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Biomedical subjects

K Nasu

Publications and source records attributed to K Nasu.

At least 145 records · Page 8Linked to original sources

Oligoclonal immunoglobulin gene rearrangements in Philadelphia chromosome-positive common acute lymphoblastic leukemia.

The occurrence of more than two rearranged bands of immunoglobulin heavy chain (IgH) genes in B precursor acute lymphoblastic leukemia (ALL) has recently been documented. To elucidate the nature of such leukemias, we studied 30 patients with common ALL, including 6 patients with Philadelphia chromosome (Ph1)-positive ALL, by immunophenotyping and genotyping. In 10 of the 30, Southern blotting showed oligoclonal patterns of IgH gene arrangements, which were frequently detected in Ph1-positive ALL. In one patient of the 10, three rearranged bands of Ig kappa chain genes were detected. Ph1 abnormality and co-expression of myeloid associated antigens were found in 5 and 5 of the 10, respectively. Detection of multiple fragments of IgH genes would be suggestive of multipotent progenitor origin of these ALL.

Cloning, Molecular↗

Interference with human immunodeficiency virus (HIV) replication by CD8+ T cells in peripheral blood leukocytes of asymptomatic HIV carriers in vitro.

A long asymptomatic period is one of the characteristics of human immunodeficiency virus (HIV) infection, despite its fatal consequences. Antiviral defense in HIV-infected individuals controls viral replication during this period. In the present study, we demonstrate that peripheral blood leukocytes (PBL) of asymptomatic HIV-1 carriers, following exogenous HIV-1 infection in vitro, do not support viral replication. These cells do not produce detectable amounts of reverse transcriptase or accumulate unintegrated proviral DNA. This is a striking contrast to the behavior of HIV-1-infected PBL of seronegative individuals, which produce large amounts of RT and unintegrated DNA. Such resistance to HIV-1 replication is not seen in PBL of patients with advanced disease. Since the binding of HIV-1 to CD4 molecule is not impaired in PBL of asymptomatic carriers, the interference with HIV replication must occur after the stage of virus binding. PBL lose their resistance when CD8+ lymphocytes are removed. In addition, these PBL are not resistant to an exogenous infection with HIV-2. These observations suggest that certain populations of CD8+ lymphocytes of asymptomatic HIV-1 carriers operate on the target cells in PBL to block viral replication in an HIV-1-specific manner. Such CD8+ lymphocyte-mediated interference with HIV replication could play an important role in the maintenance of the period of disease latency.

AIDS-Related Complex↗

Frequent expression of myeloid antigen (CD13) on immature T cells in culture.

Leukemic cells from 12 patients with lymphoblastic lymphoma (LBL) and T cell acute lymphoblastic leukemia (T-ALL) were studied to determine the inducibility of myeloid antigens in culture in the presence and absence of 12-O-tetradecanoylphorbol-13-acetate (TPA) in association with discrete phenotypic and genotypic analyses on these cells. The investigation revealed that leukemic cells corresponding to common or mature thymocytes were never induced to express any myeloid antigens, and showed rearrangements of T cell antigen receptor (TcR) beta and gamma chain genes. Concomitant examination on leukemic cells from mature T cell malignancies, including adult T cell leukemia (ATL), T cell chronic lymphocytic leukemia (T-CLL) and T cell non-Hodgkin's lymphoma (T-NHL), also failed to express myeloid antigens in culture. By contrast, one of the panmyeloid antigens, CD13 (MCS-2) antigen was induced on leukemic cells corresponding to early thymocytes in 5 out of 7 cases in TPA-added culture and in 3 cases even in TPA-free culture. All of these CD13 antigen inducible cases exhibited the germ line configurations of TcR beta and gamma chain genes except for one case of T-ALL with sole TcR gamma chain gene rearrangement. These findings suggest that primitive T cells, still not undergoing TcR gene rearrangements, retain the characteristics of multipotent progenitor cells to possess different lineage markers and are able to express myeloid antigen not exceptionally. Both phenotypically and genotypically immature thymocytes are considered to be less restricted in the differentiation pathway of hematopoietic cells committed to T cell lineage.

Antigens, Differentiation, Myelomonocytic↗

[Clinical evaluation of combination therapy with aspoxicillin and ceftazidime for severe infections complicating hematological disorders].

Clinical effects of a combination therapy using aspoxicillin (ASPC) and ceftazidime (CAZ) were investigated in 88 patients with severe infections which were complicating hematological disorders. ASPC and CAZ were administered intravenously at daily doses of 8 g and 4 to 6 g, respectively, in 2 to 4 divided doses for at least 3 days. The treatment was markedly effective in 20 cases; effective in 31; fairly effective in 4; and ineffective in 33 cases. Seventy-seven patients with whom detailed data were obtained showed an efficacy rate of 63.6%. Bacteria were detected in 9 patients, from whom 10 strains were isolated. The results of bacteriological effects were: 3 strains disappeared, 1 decreased, 3 unchanged, and 3 unclear. The bacteriological eradication rate was 42.9%. Of the detected 10 strains, 3 were identified as Pseudomonas aeruginosa, with 2 of the 3 strains eradicated and 1 decreased. An evaluation of the relationship between clinical efficacies and neutrophil counts before and after the ASPC-CAZ combination therapy showed that the patients with 500/mm3 or higher neutrophil counts before the therapy or those with increased neutrophils after the therapy tended to be more responsive to the therapy. Side effects were observed in 4 patients, but all of them disappeared upon discontinuation of the therapy. The combination therapy with ASPC and CAZ appears to be useful for the treatment of severe infections complicating hematological disorders.

Adolescent↗

[Choroidal blood flow in chronic stage of selective retinal damage after monoiodoacetic acid injection].

The present study was carried out to determine changes in the choroidal circulation after a long period following selective damage of the outer layer of the retina. Monoiodoacetic acid was given to rabbits via an ear vein at a dosage of 40 mg/kg. The choroidal blood flow (CBF) at three and six months after selective damage was measured by the hydrogen clearance method and histological change was studied by light and electron microscopy. CBF decreased by 19% at three months and 22% at six months, the values in the experimental groups being significantly less than those of controls. Histological findings at six months were essentially the same as those at three months. The outer layer of the retina was totally replaced by glial cells. Some retinal pigment epithelial cells (RPE) had disappeared. The remaining RPE indicated proliferative or atrophic changes. At the site where RPE had disappeared, fibrous changes were evident in the inner layer of the choroid and choriocapillaris were lost. CBF at this site decreased significantly compared to that of the acute stage following monoiodoacetic acid administration. The outer layer of the retina, particularly RPE, may be reciprocally related to CBF and modulate choroidal angio-architecture.

Animals↗

Involvement of bcl-2 gene in Japanese follicular lymphoma.

A t(14;18) (q32;q21) chromosome translocation is closely associated with the follicular lymphoma, which is prevalent in the United States, and the t(14;18) causes the juxtaposition of a bcl-2 gene on chromosome 18 with an immunoglobulin heavy-chain gene locus on chromosome 14. Genomic DNAs from 30 Japanese patients with follicular lymphoma were examined for the molecular features by Southern blot hybridization. Using probe b for the major breakpoint cluster region of a bcl-2 gene, the rearrangements were detected in eight patients. Six of the eight patients had breakpoints located within the major breakpoint region, while two had breakpoints outside this cluster region but within the region of the 7.5-kb SstI fragment containing the probe b sequence. In two patients, pFL-2 probe detected the bcl-2 gene rearrangements that occurred near or within the minor breakpoint cluster region. These ten patients had a rearranged JH-containing fragment that migrated with the rearranged bcl-2 fragment. In the other 20 patients, these two chromosome 18-specific DNA probes did not detect the bcl-2 rearrangements. Compared with studies performed in the United States, the statistical analysis indicates a significant difference in frequency of the bcl-2 gene rearrangements near or within the major breakpoint cluster region (P = 0.0027) and the minor breakpoint cluster region (P = 0.029). However, the distribution difference of these events was not significant.

Blotting, Southern↗

Immunohistochemical analysis of peripheral T-cell lymphoma in Japanese patients.

The authors immunohistochemically analyzed the phenotype of 40 cases of peripheral T-cell lymphoma, including 12 adult T-cell leukemia/lymphoma (ATL) cases. Molecular genetic analysis of the T-cell receptor beta-chain and immunoglobulin heavy chain genes were also applied to cases of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-like lymphoma and so-called Lennert's lymphoma. Twenty non-ATL lymphomas expressed a helper/inducer phenotype, whereas only one extranodal case expressed a suppressor/cytotoxic phenotype. Three cases had a CD4-CD8- phenotype, and two cases a CD4+CD8+phenotype. No specific relationship between morphologic characteristics (LSG classification) and phenotype was found among non-ATL lymphomas. Six of eight AILD-like lymphomas had a helper/inducer phenotype. Monoclonality of neoplastic T-cells was demonstrated in six of the seven cases of AILD-like lymphoma by molecular genetic analysis. Two cases of Lennert's lymphoma also showed a helper/inducer phenotype and rearrangement of the T-cell receptor beta-chain gene. Serologically defined ATL cases had a helper/inducer phenotype except in one case that expressed both CD4 and CD8. None of the ATL cases had the CD7 antigen in this study using WT 1 as a CD7 antibody, which is in contrast with the non-ATL lymphomas in which 13 of 25 cases expressed CD7. CD25, strongly detectable in all ATL cases, was negative or weakly expressed in non-ATL lymphomas. These facts suggest that non-ATL and ATL are in the different biologic state, probably resulting from the integration of human T-cell leukemia virus type I (HTLV-I), although both are derived from helper/inducer T-cells.

Antigens, Differentiation, T-Lymphocyte↗

[Therapeutic effects of imipenem/cilastatin sodium against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group].

One hundred ninety-eight patients with severe infections associated with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS), and the efficacy and safety of the drug were evaluated. The results obtained are summarized below. 1. Out of 182 patients in whom efficacies are evaluable, responses were excellent in 50 patients, good in 52, fair in 21 and poor in 59, and the efficacy rating was 56.0%. 2. The efficacy rating in 87 patients who had failed to respond to prior treatment with other antibiotics was 58.6%. 3. There were significant differences in efficacy ratings when patients were grouped according to differences the number of neutrophils after treatment, less than 100, 101 approximately 500 and over 501/mm3. 4. The eradication rate in 38 patients from whom causative organisms were isolated was 75.8%. 5. Out of 197 patients in whom the safety was evaluable, side effects were observed in 19 patients (9.6%) and abnormal laboratory test values in 15 (7.6%).

Adolescent↗

[Factor V inhibitor with double cancer].

A 84-year-old man was admitted with palpitation, edema of legs and anemia during a long course of diabetes mellitus, prostatic hypertrophy and prostatic cancer. He revealed purpura on the hands and massive microhematuria. He had received antibiotic therapy for a urinary tract infection for a period of time, but he had no history of hemorrhagic tendency or blood transfusion. Coagulation studies showed the prolongation of whole blood clotting time and PT (prothrombin time). Activity of factor V was 14% of that normal control plasma. The titer of factor V inhibitor was 4.9 Bethesda units/ml. The inhibitor of the patient was supposed to belong to IgA and IgG judging from inhibitor neutralization test. PT was improved after discontinuance of administration of antibiotics and administration of azathioprine. Moreover, even after administration of prednisolone with antibiotics, PT and activity of factor V recovered to normal range. He died from respiratory failure. Autopsy revealed double cancer of prostate and descending colon. The appearance of factor V inhibitor was likely caused by antibiotics, double cancer, and age-related immune disorders.

Aged↗

The development of a solitary toxic thyroid nodule following Graves' disease.

A 52-year-old woman developed a toxic, solitary, autonomously functioning thyroid nodule four years after antithyroid drug treatment for Graves' disease. When she was initially seen, a thyroid scan showed the homogeneous enlargement of both lobes with increased uptake. Graves' disease was diagnosed and the patient was treated with methimazole. Thyroid function was well-controlled with medication for 18 months, after which the patient stopped taking the drug for three years. Four years after Graves' disease was diagnosed, the patient again showed symptoms of hyperthyroidism. The etiology was a toxic, autonomously functioning nodule.

Female↗

[Clinical study of combination chemotherapy using carboquone, cisplatin, UFT and OK-432 in 7 cases of advanced gastric cancers and a relapsed gastric cancer].

In 8 cases of advanced and/or relapsed gastric cancer (7 cases advanced, 1 case relapsed), we undertook combination chemotherapy with systemic administration of cisplatin and celiac arterial infusion of carboquone intermittently under continuous administration of OK-432 i.m. and UFT p.o. The male to female ratio was 5 to 3 and the age distribution from 53 to 77 years (mean age, 70 years.) Eight cases were divided into the following histological types: 1 papillary adenocarcinoma, 1 well-differentiated tubular adenocarcinoma, 3 moderately differentiated tubular adenocarcinomas, and 3 poorly differentiated adenocarcinomas. Complete response (CR) was obtained in one case, partial response (PR) in four cases, minor response (MR) in two cases, and no change (NC) in one case. The response rate was 62.5%. CR was noted in a relapsed case. The median survival time from the beginning of the chemotherapy was 8 months (ranging from 6 to 13 months). The major toxicity was bone marrow suppression, but there were no cases of serious renal damage.

Adenocarcinoma↗