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Biomedical subjects

K Takatsuki

Publications and source records attributed to K Takatsuki.

At least 397 records · Page 22Linked to original sources

Paroxysmal nocturnal hemoglobinuria: termination in acute monocytic leukemia and reappearance after chemotherapy with N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PL-AC) and vincristine.

Acute monocytic leukemia developed in a 77-year-old woman about 18 months after a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) had been made. The classical features of PNH disappeared with the onset of the leukemia. Chemotherapy with N4-palmitoyl-1-beta-D-arabinosylcytosine and vincristine resulted in the disappearance of leukemic cells in the bone marrow, during which time intravascular hemolysis recurred and the results of a Ham's test were again positive. The anemia and thrombocytopenia, however, were not improved. The present case report suggests the disappearance of the leukemic cells to imply not bone marrow remission but the return of PNH.

Aged↗

Human erythropoietin stimulates murine megakaryopoiesis in serum-free culture.

Recombinant erythropoietin (Epo) was capable of stimulating murine megakaryopoiesis both in serum-containing and serum-free cultures, although a relatively high amount of Epo was necessary to provide sufficient stimulus for colony growth. This observation was further confirmed by experiments using nonadherent, nonphagocytic, and T-cell-depleted marrow cells in which Epo stimulated the growth of single megakaryocytes, as well as clusters or colonies. Total plate analysis revealed that twice as many single megakaryocytes and two-cell aggregates were generated by Epo than generated by pokeweed mitogen-stimulated spleen cell-conditioned medium (PWM-SCM). The number of colonies with four or more cells formed by PWM-SCM, however, was significantly higher than that generated by Epo. These results suggest that in comparison to the factor(s) in PWM-SCM, Epo stimulates the growth of more mature progenitors.

Animals↗

HTLV-I seroprevalence in patients with malignancy.

Since many malignancies often occur in patients with smoldering type adult T-cell leukemia (ATL) (5 of 18 cases in this report), the relationship between HTLV-I (human T-cell leukemia virus type I) infection, which is closely associated with ATL, with other malignancies in an HTLV-I endemic area was examined. Among the 394 patients with malignancies and who had not had blood cell transfusions, 61 (15.5%) tested positive for HTLV-I antibody. The prevalence was significantly higher in males older than age 40 years and females of all ages compared to age- and sex-matched healthy individuals. The overall seroprevalence (26.1%) in 291 patients with malignancies and who had had blood cell transfusions was higher than that of those who had not had blood transfusions. There was no significant correlation between the site of malignancy and antibody prevalence. These results suggest the possibility that development of malignancy may contribute to expression of latent HTLV-I infection and that HTLV-I infection may contribute to the risk of other malignancies.

Adolescent↗

[Clinical assessment of posterior pituitary function by direct measurement of plasma vasopressin levels during hypertonic saline infusion].

Clinical usefulness of a radioimmunoassay of plasma arginine vasopressin concentration (AVP) during hypertonic saline infusion for the assessment of posterior pituitary function was studied in comparison with the conventional water deprivation test. Infusion of 5% saline at a rate of 0.05 ml/kg/min for 120 min in 15 normal subjects induced an elevation of plasma osmolality (Posm) from 290.3 +/- 0.7 to 307.5 +/- 2.1 mOsm/kg with a resultant increase in AVP from 2.4 +/- 0.4 to 9.9 +/- 2.2 pg/ml. During the infusion, a highly significant correlation between AVP and Posm was observed with a regression line expressed as AVP = 0.40 (Posm - 283.0). In 22 polyuric patients, on the other hand, the infusion induced a marked elevation of Posm from 302.6 +/- 2.5 to 321.3 +/- 2.9 mOsm/kg, but caused a slight (less than 5.8 pg/ml) or no increase in AVP from the basal levels (0.5 +/- 0.1 pg/ml). A conventional water deprivation test was carried out in ten patients with neurogenic diabetes insipidus, including one who had coincidental nephrogenic diabetes insipidus. As would be expected, urine osmolality (Uosm) did not rise beyond Posm in seven of them. However, two of three other patients, who had a complete lack of AVP response to the hypertonic saline, were able to concentrate their urine with a maximal Uosm/Posm of 1.3 and 1.1 respectively. The concurrent decrease in creatinine clearance to 49 and 57% of the initial values, respectively, indicated that a marked reduction in glomerular filtration rate due to severe dehydration was responsible for the unexpected concentration of urine in the patients with totally impaired AVP secretion. Based on these results, we conclude that the direct measurement of AVP during hypertonic saline infusion is an essential procedure for the accurate evaluation of posterior pituitary function.

Adolescent↗

Detection of pyrimidine 5'-nucleotidase deficiency using 1H- or 31P-nuclear magnetic resonance.

We describe here a further Japanese family with pyrimidine 5'-nucleotidase (P5'N) deficiency diagnosed using a nuclear magnetic resonance (NMR) spectrum, in Kumamoto prefecture where two families having the disease have been reported before. The specific spectra in 1H-NMR of P5'N deficient erythrocytes were due to three methyl protons of CDP-choline at 3.22 ppm and to H-2, H-8 and ribose-1' of pyrimidine nucleotide phosphate(s) in the lower fields (at 5.82 and 8.00 ppm). The other specificities in 31P-NMR spectra were due to CDP-choline, CDP-ethanolamine and UDP-glucose. Those spectra were not detected in other types of hemolytic anemia.

5'-Nucleotidase↗

Chromosomal abnormalities in a patient with smoldering adult T-cell leukemia: evidence for a multistep pathogenesis.

A cytogenetic study was performed on peripheral blood cells from a patient with smoldering adult T-cell leukemia (ATL). Four types of primary abnormal clones were found upon examination of a large number of karyotypically analysed cells cultured with and without phytohemagglutinin (PHA). However, human T-cell leukemia virus (HTLV) proviral DNA was confirmed to be monoclonal. This discrepancy can be explained by the hypothesis that these four primary abnormal clones were all derived from a leukemic clone with a normal karyotype and the same integration site of HTLV proviral DNA.

Chromosome Aberrations↗

Clinical consequences of 2'-deoxycoformycin treatment in patients with refractory adult T-cell leukaemia.

Five patients from the Kyushu area in Japan with adult T-cell leukaemia (ATL) refractory to conventional chemotherapeutic agents were treated with 5 mg/m2 of the adenosine deaminase inhibitor, 2'-deoxycoformycin (DCF), intravenously (i.v.) for 3 consecutive days, followed by 5 mg/m2 i.v. weekly. Two patients showed a good response, and three were resistant to DCF. One patient with ATL receiving DCF had a continuous remission without further therapy. Another patient in the terminal stage received three daily injections of 7.5 mg of DCF. The most prominent change was the drop in the leucocyte count. The cell count fell from 116.4 X 10(9)/l to 2.0 X 10(9)/l on day 7. The only adverse effects of DCF therapy were gastrointestinal toxicity, nausea and vomiting. These results suggest that DCF may be a valuable drug for treating refractory ATL.

Adenosine Deaminase Inhibitors↗

Expression of Tac antigen on human immature B-cell lineage leukemic cells.

Expression of interleukin 2 (IL-2) receptor (Tac antigen) on leukemic cells from 4 patients with acute lymphocytic leukemia (ALL) and 3 patients with blastic crisis of chronic myelogenous leukemia (CML-BC) was examined. Cells from 6 out of 7 patients did not carry immunoglobulins on their surfaces, but reacted with monoclonal antibodies (mAb) detecting B-cell related antigens such as B1, OKB2 and Leu12. Cells from two cases expressed Tac antigen immediately after cell separation. Phorbol 12-myristate 13-acetate (PMA) could induce Tac antigen in all cases. SDS-PAGE analysis of immunoprecipitates by anti-Tac mAb demonstrated that the molecular weight of Tac antigen on most of the leukemic cells was similar to that of Tac antigen present on Con A-stimulated normal lymphocytes. These leukemic cells poorly responded to exogenous recombinant IL-2. These findings suggest that IL-2 may interact with the immature and mature B cells, and play an important role in the differentiation of B lymphocytes.

Antibodies, Monoclonal↗

Analysis of anti-HTLV-I antibody by strip radioimmunoassay--comparison with indirect immunofluorescence assay, enzyme-linked immunosorbent assay and membrane immunofluorescence assay.

Antibodies against human T-cell lymphotropic virus type I (HTLV-I) in the sera from 60 patients with adult T-cell leukemia and 21 carriers who were suspected of having HTLV-I infection were investigated by indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), membrane immunofluorescence assay (MIA) and strip radio immunoassay based on the western blotting technique (SRIA). The sera of 2 of the carriers who were seropositive in IFA and ELISA were negative in MIA and did not react with virus-specific proteins by SRIA. Two sera were negative in IFA and ELISA. These sera were positive in MIA and reacted with only the envelope-related glycoprotein (gp46) and not with gag-related proteins (p28, p24, p19) by SRIA. These findings suggest that the main antigens defined by IFA and ELISA are gag-related proteins and some sera which do not contain anti-HTLV-I antibodies give false-positive results because of the reaction to unknown cellular components. Also some sera may have antibodies against only envelope glycoproteins, and these sera may give false-negative results in IFA and ELISA.

Antibodies, Viral↗

Human urinary megakaryocyte colony-stimulating factor in thrombopoietic disorders.

The level of urinary Meg-CSF activity in patients with various thrombopoietic disorders was studied. Five out of eight patients with idiopathic thrombocytopenic purpura had megakaryocytic hyperplasia in the marrow and increased Meg-CSF activity in the urine. Urinary Meg-CSF activity in patients with polycythaemia vera and essential thrombocythaemia was normal. There was a significant inverse correlation between urinary Meg-CSF activity and peripheral blood platelet count but not bone marrow megakaryocyte mass. There was a significant increase of urinary Meg-CSF activity during the period of thrombocytopenia after chemotherapy in patients with acute leukaemia who were in complete remission. The timing of maximal Meg-CSF levels corresponded to the nadirs of platelet counts. These results support the concept that Meg-CSF may play a significant role in the regulation of megakaryopoiesis and/or thrombopoiesis in vivo.

Blood Platelet Disorders↗

Analysis of antibody to neutrophils associated with autoimmune neutropenia: possible recognition of Fc-receptor-related molecules.

The serum of a 50-year-old male with neutropenia and a bout of bacterial infection was studied. Anti-neutrophil IgG antibody was detected by indirect immunofluorescence using a laser flow cytometry system. Purified IgG from our patient's serum did not inhibit chemotaxis of neutrophils, but inhibited rosette formation of neutrophils with ox red blood cells (ORBC) coated with anti-ORBC rabbit IgG dose-dependently. Surface iodination of neutrophils followed by their immunoprecipitation by purified IgG and sodium dodecylsulfate polyacrylamide gel electrophoresis showed a single band that corresponded to 45 kilodaltons. Possibly the IgG antibody in our patient's serum recognizes molecules related to Fc receptors.

Agranulocytosis↗

Clinical significance of serum bone Gla protein and urinary gamma-Gla as biochemical markers in primary hyperparathyroidism.

The serum bone Gla-protein (BGP) and urinary gamma-carboxyglutamic acid (gamma-Gla) levels were determined in patients with primary hyperparathyroidism (PHP). The mean serum BGP and urinary gamma-Gla levels were 18.6 +/- 2.34 ng/ml and 65.5 +/- 4.62 nmoles/mgCr, respectively, for the 11 patients with the skeletal type of PHP, 5.13 +/- 0.85 ng/ml and 45.2 +/- 1.33 nmoles/mgCr for the 4 with the chemical type, and 7.91 +/- 2.43 ng/ml and 43.2 +/- 3.47 nmoles/mgCr for the 5 with the renal type. Thus, patients with skeletal-type PHP had significantly higher serum BGP and urinary gamma-Gla levels than those with the other type of PHP. Serum BGP levels had significant positive correlations with serum Ca (r = 0.64, P less than 0.005), serum A1-p (r = 0.77, P less than 0.001) and serum PTH (r = 0.45, P less than 0.005). Urinary gamma-Gla levels also had significant positive correlations with serum Ca (r = 0.50, P less than 0.05), serum A1-p (r = 0.67, P less than 0.005), serum 1,25(OH)2D (r = 0.62, P less than 0.02), and serum BGP (r = 0.72, P less than 0.001). Mineral content in the left radius had significant negative correlations with serum BGP levels (r = -0.73, P less than 0.001) and urinary gamma-Gla levels (r = -0.59, P less than 0.01). As these data show, serum BGP and urinary gamma-Gla levels clearly reflect the abnormal bone metabolism and can therefore be useful biochemical markers in PHP.

1-Carboxyglutamic Acid↗

T3 surface molecules on adult T cell leukemia cells are modulated in vivo.

Cells from eight patients with adult T cell leukemia (ATL) and from four patients with non-ATL were examined to see if the T3 antigen of these cells could be modulated in vitro. We found a low density of T3 antigen and the presence of Tac antigen on cells from all patients with ATL. The density of T3 antigen on non-ATL cells was normal, and Tac antigen was not detected. Modulation of T3 antigen and an increase in Tac antigen-positive cells occurred when cells from patients with T4 non-ATL were cultured with OKT3 monoclonal antibody (mAb). Those changes in T3 antigen density and the appearance of Tac antigen-bearing cells by OKT3 mAb were not so marked when ATL cells were used. But the modulation of T3 antigen and the increase in Tac antigen-bearing cells by OKT3 mAb were closely related in cells from six ATL patients. These findings suggest that T3 T cell antigen receptor complexes on ATL cells are not functionally "frozen" by leukemic changes and might be modulated in vivo. In addition, modulation of T3 surface antigen on ATL cells was not induced by cultivation with human T cell leukemia virus type I particles and envelope proteins obtained by gene technology.

Acute Disease↗