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Biomedical subjects

K Takatsuki

Publications and source records attributed to K Takatsuki.

At least 145 records · Page 8Linked to original sources
PubMed1994

Alcaptonuria: a case complicated with valvular heart disease and immunodeficiency.

A 75-year-old man was diagnosed with alcaptonuria by direct identification of homogentisic acid in the urine using gas chromatography-mass spectrometry. Complications included valvular heart disease with marked calcification detected by two-dimensional color-Doppler echocardiography and recurrent bacterial infection. Immunological analyses revealed a reduced number of T cells with compensatory expansion of CD56+, CD57+ natural killer (NK) cell population and impaired functions of cellular immunity such as phytohemagglutinin response, antibody-dependent cellular cytotoxicity, NK activity and interleukin-2 production. Humoral immunity and neutrophil functions were considered to be normal. This is the first reported case of alcaptonuria to our knowledge in which immunological abnormality was documented.

Aged↗
PubMed1994

Radiation therapy of adult T-cell leukemia.

Between January, 1983 and December, 1991, 30 adult patients with T-cell leukemia (ATL) and lymph node or skin lesions resistant to chemotherapy were treated by irradiation. Thirty Gy of high energy x-rays, 60Co gamma rays or electrons was delivered to 22 lymph node lesions in 17 patients, for focal cutaneous lesions in 6 patients, and as total skin irradiation in 7 patients. Irradiation therapy was effective in all patients with skin lesions and in 12 of 17 patients with lymph node lesions. Symptoms such as pain or itching diminished in all cases and no severe side effects were observed. Radiation therapy thus achieved good control of ATL associated focal lesions resistant to chemotherapy. Even if the prognosis of ATL is poor, radiation therapy should be considered as a palliative therapy.

Adult↗
PubMed1994

Adult T-cell leukemia derived from S100 beta positive double-negative (CD4- CD8-) T cells.

Adult T-cell leukemia (ATL) is a mature T-cell malignancy which is caused by human T lymphotropic virus type-I (HTLV-I). Most of the ATL cells are CD3+, CD4+, CD8-, and T-cell receptor (TCR) alpha beta+ and also express activated antigens such as HLA-DR and interleukin-2 receptor (IL2R) alpha chain (CD25). Diminished surface expression of the TCR alpha beta/CD3 complex is a specific feature of ATL cells. Since the gene transcript for each chain of this complex has been detected and surface expression of this complex is further decreased, accompanied by the induction of IL2R alpha chain, after stimulation with anti-CD3 monoclonal antibody (mAb), the TCR alpha beta/CD3 complex is considered to be down-modulated in vivo. We recently reported four ATL patients whose leukemic cells were CD4-, CD8- (double-negative; DN), TCR alpha beta+. These DN-ATL cells expressed S100 beta protein which was not detected in CD4+ ATL cells. Similar to CD4+ ATL cells, surface expression of the TCR alpha beta/CD3 complex on DN-ATL cells was decreased in vivo despite the lack of CD4 or CD8 as coreceptor. Therefore, the TCR alpha beta+ T-cell with or without CD4 is the sole target of HTLV-I induced leukemia and the down-modulation of the TCR alpha beta/CD3 complex is considered to play a key role in the development of ATL.

Animals↗
PubMed1994

Antibody to hepatitis C virus in volunteer blood donors of the Hospital de Especialidades, National Medical Center, Mexico City.

The present survey was performed to assess the hepatitis C virus seroprevalence in volunteer blood donors of the National Medical Center, Hospital de Especialidades, Mexico City. Serum samples from 1100 individuals were collected. We selected second generation enzyme-linked immunosorbent assay (ELISA) (Abbott HCV EIA) test for the screening. The antibodies against hepatitis C virus (anti-HCV) in the volunteer blood donors were positive in 0.7%. The second generation ELISA test is useful as a screening test and may lead to decreasing the incidence of posttransfusional hepatitis C virus infection.

Blood Donors↗
PubMed1994

[Bronchial hyperresponsiveness and relaxability in patients with mitral stenosis].

To study the differences in bronchial responsiveness to inhaled methacholine and salbutamol between patients with mitral valve disease those with bronchial asthma a bronchial provocation test (Astograph) and pulmonary function tests were done in 25 patients with mitral stenosis (MS) and 18 patients with bronchial asthma (BA). We derived an index of airway reloxability from the effect of salbutamol after precontraction with inhaled methacholine. This index was the change in respiratory conductance (Grs) over time during inhalation of salbutamol (SGrs-d). It was computed as SGrd = delta Grs/delta t. Eighteen patients with MS (72%) showed bronchial hyperresponsiveness (BHR) to methacholine. The MS patients with BHR (MS(+)) had lower values of the ratio of the forced expiratory volume in one second to the forced vital capacity (FEV/FVC) and maximal expiratory flow at 25% of vital capacity (V25) than MS patients without BHR (MS(-)). There was a significant correlation between V25 and the log cumulative dose producing a 35% decrease in respiratory conductance (PD35Grs) in MS(+). The mean log Dmin of MS(+) was significantly higher than that of the patients with BA (0.14 +/- 0.64 log units and -0.30 +/- 0.65 log units, p < 0.05, respectively). The mean log PD35Grs of MS(+) was also significantly higher than that of the patients with BA (1.09 +/- 0.53 log units and 0.45 +/- 0.66 log units, p < 0.01, respectively). Indices of relaxability (SGrs-d and SCrs-d/Grs-d) in MS(+) were significantly lower than in BA patients. Indices of hyperresponsiveness and relaxability were both significantly lower in patients with MS than in patients with BA.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗
PubMed1994

[Primary plasma cell leukemia complicated with high-output cardiac failure and hyperammonemia].

A 23-year-old male patient with plasma cell leukemia showed characteristic clinical features: accelerating heart failure and consciousness disturbance accompanied with an increase of plasma cells in peripheral blood. Evaluation of cardiac function revealed a hyperdynamic cardiac state with low somatic vascular resistance, indicating high-output cardiac failure. However no disorders causing high-output cardiac failure were found. Consciousness disturbance and hyperammonemia with serum amino acid abnormality of unknown origin were also demonstrated. After intensive combined chemotherapy (MVD + VAD), high-output cardiac failure and hyperammonemia improved with disappearance of plasma cells, suggesting that these symptoms were closely related with progression of plasma cell leukemia.

Adult↗
PubMed1994

Increased serum levels of C-terminal parathyroid hormone-related protein in different diseases associated with HTLV-1 infection.

We analyzed the serum levels of C-terminal parathyroid hormone-related protein (C-PTHrP) in asymptomatic carriers of human T lymphotropic virus type 1 (HTLV-1) and patients with three HTLV-1 related diseases; adult T-cell leukemia (ATL), HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 uveitis (HU). Serum C-PTHrP levels were significantly elevated in HTLV-1-infected individuals, irrespective of whether they were symptomatic or asymptomatic, when compared with that of the seronegative controls. In ATL patients, a good correlation was demonstrated between the serum C-PTHrP level and serum calcium or lactic dehydrogenase (LDH) level. Thus the elevated serum C-PTHrP level could be a characteristic marker of HTLV-1 carrier state, and the determination of its level in ATL patients could be useful for the assessment of the prognosis and as one of the tumor markers. The determination of the serum level of C-PTHrP in various stages of the HTLV-1 carrier state would help to understand the mechanism of the development of hypercalcemia in ATL.

Adult↗
PubMed1994

Establishment of a CD45-positive immature plasma cell line from an aggressive multiple myeloma with high serum lactate dehydrogenase.

A myeloma cell line (KHM-11) was established from the pleural effusion of a patient with IgA-kappa type aggressive myeloma with high serum lactate dehydrogenase who was extremely resistant to vincristin, adriamycin and dexamethasone combination therapy (VAD). The morphology of fresh tumor cells and KHM-11 was plasmablast according to Greipp's criteria. In addition to the expression of regular plasma cell antigens, CD38 and PCA-1, CD45 was found on both fresh cells and KHM-11. Other T- or B-cells antigens, such as CD2, 4, 8, 19, and 20 were negative. Cytoplasmic immunoglobulin kappa light chain in KHM-11 was found by flowcytometry. Southern blot analysis revealed that fresh sample and KHM-11 shared the same immunoglobulin gene rearrangement. IL-6 was found in the culture supernatant of KHM-11, and this supernatant stimulated the growth of this cell line, indicating an IL-6 autocrine mechanism. These findings indicate that KHM-11 is a CD45-positive immature plasma cell line. As far as we know, there is no report of CD45-positive myeloma cell line. KHM-11 should be a useful tool for understanding not only the pathogenesis of aggressive multiple myeloma with high LDH but also for understanding the mechanism which underlies the terminal differentiation of B-cells.

Antigens, Surface↗
PubMed1994

A new classification of clinical stages of adult T-cell leukemia based on prognosis of the disease.

Adult T-cell leukemia (ATL) has been classified into three clinical subtypes: acute, chronic, and smoldering type. However, these clinical subtypes of ATL do not always correlate with prognosis. We propose a new criterion for classification of clinical stages of ATL, based on the expression of Ki-67 antigen in peripheral blood T lymphocytes. We analyzed Ki-67 antigen expression in 45 ATL patients, classified as 18 acute, 17 chronic, and ten smoldering type. We found that in 23 patients with more than 18% Ki-67 antigen-positive T cells, the disease progressed very aggressively, and all patients died within 1 year (mean survival, 105 days). This group included 15 of 16 patients classified as 'acute', seven of 15 patients classified as 'chronic', and one of nine patients classified as 'smoldering' type. In contrast, 15 out of 17 patients with less than 18% Ki-67 antigen-positive T cells were still alive at the end of the study, with a mean survival of 750 days. Only two patients died in this group, and after a very long survival (599 and 978 days, respectively). We therefore propose the following new classification for ATL: (i) Aggressive ATL; percentage of Ki-67 antigen-positive cells more than 18% in peripheral blood T lymphocytes, (ii) Stable ATL; percentage less than 18%. This classification strongly correlates with the prognosis of patients with ATL.

Acute Disease↗
PubMed1994

CD4+ CD8+ granular lymphocytic leukemia arising in a patient with acute myeloblastic leukemia.

A 59-year-old woman who had an 8-year history of acute myeloblastic leukemia (AML) developed granular lymphocytic leukemia (GLL). She had a small number of granular lymphocytes (GL) in her bone marrow (BM) at the onset of AML. The GL increased during complete remission (CR) of AML, but not at the relapse. During the third CR state of AML, GL increased to 4.0 x 10(9)/l in the peripheral blood (PB). The GL were T-cell receptor (TCR) alpha beta+ T cells and expressed both CD4 and CD8 antigens. Rearrangements of TCR beta and gamma chain genes were detected in the peripheral blood mononuclear cells (PBMNC), confirming that this patient had GLL. The PBMNC from the patient responded weakly to PHA or ConA, yet they responded to her own bone marrow mononuclear cells (BMMNC) or CD4-depleted BMMNC that contained AML cells stronger than her own PBMNC or normal PBMNC. These observations suggest that monoclonal proliferation of GL developed after the reactive proliferation of GL in response to AML cells.

CD4-Positive T-Lymphocytes↗
PubMed1994

Combination chemotherapy with MCNU, vindesine, melphalan, and prednisolone (MCNU-VMP therapy) in induction therapy for multiple myeloma. Japan Myeloma Study Group.

From January 1988 until December 1990, 99 previously untreated patients with multiple myeloma (MM) were enrolled in a randomized prospective study comparing two combination chemotherapies with and without MCNU as induction therapy for MM; 49 patients with vindesine, melphalan and prednisolone (VMP therapy) versus 50 patients with MCNU, vindesine, melphalan and prednisolone (MCNU-VMP therapy). Seventy-two evaluable patients (34 patients in the VMP group, 38 in the MCNU-VMP group) were analyzed. The response rate was slightly higher with MCNU-VMP than with VMP (81.6% vs. 64.7%). In 43 responders (21 patients in the VMP group and 22 in the MCNU-VMP group) who were treated with the same regimen as the induction therapy to maintain remission, the remission duration was significantly longer in patients treated with MCNU-VMP than in those treated with VMP (median > 10.1 vs. 8.0 months, P = 0.018), particularly in patients with PS 3-4. The remission duration in the MCNU-VMP group was also slightly longer in the patients with stage III disease and who were older than 65 years. The median survival time showed no significant difference between the VMP group (20.3 months) and the MCNU-VMP group (> 15 months). Leukopenia, thrombocytopenia and nausea/vomiting were found to be somewhat severe in the MCNU-VMP group. In summary, MCNU-VMP therapy is effective as induction therapy for MM.

Adult↗
PubMed1994

[Drug-resistant multiple myeloma with high serum levels of lactate dehydrogenase and neutrophil infiltration in pleural effusion].

A 57-year-old male patient with multiple myeloma showed an aggressive course with characteristic clinical features: rapid progression of plasmacytoma in the thoratic cavity, high serum levels of lactate dehydrogenase (LDH), which is usually not elevated in myeloma patients, and neutrophil infiltration in pleural effusion. Despite treatment with vincristine, doxorubicin and dexamethasone, the tumor mass had become non-responsive to chemotherapy and been increasing in size in correlating with the increase of serum levels of LDH. The patient died of respiratory failure 4 months after treatment. Thus the serum level of LDH is thought to be a useful clinical marker to monitor disease activity as well as other markers such as monoclonal immunoglobulin and beta 2-microglobulin. To investigate the cause of neutrophil infiltration into pleural effusion, we cultured plasma cells obtained from the effusion for 3 days in serum-free medium and examined the activity of neutrophil chemotaxis in the culture supernatant. The results showed chemotactic activity in the supernatant as high as in positive controls stimulated with a chemotactic factor, formyl-methionyl leucyl phenyl-alanine, suggesting that tumor cells produced neutrophil chemotactic factor(s).

Chemotaxis, Leukocyte↗
PubMed1994

Human T-lymphotropic virus type I uveitis.

In addition to adult T-cell leukemia (ATL) and chronic myelopathy (HAM/TSP), our current study indicates that human T lymphotropic virus type I (HTLV-I) is a causative agent for a specific type of uveitis with unknown etiology (idiopathic uveitis). The present paper describes the seroepidemiological, clinical, and molecular biological evidences that indicate uveitis seen in HTLV-I asymptomatic carriers (HTLV-I uveitis) is a distinct clinical entity. In an HTLV-I endemic area in Japan, the seroprevalence of HTLV-I in idiopathic uveitis was 38%, while those in uveitis with defined etiology and in non-uveitic ocular diseases were 10% and 19%, respectively. Strikingly, the HTLV-I seroprevalence in younger aged patients (20-49 years) with idiopathic uveitis was 49%, while only 8% in the control group (P < 0.001). A very similar observation was recorded even in HTLV-I less endemic area, suggesting that HTLV-I infection plays a role as a risk factor for idiopathic uveitis. Clinical analysis revealed that an intermediate uveitis characterized by moderate opacities in the vitreous body and retinal vasculitis was seen in the majority the patients. The proviral DNA of HTLV-I was detected from inflammatory cells in the eye of all tested patients using PCR technique. These data thus indicate that HTLV-I is closely related to a certain type of uveitis and the uveitis (HTLV-I uveitis) is a distinct clinical entity.

Adolescent↗
PubMed1994

Granulocyte proteases and hydrogen peroxide synergistically inactivate thrombomodulin of endothelial cells in vitro.

Leukocytes release lysosomal proteases and reactive oxygen species in response to various stimuli that damage the adjacent endothelial cells. We investigated the effects of granulocyte lysosomal proteases (granulocyte elastase [GE] and cathepsin G [CG] and/or hydrogen peroxide (H2O2) on thrombomodulin (TM) activity of endothelial cells. We wished to determine whether the activated leukocytes damage the nonthrombogenic systems of endothelial cells. When cultured human umbilical vein endothelial cells (HUVECs) were incubated with GE, TM activity of the cells (as judged by the protein C activation capacity) decreased to about 10% of control with the concomitant increase of immunoreactive TM concentration in the conditioned media. CG also decreased TM activity to about 20% of control with the concomitant increase in immunoreactive TM concentration in the conditioned media. The GE- or CG-induced inactivation of TM was not observed in the presence of alpha 1-proteinase inhibitor. Immunoblot analysis showed that CG cleaved purified TM to yield one major fragment with an M(r) of 43,000; TM activity of this fragment was about 10% of the control activity. When purified TM was incubated with GE, TM activity decreased to 10% of control, and no detectable band was found on immunoblotting, suggesting that CG and GE cleave TM into inactive fragments and that GE degrades the epitope structure of TM. Although H2O2 (1.0 mmol/L) enhanced chromium 51 release from prelabeled HUVECs after 30 minutes of incubation, it decreased TM activity only slightly.(ABSTRACT TRUNCATED AT 250 WORDS)

Cathepsin G↗
PubMed1993

Applications of biotinylated V3 loop peptides of human immunodeficiency virus type 1 to flow cytometric analyses and affinity chromatographic techniques.

A principal neutralizing determinant of human immunodeficiency virus type 1 (HIV-1) lies within the V3 loop of gp120, the external major envelope glycoprotein. V3 loop peptides derived from two HIV-1 strains, HTLV-III BH-10 (V3-BH10) and LAVELI (V3-ELI), were synthesized and biotinylated. The binding of both biotinylated V3-BH10 and V3-ELI to the surfaces of MOLT-4 clone 8 cells was demonstrated by flow cytometric analyses. Both the peptides (more than 2 microM) bound to the cells (2 x 10(5) in a dose-dependent manner. The binding of biotinylated V3-BH10 was specifically inhibited by a neutralizing monoclonal antibody (0.5 beta). The binding of both of the biotinylated V3 loop peptides was enhanced by the addition of unlabeled V3-BH10. In addition, the peptides were employed as ligands on affinity columns. A major V3 loop binding protein (V3BP) was purified from the membrane soluble fraction of MOLT-4 cells by successive application to two different V3 loop columns. V3BP consisted of two major polypeptides (32 and 33 kDa). The SDS-PAGE profile of V3BP did not change under non-reducing conditions, but only a single band was observed after analysis on native PAGE. The major peak of the eluate as determined by size exclusion chromatography was broad and the estimated relative molecular mass was much larger than 33 kDa, suggesting that V3BP comprises several subunits. Taken together, we confirmed that the V3 loop peptides are useful in the characterization of V3BP(s) of which they are conformational ligands.

Amino Acid Sequence↗
PubMed1993

Impaired glycosylation of glycosylphosphatidylinositol-anchor synthesis in paroxysmal nocturnal hemoglobinuria leucocytes.

Metabolic labeling with [3H]sugars in vivo or [3H]sugar nucleotides in vitro of glycosylphosphatidylinositol (GPI)-anchor precursors in peripheral blood granulocytes and cultured T lymphocytes of paroxysmal nocturnal hemoglobinuria (PNH) patients showed a synthetic defect in the GPI-anchor. Among the GPI-anchor precursors, phosphatidylinositol (PI) was normally synthesized, while the synthesis of glucosaminylphosphatidylinositol (GlcN-PI) and subsequent mannosylation of GlcN-PI were inhibited in affected cells. The defect in the GPI-anchor synthesis in PNH is thus attributed to interrupted glycosylation at plural sites in the synthesis of the common carbohydrate structure of the anchor.

Carbohydrate Sequence↗