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Biomedical subjects

A Manabe

Publications and source records attributed to A Manabe.

At least 37 records · Page 2Linked to original sources

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

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

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

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

Adhesion-dependent survival of normal and leukemic human B lymphoblasts on bone marrow stromal cells.

We investigated the requirement for intimate contact between bone marrow stroma and B lymphoblasts from normal donors and children with leukemia. By scanning electron microscopy, both normal and leukemic cells seeded onto stroma were surrounded by folds of stromal cells or were linked to the stroma by fine tendrils and uropods. Separation of normal B progenitors from stroma by use of microporous membranes led to significantly lower cell recoveries compared with results when contact was unimpeded. For instance, 22.5% +/- 1.8% (mean +/- SEM) of CD19+, CD34+ cells (most immature subset) were recovered after a 7-day culture directly on stroma, compared with 5.2% +/- 0.7% after growth on membranes (P < .001 by Student's t test). In 6 of 11 cases of B-lineage acute lymphoblastic leukemia, separation of progenitors from stroma resulted in apoptosis and a greater than 60% reduction in cell recovery. In the remaining 5 cases, however, this effect was much less pronounced, with reductions in cell recoveries ranging from 48.5% to less than 1% (median, 39.0%) of control values. Inhibition of very late antigen-4, a surface molecule critical for adhesion of B lymphoblasts to stroma, was associated with a greater loss of normal CD34+ B progenitors compared with that for equivalent leukemic cells. These results establish direct contact with stroma as a survival requirement of normal B lymphoblasts and show marked heterogeneity in stromal dependency among B-lineage leukemic cells.

Adolescent

Efficacy of various commercial dentin bonding systems.

OBJECTIVES: The purpose of this study was to test the bonding efficacy of fifteen commercial dentin bonding systems and also to determine the effect of various commercial dentin cleaners on bonding and dentin hardness. METHODS: Each commercial bonding system was examined by two methods: 1) measuring the maximum contraction gap of a light-cured composite in a cylindrical dentin cavity; and 2) determine the tensile bond strength to a flat dentin surface. In addition, various commercial dentin cleansers were investigated to determine if dentin hardness was reduced after cleaning. As a control, the dentin surface was cleaned with neutralized EDTA prior to the combined application of an experimental dentin primer, a commercial bonding agent, and a commercial light-cured composite. RESULTS: The study demonstrated that complete marginal adaptation was obtained by the experimental dentin bonding system used as the control. However, it was not possible to completely prevent gap formation with the commercial dentin bonding systems tested. A high correlation (R = 0.88) was observed between maximum contraction gap width and reduction of hardness only in the group in which the dentin was rinsed after cleaning. SIGNIFICANCE: It is very important to combine optimal dentin cleansers, primers, and bonding agents to compensate for the polymerization contraction stress of the composite. Therefore, it was speculated that the commercial dentin bonding systems tested in this study consisted of unsuitable materials.

Acid Etching, Dental

Mathematical modeling of fetal organ growth using the Rossavik growth model: III. Cardiac ventricle.

Growth of the fetal cardiac ventricle has been monitored by total cardiac diameter (TCD), left ventricular systolic (LVSD) and diastolic diameter (LVDD), right ventricular systolic (RVSD) and diastolic diameter (RVDD), left ventricular width (LVW), interventricular septal width (IVSW), and right ventricular width (RVW) from 19 to 39 weeks, menstrual age, in 114 normal Japanese fetuses. Growth curves for these parameters have been determined using a Rossavik growth model [P = c(t)k+s(t)]. R2 values of 89.7, 58.0, 65.3, 77.9, 80.3, 31.1, 30.1, and 26.9 were obtained for TCD, LVSD, LVDD, RVSD, RVDD, LVW, IVSW, and RVW, respectively. Variability analysis indicated a progressive increase in variability with fetal age for these eight 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 cardiac growth in the fetus and for identifying congenital heart anomalies in utero.

Embryonic and Fetal Development

Fetal circulatory system in growth-retarded fetus with late decelerations and oligohydramnios.

We present 4 cases of growth-retarded fetuses with fetal heart rate late decelerations and oligohydramnios. Doppler ultrasound revealed significantly decreased pulsatility index (PI) values of the middle cerebral artery; however, the PI values of the renal artery, femoral artery and umbilical artery were within normal ranges in all fetuses. Relative redistributions in the fetal circulatory system were shown with fetal hypoxemia without acidosis.

Adult

Self-etching dentin primers containing phenyl-P.

The dentin bonding efficacies of two commercial dentin bonding systems and experimental self-etching dentin primers composed of methacryloxyethyl hydrogen phenyl phosphate (Phenyl-P) and either hydroxyethyl methacrylate (HEMA) or glyceryl methacrylate (GM,2,3-dihydroxypropyl methacrylate) were examined. The wall-to-wall polymerization contraction gap width of a commercial light-activated resin composite in a cylindrical dentin cavity and the tensile bond strength to a flat dentin surface were measured. Changes in dentin hardness were determined by Micro Vickers Hardness measurement, and an SEM observation was performed after priming. Formation of a contraction gap was completely prevented by the application of Phenyl-P diluted in HEMA or GM solution combined with a commercial dentin bonding agent, although gap formation was evident in nearly half of the specimens with both commercial dentin bonding systems. The mean tensile bond strengths of the tested groups varied from 16.3 to 20.7 MPa, and there were no significant differences between groups. Based on the measurement of Micro Vickers Hardness and SEM observation after priming, a slight reduction in dentin hardness was observed. However, this reduction in dentin hardness due to self-etching priming did not significantly correlate with either contraction gap width or tensile bond strength.

Acid Etching, Dental

Polyhydramnios: ultrasonic detection of fetal and maternal conditions.

Estimation of amniotic fluid volume is an important part of routine obstetric sonography. A relationship between polyhydramnios and poor perinatal outcome has been reported. This study correlates the severity of polyhydramnios with perinatal morbidity and mortality. Among 67 cases of polyhydramnios detected in singleton pregnancies, 8 were associated with maternal conditions including noninsulin-dependent diabetes (5 cases), insulin-dependent diabetes (1 case) and gestational diabetes (2 cases). Forty-four were associated with fetal conditions, including fetal anomalies (31 cases), fetal chromosomal disorders (10 cases) and fetal functional disorders (3 cases). Fifteen of the 67 cases had no apparent underlying fetal or maternal cause. Perinatal death occurred in 19 cases (28%) and was associated with fetal anomalies (12 cases), chromosome disorders (6 cases) and a functional fetal abnormality (1 case). Severe polyhydramnios with amniotic pocket dimensions > or = 120 mm (91%) or with a need for amniocentesis (91%) were associated with fetal abnormalities in most cases. The rate of perinatal death was not increased, indicating that severe polyhydramnios does not always result in lethal abnormalities.

Female

Growth requirements of normal and leukemic human B cell progenitors.

Leukemic lymphoblasts in B-lineage acute lymphoblastic leukemia (ALL) express morphologic, phenotypic and genotypic features which resemble those of B lymphocyte progenitors in normal bone marrow. Normal immature B cells and cells from most cases of B-lineage ALL rapidly die in vitro unless they are supported by bone marrow-derived stromal feeder layers. Techniques suitable for maintaining normal and leukemic immature B cells in culture have been developed. Thus, the stromal cell types and growth factors that generate a milieu suitable for immature B-cell development can now be elucidated. In addition, the similarities and discrepancies in survival requirements of normal and leukemic B cell precursors can be studied. We postulate that leukemic B cell precursors can survive and expand in microenvironments incapable of supporting their normal counterparts, and that the study of the survival requirements of ALL cells will provide indications about the aggressivity of the disease in vivo. In this review, we discuss the culture conditions that support in vitro survival of human immature B cells, some of the factors that influence their expansion, and the putative molecular basis for the prolonged life-span of leukemic lymphoblasts.

Animals

Use of stroma-supported cultures of leukemic cells to assess antileukemic drugs. II. Potent cytotoxicity of 2-chloro-deoxyadenosine in acute lymphoblastic leukemia.

We used a recently established stroma-supported tissue culture technique that allows long-term culture of acute lymphoblastic leukemia (ALL) cells to study 2-chloro-2'-deoxyadenosine (2CdA) cytotoxicity to leukemic lymphoblasts. In the 20 cases of ALL studied, the number of cells recovered after 7 days of culture on allogeneic stromal layers were 58-192% (median, 95.5%) of those originally seeded. In parallel cultures with 2CdA (100 nM), 74- > 99% (median, 97.5%) of leukemic lymphoblasts were killed. The cytotoxicity of 2CdA extended to all ten samples with either the t(9;22) (q34;q11) or 11q23 chromosomal abnormalities, karyotypes associated with an extremely poor outcome, as well as to two samples collected at the time of relapse. The effects of 2CdA were dose-dependent, and were due to triggering of apoptosis as shown by typical morphologic changes and occurrence of DNA fragmentation. Stromal layers were apparently not affected by 2CdA treatment, even when used at 1000 nM. We also tested 2CdA cytotoxicity to multidrug resistant subclones of the CCRF-CEM ALL cell line. CEM/VLB100 expresses P-glycoprotein, whereas CEM/VM-1 and CEM/VM-1-5 have topoisomerase II mutations that are associated with resistance to topoisomerase II inhibitors. Overexpression of P-glycoprotein or alterations in topoisomerase II did not protect cells from 2CdA cytotoxicity. We conclude that 2CdA is cytotoxic in most cases of ALL. The method used in this study may be applied to evaluate leukemic blast cell sensitivity to compounds with potential anti-leukemic activity, and to select patients for entry into clinical trials.

ATP Binding Cassette Transporter, Subfamily B, Mem

Prolonged survival of B-lineage acute lymphoblastic leukemia cells is accompanied by overexpression of bcl-2 protein.

Overexpression of bcl-2 delays the onset of apoptosis in lymphohematopoietic cells. We measured levels of bcl-2 protein in normal and leukemic human B-cell progenitors with a specific monoclonal antibody and flow cytometry. Normal immature B cells had low levels of bcl-2 protein; the intensity of fluorescence, expressed as molecules of soluble fluorochrome per cell, within CD10+ cells was 3,460 +/- 1,050 (mean +/- SD; 5 samples). In 16 cases of B-lineage acute lymphoblastic leukemia (ALL), cells had levels of bcl-2 that were strikingly higher than those of their normal counterparts (33,560 +/- 14,570; P < .001 by t-test analysis). We next investigated whether the intensity of bcl-2 expression correlated with the resistance of immature B cells to in vitro culture. In 12 cases of B-lineage ALL, the cells recovered after 7 days of culture on allogeneic bone marrow stromal layers were 69% to 178% (median, 95.5%) of those originally seeded. Prolonged survival of leukemic cells in vitro was observed even in the absence of stromal layers in 6 of these 12 cases; the intensity of bcl-2 protein expression in these cases was 45,000 +/- 13,270, compared with 21,500 +/- 7,260 in the 6 cases in which greater than 99.5% of cells rapidly died by apoptosis under the same culture conditions (P = .003). Five immature B-cell lines, continuously growing in the absence of stroma, had the highest bcl-2 expression (79,400 +/- 20,330). By contrast, most normal CD19+, sIg-immature B cells died despite the presence of bone marrow stromal layers; 9.7% to 28.2% were recovered after 7 days of culture in three experiments. We conclude that abnormal bcl-2 gene expression influences the survival ability of B-cell progenitors. This may contribute to leukemogenesis and explain the aptitude of leukemic lymphoblasts to expand outside the bone marrow microenvironment.

Adolescent

Quantitative characterization of arcuate artery hemodynamic change in normal pregnancy with Doppler ultrasonography.

Using color and pulsed Doppler ultrasonography, arcuate arterial velocimetry was carried out in 91 normal women, at 16-40 weeks, menstrual age. The arcuate arterial hemodynamics was assessed by the calculation of the resistance index (RI). A curvilinear relationship was found between the RI value of the arcuate artery obtained from the placental site in the uterus and menstrual age (R2 = 0.328). The relationships between the RI value of the arcuate artery obtained from the nonplacental site (R2 = 0.268) or the averaged RI value between the placental and nonplacental sites (R2 = 0.321) and menstrual age were both linear. Normal ranges of RI values of arcuate arteries during pregnancy for the placental site, nonplacental site, and their average values were generated. These results provide a foundation for evaluating uteroplacental velocimetry in normal pregnancy using Doppler ultrasonography.

Arteries

Effect of delayed light curing of a resin composite on marginal integrity in cylindrical dentine cavities.

The effect of delayed light curing of resin composite on marginal adaptation has been examined by measuring the wall-to-wall polymerization contraction gap when using a commercial resin composite together with experimental dentine bonding systems to restore cylindrical preparations in dentine. Morphological changes in dentine during dentine bonding procedures were observed using a scanning electron microscope. In a previous report, the contraction gap width for a resin composite increased when irradiation of the resin system was delayed, despite the use of a dentine bonding system considered to be 'contraction' gap free. Such deterioration in marginal adaptation was minimized by use of an experimental dentine primer, 40% erythritol methacrylate aqueous solution (EM), followed by the use of a commercial dual- or autocured dentine bonding agent. Under scanning electron microscopy, the dentine surface microstructure became unclear after EM priming, and a polymer film was detected after polymerization of the dual-cured dentine bonding agent. The hydrogelled primer and the formation of a polymer network on the dentine surface may prevent the flow of fluid from the pulp through the dentine tubules, and maintain marginal integrity if there is delay in light curing of light-activated resin composite systems.

Analysis of Variance

Stroma-supported immunocytometric assay (SIA): a novel method for testing the sensitivity of acute lymphoblastic leukemia cells to cytotoxic drugs.

The accuracy of drug-sensitivity assays for neoplastic cells depends on the ability to sustain cell survival in vitro, but cells in most cases of acute lymphoblastic leukemia (ALL) rapidly die by apoptosis in culture. We recently reported that allogeneic bone marrow stromal layers support long-term culture of ALL cells. We now describe the standardization of a novel drug-sensitivity assay for ALL lymphoblasts maintained on stromal layers, in which the viability of treated and untreated cells is compared using flow cytometry. Cultures were performed in U-bottomed 96-well plates: 2 x 10(4) stromal cells per well produced rapidly confluent layers which supported the survival of ALL blasts. In four ALL cases studied, 68.8-106% (median 94.8%) of the lymphoblasts originally seeded were recovered after 7 days of culture, in contrast to < 5% recovered in the absence of stroma. Sensitivity to five antileukemic drugs was tested at the indicated concentrations: vincristine (0.001-1 microgram/ml); dexamethasone (0.001-100 microM); 6-thioguanine (0.078-20 micrograms/ml); teniposide (0.001-10 microM); cytosine arabinoside (0.039-10 microM). After 4 days of culture, cells were labeled with CD19 monoclonal antibody and analyzed by flow cytometry. The concentration of each antileukemic agent producing 50% cytotoxicity (LC50) was determined for each patient by fitting a sigmoid model to the drug concentrations versus percentage viability data. Clinically relevant drug concentrations produced cytotoxic effects, and ALL blast sensitivity varied considerably among patients. We conclude that this is an informative method of systematically evaluating drug sensitivity in ALL patients.

Adolescent