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Biomedical subjects

N Arai

Publications and source records attributed to N Arai.

At least 199 records · Page 11Linked to original sources

[Sudden death due to bilateral pulmonary thromboembolism in a patient with multiple myeloma: an autopsy case report].

We encountered a patient with multiple myeloma who died suddenly, in whom bilateral pulmonary artery thrombosis was found at autopsy. The patient was a 50-year-old woman who had received chemotherapy for multiple myeloma at a local clinic for 4 years, and was transferred to our hospital because of recurrence of multiple myeloma in August 1990. Despite chemotherapy performed after admission, serum globulin level increased and her low back pain worsened, and she was generally restricted to bed. On October 21, she developed sudden dyspnea, became markedly cyanotic, lost consciousness, and then suffered a cardiopulmonary arrest. Autopsy revealed bilateral pulmonary artery thrombosis as well as thrombosis in the pelvic veins. Hyperviscosity due to multiple myeloma and long-term recumbency were the probable causes of pelvic venous thrombosis and subsequent pulmonary artery thrombosis. We report a rare case of bilateral pulmonary artery thrombosis which developed during the course of multiple myeloma and led to sudden death.

Death, Sudden↗

Transcriptional activator Tax of HTLV-1 binds to the NF-kappa B precursor p105.

Human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia and also a neurological disease, tropical spastic paraparesis. Tax protein (p40tax) of HTLV-1 activates in trans its own transcriptional enhancer in the long terminal repeat and also those in some cellular genes such as interleukin 2 receptor alpha, granulocyte-macrophage colony-stimulating factor, Fos, Jun and MHC class I. Thus, Tax has been proposed to play a critical role in the pathogenesis induced by HTLV-1 infection. Here, we report formation of a complex of Tax protein with the precursor protein p105 of the NF-kappa B p50 subunit. p105 was co-immunoprecipitated with Tax protein from cells infected with HTLV-1 from cells transfected with the Tax expression plasmid, but not from cells transfected with inactive mutants of Tax. Furthermore, a GST-p105 fusion protein produced in Escherichia coli bound to Tax protein. These results strongly suggest that the trans-activator Tax protein forms a complex with precursor NF-kappa B p105 and plays a role in trans-activation of transcriptional initiation.

Gene Products, tax↗

[Chronic cold agglutinin disease occurring after a diagnosis of aplastic anemia].

We report herein a 61-year-old man with chronic cold agglutinin disease which occurred after a diagnosis of aplastic anemia. The patient's pancytopenia was recognized upon visiting a local doctor because of high fever and cough on December 21, 1985. He was subsequently admitted to our hospital because of anasarca on January 31, 1986, and was diagnosed as having aplastic anemia. He was treated with prednisolone, and was discharged after his anemia improved. He was readmitted on October 23, 1988, because of icterus. Laboratory data on the patients second admission revealed increased reticulocyte count, hyperplastic bone marrow with a predominance of erythroblasts, increased serum indirect bilirubin, increased serum LDH1 value and decreased serum haptoglobin. Moreover, cold agglutinin titer was increased, anti-IF antibody was positive, and anti-IgM antibody was recognized with direct anti-globulin test. There was no precedent infection such as mycoplasma pneumonia or infectious mononucleosis. Hence, this patient was diagnosed as having chronic cold agglutinin disease.

Anemia, Aplastic↗

[Pulmonary thromboembolism associated with myelodysplastic syndrome].

We present a 65-year-old female with myelodysplastic syndrome (MDS) who has attended our O.P.D. since 1983. In early December, 1990, dyspnea on effort developed which then progressed to dyspnea at rest at the end of December. She was admitted on January 8 with orthopnea. Chest X-ray films revealed loss of vascular shadows of the right lung. Blood gas analysis showed hypoxemia and hypocapnemia. Abnormalities in the coagulation-fibrinolytic system (increased TAT (thrombin-anti-thrombin III complex) and alpha 2-PIC (plasmin inhibitor complex)), possibly due to MDS, were detected. The diagnosis of pulmonary thromboembolism was made by pulmonary perfusion scintigram and pulmonary arteriography. After commencement of anticoagulation therapy on January 15, the subjective symptoms, blood gas analysis, pulmonary scintigram, and disorders of the coagulation-fibrinolytic system improved. The patient was discharged on March 5, 1991. The present case of myelodysplastic syndrome was associated with abnormalities of the coagulation-fibrinolytic system and was complicated by pulmonary thromboembolism.

Aged↗

Two cases of a renal epithelial tumour resembling immature nephron.

Two cases of renal epithelial tumours are reported in females aged 46 and 66 years respectively. In spite of the large size of the tumours, neither invasive growth nor metastasis was observed. Histologically, the tumours were composed of immature epithelial cells forming tubules with abortive glomeruloid structures. Electron microscopy of tumour cells revealed poorly developed polarity and intracytoplasmic organelles. They showed similar immunohistochemical reactions to those of developing nephrons, particularly to those of the S-shaped body. The nuclear DNA content of the tumour cells was almost euploid. We conclude that the lesions were epithelial tumours of the kidney histologically mimicking developing renal parenchyma.

Aged↗

A nuclear factor NF-GM2 that interacts with a regulatory region of the GM-CSF gene essential for its induction in responses to T-cell activation: purification from human T-cell leukemia line Jurkat cells and similarity to NF-kappa B.

Activation of T cells by antigen, lectin, or a combination of phorbol-12-myristate acetate (PMA) and calcium ionophore (A23187) leads to the induction of genes for a set of lymphokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF). We demonstrated in earlier studies that the upstream region of the mouse GM-CSF promoter at positions between -95 and -73 is essential for transcriptional activation in response to PMA/A23187. This region contains two DNA-binding motifs, GM2 and GC-box. The GM2 sequence (GGTAGTTCCC) is recognized by an inducible factor NF-GM2; the other (CCGCCC) by constitutive factors A1, A2, and B. To elucidate the mechanism of GM-CSF gene activation, we have purified the inducible factor NF-GM2 from the nuclear extract of stimulated Jurkat cells on the basis of specific DNA-binding activity. The purified NF-GM2 consists of 50 (p50) and 65 kDa (p65) polypeptides and has a binding activity specific for both the GM-CSF and immunoglobulin kappa (GGAAAGTCCC) enhancers. Electrophoretically purified p50 alone can form a protein-DNA complex, but in the mixture, p50 associates preferentially with p65 to form the NF-GM2 complex. In addition, p65 gave per se, with low affinity, a protein-DNA complex that migrated more slowly than native NF-GM2 complex. Furthermore, an antiserum against KBF1 (identical to 50 kDa NF-kappa B protein) reacted with the p50 of NF-GM2, indicating that the NF-GM2 polypeptide cannot be immunologically differentiated from the 50 kDa subunit of NF-kappa B. The purified NF-GM2 activated in vitro transcription from the kappa B enhancer, while it failed to stimulate transcription from the GM-CSF promoter harboring the GM2 sequence. This suggests that the activation mechanism of the GM-CSF gene through the GM2/GC-box sequence is different from that of genes carrying the kappa B enhancer alone.

Base Sequence↗

Characterization of the mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) gene promoter: nuclear factors that interact with an element shared by three lymphokine genes--those for GM-CSF, interleukin-4 (IL-4), and IL-5.

The region extending from -40 to -54 of the 5'-flanking region of the mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) gene shows homology to sequences found in the 5'-flanking regions of other cytokine genes, those encoding interleukin-4 (IL-4), IL-5, and granulocyte colony-stimulating factor (G-CSF). This sequence element is referred to as conserved lymphokine element 0 (CLE0). Saturation mutagenesis of the CLE0 element indicates that in addition to the previously mapped region between -73 and -91 (CLE2+ GC box), the CLE0 element is necessary for induction of the mouse GM-CSF gene by phorbol myristate acetate/Ca ionophore (A23187) stimulation in T cells. The presence of the CLE0 element is necessary to observe stimulation of the transcription activity of the mouse GM-CSF promoter in vitro. Mobility shift assays revealed that this region forms an inducible DNA-protein complex, NF-CLE0, which consists of two complexes of similar mobility, NF-CLE0a and NF-CLE0b. NF-CLE0a and NF-CLE0b recognize the 3' half and 5' half of the CLE0 element, respectively, with an overlapping region recognized by both proteins. The recognition sequence of NF-CLE0a corresponds to the region required for induction by phorbol myristate acetate/A23187, while the recognition sequence of NF-CLE0b contains bases that have inhibitory activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Nanomolar L-dopa facilitates release of dopamine via presynaptic beta-adrenoceptors: comparative studies on the actions in striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black mice, an animal model for Parkinson's disease.

Effects of L-DOPA (0.1-10,000 nM) on spontaneous release (Sp), evoked release (S) and tissue content (C) of dopamine (DA) were studied comparatively in superfused striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57 black mice to obtain evidence for L-DOPA-induced facilitation of S via presynaptic beta-adrenoceptors. In control slices, isoproterenol-induced concentration-dependent increases in S were propranolol-sensitive. L-DOPA at 0.1-3 nM tended to increase the S of DA with a concomitant tendency of increases in Sp. L-DOPA at 10-1 x 10(4) nM concentration-dependently increased Sp. L-DOPA at 1-10 microM tended to increase S and 10 microM increased C. In slices from MPTP-treated mice, the absolute amounts of Sp, S and C decreased by half compared to those in control slices. L-DOPA at 3 nM facilitated S without increasing Sp. This facilitation was antagonized by propranolol at 3 nM. L-DOPA at 30 nM decreased S from the peak facilitation, which contrasted with no effect in the control slices. However, 10-100 nM L-DOPA increased Sp more markedly than that in the control slices. L-DOPA at 100 nM increased S and C, which contrasted with no effect in the control slices. In conclusion, nanomolar L-DOPA facilitates the S of DA via presynaptic beta-adrenoceptors at concentrations lower than those required to induce conversion to DA even in striatal slices from the MPTP-treated mice model for Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

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

[A comparative study of CHOP therapy and COP-BLAM therapy for non-Hodgkin's lymphoma in elderly patients].

Elderly patients (aged greater than or equal to 65 years) with non-Hodgkin's lymphoma were treated either with CHOP or COP-BLAM therapy, and the effectiveness and reverse effects of COP-BLAM therapy were compared with those of CHOP therapy. Thirty-three patients (aged greater than or equal to 65 years) with previously untreated non-Hodgkin's lymphoma were entered either on CHOP or COP-BLAM regimen between September, 1979 and February 1990. To CHOP therapy was performed in 15 patients (median age; 70 years). Eight of them had diffuse large cell type lymphoma (large), five had diffuse medium-sized cell type (medium) and two had diffuse mixed cell type (mixed). As to clinical stage, there were patients in stage II, 4 in stage III and 9 in stage IV in CHOP group. Of 18 patients (median age; 68 years), who were treated with COP-BLAM therapy, 8 had of large lymphoma and 10 medium lymphomas in histopathological classification. In terms of clinical stage, there were 5 patients in stage II, 4 in stage III and 9 in stage IV. CHOP therapy and COP-BLAM therapy were performed according to the method reported by McKelvey et al, and by Laurence et al., respectively, using the full doses of drugs without consideration the age. Complete remission (CR) was achieved in seven (46.7%) of 15 patients treated with CHOP therapy. In this group, five (38.5%) of 13 patients in advanced stages (stage III or IV) entered CR. Of 18 patients subjected to COP-BLAM therapy, 15 (83.3%) achieved CR. Among 13 patients in advanced stage treated with COP-BLAM therapy, CR was achieved in 11 (84.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[A case of EEC (ectrodactyly, ectodermal dysplasia, and cleft lip) syndrome].

EEC syndrome is a rare congenital malformation characterized by ectrodactyly, ectodermal dysplasia, cleft lip and/or palate. We reported a case of EEC syndrome with cleft palate. The patient was a 15-month-old girl. She had split hands of the upper extremities, syndactyly and polydactyly of the right lower extremity, ectodermal dysplasia including sparse hair, enamel hypoplasia and cleft palate. The patient underwent palatoplasty at the age of 18 months.

Abnormalities, Multiple↗

[Salvage chemotherapy with IMV-triple P for relapsed or refractory malignant lymphoma].

Twelve patients with relapsed or refractory malignant lymphoma were treated with IMV-triple P regimen consisting of ifosfamide (IFM), mitoxantrone (MIT), vindesine (VDS), pepleomycin (PEP), procarbazine (PCZ) and prednisolone (PDN). Three of 12 patients achieved complete remission (CR), and 5 patients achieved partial remission (PR). Hence, the overall response rate was 66.7% (8/12). Of 9 relapsed patients who had attained CR after the former chemotherapy, 3 had CR and 4 had PR. The overall response rate was 77.8% (7/9). Side effects were relatively mild, including leukopenia (less than 1,000/microliters) (33.3%) and thrombocytopenia (less than 5 X 10(4)/microliters) (8.3%). There was no severe cardiac toxicity such as heart insufficiency and severe arrythmia. These results suggest that IMV-triple P regimen is effective in the treatment of relapsed or refractory malignant lymphoma.

Adult↗

[Immunohistochemical study of glial cytoplasmic inclusion in multiple system atrophy].

Recently, glial cytoplasmic inclusion (GCI) has been demonstrated to be argyrophilic cytoplasmic body by silver staining in the oligodendroglia of patients with multiple system atrophy. We observed such GCIs in all 20 cases of multiple system atrophy. No GCI was noticed in all 6 cases of hereditary spinocerebellar degenerations. Immunohistochemically, GCI was stained positively with antibodies to ubiquitin, alpha-tubulin, and beta-tubulin, of which characteristics is consistent with previous reports. In addition, GCI was first demonstrated to react with an antibody to microtubule-associated protein-1B(5), which is one of the proteins of cytoskeleton organization and a component of cross-bridges between microtubular assembly. The result suggests strong relationship between the formation of the OCI and immunohistochemical expression of MAP-1B(5).

Antibodies, Monoclonal↗

[The COP-BLAM III therapy of non-Hodgkin's lymphoma].

COP-BLAM III therapy was given to 18 patients with non-Hodgkin's lymphoma, and the therapeutic effects as well as adverse effects of the treatment were examined. Of the 18 patients 16 had a complete remission (CR) and 2 showed an partial remission (PR) with a total response rate of 100%. In terms of the stage of disease, CR was achieved in all patients in stage III and in 11 of 13 patients in stage IV. Patients with neutrophil counts less than 1,000/microliters were given rhG-CSF (1.5 micrograms/kg/day, sc), which significantly shortened the duration of neutropenia and decreased the number of days with episodes of fever when compared with those not given rhG-CSF, consequently facilitating the treatment without prolonging the dosing intervals. No serious infection was observed. Adverse effects included neutropenia of less than 1,000/microliters in 6 of the 18 patients (33.3%), thrombocytopenia less than 5 x 10(4)/microliters in 3 (16.7%), nausea and vomiting in 8 (44.4%), peripheral neuropathy in 4 (22.2%) and stomatitis in 4 (22.2%). There were no fatalities caused by the treatment. The above findings indicate that COP-BLAM III therapy is capable inducing high frequency of complete remissions in non-Hodgkin's lymphoma and that its combination with G-CSF can improve the results of the therapy and relieve adverse reactions.

Adolescent↗

[Hodgkin's disease associated with LDH-M subunit deficiency].

The patient was a 60-year-old man who had complained of left cervical swelling from the end of June, 1984. He was diagnosed as having Hodgkin's disease (mixed-cell type) by lymph node biopsy, and was admitted to our hospital for thorough examination and treatment on July 23rd. Diagnosis of stage IA Hodgkin's disease involving only the left cervical lymph node was made. On admission, laboratory data revealed that the LDH activity in his serum and erythrocytes consisted of only type 1 (LDH-H4), hence LDH-M subunit deficiency (homogeneous type) was diagnosed. However, the muscle rigidity, myoglobinuria, and skin lesions that are usually seen in this abnormality were not observed. After two course of C-MOPP therapy, beginning on August 1st. complete remission was obtained. He was subsequently given a total of 6 courses of C-MOPP therapy and 40 Gy of irradiation on an outpatient basis. He eventually died of heart failure on November 3rd, 1986. Only five families with LDH-M subunit deficiency have been reported to date in Japan. This is the first report in Japan of the condition being complicated by Hodgkin's disease.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical trial of alpha-interferon (human lymphoblastoid interferon) in combination with VCAP chemotherapy in multiple myeloma].

We compared the effect of combined natural interferon-alpha (HLBI)/VCAP chemotherapy with VCAP chemotherapy alone on multiple myeloma. Sixteen previously untreated patients with multiple myeloma were treated with a combination of IFN-alpha and VCAP chemotherapy; nine of them were treated with HLBI-VCAP (I) regimen (HLBI 3 x 10(6) units/day, daily, 56 days) only for induction chemotherapy, and seven with continuous HLBI-VCAP (II) regimen (HLBI 3 x 10(6) units/day, twice a week) both for induction and maintenance chemotherapy. Thirty-one control patients were treated with a VCAP regimen only. HLBI-VCAP (II) regimen exhibited an 85.7% (6/7) response rate, while VCAP and HLBI-VCAP (I) regimen showed 74.2% (23/31) and 77.8% (7/9) response rates, respectively. The median duration of survival was 43 months in the control group, greater than 44 months in HLBI-VCAP (I) group and greater than 45 months in HLBI-VCAP (II) group. No significant difference in survival duration has yet been observed between the VCAP group and HLBI-VCAP groups. We conclude that continuous, long-term combination therapy with HLBI and VCAP regimen for induction and maintenance therapy may be most effective, and found that intensive HLBI-VCAP regimen, for only remission induction therapy, was not more effective than VCAP regimen alone.

Adult↗

[Chronic myelocytic leukemia induced into remission by interferon-alpha associated with early esophageal cancer].

A fifty-one-year-old male patient visited the Department of Dermatology of Toho University Ohashi Hospital with a complaint of generalized exanthema, which was diagnosed assyringoma; at that time his leukocytosis was recognized. He was admitted to our department on August 8, 1988. Physical examination on admission revealed slight hepatosplenomegaly. WBC count was elevated (50,700/microliters). He was diagnosed as having Ph1-positive CML in the chronic phase and was treated with IFN-alpha (HLBI, Sumitomo, 3 x 10(6) units/day, daily, I. M.) from August 12, but an elevated lesion was detected at the lower part of his esophagus by endoscopy, and it was diagnosed by biopsy as squamous cell carcinoma. Radical operation for esophageal cancer was performed on September 26; at that time his WBC count was 17,400/microliters. After discharge, his WBC level was maintained within normal range by IFN-alpha. On August 2, 1989, he was readmitted to our hospital because of lymphoblastic crisis. Although he attained transient complete remission, he died of pneumonia after the relapse on January 10, 1990. IFN-alpha therapy is suggested to be useful for the treatment of CML associated with gastrointestinal cancer because of its possible parenteral administration and mild toxicity.

Carcinoma, Squamous Cell↗

[Non-Hodgkin's lymphoma localized at the right ocular medial rectal muscle].

This paper reports a rare case of extranodal non-Hodgkin's lymphoma localized at the ocular muscle, which achieved a long-term remission by combination chemotherapy and irradiation. A 41-year-old man visited the ophthalmology department of Toho University Hospital in December, 1982 because of right conjunctival injection and right exophthalmos which were first manifested in June. The patient was diagnosed as having non-Hodgkin's lymphoma (diffuse medium-sized cell type) by biopsy of the right medial rectal muscle, and was referred to our department on January 17, 1983. A series of examinations revealed that the disease had no invasion into any lymph nodes and other organs. After treatment with two courses of C-MOPP regimen and two courses of ACOP regimen, the patient achieved complete remission and was discharged on July 30. Subsequently he completed two courses of CHOP regimen followed by irradiation (46 Gy). Seven years and three months after the initiation of chemotherapy, the patient has been in a complete remission, requiring no treatment.

Adult↗