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Biomedical subjects

A Manabe

Publications and source records attributed to A Manabe.

At least 19 recordsLinked to original sources
PubMed1997

Prevalence and growth characteristics of malignant stem cells in B-lineage acute lymphoblastic leukemia.

We used a stroma-supported culture method to study the prevalence and growth characteristics of malignant stem cells in acute lymphoblastic leukemia (ALL). In 51 of 108 B-lineage ALL samples, bone marrow-derived stroma not only inhibited apoptosis of ALL cells but also supported their proliferation in serum-free medium. When single leukemic cells were placed in the stroma-coated wells of microtiter plates, the percentage of wells with leukemic cell growth after 2 to 5 months of culture ranged from 6% to 20% (median, 15%; 5 experiments). The immunophenotypes and genetic features of cells recovered from these cultures were identical to those noted before culture. All cells maintained their stroma dependency and self-renewal capacity. Leukemic clones derived from single cells contained approximately 10(3) to 10(6) cells after 1 month of culture; other clones became detectable only after prolonged culture. Cell growth in stroma-coated wells correlated with the number of initially seeded cells (1 or 10; r = .87). However, the observed percentages of positive wells seeded with 10 cells always exceeded values predicted from results with single-cell-initiated cultures (P < .003 by paired t-test), suggesting stimulation of leukemic cell growth by paracrine factors. In conclusion, the proportion of ALL cells with clonogenic potential may be considerably higher than previously thought.

Adipose Tissue↗
PubMed1996

Transcriptional repression activity of N-MYC protein requires phosphorylation by MAP kinase.

The transrepressing function of the N-myc protein is due to the distinct domains located at the N-terminus. In this report we introduced various point mutations around the myc boxes of the N-myc protein to examine whether the phosphorylation of the protein affected its transrepressing function. Serine (Ser) residues located at amino acid numbers 12, 31, 51, and 65 were changed to leucine or arginine, and the expression vectors of the mutant proteins were transfected to HeLa cells together with the luciferase gene linked to the MHC class I gene. Among the mutants, only the N(51)-myc carrying mutation at Ser(51), a target for mitogen-activated protein kinase (MAP kinase), lost the repression activity, while the other mutant proteins preserved it. Formation in vitro of the specific nucleoprotein complexes on the H2TF1/NFkappaB element, a major target for transrepression by N-myc protein, was interfered by the wild-type N-myc protein, but not by the Ser(51)-mutated protein. The results suggest that the phosphorylation of the N-myc protein at Ser(51) by MAP kinase is required for the transcriptional repression activity of the protein.

Amino Acid Sequence↗
PubMed1996

Stroma-supported culture in childhood B-lineage acute lymphoblastic leukemia cells predicts treatment outcome.

We developed a stroma cell culture system that suppresses apoptosis of malignant cells from cases of B-lineage acute lymphoblastic leukemia. By multiparameter flow cytometric measurements of cell recovery after culture on stromal layers, we assessed the growth potential of 70 cases of newly diagnosed B-lineage acute lymphoblastic leukemia and related the findings of treatment outcome in a single program of chemotherapy. The numbers of leukemic cells recovered after 7 d of culture ranged from < 1 to 292% (median, 91%). The basis of poor cell recoveries from stromal layers appeared to be a propensity of the lymphoblasts to undergo apoptosis. The probability of event-free survival at 4 yr of follow-up was 50 +/- 9% (SE) among patients with higher cell recoveries ( > 91%), and 94 +/- 6% among those with reduced cell recoveries (+/- 91%; P = 0.0003). The prognostic value of leukemic cell recovery after culture exceeded estimates for all other recognized high-risk features and remained the most significant after adjustment with all competing covariates. Thus, the survival ability of leukemic cells on bone marrow-derived stromal layers reflects aggressiveness of the disease and is a powerful, independent predictor of treatment outcome in children with B-lineage acute lymphoblastic leukemia.

Analysis of Variance↗
PubMed1996

Dietary wheat gluten alleviates the elevation of serum transaminase activities in D-galactosamine-injected rats.

The effects of dietary protein on the elevation of activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in D-galactosamine-injected rats were investigated. The rats fed with experimental diets containing test protein sources for 2 weeks were injected with D-galactosamine (0.8 g.kg-1 body weight). The activities of AST and ALT in serum were assayed after 20 h. According to the results, these enzyme activities in the rats fed 40% casein diet were higher than those of 5, 10, or 20% casein groups. In the 40% gluten group, these enzyme activities were lower than in the 40% casein group. This difference was not considered to be caused by the deficit of L-lysine and L-threonine in gluten. The extent of the reduction of UTP and UDP-glucose in liver by D-galactosamine was almost the same in the 40% gluten and 40% casein groups. These results suggest that levels and quality of dietary protein affect the susceptibility of animals to the hepatotoxin D-galactosamine and dietary gluten was found to alleviate the elevation of serum transaminases in rats by the drug.

Alanine Transaminase↗
PubMed1996

Contact dermatitis caused by 2-HEMA and GM dentin primer solutions applied to guinea pigs and humans.

The purposes of this study were to examine whether 2-HEMA, GM, and methacrylic acid cause contact dermatitis, and to determine the optimum concentrations of these primers for sensitization and challenge in guinea pigs. A sensitizing concentration of 0.2% 2-HEMA resulted in strong rubefaction and several vesiculopapules in response to the challenge, and a sensitizing concentration of 0.5% GM produced strong rubefaction at 24 hours. We also observed the development of contact dermatitis on human brachia in a closed-patch test. Skin that was treated with both 2-HEMA and GM clearly showed the onset of rubefaction and itchiness. 2-HEMA caused sensitized delayed allergic reactions at all the concentrations tested.

Animals↗
PubMed1996

Contact angle of dentin bonding agents on the dentin surface.

Physical changes in the surface characteristics of dentin during bonding procedures were evaluated by measuring the contact angles of three standard liquids, to determine the surface free energy, and that of a commercially available dual cured dentin bonding agent dropped on the primed dentin surface. The commercial dentin bonding agent did not form a hemispherical shape on the ground dentin surface, probably because it penetrated into the smear layer due to the microcapillary effect. Not could the contact angle be measured on the dentin surfaces treated with any of four experimental primers, because the bonding agent rapidly spread over the primed dentin surface. It was concluded that the priming of the dentin surface after removing the smear layer served to increase the surface free energy and to improve the wettability of the bonding agent on the dentin.

Chemical Phenomena↗
PubMed1996

Human B-cell progenitors and bone marrow microenvironment.

Apoptosis of normal and leukemic immature B-cells in vitro is suppressed by contact with bone marrow-derived stromal layers. In stroma-supported cultures of immature B-cells, we found that ligation of CD38, a type II transmembrane protein, inhibited the cell growth and induced apoptosis. CD38 ligation also induced tyrosine phosphorylation and activation of intracellular substrates, including syk, phospholipase C-gamma, c-cbl, and phosphatidylinositol 3-kinase (PI 3-K). Wortmannin and LY294002, two potent inhibitors of PI 3K, rescued immature B cells from CD38-mediated growth suppression. In vitro culture of leukemic lymphoblasts may have potentially important clinical application. First, stroma-supported cultures of acute lymphoblastic leukemia (ALL) cells can determine the growth potential of leukemic cells. In a series of 70 children enrolled in a single program of chemotherapy, cell growth on stroma was a powerful and independent prognostic indicator. Second, a culture system capable of maintaining the majority of ALL blast cells at high levels of viability is also ideally suited for testing antileukemic drugs. Promising results were obtained with 2-chloro-deoxyadenosine and interleukin-4, leading to clinical trials of these two compounds in children with refractory ALL. In addition, we compared the direct antileukemic activities of dexamethasone and prednisolone and found that dexamethasone is five to six times more cytotoxic (on a molar basis) than prednisolone, in agreement with the anti-inflammatory activities of these drugs. This finding may serve to guide the selection of dexamethasone dosage in the treatment of ALL.

ADP-ribosyl Cyclase↗
PubMed1995

Molecular cloning of the complementary DNA for the mouse pyruvate kinase M-2 gene whose expression is dependent upon cell differentiation.

A cDNA encoding M2-type pyruvate kinase from mouse was cloned and its nucleotide sequence was determined. The cDNA encoded a protein containing 531 amino acids, the nucleotide and amino acid sequences of which were 93.2% and 98.1%, respectively, homologous to those of rat M2 pyruvate kinase. Expression of the pyruvate kinase in mouse embryonal carcinoma P19 cells altered according to differentiation stages; high at undifferentiated and low at differentiated stages.

Amino Acid Sequence↗
PubMed1995

Hypertensive intra-arterial chemotherapy for endometrial carcinoma assessed by transvaginal Doppler ultrasound and magnetic resonance imaging.

We examined the effectiveness of hypertensive intra-arterial chemotherapy for endometrial carcinoma using transvaginal Doppler ultrasound and magnetic resonance imaging. Angiotensin II, 100 mg cisplatin, and 40 mg doxorubicin were prescribed for 8 patients with endometrial carcinoma (3 stage Ia; 3 stage Ib; 2 stage II). The resistance index (RI) was obtained for intratumoral blood flow velocity waveforms by transvaginal Doppler ultrasound and changes in RI (delta RI: differences before and after chemotherapy) were calculated. The tumor volume (TV) was also evaluated, based on the T2-weighted image of magnetic resonance imaging (MRI). The decrease in tumor size [DR-T: (TV before chemotherapy--TV after chemotherapy)/TV before chemotherapy x 100] was determined. RI measurements did not correlate with TV, either before or after chemotherapy. The delta RI varied from 0.007 to 0.615 (mean: 0.207) and DR-T varied from 20.1% to 65.0% (mean: 45.5%). The correlation between delta RI and DR-T [DR-T = 23.5 + 167.2 (delta RI)-165.6 (delta RI)2; R2 = 0.772, p < 0.05] was significant. Therefore, we confirmed the effectiveness of hypertensive intra-arterial chemotherapy for endometrial carcinoma using both transvaginal Doppler ultrasound and MRI.

Adenocarcinoma↗
PubMed1995

A delayed hypersensitivity reaction to dentine primer in the guinea-pig.

OBJECTIVE: This study was undertaken to examine the possibility of a delayed hypersensitivity reaction or contact dermatitis occurring in the guinea-pig in response to methacrylate derivatives used as experimental dentine primers. METHODS: The dentine primers 2-HEMA, GM, MA and MMA were tested in a guinea-pig maximization test. RESULTS: All the dentine primers tested produced positive delayed hypersensitivity reactions in the guinea-pig. MMA produced the most severe reaction. CONCLUSION: It is concluded that in the clinical situation, clinicians and other members of the dental team should be aware of the need for careful handling of the dentine primers tested.

Animals↗
PubMed1995

Changes in blood velocities of fetal circulation in association with fetal heart rate abnormalities: effect of sublingual administration of nifedipine.

Nifedipine has been used to treat hypertension in pregnancy, and does not influence fetal or uteroplacental circulations in patients with preeclampsia. A 29-year-old multi-gravid woman presented at 32 weeks' gestation with significant elevation of her blood pressure. After sublingual administration of nifedipine, the blood pressure decreased from 208/122 to 136/96 mm Hg at 30 minutes. In her growth-retarded fetus with abnormal flow velocity waveforms, pulsatility index values for middle cerebral artery and umbilical artery did not change; however, peak systolic velocities, end-diastolic velocities, and time-averaged mean peak velocities for these arteries became significantly elevated. Simultaneously, severe variable decelerations and late decelerations occurred. The adverse effect of nifedipine on fetal circulation might occur in a growth-retarded fetus with abnormal flow velocity waveforms.

Administration, Sublingual↗
PubMed1995

Mathematical modeling of fetal organ growth using the Rossavik growth model: IV. Lung.

Growth of the fetal lung has been monitored by left lung area (LLA), right lung area (RLA), and total lung area (TLA) from 14 to 41 weeks menstrual age in 116 normal Japanese fetuses. Growth of the fetal heart and chest has also been monitored by heart area (HA) and chest area (CA), respectively. Growth curves for these parameters have been determined by using a Rossavik growth model [p = c(t)k+s(t)]. R2 values of 95.3%, 90.3%, 89.0%, 88.7%, and 92.1% were obtained for CA, HA, LLA, RLA, and TLA, respectively. Variability analysis indicated a progressive increase in variability with fetal age for these five parameters. Variability data were used with the growth curve models to determine standard curves for these parameters. These standard curves provide a superior means for evaluating the normal fetal lung growth in the fetus and for identifying pulmonary hypoplasia in utero.

Female↗
PubMed1995

Hypoplastic left heart syndrome: color Doppler sonographic and magnetic resonance imaging features in utero.

A 26-year-old Japanese woman, gravida 2, para 1, was referred to our ultrasonography clinic at 27 weeks' gestation, because of a suspected fetal heart anomaly. The hemodynamic examination, specific for hypoplastic left heart syndrome and obtained with color Doppler sonography, gave a clue to an accurate diagnosis of this entity. Moreover, the use of magnetic resonance imaging provided information complementary to the sonographic findings. The sophisticated type of fetal cardiac examination with color Doppler sonography and magnetic resonance imaging was very effective to interpret hypoplastic left heart syndrome with total anomalous pulmonary venous return. An accurate prenatal diagnosis of congenital heart anomalies is useful for obstetrical management.

Adult↗
PubMed1995

Longitudinal Doppler ultrasonographic assessment of alterations in regional vascular resistance of arteries in normal and growth-retarded fetuses.

The objective of this longitudinal study was to evaluate alterations in regional vascular resistance of arteries with advancing gestation in normal and growth-retarded fetuses. Color Doppler flow imaging and pulsed Doppler ultrasonographic assessments were performed on 13 normal and 7 growth-retarded fetuses, ranging from 15 to 40 weeks menstrual age. The pulsatility index was calculated for middle cerebral artery, descending aorta, splenic artery, renal artery, femoral artery and umbilical artery, respectively. Optimal models for these pulsatility index values were determined by regression analysis. A normal range of the pulsatility index for each artery generated in the normal fetuses. In the middle cerebral artery, the models showed a parabolic pattern during pregnancy in the two groups and the predicted pulsatility index values in growth-retarded fetuses were always lower than those in the normal fetuses, especially late in pregnancy. In the renal artery, the predicted pulsatility index values in growth-retarded fetuses were higher than those in normal fetuses near term. In other arteries, the predicted pulsatility index values showed their own specific patterns and there were no significant differences in predicted pulsatility index values in the two groups. In conclusion, alterations in regional vascular resistance of arteries with advancing menstrual age occur evidenced in both normal and growth-retarded fetuses.

Adult↗
PubMed1995

A novel monoclonal antibody, KOR-SA3544 which reacts to Philadelphia chromosome-positive acute lymphoblastic leukemia cells with high sensitivity.

A monoclonal antibody which primarily reacted with Philadelphia chromosome (Ph1)-positive ALL cells was produced. The reactivity of a monoclonal antibody, KOR-SA3544 (IgG2a) was evaluated on normal hemopoietic cells, 68 leukemic cell lines and freshly obtained cells from 190 patients with leukemia and lymphoma. In cultured cells, KOR-SA3544 reacted with Ph1-positive ALL cell lines (5/5) and leukemic cell lines with 11q23 translocation (3/11). In lymphoid cells, KOR-SA3544 was reactive with all of Ph1-positive ALL (26/26), a part of common ALL (5/38) and one case of early B precursor leukemia with 11q23 translocation, but not with peripheral lymphocytes. Normal mature granulocytes were also strongly stained. In myeloid leukemias, KOR-SA3544 was positive (16/56) only in patients with acute myeloid leukemia with FAB-M2 and overt leukemia following myelodysplastic syndrome, but neither with other types of myeloid leukemias nor with blast crisis in chronic myelogenous leukemia. KOR-SA3544 recognized a 90 KDa protein on the membrane of a leukemic cell line, KOPN-57bi. In normal bone marrow, CD19+/KOR-SA3544+ cells were not identified, while Ph1-positive ALL cells were strongly positive for both antibodies. KOR-SA3544 is useful not only for making the diagnosis of Ph1-positive ALL but for detection of the minimal residual disease during remission.

Antibodies, Monoclonal↗
PubMed1994

Interleukin-4 induces programmed cell death (apoptosis) in cases of high-risk acute lymphoblastic leukemia.

We investigated the effects of interleukin-4 (IL-4) on the survival of leukemic and normal B-cell progenitors cultured on bone marrow stroma. IL-4 (at 100 U/mL) was cytotoxic in 16 of 21 cases of B-lineage acute lymphoblastic leukemia, causing reductions in CD19+ cell numbers that ranged from 50% to greater than 99% (median 83.5%) of those in parallel cultures not exposed to the cytokine. All nine cases with the t(9;22)(q34;q11) or the t(4;11)(q21;q23), chromosomal features that are often associated with multidrug resistance and a fatal outcome, were susceptible to IL-4 toxicity. IL-4 cytotoxicity resulted from induction of programmed cell death (apoptosis); there was no evidence of cell killing mediated by T, natural killer, or stromal cells. IL-4 cytotoxicity extended to a proportion of normal B-cell progenitors. After 7 days of culture with IL-4 at 100 U/mL, fewer CD19+, CD34+ normal lymphoblasts (the most immature subset) survived: in five experiments the mean (+/- SEM) reduction in cell recoveries caused by IL-4 was 60.0% +/- 6.0%. By contrast, reductions in recovery of more differentiated bone marrow B cells (CD19+, CD34-, surface Ig+) were low (6.6% +/- 2.2%; P < .001 by t-test). Our findings indicate that IL-4 is cytotoxic for human B-cell precursors and support clinical testing of IL-4 in cases of high-risk lymphoblastic leukemia resistant to conventional therapy.

Adolescent↗