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Biomedical subjects

K Takatsuki

Publications and source records attributed to K Takatsuki.

At least 325 records · Page 18Linked to original sources

Rearrangements of T-cell antigen receptor delta chain gene in hematologic neoplasms.

Rearrangements of the T-cell antigen receptor (TCR) delta chain gene were studied in primary neoplastic cells from 137 patients with leukemia or lymphoma. TCR delta gene rearrangements or deletions were observed in all 50 T-cell neoplasms: 5 of 8 CD3- T-cell neoplasms showed rearrangements, whereas biallelic deletion of TCR delta gene was the most common pattern in CD3+ T-cell neoplasm (39 of 42 patients). Rearrangements of TCR delta gene were also detected in 23 of 40 immature B-cell leukemias, including 22 of 25 patients with rearrangements of TCR gamma gene, 2 of 17 mature B-cell neoplasms, and 3 of 30 myeloid leukemias. Thus, TCR delta gene rearrangement or deletion is always found in T-cell neoplasms and is frequently found in immature B-cell leukemias associated with TCR gamma gene rearrangement. Furthermore, TCR delta gene rearrangements associated with the germline configuration of the TCR beta, gamma, and immunoglobulin heavy chain genes were observed in two immature T-cell leukemias, suggesting that TCR delta gene rearrangements precede TCR gamma and beta gene rearrangements. These results indicate that an analysis of TCR delta gene rearrangement provides potential tools to establish the clonality of immature T-cell neoplasms and to identify the normal stages of lymphocyte differentiation.

Antigens, CD↗

[Relapse of gingival tumor during hematological remission in acute promyelocytic leukemia].

A 56-year-old man was admitted to the hospital in April, 1986, with the chief complaint of fatigue. The diagnosis of acute promyelocytic leukemia (APL) was made based on the proliferation of atypical promyelocytes in the bone marrow. No gingival swelling was found on admission. A complete remission was achieved by the BHAC-DMP therapy and maintained by the consolidation therapy and the intensification therapy. In July, 1987, he noticed a solitary gingival tumor around the left lower second molar. The biopsy showed the massive infiltration of leukemic cells, despite the hematological remission. Combination chemotherapy was not effective but the tumor disappeared by irradiation. A hematological relapse occurred in November, 1987, but the second complete remission was achieved by the AB-triple V therapy. He died because of the second hematological relapse in July, 1988. Along with the wide use of intensive chemotherapy for acute leukemia, tumor forming leukemia during the hematological remission, as seen in this case, would be increasing. Thus, we should not overlook any newly formed tumor in the treatment of leukemia.

Aclarubicin↗

[Role of protein C in endotoxin-induced release of plasminogen activator inhibitor from endothelial cell].

To elucidate the role of protein C (PC) in the release of plasminogen activator inhibitor (PAI) from endothelial cells, the effect of PC and activated protein C (APC) on plasma levels of PAI in endotoxin (ET)-treated rats was examined. When activated by snake venom, human PC significantly prolonged the activated partial thromboplastin time (APTT) of both human and rat plasma samples. Addition of APC also prolonged the APTT of both human and rat plasma samples. PAI activity in plasma from septicemic patients and ET-treated rats was neutralized by APC. A small dose of ET (0.1 microgram/kg) gradually increased plasma PAI activity, which became maximum 3h after ET-treatment. APC administered prior to ET-treatment, PC decreased PAI activity, however, no such inhibition was seen when administered after ET-treatment. A significant negative correlation between PC concentrations and PAI activities was observed in plasma from septicemic patients. These findings indicated that activation of PC on endothelial surface plays a regulatory role in releasing PAI and that endotoxin might inhibit the surface activation of PC.

Animals↗

Frequent infection with human T-cell lymphotropic virus type I in patients with AIDS but not in carriers of human immunodeficiency virus type 1.

Antibody to human T-cell lymphotropic virus type I (HTLV-I) was measured in 49 Japanese patients (48 with hemophilia) infected with human immunodeficiency virus type 1 (HIV-1) and in 18 hemophiliacs who were not infected with HIV-1, by use of an enzyme-linked immunosorbent assay (ELISA). The antigen used was a gag-env hybrid protein constructed in vitro and expressed in Escherichia coli. This assay detected a specific antibody against HTLV-I. Four of the 18 HIV-1-negative hemophiliacs (22%) were positive for anti-HTLV-I antibody; their geometric mean titer was 951 U/ml. Seven of the 12 patients (58%) with acquired immune deficiency syndrome (AIDS) were positive for anti-HTLV-I antibody, and 8 of 35 HIV-1 + AIDS-free carriers (23%) were positive. The difference between the prevalence of HTLV-I infection in the two groups was statistically significant (p less than 0.0297). The geometric mean titer of antibody in the patients with AIDS was 318 U/ml and that for the HIV-1 + AIDS-free carriers was 1,496 U/ml. These findings suggest that HTLV-I infection could be one of the factors in the development of AIDS in individuals infected with HIV-I.

AIDS-Related Complex↗

["AB-Triple V" therapy of relapsed or refractory acute myelogenous leukemia].

Sixteen adults with acute myelogenous leukemia (AML) in relapse or refractory to conventional therapy were treated with AB-Triple V therapy. This regimen consists of aclarubicin, behenoyl cytosine arabinoside, etoposide, vincristine, and vinblastine or vindesine. Patients who obtained complete remission (CR) were then given monthly three courses of AB-Triple V therapy, and further courses of AB-triple V therapy every three months. Eleven of the 16 patients entered CR, three were no response, and two died early after initial AB-Triple V therapy. Among 11 patients who achieved CR, 7 are alive and in CR during 1 to 13 months, one died of hepatic failure, and three patients died of infection in CR. Systemic arthralgia following the administration of vinblastine were frequently observed. These results indicate that this salvage therapy are useful relapsed or refractory AML. Therefore, the role of this combination chemotherapy as a part of the initial post-remission therapy needs to be evaluated.

Aclarubicin↗

[Adult T-cell leukemia (ATL)].

Adult T-cell leukemia (ATL) was first discovered and reported in Japan, where it has a high incidence in the southwest region. The retrovirus HTLV-I (human T-cell lymphotropic virus type I) is considered to be related to its etiology. In ATL endemic areas, HTLV-I carriers are found at a fairly high percentage even among healthy individuals. ATL shows diverse clinical features. It can be divided into 5 types (acute type, chronic type, smoldering type, crisis type, and lymphoma type). ATL cells originate from the CD4-positive subset of peripheral T cells; they show a characteristic notch in the nucleus and a lobulation tendency. ATL resists chemotherapy, and patients with acute and lymphoma types have quite a poor prognosis. A definite diagnosis of ATL is made by documenting the presence of HTLV-I proviral DNA in the DNA of tumor cells. HTLV-I infection is caused by transmission of live lymphocytes via three routes (from mother to children, from males to females, and by transfusion). Familial occurrence of ATL is frequently seen. HTLV-I infection is also seen in other countries, but its incidence is highest in Japan. It is thus an urgent task for Japanese physicians to eliminate HTLV-I infection.

Antigens, Differentiation, T-Lymphocyte↗

Elevated serum levels of soluble interleukin-2 receptors in HTLV-I--associated myelopathy.

Using an enzyme-linked immunosorbent assay, we measured the level of soluble interleukin-2 receptors (sIL-2Rs) in the serum of 50 normal controls, 48 human carriers of T cell leukemia virus type I (HTLV-I) antibody who had no symptoms, 11 patients with HTLV-I-associated myelopathy (HAM), and 39 patients with adult T cell leukemia (ATL) (four smoldering, 10 chronic, nine lymphoma, and 16 acute type). The highest levels of sIL-2R were observed in patients with acute and lymphoma-type ATL, as opposed to those with chronic and smoldering-type ATL. The levels of sIL-2R in patients with HAM were roughly between those of smoldering ATL and healthy HTLV-I carriers. Serum sIL-2R levels in healthy carriers were also elevated compared with those in normal controls. These observations suggest that the measurement of sIL-2R levels in patients with ATL can be useful as a noninvasive measure of tumor burden and should aid in the understanding of the natural history of HTLV-I infection leading to the development of ATL.

Adult↗

Mode of action of erythropoietin (Epo) in an Epo-dependent murine cell line. II. Cell cycle dependency of Epo action.

Erythropoietin (Epo), a glycoprotein hormone, regulates the proliferation and differentiation of committed erythroid progenitor cells. We investigated the effect of Epo on the kinetics of an Epo-dependent cell line (DA-1ER), which was cloned from the murine interleukin 3-dependent cell line, DA-1. Flow cytometry and [3H]thymidine incorporation were used to analyze the cell cycle. Removal of Epo from the culture medium resulted in the accumulation of the cells in the G1 phase. Eighteen hours after the removal of Epo, 75%-80% of the cells were arrested in G1 phase. Readdition of Epo to these quiescent cells allowed them to progress from the G1 to the S phase with a lag period of 10 h. Epo was required throughout the lag period in order to achieve maximal DNA synthesis. When the cells were arrested in the G2/M phase or the G1/S interphase by colcemid and thymidine, respectively, and then released from the arrest, they could complete the cell cycle in the absence of Epo. These findings suggest that Epo is only required in the G1 phase for the cells to progress through the cell cycle.

Animals↗

Ectopic production of salivary-type amylase by a IgA-lambda-type multiple myeloma.

A patient with IgA-lambda-type multiple myeloma who appeared to be secreting salivary-type amylase ectopically is reported. Both the patient's serum and urine contained high levels of amylase. Amylase activity in the supernatant of cultured myeloma cells, obtained from the patient's pleural effusion while he had malignant pleuritis, increased almost linearly from the time of cell seeding. The presence of IgA and S-type amylase in the myeloma cells was demonstrated cytochemically and by immunoelectron microscopy. These observations showed that amylase was produced by these human myeloma cells.

Amylases↗

[Impaired vasopressin secretion in patients with myotonic dystrophy].

Hypernatremia has occasionally been observed in patients with myotonic muscular dystrophy (MyD). To elucidate the possibility of osmoregulatory dysfunction, we investigated hypothalamo-posterior pituitary function as well as serum electrolytes in eight patients with MyD. Blood samples were obtained early in the morning after overnight dehydration. Renal function was estimated by blood urea nitrogen, serum creatinine and creatinine clearance. Posterior pituitary function was evaluated by direct measurement of plasma vasopressin (AVP) during a 5% hypertonic saline infusion. Plasma AVP concentrations were determined by sensitive radioimmunoassay. In five patients, circulating blood volume (CBV), plasma renin activity (PRA) and serum aldosterone (S-Aldo.) were also measured. The mean serum sodium level (143.9 +/- 1.7mEq/1: Mean +/- SD) was significantly higher than in the controls (139.4 +/- 2.2mEq/1). A 5% hypertonic saline infusion showed a subnormal increase in AVP and diminished thirst, despite sufficient elevation of plasma osmolality, in all patients as compared with healthy adults. Renal function was intact. Biochemical evidence of dehydration, estimated by PRA, S-Aldo and CBV, was unremarkable in four of the five patients. These findings suggest that patients with MyD have neurogenic disorders of osmoregulation in addition to previously reported endocrine abnormalities. Impaired AVP secretion in response to osmotic stimuli and reduced thirst might be responsible for such failure.

Adolescent↗

Alteration of cell cycle progression in human leukemia cell line (KOPM-28) induced by 12-o-tetradecanoylphorbol-13-acetate.

Terminal cell differentiation usually results in an irreversible arrest in the G1 phase of the cell cycle and loss of cell renewal ability. Human promyelocytic leukemia HL-60 cells induced with 12-o-tetradecanoylphorbol-13-acetate (TPA) differentiate into monocytes/macrophages and accumulate in G1. We determined the effect of TPA on the growth kinetics of a human leukemia cell line (KOPM-28), which developed several of the characteristics of megakaryocytes in response to TPA, such as the surface antigen complex IIb/IIIa, platelet peroxidase and polyploidy. Cell growth was immediately and completely inhibited by TPA. Flow cytometric analysis of cellular DNA content revealed a gradual decrease in cells in G1 and an accumulation of cells in G2. These data suggest that TPA prolonged G1 and rapidly arrested the cells in G2. Synchronized cells were utilized to further analyze the rapid G2 arrest. Cells arrested with aphidicolin at the G1/S interphase were released, and the effects of TPA (added at different intervals) on cell cycle progression were examined 14 h after release. The results showed that TPA added at the end of the S phase, as well as at the G1/S interphase incompletely but distinctly arrested cells in G2. Moreover, G2 arrest was observed when TPA was added to cells released from a colcemid-induced G2/M block, suggesting that cells already in G2 were inhibited by TPA from moving through M to G1. Since some cells became multi-nucleated in the course of incubation with TPA, this G2 accumulation may have resulted at least in part from a prolongation of the phase or a transient G2 block. These changes in cell cycle progression induced by TPA may be characteristic of and/or related to megakaryocytic differentiation of hemopoietic precursor cells.

Cell Cycle↗

A new approach to the modification of cell membrane glycosphingolipids: ganglioside composition of JTC-12 P3 cells altered by feeding with galactose as a sole carbohydrate source in protein- and lipid-free synthetic medium.

A significant difference in the glycosphingolipid composition of JTC-12 P3 cells established from monkey kidney tissue was observed when cells cultured in a protein- and lipid-free synthetic medium containing glucose (DM-160) as a sole carbohydrate source were transferred and cultured in the same medium containing galactose and pyruvic acid (DM-170) in place of glucose. In particular, the amounts of gangliosides GM3, GM2, and GD3 in the cells cultured in DM-170 were 5.3-, 17.8-, and more than 8-fold those in the cells cultured in DM-160, respectively, indicating that anabolism of gangliosides is greatly enhanced in cells cultured in the presence of galactose and pyruvic acid, as compared with cells cultured in the presence of glucose. In fact, after cultivation of cells in the medium with N-acetyl-D-[14C]mannosamine for 96 h, the radioactivity incorporated into the gangliosides of the cells in DM-170 was 10-fold that of the cells in DM-160. Among the gangliosides of the cells in DM-170, highly sialylated molecules such as GD3, GD1a, GD1b, and GT1b were preferentially labeled, indicating that the sialyltransferases responsible for the synthesis of gangliosides are significantly more activated in cells cultured in DM-170 than in DM-160. These observations reveal that the glycosphingolipid composition of the plasma membrane can be modified epigenetically under well-defined conditions and provide important clues for clarifying the roles of glycosphingolipids associated with particular cell functions.

Animals↗