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Biomedical subjects

K Takatsuki

Publications and source records attributed to K Takatsuki.

At least 379 records · Page 21Linked to original sources
PubMed1987

Determination of enolase isozymes in various adrenal gland tumours.

Enolase isozymes (alpha enolase and gamma enolase) in the extracts of adrenal tumours (phaeochromocytoma, adenoma of primary aldosteronism and Cushing's syndrome, and neurinoma) were determined by means of enzyme immunoassay systems. The mean +/- SEM, respectively, of alpha and gamma enolase levels were 2.5 +/- 0.37 microgram/mg protein and 3.2 +/- 0.69 micrograms/mg protein for 9 phaeochromocytomas, 15.2 +/- 3.1 microgram/mg protein and 0.65 +/- 0.18 microgram/mg protein for three adenomas with primary aldosteronism, 10.8 +/- 3.0 micrograms/mg protein and 0.23 +/- 0.02 micrograms/mg protein for five adenomas causing Cushing's syndrome, and 3.8 +/- 0.88 micrograms/mg protein and 0.30 +/- 0.15 micrograms/mg protein for three neurinomas. Thus, the gamma enolase concentration in the extract of phaeochromocytoma was higher than that of other adrenal tumours. The serum level of gamma enolase was determined in 36 patients with adrenal tumours and 26 normal controls by radioimmunoassay. The mean +/- SEM for gamma enolase level was 5.4 +/- 0.3 ng/ml in normal controls, 9.1 +/- 0.9 ng/ml for 10 patients with phaeochromocytoma, 6.3 +/- 0.3 ng/ml for 11 with primary aldosteronism, 5.5 +/- 0.4 ng/ml for 11 with Cushing's syndrome, and 5.1 +/- 0.7 ng/ml for four with neurinoma. Thus, patients with phaeochromocytoma had a significantly higher serum gamma enolase levels than did those with tumours derived from adrenal cortex and normal controls. In patients with phaeochromocytoma, serum gamma enolase levels showed a significant positive correlation with urinary adrenaline levels (P less than 0.05), and after resection the elevated level of gamma enolase fell significantly (P less than 0.05) and returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1987

Multiple myeloma, IgA kappa type, accompanying crystal-storing histiocytosis and amyloidosis.

An autopsy case of multiple myeloma, IgA kappa type, accompanying systemic crystal-storing histiocytosis and generalized amyloidosis, is reported. Besides multiple destructive lesions in the skeletal bones, nodular myeloma cell infiltrates were scattered in the liver, spleen, and both kidneys. Not only in these lesions but also in the reticuloendothelial organs, crystal-storing macrophages appeared dispersively or in clusters. Electron microscopically, numerous crystalline inclusions contained in the cytoplasm of macrophages were membrane-bound and of variable configuration, comprising of a homogeneous electron-lucid material. Enzyme cytochemically, almost all of the inclusions showed acid phosphatase activity. On the basis of the results obtained from the immunohistochemical, immunofluorescent and immunoelectron microscopic studies, it was considered that the crystalline inclusions stored in the macrophages were derived from IgA kappa immunoglobulin secreted from the myeloma cells and were formed within secondary lysosomes by crystallization during lysosomal digestion and degradation of the ingested immunoglobulin by macrophages. Generalized amyloidosis developed in different sites from those of the crystal-storing histiocytosis and were proven immunohistochemically to belong to AL amyloidosis probably derived from a certain group of A kappa precursor protein.

Amyloidosis↗
PubMed1987

Anti-HTLV-III and anti-HTLV-I antibodies and T cell subsets in hemophiliacs living in HTLV-I endemic and nonendemic areas of Japan.

Sera from 154 hemophiliacs, including 132 with hemophilia A and 22 with hemophilia B, were examined for antibodies against human T cell lymphotropic virus type III (HTLV-III) and type I by strip radioimmunoassay based on the Western blotting technique. Sixty-two patients lived in Kyushu, a known endemic area of HTLV-I and 92 patients lived in Tokyo, a nonendemic area of HTLV-I. Results showed a prevalence of HTLV-III antibodies of 64.5% in Kyushu and of 57.6% in Tokyo. There were no significant differences between these two groups. Helper/suppressor (T4/T8) ratios of seropositive patients were 0.69 +/- 0.41 and those of seronegative patients were 1.05 +/- 0.56. Ratios of both groups were lower than those of normal healthy people (1.35 +/- 0.45). Our findings confirmed that hemophiliacs living in an HTLV-I endemic area and those living in a nonendemic area in Japan equally possessed antibodies to HTLV-III. Low T4/T8 ratios and increases of serum IgG and IgM levels were found even in seronegative hemophiliacs.

Antibodies, Viral↗
PubMed1987

T cell gamma chain gene rearrangement without T cell receptor beta chain gene rearrangement in two cases of non-Hodgkin's lymphoma.

We report two patients with non-Hodgkin's lymphoma whose neoplastic cells had rearranged T cell gamma chain (T gamma) genes, and had the germ line DNA of T cell receptor beta chain (T beta) and immunoglobulin genes. Surface marker analysis of the neoplastic cells revealed that leukemic cells from one patient were derived from common thymocytes, while in the other patient the clonality and cell lineage could not be identified, probably due to the low percentage of neoplastic cells in the specimen. No phenotypic changes were observed after cultivation with phorbol myristate acetate, except for induction of Tac antigens on cells of one patient. Leukemic cells with only the T gamma gene rearrangement are thought to be precursor T cells that differentiate into mature T cells following T beta gene rearrangement. This suggests that such T cells with only the T gamma gene rearrangement exist among common thymocytes.

Aged↗
PubMed1987

Interleukin 1 gene expression in adult T cell leukemia.

The adult T cell leukemia (ATL) is a T cell neoplasm etiologically associated with human T lymphotropic virus type I (HTLV-I) infection. ATL cells often abnormally express interleukin 2 (IL-2) receptors, and ATL patients may show clinical evidence of hypercalcemia, osteolytic bone lesions, or increased bone turnover. Whereas interleukin 1 (IL-1) is not generally recognized as a product of T cells, this cytokine is capable of both altering IL-2 receptor expression and activating osteoclasts. Thus, we investigated the possibility that primary ATL leukemic T cells and HTLV-I-infected long-term ATL cell lines produce IL-1. S1 nuclease protection assays demonstrated that primary leukemic ATL cells from five out of six patients, as well as one patient with T4+ chronic lymphocytic leukemia, contained considerable quantities of IL-1 beta messenger RNA (mRNA) and small amounts of IL-1 alpha mRNA. These primary leukemic T cells also released biologically active IL-1 protein as evaluated in the murine thymocyte comitogenesis bioassay. In contrast to primary tumor cells, four out of six long-term ATL cell lines produced variable amounts of IL-1 alpha mRNA in the absence of detectable IL-1 beta mRNA as measured by S1 nuclease protection. These data demonstrate that IL-1 gene (especially IL-1 beta) expression occurs in many primary HTLV-I-infected leukemic T cells raising the possibility that this mediator may play a role in the pathological changes associated with this leukemia. Also, these studies show that the pattern of IL-1 alpha and IL-1 beta gene expression differs between primary ATL tumor cells and long-term cultured ATL cell lines, indicating an interesting biological difference in these two HTLV-I-infected cell populations.

Adult↗
PubMed1987

Pathophysiological role of thyroid blocking antibody in patients with primary hypothyroidism.

The pathophysiological role of thyroid blocking antibody (TBAb) in patients with adult primary hypothyroidism and the mechanism of TBAb action were studied. A sensitive bioassay for TBAb, which inhibits the TSH-induced cAMP accumulation, was established using normal human thyroid cells in culture. Thirty-four patients with primary hypothyroidism consisting of 17 goitrous and 17 non-goitrous patients were examined. Two out of 17 goitrous patients (11.8%) and three out of 17 non-goitrous patients (17.6%) were TBAb positive. There were no significant differences between TBAb positive and negative patients in terms of the severity of hypothyroidism or the titers of MCHA or TGHA. Four out of the five TBAb-positive IgGs had strongly positive thyrotropin binding inhibitor immunoglobulin activities. All five TBAb-positive IgGs inhibited the cAMP increase induced by Graves' IgG, but did not affect the action of either prostaglandin E1 or cholera toxin. However, three TBAb positive IgG also inhibited the cAMP increase induced by forskolin. These findings indicate: 1) TBAb is present in hypothyroid patients with autoimmune thyroiditis and TBAb may play a role in the pathophysiology of these patients. 2) TBAb may inhibit the action of TSH not only at the level of the TSH receptor, but also at a different site from the TSH receptor.

Adolescent↗
PubMed1987

Evaluation of the safety of blood products with respect to human immunodeficiency virus infection by using an HTLV-I-infected cell line (SKT-1B).

Human immunodeficiency virus (HIV), the etiologic agent of acquired immunodeficiency syndrome (AIDS), was rapidly cytopathic to SKT-1B, a cell line established from a patient with adult T cell leukemia, in vitro. This cytopathic effect was preceded by the expression of HIV antigen, defined with a monoclonal antibody (mAb) specific for the core protein (p24) of HIV. SKT-1B is highly susceptible to HIV as compared with MT-2 and H9 cells. HIV is known to be transmitted via blood products, and thus we examined whether or not currently used procedures for manufacturing blood products are safe by using SKT-1B. Lyophilized HIV was heated at 65 degrees for time periods in the range of 10 min to 48 hr, and the infectivity was examined. The results showed that heating at 65 degrees for less than 2 hr was not sufficient to inactivate HIV, but the virus heated for 48 hr had no effect on SKT-1B. In addition, HIV completely lost its infectivity on sulfonation, which is commonly used to avoid anaphylactic shock on intravenous infusion of human immunoglobulins. These findings indicate that blood products manufactured by currently used procedures are probably safe with respect to HIV infection.

Antigens, Neoplasm↗
PubMed1987

[Overview of ATL (adult T-cell leukemia) research].

ATL is a unique T-cell malignancy first described by Takatsuki and colleagues in 1970s. We estimate that more than 300 patients a year have been detected in the endemic areas of Kyushu, Japan. The surface phenotype of ATL cells characterized by monoclonal antibodies is T3+, T4+, T8-, T11+ and Tac+. In all cases the serum is positive for anti-HTLV-I antibodies and the ATL cells contain the proviral DNA of HTLV-I. Variations in the clinical features of atypical ATL suggested a division of the spectrum of ATL into five types: acute; chronic; smoldering; crisis; and lymphoma. Typical ATL takes an acute course. The survival time is short, with 50% mortality within approximately 5 months. In general a poor prognosis is indicated by the elevation of serum lactate dehydrogenase, calcium, and bilirubin, as well as by high WBC. Smoldering ATL is characterized by the presence of a few abnormal cells (0.5%-3%) in the peripheral blood over a long period. Crisis in chronic or smoldering ATL means the progression of the disease to acute ATL. The lymphoma type of ATL is considered to be a form of T-cell-type non-Hodgkin's lymphoma in which malignant cells contain proviral DNA of HTLV-I. Screening of the sera from healthy adults for presence of the anti-HTLV-I antibodies revealed that 3.6% of healthy individuals in Kumamoto Prefecture, which is located in the middle of Kyushu, were HTLV-I carriers. Family studies showed that the routes of natural infection of HTLV-I are from mother to child and also from husband to wife. The borderline between the healthy carrier state and smoldering ATL remains unclear. Smoldering ATL is frequently diagnosed in patients with fungus infection of the skin, chronic lymphadenopathy, interstitial pneumonitis, chronic renal failure and strongyloidiasis. Five patients with ATL refractory to conventional chemotherapeutic agents were treated with 2'-deoxy-coformycin (DCF), a potent inhibitor of adenosine deaminase. Two patients showed a good response, and three were resistant to DCF. In addition our experiences with a concurrence of lymphoma-type ATL in three sisters and spontaneous remissions in a patients with chronic ATL will be referred.

Carrier State↗
PubMed1987

Evidence for the interleukin-2 dependent expansion of leukemic cells in adult T cell leukemia.

Interleukin 2 (IL-2) receptor/Tac antigen is abnormally expressed on cells of patients with adult T cell leukemia (ATL) caused by infection with human T lymphotropic virus type I (HTLV-I). Twenty-five patients with ATL were examined to determine whether their leukemic cells continued to show IL-2-dependent proliferation. In 21 patients, the in vitro proliferation of HTLV-I-infected nonleukemic T cell clones was found to be dependent on IL-2. However, clonality analysis based on T cell receptor gene rearrangement profiles and the site of HTLV-I provirus integration revealed IL-2-dependent growth in leukemic cells in four patients with ATL. These results provide evidence for the IL-2-dependent proliferation of leukemic cells in some ATL patients.

Antigens, Surface↗
PubMed1987

T cell gamma gene rearrangements in hematologic neoplasms.

Rearrangements of the T cell gamma (T gamma) gene were studied in primary neoplastic cells from 75 patients with leukemia or lymphoma. T gamma gene rearrangements were observed in 19 of 21 T cell neoplasms; 14 of 21 immature B cell leukemias, including 4 out of 5 patients with rearrangements of both immunoglobulin heavy-chain (JH) and T cell receptor beta chain (T beta) genes; none out of 16 nonlymphoid leukemias. Thus, T gamma gene rearrangement is frequently found in immature B cells and is not always found in T cells showing T beta gene rearrangement, but it is not detected in nonlymphoid cells. Furthermore, T gamma gene rearrangement in cells with the germline configuration of the JH and T beta genes was observed. These results indicate that the detection of T gamma gene rearrangement does not allow a clear assignment to a particular lineage. However, an analysis of T gamma gene rearrangement provides a further potential tool to establish the lymphoid cellular origin and clonality of hematologic neoplasms and identify the normal stages of lymphocyte differentiation.

B-Lymphocytes↗
PubMed1987

Characterization of three monoclonal antibodies (VAK3-5) that identify p24, core protein of human immunodeficiency virus, and its precursors.

VAK3, VAK4 and VAK5 monoclonal antibodies (mAbs) were raised by using disrupted purified human immunodeficiency virus (HIV) as an antigen. These mAbs exclusively reacted with an HIV-infected cell line, H9/HIV, and did not react with human T cell lymphotropic virus (HTLV)-I or -II infected cell lines. Strip radioimmunoassay based on the Western blotting technique revealed that these mAbs recognize a single band that corresponds to a 24-kd (p24) core protein of HIV when disrupted viruses were used as antigens. When cell lysates of H9/HIV were used as antigens, these mAbs gave two bands with molecular weights of 40 kd (p40) and 57 kd (p57) in addition to p24. VAK5-conjugated Sepharose 4B beads precipitated non-glycosylated proteins, p24, p40 and p57 from [L-35S]methionine-labeled H9/HIV. P57 and p40 appear to be a precursor and an intermediate precursor of p24, respectively. Purified IgG of VAK3 and VAK4, and the serum from an individual infected with HIV inhibited the binding of VAK5 mAb to HIV. These findings suggest that p24 of HIV contains structure(s) with strong antigenicity.

Animals↗
PubMed1987

Genotypic analysis of lymph node cells from patients with phenotypically undetermined cell lymphoma.

Rearrangements of immunoglobulin (Ig) heavy chain (JH) and T cell receptor beta chain (T beta) genes of lymph node cells from 28 patients with malignant lymphoma were studied. Fourteen of 28 patients were diagnosed as undetermined cell lymphomas, since a marked predominance of cells expressing a single light chain of Ig or T cell associated antigens was not demonstrated by phenotypic analysis. Of these patients, JH gene rearrangements were observed in 8 patients, whereas T beta gene rearrangements were detected in 9 patients. Although bigenotypes were seen and cell lineage was not determined in three cases, these results indicate that demonstration of Ig and T beta gene rearrangements is a powerful tool to determine cell lineage and clonality of lymphoma cells that do not express definitive surface phenotypes. Interestingly, 12 of 14 lymphoma cells whose lineage had been determined by phenotypic analysis showed rearrangements of two alleles; however, only single allelic gene rearrangement was observed in 11 of 14 lymph node cells from phenotypically undetermined cell lymphoma.

Genotype↗