-kappa B binding sequence, suggesting that it has NF-kappa B-like activity. By UV cross-linking analysis, three cross-linked bands, corresponding to Mr 165, 70, and 60 kd for NF-GM2, and 110 and 130 kd for A1 and A2, respectively, were identified. Transfection experiments showed that activation of the GM-CSF gene in response to PMA/A23187 stimulation was abolished by point mutations in either the GC-box or the NF-GM2 site; these mutations also abolished binding of the respective proteins. These results indicate that constitutive (GC-box binding factor) and inducible (NF-GM2) factors regulate the GM-CSF promoter co-operatively in a PMA/A23187-inducible manner in vivo.

Animals↗
PubMed1990

[The COP-BLAM therapy for non-Hodgkin's lymphoma in elderly patients].

COP-BLAM therapy, which has recently been reported to be useful in the treatment of malignant lymphoma, was performed on aged patients with non-Hodgkin's lymphoma, and the results and adverse effects of the treatment were evaluated. The subjects of the present study included 13 patients with non-Hodgkin's lymphoma, aged 60 years or older, treated during the period from October, 1987 to June, 1989. They included four recurrent cases after CHOP therapy. According to the Ann-Arbor classification of pathological stage there were two patients in stage I, one in stage II, two stage III and eight in stage IV. COP-BLAM therapy was conducted using the following procedure, irrespective of the patient's age, intravenous drip infusion of cyclophosphamide (CPM) at a dose of 400 mg/m2 and intravenous infusion of 1 mg/m2 vincristine (VCR), and 30 mg/m2 adriamycin (ADM), on day 1; oral administration of 40 mg/m2 prednisone (PSL), and 100 mg/m2 procarbazine (PCZ), from day 1 through day 10, followed by intravenous infusion of bleomycin (BLM), 10 mg/body on day 14. BLM was withdrawn or decreased to less than 70% of the initial dose in patients who exhibited disturbed pulmonary function. Treatment resulted in complete remission (CR) in 11 and partial remission (PR) in 2 out of the 13 patients. Analyzing results according to pathological stage. CR was obtained in all of those in staged I and II, and eight out of the 10 in staged III and IV. The four patients with recurrent disease after CHOP therapy exhibited a CR rate of 50%, indicating that therapy is highly effective in recurrent cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

[The COP-BLAM therapy for malignant lymphoma].

COP-BLAM therapy, which has recently been reported to be useful in the treatment of malignant lymphoma, was performed on 36 patients, and the results and adverse effects of treatment were evaluated. Complete remission (CR) and partial remission (PR), was obtained in 32 (88.9%) and in 4 (11.1%) out of the 36 patients, respectively. So the effective ratio was 100%. Analyzing results according to staging classification, CR was obtained in all of those in stages I and II, and in 84% of those in stages III and IV. The four patients with recurrent disease after CHOP therapy exhibited a CR ratio of 50% indicating that therapy is effective in recurrent cases. Adverse effects observed among the patients included leukocytopenia under 1,000/microliters (5.6%), thrombocytopenia under 5 x 10(4)/microliters (2.8%), gastrointestinal symptoms (25%), peripheral neuropathy (8.3%) and alopecia (27.3%). The efficacy of COP-BLAM therapy appears to be satisfactory with malignant lymphoma, and all adverse effects were of mild degree. In addition, it may be effective in the treatment of recurrent cases which remitted after CHOP and other therapies.

Adult↗
PubMed1990

[Massive bilateral non-Hodgkin's lymphoma of the adrenal glands].

The patient was a 47-year-old male who attended our hospital complaining of back pain. Masses in the bilateral adrenal glands were noted on abdominal ultrasonography and the patient was admitted to the hospital on August 9, 1988. Upon test laparotomy, non-Hodgkin's lymphoma (diffuse small-cell type, B-cell type) was diagnosed, and endocrinological examination revealed hypofunction of the adrenal gland. The results of various tests showed absence of distance metastasis except for that to the bilateral adrenal glands. Since complete remission was attained after 2 courses of COP-BLAM III therapy, and adrenal function also became normal, the patient was discharged on January 9, 1989. Malignant lymphoma originating from the adrenal gland seems to be a rare condition, and only 16 cases have been reported to this date.

Adrenal Gland Neoplasms↗
PubMed1990

[Cyclic neutropenia complicated of non-Hodgkin lymphoma].

This paper reports a case of non-Hodgkin's lymphoma concurrent with cyclic neutropenia. A 59-year-old man who exhibited a neutropenia at a periodicity of 14-20 days from July 1986 was diagnosed as having cyclic neutropenia, and was re-admitted to our hospital because of an abdominal tumor in April 1988. Gastroscopy revealed a Borrmann II-like elevated lesion, and abdominal CT scanning showed a low density area in the liver and swelling of the para-aortic lymph nodes. According to histological examination of the stomach and the liver, the patient was diagnosed as having non-Hodgkin's lymphoma (diffuse, medium-cell type). After completion of three courses of COP-BLAM III therapy, which was started on June 7, a partial response was achieved. However, the patient had a relapse and died on May 12, 1989. Cyclic neutropenia in this case was not considered to be due to an immunological abnormality mediated by lymphocytes, but may have been caused by an excessive response of the negative feedback mechanism due to an increase in CIA (Colony-inhibiting activity) of neutrophils. The fact that the patient's EB virus antibody titer became higher than at this initial hospitalization suggests the possible transition from chronic EB virus infection into malignant lymphoma.

Agranulocytosis↗
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↗
PubMed1989

Multiple forms of recombinant murine interleukin-4 expressed in COS-7 monkey kidney cells.

Recombinant murine interleukin-4 (muIL-4) expressed in COS-7 monkey kidney cells was purified to homogeneity by sequential CM-Sepharose, Sephadex G-100 chromatography and mono-S FPLC to a specific activity of 6.10(7) units per mg of protein based on an in vitro HT-2 cell proliferation assay. Two electrophoretic variants, designated a and b, which migrated on SDS-PAGE as a closely spaced doublet with Mr 19,000, were present in the final product. Gas phase sequencing of the purified protein revealed the presence of an N-terminus corresponding to the mature protein predicted from the cDNA sequence and sequencing of a cyanogen bromide digest confirmed 75 of the 120 predicted amino acids. Elution behavior on gel filtration corresponded to that of a monomer of Mr 19,000. Since there are three potential sites of N-glycosylation predicted by the cDNA sequence, the contribution of glycosylation to the observed heterogeneity was examined by treatment with endoglycosidases. Variant b was digested by either endo-beta-N-acetylglucosaminidase H (endo H) or endo-beta-N-acetylglucosaminidase F (endo F) to protein of Mr 15,000 on SDS-PAGE but was unaffected by treatment with endo-beta-N-acetylglucosaminidase D (endo D), thus indicating the presence of high mannose type of N-glycan. In contrast, variant a was resistant to endo H, F and D. Complete conversion of a mixture of variants a and b to a single protein of Mr 15,000 on SDS-PAGE was obtained only after treatment with N-glycanase. Both variants were resistant to neuraminidase and O-glycanase treatment. These data show that the microheterogeneity observed in purified muIL-4 preparations is due to differences in the nature of the N-linked oligosaccharides. The availability of purified recombinant muIL-4 and a methodology for both total and selective deglycosylation provides a basis for the initiation of structure-function studies of this novel T-cell lymphokine.

Amino Acid Sequence↗
PubMed1989

Interleukin-4 and interleukin-5 map to human chromosome 5 in a region encoding growth factors and receptors and are deleted in myeloid leukemias with a del(5q).

Interleukin-4 (IL-4) is a potent mediator of growth and differentiation of cells of several hematopoietic lineages. Interleukin-5 (IL-5) is a lineage-specific hematopoietic growth factor that stimulates the production of eosinophils and eosinophil colonies from normal human bone marrow cells. By using somatic cell hybrids and in situ chromosomal hybridization, we localized the IL-4 and IL-5 genes to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the IL-4 and IL-5 genes were found to be deleted in the 5q- chromosome of four patients with refractory anemia (RA) or therapy-related acute nonlymphocytic leukemia (t-ANLL), who had a del(5q). Thus a small segment of chromosome 5 contains IL-4, IL-5, IL-3, and GM-CSF as well as other genes such as CD14 and EGR1. Our findings that each of these genes was deleted in the 5q- chromosome suggest that loss of function of one or more of these genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q).

Chromosome Deletion↗
PubMed1989

Complete nucleotide sequence of the chromosomal gene for human IL-4 and its expression.

We have isolated a chromosomal DNA segment of the human IL-4 gene based on homology with a human IL-4 cDNA sequence and determined its complete nucleotide sequence. The human IL-4 gene, which occurs as a single copy in the haploid genome, is mapped on chromosome 5. It is composed of four exons and three introns and is approximately 10 kilobase pairs in size. 5'-Flanking regions of human and mouse IL-4 genes share about 85% homology extending more than 500 base pairs upstream of a "TATA" like sequence. Several patches of sequences are found in the 5'-flanking region of the human IL-4 gene which are homologous to sequence in the 5'-flanking regions of the IL-2, IL-3, IL-5, and granulocyte-macrophage (GM)-CSF genes. The IL-4 gene is inducible after treatment of human T cell clone by phorbol-12-myristate-13-acetate (TPA) and calcium ionophore A23187. The 2.3-kb 5'-flanking region of the human IL-4 gene transiently transfected into Jurkat human T cell leukemia cells is activated efficiently in response to TPA and A23187 stimulation and, although less efficiently, by human T cell leukemia virus type I-encoded p40x or BPV-encoded E2 protein. Combination of TPA/A23187 and p40x or E2 protein further augmented the level of expression.

Amino Acid Sequence↗
PubMed1989

Bovine papilloma virus encoded E2 protein activates lymphokine genes through DNA elements, distinct from the consensus motif, in the long control region of its own genome.

Activation of T cells by antigen, lectin or a combination of phorbol ester (PMA) and calcium ionophore (A23187) leads to the induction of a set of lymphokine genes. Transfection of a human T cell leukemia cell line, Jurkat, or an African green monkey kidney cell line, CV1, with a cDNA encoding E2 protein, a trans-activator of bovine papilloma virus type 1, results in activation of interleukin 2 (IL-2), interleukin 3 (IL-3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) genes in a transient transfection assay. 5' deletion and mutation analyses showed that the sequence between positions -60 and a TATA-like sequence is required for basic promotor function and that the sequence between positions -95 and -73 containing conserved lymphokine element 2 (CLE2) and a GC box (CLE2/GC box) mediates the positive response to E2 protein. The latter has been previously shown to respond to PMA/A23187 stimulation or to p40tax, a trans-activator encoded by human T cell leukemia virus type 1 (HTLV-I). The sequence located between -108 and -99 (CLE1) is inhibitory to E2 protein or PMA/A23187 stimulation. The combination of E2 protein and PMA/A23187 appears to eliminate an inhibitory effect of the upstream region. However, E2 protein, like p40tax, mediates a positive response through CLE1 alone linked to the basic promoter sequence. The level of activation of the long control region (LCR) by E2 protein is unaffected by the number of CLE2/GC box sequences.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

"Grumose degeneration" of the dentate nucleus. A light and electron microscopic study in progressive supranuclear palsy and dentatorubropallidoluysial atrophy.

So-called "grumose degeneration" (GD) of the dentate nucleus (DN) which is a unique alteration in progressive supranuclear palsy and dentatorubropallidoluysial atrophy was studied by light and electron microscope. Light microscopically, the presence of a large amount of eosinophilic granular and/or amorphous material around the neurons is the most conspicuous feature of GD. In addition, the number of neurons is decreased and some of them are swollen as with central chromatolysis. Electron microscopically, the granular and/or amorphous material mainly consists of the altered axon terminals of the Purkinje cells (Pax), which are relatively electron-dense and characteristically contain varying numbers of deformed lamellar bodies, highly electron-dense mitochondria and many vacuoles which are adherent to the astrocytic processes. GD is a unique histological change of both the chromatolytic DN neurons and the grumose appearance of the altered Pax. Possible mechanisms are discussed.

Adult↗
PubMed1989

"Grumose degeneration" of Trétiakoff.

We reviewed Trétiakoff's "grumose degeneration (GD)" which described pathologic cellular change in the substantia nigra (SN). This term has been occasionally used up to the mid-1960s by Greenfield et al.; it has rarely been used after the 1970s. This study emphasises the following: (1) after the 1970s, GD has sometimes been signalled in the SN under various names, such as "spheroid with foamy appearance", "granular spheroid", "saccular structure", or "foamy spheroid body"; (2) the ultrastructure of GD is unknown, being entirely different from that of typical axonal swellings (so-called "spheroids"); (3) more attention should be paid to GD in the SN because its nature has remained unclarified since the original description; and (4) "GD" in the cerebellar dentate nucleus is essentially different from Trétiakoff's GD.

Cerebellar Nuclei↗