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Biomedical subjects

T Inaba

Publications and source records attributed to T Inaba.

At least 307 records · Page 17Linked to original sources
PubMed1991

Functional and molecular characteristics of acute lymphoblastic leukemia cells with a mature T-cell phenotype from a patient with ataxia telangiectasia.

A 12-year-old male patient with ataxia telangiectasia developed an acute lymphoblastic leukemia of T-cell phenotype. The lymphoblasts showed uniform surface expression of CD3, CD7, CD8, and T-cell receptor (TCR) alpha/beta chains, positive immunofluorescent staining of terminal deoxynucleotidyl transferase, complex cytogenetic aberrations including t(14;14) (q11;q32) and unique rearrangements of TCR beta and gamma chain genes, indicating the clonal expansion of leukemic cells. CD25 expression could be readily induced on the leukemic cells by mitogenic stimulation, followed by CD71 expression, but interleukin-2 production and subsequent proliferation in response to mitogens were subnormal.

Antigens, CD↗
PubMed1991

[Successful pregnancy after 6 years complete remission in patient with acute myeloblastic leukemia].

A 25-year-old woman was diagnosed as acute myeloblastic leukemia (M1 in FAB classification) in May 1983, and treated with DCMP regimen, which led to the complete remission. Intensification therapies and maintenance therapy with OK-432 were continued until August 1988, and 10 months later she conceived. She delivered a healthy 2,680 g male baby at 36th week of pregnancy by Cesarean section because of abruptio placentae. This case suggests that normal pregnancy is possible in patients with acute leukemia who received anti-cancer drugs.

Adult↗
PubMed1990

Translocation between chromosomes 8q24 and 14q11 in T-cell acute lymphoblastic leukemia.

Cytogenetic study was performed on a patient with T-cell acute lymphoblastic leukemia (T-ALL). It revealed a chromosomal translocation between chromosome bands 8q24 and 14q11. 8q24 is known to encode the oncogene c-myc, while 14q11 encodes the genes for T-cell receptor-alpha (TCR-alpha) and T-cell receptor-delta (TCR-delta). Therefore, this chromosomal translocation t(8;14) (q24;q11) seemed to be unique and specific to T-cell malignancy.

Adult↗
PubMed1990

Monocyte colony-stimulating factor enhances uptake and degradation of acetylated low density lipoproteins and cholesterol esterification in human monocyte-derived macrophages.

We have investigated effects of monocyte colony-stimulating factor (M-CSF) on the uptake of acetylated low density lipoproteins (acetyl-LDL) and the activity of cholesterol esterification in human monocyte-derived macrophage. The cells were cultured with M-CSF for 10 days and then incubated with acetyl-LDL for 24 h. M-CSF (128 ng/ml) enhanced the uptake and degradation of 10 micrograms/ml of 125I-acetyl LDL 7.5-fold (n = 6) and the effect of M-CSF was dose-dependent at the concentrations of 0.5-32 ng/ml. The binding experiments at 4 degrees C demonstrated that the number of acetyl-LDL receptor was increased by the addition of M-CSF. Supporting this, ligand blotting analysis revealed a significant increase in a receptor protein for acetyl-LDL (240 kDa). Binding of LDL was also enhanced by M-CSF but less significantly than that of acetyl-LDL. Cellular cholesterol esterification in the presence of 10 micrograms/ml acetyl-LDL was enhanced 24.1-fold (n = 13) by 128 ng/ml M-CSF. It was evident that M-CSF enhanced cholesterol esterification to a greater extent than the cellular uptake of acetyl-LDL (24.1- versus 7.5-fold). Cholesterol esterification was also enhanced by the addition of granulocyte-macrophage colony-stimulating factor and interleukin 1. We conclude that M-CSF enhances the uptake of both acetyl-LDL and LDL by increasing their receptor number, and further enhances the process of cholesterol esterification, resulting in a remarkable increase in cholesterol esterification in macrophages. These findings strongly suggest the significant involvement of cytokines such as M-CSF in cholesterol metabolism of macrophages.

Biological Transport↗
PubMed1990

Human monocyte colony-stimulating factor enhances the clearance of lipoproteins containing apolipoprotein B-100 via both low density lipoprotein receptor-dependent and -independent pathways in rabbits.

To investigate the effects of recombinant human monocyte colony-stimulating factor (M-CSF) on plasma cholesterol metabolism, we injected M-CSF intravenously into New Zealand White rabbits (n = 13) at a dose of 100 micrograms/day for 7 days. After the treatment, the plasma cholesterol levels fell by 33.2% from 61.4 +/- 25.9 to 41.0 +/- 10.2 mg/dl (mean +/- S.D.). We also injected a large dose of M-CSF (500 micrograms/day) for 6 days into Watanabe Heritable Hyperlipidemic rabbits, which are deficient in low density lipoprotein (LDL) receptors. Again, there was a significant reduction in plasma cholesterol levels by 36.2% from 730.5 +/- 176.4 to 466.0 +/- 104.9 mg/dl (n = 4). In the kinetic studies in New Zealand White rabbits with very low density lipoprotein, LDL, and methylated LDL, the removal rates of those lipoproteins were increased 1.9-, 1.7-, and 2.0-fold, respectively, after the treatment. Immunoblot analysis of LDL receptors in the treated rabbits showed no significant changes in LDL receptor proteins in livers but a great increase in spleens and bone marrows compared with the controls. Messenger RNA was also estimated by Northern blotting in both groups, and the results were compatible with those from the immunoblot. The data suggest that M-CSF stimulates the clearance of lipoproteins containing apolipoprotein B-100 via both LDL receptor-dependent and -independent pathways in target cells of M-CSF and reduces plasma cholesterol.

Animals↗
PubMed1990

Characterization of an embryonal rhabdomyosarcoma cell line showing amplification and over-expression of the N-myc oncogene.

A parent rhabdomyosarcoma cell line designated SCMC-RM2 was established from bone-marrow tumor cells taken from an 11-year-old girl with an embryonal rhabdomyosarcoma. Subsequently a cloned SCMC-RM2-1 cell line was isolated from a parent line. These cell lines grew as adherent monolayers in liquid culture with a doubling time of 50 and 52 hr, respectively. In addition, colonies were established in soft agar, which grew in a dose-dependent fashion with a cloning efficiency of 0.7 and 0.8%, respectively. Chromosomal analysis showed these cell lines had neither double minutes nor homogeneously staining regions. Chromosome number ranged from 61 to 93, translocation; t(9;13)(p22;q14) was identified, and no alteration of chromosome 2 was observed. Surface membrane antigen profile of parent and cloned lines by using a panel of 24 monoclonal antibodies (MAbs) excluded the possibility of these being neuroblastoma cell lines. In addition, MAbs to the cytoplasmic protein desmin, myoglobin, muscle actin (alpha and gamma) and alpha-sarcomeric actin reacted with these cell lines, SCMC-RM2 and SCMC-RM2-1 being thus identified as rhabdomyosarcoma. Southern blot analyses revealed 8- and 7-fold amplification of the N-myc gene in SCMC-RM2 and SCMC-RM2-1 as compared with the promyelocytic cell line HL60. Over-expression of the N-myc mRNA was noted over control cell lines.

Antigens, Neoplasm↗
PubMed1990

The dopamine transporter and cytochrome P45OIID1 (debrisoquine 4-hydroxylase) in brain: resolution and identification of two distinct [3H]GBR-12935 binding proteins.

Two [3H]GBR-12935 binding proteins, identified as the dopamine transporter and cytochrome P45OIID1, were solubilized in digitonin from canine striatal membranes, and were resolved following wheat germ agglutinin (WGA)-lectin column chromatography. Protein adsorbed to and specifically eluted from WGA-lectin with N-acetylglucosamine displayed saturable, high affinity (KD approximately 3 nM), and sodium-dependent binding of [3H]GBR-12935, which was inhibited in a concentration-dependent and stereoselective manner by dopamine uptake blockers and substrates with a pharmacological profile indicative of the dopamine uptake site. Protein not adsorbed to WGA-lectin also bound [3H]-GBR-12935 with high affinity (approximately 7 nM), in a sodium-independent manner, and was insensitive to classical dopamine uptake blockers and substrates such as mazindol or dopamine, corresponding to the so-called "piperazine acceptor" site seen in native membranes. [3H]GBR-12935 binding to this latter protein was, however, inhibited by various compounds with a pharmacological profile indicative of a form of cytochrome P450 designated P45OIID1 (debrisoquine/sparteine monooxygenase) with the following rank order of inhibitory potency: GBR-12909 greater than budipine greater than alpha-lobeline greater than quinidine greater than alpha flupenthixol greater than SKF-525A greater than sparteine greater than quinine. Ki values obtained for inhibition of [3H]-GBR-12935 binding to neuronal WGA passthrough fractions by these drugs correlate well with their respective Ki values for liver P45OIID1 activity. Western blotting and immunoprecipitation analysis with rabbit anti-rat P45OIID1 antibody also supported the identity of the mazindol-insensitive [3H]GBR-12935 binding site (or piperazine acceptor site) as P45OIID1. Furthermore, a [3H]GBR-12935 binding protein with pharmacological and immunological characteristics similar to those of P45OIID1 was solubilized from both bovine and human liver membranes, and GBR-12909 was found to be a potent competitive inhibitor (Ki approximately 100 nM) of sparteine monooxygenase activity in human liver microsomes. These data clearly indicate that [3H]GBR-12935 and its analogs display similar affinities for both the dopamine transporter and neuronal P45OIID1, and that this radioligand may be a useful probe of P45OIID1 activity in brain and liver. The exact molecular and functional association (if any) between these two distinct binding protein populations remains to be established; however, it is tempting to speculate that P45OIID1 is involved in the catabolism and processing of neurotransmitters subsequent to their reuptake into target cells.

Animals↗
PubMed1990

Phenytoin: pharmacogenetic polymorphism of 4'-hydroxylation.

The metabolism of phenytoin via 4'-hydroxylation is subject to large inter-individual variability. The ratio of drug/metabolite (DPH/HPPH) in plasma and the reverse ratio for urine, metabolite/drug (HPPH/DPH), have been adopted to characterize the variability. Early recognition of the genetic/familial control of para(4'-)hydroxylation of phenytoin by Kutt and associates in the early 1960s was substantiated some 20 years later by Vasko et al. (1980) and Vermeij et al. (1988). The mode of inheritance has not been established. The frequency of 'insufficient' or slow hydroxylators is low, in the order of 1 in 500. The finding by Sloan et al. (1981) of an association between phenytoin 4'-hydroxylation and the well known debrisoquine/sparteine polymorphism was not confirmed later by several other groups. Formation of the R-enantiomer of HPPH was clearly deficient in some Caucasian subjects and was linked to the mephenytoin polymorphism as shown by Fritz and associates (1987).

Animals↗
PubMed1990

Reduced haloperidol/haloperidol ratios in plasma: polymorphism in Japanese psychiatric patients.

We measured plasma concentrations of haloperidol (HAL) and its metabolite, reduced haloperidol (RHAL), by high performance liquid chromatography (HPLC) in 45 Japanese psychiatric patients receiving HAL. Plasma levels of HAL had a highly positive correlation with daily dose per body weight. Plasma RHAL/HAL ratios had also a dose-dependent relationship, but their distribution was nonnormal and a bimodal pattern with an antimode at 0.7 was apparent by probit analysis. There were 8 subjects (18%) with high RHAL/HAL ratios (mean = 1.26, SD = 0.41) and 37 subjects (82%) with low RHAL/HAL ratios (mean = 0.42, SD = 0.13). RHAL/HAL ratios showed little intraindividual variability (+/- 10.6%), while interindividual variability was large. This may suggest that pharmacogenetic factors are involved in the metabolism of HAL and RHAL.

Adolescent↗
PubMed1990

Unimodal distribution of the metabolic ratio for debrisoquine in Cuna Amerindians of Panama.

1. The metabolic oxidation of debrisoquine (DB) was studied in 89 non-related Cuna Amerindian subjects. 2. Means and standard deviations for urinary recoveries of the intact drug and its 4-hydroxy metabolite (4-HD) were: %DB: 6.8 +/- 4.5; %4-HD: 16.0 +/- 9.1; %sum: 22.8 +/- 12.0. The log10 metabolic ratios for DB (LMRDB) were distributed within a single mode of insignificant skewness (-0.01, P greater than 0.10), which was unimodal (log kernel density and maximum likelihood methods) and normal (chi 2 = 22.5; d.f. = 15; P greater than 0.09; power of the test greater than 80%). 3. Therefore, no poor metabolizers (95% C.I.: 0.1%, 5.2%) were detected in the population sample studied.

Debrisoquin↗
PubMed1990

Sparteine metabolism capacity in human liver: structural variants of human P450IID6 as assessed by immunochemistry.

An antibody raised against rat P450dbl was used to examine the heterogeneity of the human enzyme involved in the sparteine/debrisoquine polymorphism. The extent to which the antibody was able to inhibit sparteine metabolism varied in different human livers (10-80%, n = 9) and reflected the amount of sparteine metabolism carried out by the polymorphic P450IID6 in individual liver specimens. The individual sample variation in inhibition by the antibody correlated with the inhibition caused by quinidine, a prototype competitive inhibitor of the P450IID6 enzyme active site. Western immunoblots of the liver microsomes confirmed that the variation in the inhibition of sparteine metabolism by this antibody reflected the amount of P450IID6 protein. In addition, a detailed study of one of the livers (K19) which demonstrated a lack of inhibition by the antibody was performed which confirmed the lack of P450IID6 in this liver specimen and suggested that the nascent sparteine metabolism activity was due to other forms of P450.

Animals↗
PubMed1990

[Relationship between aging and renal function: a positron emission tomographic study].

Blood volume (V), blood flow (F) and glomerular filtration rate (GFR) per 100 g (100 ml) of kidney were calculated with C15O, H(2)15O and 68Ga-EDTA, to study age-related changes per unit tissue in 19 subjects using positron emission tomography. Age was negatively correlated with V, F and GFR. The aging-related decrease in V was less marked than those in F and GFR. Analysis by regression formula induced that F, GFR for subjects in their 70s are 76%, 46% and 55% for those in their 20s, respectively.

Adult↗
PubMed1990

[Evaluation of renal blood volume by PET--the aorta-kidney equilibrium monitored with C15O].

Twenty subjects inhaled C15O and its dynamics were monitored to determine when equilibrium between the aorta and kidney occurred. One minute after inhalation, the increase in radioactivity in the aorta paralleled that in the kidney, but thereafter, both declined slowly. The ratio of aorta/kidney radioactivity become constant 1 min after inhalation and remained unchanged for 4 min. Thus renal blood volume can be measured 1 min after inhalation of C15O its distribution in the aorta and kidney has attained equilibrium.

Administration, Inhalation↗
PubMed1990

[Bone marrow transplantation for girls with aplastic anemia utilizing modified field of total lymphoid irradiation and cyclophosphamide: with emphasis on the field of pelvic cavity].

A preparative regimen for allogeneic bone marrow transplantation, consisting of total lymphoid irradiation (TLI) with 750 cGy and cyclophosphamide (CY), was used in five girls with aplastic anemia. All patients received bone marrow from HLA matched/mixed lymphocyte culture negative siblings. In our regimen the "inverted Y" field to irradiate the pelvic nodes was modified, which did not include the whole pelvic cavity in an attempt to protect the ovaries from irradiation. Although some of the pelvic nodes was supported not to be irradiated in order to protect the ovaries, engraftment occurred in all five patients including four who had been transfused prior to transplantation. All five are alive from 47 days to 1378 days (median 285 days) after transplantation without transplantation-associated complications. The calculated dose to the ovaries was sixteen percent of the entire dose of the regimen. Both of the two evaluable patients that had received transplantation just before or during the puberty are developing normal sex maturity including menstruation. This study suggests that our preparative regimen is effective not only for engraftment of the donor marrow but also for protecting the ovaries from irradiation.

Adolescent↗
PubMed1990

Karyotypic patterns in acute mixed lineage leukemia.

We performed cytogenetic and immunologic studies of blast cells from 13 children with acute mixed lineage leukemia (AMLL) to discern patterns of chromosome alteration and antigen expression that would assist in classification of this disease entity. Six patients with 11q23 translocations--including four with the t(11;19), one with the t(9;11), and one with the t(1;11)--were characterized by a young age and hyperleukocytosis. A B cell-associated antigen (CD19) and HLA-DR antigens were expressed by blast cells from all patients; only one case was positive for the common acute lymphocytic leukemia antigen (CALLA, CD10). A myeloid-associated antigen (CD13) was expressed by blast cells from one patient at diagnosis and from another at relapse; it was also expressed by cells from the remaining four patients after brief in vitro culture without addition of differentiating agents. Four patients with t(9;22)(q34;q11) were characterized by an older age and hyperleukocytosis. Each of these cases was positive for CD13, CD19, and HLA-DR, and three were positive for CALLA. The 11q23 translocation was associated with CALLA- ALL marked by a myeloid phenotype, whereas the t(9;22) occurred in cases of acute myeloid leukemia with a CALLA+ lymphoid phenotype. One case had a 7q35-q36 translocation, which involves the region of the T cell receptor beta-chain gene. Our results suggest that karyotypic alterations can be used to refine the classification of AMLL.

Antigens, CD↗
PubMed1990

[Large granular lymphocyte leukemia containing oligoclonal EB viral DNA].

A 32-year-old female was admitted to our hospital because of abdominal fullness, jaundice and pretibial edema in November, 1987. Leukocyte count of peripheral blood showed 13300/microliters with 84% leukemic cells and bone marrow was normocellular with 63.6% leukemic cells. Leukemic cells had azurophilic large granules with basophilic cytoplasm and positive for CD 2, OKIa 1, NKH-1 and negative for CD 3, CD 4, CD 8, CD 16. T cell receptor (TCR) genes for beta, gamma and delta chain and immunoglobulin heavy chain gene were in germ line configuration. These cells also had natural killer (NK) activity and antibody dependent cell mediated cytotoxicity (ADCC) activity. These observations suggested that they were derived from NK cell lineage. It is often difficult to demonstrate their clonalities in lymphoproliferative disorder of granular lymphocytes (LDGL). In the present case, the analysis of EBV genome using termini probe demonstrated polyclonal bands, while we found constant chromosome abnormalities; 47 XX, +3. From these observations, this case was considered to have several clones, and one of which could be detected by chromosome analysis. The analysis of EBV genome using termini probe may be useful to demonstrate their clonalities in LDGL in addition to conventional chromosome analysis.

Adult↗