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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
PubMed2001

Efficacy of dentin adhesives in primary and permanent teeth.

The purpose of the present study was to investigate the efficacy of dentin adhesives and to examine acid resistance in primary and permanent teeth. The efficacy of dentin adhesives was evaluated by SEM observation and by measuring the wall-to-wall polymerization contraction gap and dentin hardness before and after conditioning. The detailed mechanism of dentin bonding was the same in both primary and permanent teeth.

Acid Etching, Dental↗
PubMed2001

Surfactant protein D and KL-6 as serologic indicators of Pneumocystis carinii pneumonia in a child with acute lymphoblastic leukemia.

Pneumocystis carinii pneumonia (PCP) in immunocompromised patients is one of the important causes of morbidity and mortality. Serum levels of surfactant protein D (SP-D) and KL-6 are useful biomarkers for understanding some pulmonary inflammatory responses in patients with idiopathic pulmonary fibrosis (IPF). We present a child with PCP following bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL), for whom both SP-D and KL-6 in sera were simultaneously measured through the clinical course of PCP. Both serum levels of SP-D and KL-6 were rapidly elevated reflecting some inflammatory processes in the lung that chest X-ray films and CT scans showed as ground-glass attenuations. He died due to respiratory failure 40 days after PCP developed. A combination of the assays for SP-D and KL-6 in sera may be helpful in predicting the treatment results for PCP.

Adolescent↗
PubMed2000

Efficacy and safety of oral estriol for managing postmenopausal symptoms.

OBJECTIVE: to assess the therapeutic efficacy and safety of oral estriol for the treatment of climacteric symptoms in postmenopausal women. METHODS: 68 postmenopausal women with climacteric symptoms received oral estriol, 2 mg/day, daily for 12 months. We evaluated the degree of climacteric complaints with estriol therapy; serum levels of gonadotropins, estradiol (E2) and lipids; biochemical markers of bone metabolism; blood pressure; and side effects both at baseline and during treatment. Climacteric symptoms were assessed according to the menopausal index (MI), a version of the Kupperman index that had been modified for Japanese women. RESULTS: oral estriol therapy significantly reduced total MI scores. The greatest relief was noted for hot flushes, night sweats, and insomnia. Estriol treatment significantly lowered serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations but did not affect any of the other parameters (lipids, bone, liver and blood pressure) during the study period. Slightly vaginal bleeding occurred in 14.3% of those who underwent natural menopausal women. Histologic evaluation of the endometrium and ultrasound assessment of the breasts following 12 months of estriol treatment found normal results in all women. CONCLUSION: Estriol is a safe and effective alternative for relieving climacteric symptoms in postmenopausal Japanese women.

Administration, Oral↗
PubMed2000

Improvement in bronchiolitis obliterans organizing pneumonia in a child after allogeneic bone marrow transplantation by a combination of oral prednisolone and low dose erythromycin.

We report a 13-year-old boy who developed dyspnea at rest 1 year after the occurrence of cGVHD following an allogeneic bone marrow transplant (BMT). Pulmonary function data, imaging studies, lung biopsy, and bronchoalveolar lavage were consistent with the diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP). Although reports suggest that oral methylprednisolone or methylprednisolone pulse therapies improve BOOP after BMT, we treated our patient with a combination of oral prednisolone (1 mg/kg) and low dose erythromycin (10 mg/kg) to avoid the side-effects of high-dose steroids. With this therapy, our patient showed clinical and radiological improvements within 1 week. The steroids were tapered off 12 months later and erythromycin was given for 14 months. We conclude that therapy consisting of a combination of oral prednisolone and low-dose erythromycin for BOOP after BMT may minimize the dose and duration of steroid use.

Administration, Oral↗
PubMed2000

Natural killer cell depletion by anti-asialo GM1 antiserum treatment enhances human hematopoietic stem cell engraftment in NOD/Shi-scid mice.

The scid mutation was backcrossed on to the NOD/Shi mouse background, resulting in the development of NOD/Shi-scid mice, which showed lack of mature lymphocytes, macrophage dysfunction and absence of circulating complement, but were not as impaired in natural killer (NK) cell activity as NOD/LtSz-scid mice. We then examined the effect of recipient NK cell depletion by anti-asialo GM1 antiserum on the repopulation of human cord blood (CB) hematopoietic stem cells (HSC) in NOD/Shi-scid mice to clarify the role of recipient NK cells in human HSC engraftment. The anti-asialo GM1 antiserum treatment significantly enhanced the engraftment of CB CD34+ cells, but did not affect the differentiation of the engrafted HSC into each hematopoietic lineage. The NK cell depletion was effective at early stages of the engraftment, but not 3 weeks after the transplantation. The anti-asialo GM1 antiserum treatment did not improve the engraftment by human HSC in scid mice which lack mature lymphocytes, but show neither macrophage dysfunction nor a reduction in circulating complement, indicating that macrophages and/or complement also have roles in HSC graft rejection. The present study indicates that the preconditioning targeting of recipient NK cells in addition to T cell suppression and myeloablation might prevent HSC graft failure, and that NOD/Shi-scid mice treated with anti-asialo GM1 antiserum could provide a useful tool for evaluating the repopulating ability of transplantable human HSC.

Animals↗
PubMed2000

Long-term follow-up of childhood acute lymphoblastic leukemia in Tokyo Children's Cancer Study Group 1981-1995.

The objectives were as follows: Firstly, to estimate the overall probability of event-free survival (EFS) and isolated CNS relapse in the studies for children with acute lymphoblastic leukemia (ALL) during the 1980s and 1990s. Secondly, to report the EFS according to presenting features and lineage. Thirdly, to evaluate the treatment results re-classified by the risks of NCI criteria. Four consecutive protocol studies were performed in the Tokyo Children's Cancer Study Group: L81-10 protocol (1981-1984, 189 patients), L84-11 (1984-1989, 484 patents), L89-12 (1989-1992, 418 patients) and L92-13 (1992-1995, 347 patients). Overall EFS at 5 years in each protocol was 56.5 +/- 3.8(1 s.e.)%, 71.0 +/- 2.1%, 67.8 +/- 2.3%, and 63.4 +/- 2.7%, respectively. The cumulative isolated CNS relapse rate at 5 years was 8.1 +/- 2.1%, 3.5 +/- 0.9%, 3.6 +/- 1.0%, 1.0 +/- 0.6. The EFS in SR/HR (standard risk/high risk) according to the NCI criteria in B-precursor ALL at 5 years was 61.9 +/- 4.3%/41.4 +/- 7.4% (lineage was not confirmed.), 72.5 +/- 2.6%/63.4 +/- 5.0%, 77.4 +/- 2.7%/56.3 +/- 4.7%, and 67.8 +/- 3.4%/56.7 +/- 5.4% in each protocol. Also EFSs according to NCI SR/HR at 5 years of T-ALL in protocols L84-11, L89-12 and L92-13 were 55.6 +/- 16.6%/60.9 +/- 10.1%, 72.7 +/- 13.4%/51.6 +/- 9.1%, and 77.1 +/- 14.4%/53.6/10.1%, respectively. The truncation of maintenance therapy to 6 months resulted in a decreased EFS in L92-13, particularly due to an increase of bone marrow relapse after cessation of therapy in SR and HR. The NCI risk criteria work properly even in the patients treated by different intensities, so that it makes the comparison possible among the patients in various groups. The overall EFSs in childhood ALL improved in 1980s, but it seemed stable or decreased in 1990s. The short maintenance therapy resulted in poor outcome in SR on the L92-13 protocol. Many of these late relapsers were effectively rescued and overall survival remained at a high level. The proportion of patients who received cranial irradiation reduced without any increase of the CNS events.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Exclusive expression of G-CSF receptor on myeloid progenitors in bone marrow CD34+ cells.

Although granulocyte colony-stimulating factor (G-CSF) has been reported to act on cells of neutrophilic lineage, the administration of G-CSF to induce the mobilization of various haematopoietic progenitors into the circulation. We analysed the expression of receptors for G-CSF (G-CSFR) on human bone marrow and G-CSF-mobilized peripheral blood CD34+ cells, and examined the proliferation and differentiation capabilities of sorted CD34+G-CSFR+ and CD34+G-CSFR- cells using methylcellulose clonal culture. Flow cytometric analysis showed that G-CSFR was expressed on 14.9 +/- 4.9% of bone marrow CD34+ cells, most of which were included in CD34+CD33+ and CD34+CD38+ cell fractions. In clonal cultures, CD34+G-CSFR+ cells produced only myeloid colonies, whereas CD34+G-CSFR- cells produced erythroid bursts, megakaryocyte and multilineage colonies. When incubated with the cytokine cocktail for 5 d, CD34+G-CSFR- cells generated CD34+G-CSFR+ myeloid progenitors. In G-CSF-mobilized peripheral blood, CD34+ cells contained 10.8 +/- 5.8% of G-CSFR+ cells, most of which were also myeloid progenitors, although CD34+G-CSFR- cells contained a substantial number of myeloid progenitors. These results indicated that the expression of G-CSFR on CD34+ cells is restricted to myeloid progenitors, suggesting that the specific activity of G-CSF on myelopoiesis depends on the exclusive expression of its receptor on myeloid progenitors, and that the mobilization of various haematopoietic progenitors is not a direct effect of G-CSF in humans.

Adult↗
PubMed2000

Cytokine requirement for the development of T-lymphoid lineage potential in clonal lymphohaematopoietic progenitors in vitro.

The early process of T-cell development prior to thymic colonization has been poorly investigated because of the lack of a sensitive assay. We have developed a two-step in vitro culture system by combining a clonal culture with a fetal thymus organ culture (FTOC) and analysed the early development of T cells from lymphohaematopoietic progenitors. Cells of immature colonies derived from bone marrow cells of 5-fluorouracil (5FU)-treated mice using various combinations of early acting cytokines were transferred into a FTOC. All the combinations of stem cell factor (SCF), interleukin (IL)-3 and IL-6 capable of inducing colony formation supported T-cell generation. IL-11 and the Flt3 ligand possessed T-lineage promotional effects similar to IL-6 and SCF respectively. However, there were some quantitative differences in the final T-cell yield among cytokine combinations. Thus, the commitment towards T lineage in lymphohaematopoietic progenitors may be an event determined intrinsically rather than induced by specific stimuli, but there may be a hierarchy between the activity of cytokines in further development. Furthermore, we examined the T-lineage potential of individual colonies derived from Lin(-)c-Kit(+)Sca-1(+) cells clone-sorted from post-5FU marrow cells. No colonies that contained only myelocytic progenitors showed T-lineage potential, but 23.3% of colonies with a haematopoietic multipotentiality did. Therefore, the divergence of the T lineage from other lineages such as myeloid potential may occur at an early stage of the hierarchy of haematopoiesis. The proposed method should prove valuable for exploring the molecular and cellular changes that occur during early T-cell development before thymic colonization.

Animals↗
PubMed2000

Safety and efficacy of oestriol for symptoms of natural or surgically induced menopause.

To assess the safety and efficacy of oestriol in relieving post-menopausal symptoms 53 post-menopausal Japanese women with climacteric symptoms, 27 with natural menopause (group I) and 26 with surgically induced menopause (group II), received oral oestriol, 2 mg daily for 12 months. Clinical parameters including Kupperman index (KI) and the degree of satisfaction with symptomatic relief; serum concentrations of oestradiol, FSH and LH; serum lipids; blood pressure; bone mineral density, serum calcium (Ca), alkaline phosphatase (ALP), and urinary Ca were compared between the two groups. Oestriol improved KI in groups I and II by 49 and 80% respectively. Satisfaction with treatment was 85% in group I and 93% in group II. For both parameters, values were significantly different between groups I and II (P < 0.05 for both). Serum concentrations of oestradiol, FSH and LH changed in group I versus group II 6 months after initiation. A significant decrease in serum ALP and Ca/Cr was observed in group I at 6 months. Except for serum triglycerides, oestriol had no significant effect on lipids. Systolic and diastolic blood pressures were significantly decreased in group I at 3 months versus baseline. Slight vaginal bleeding occurred in 14.3% of group I. Histological evaluation of the endometrium in all women of group I and ultrasound assessment of the breasts following 12 months of oestriol treatment found normal results in all women. Therefore, oestriol appeared to be safe and effective in relieving symptoms of menopausal women. The beneficial biochemical effects of oestriol were marked in the natural menopause. Overall, oestriol may serve as a good choice for hormone replacement therapy to protect against other climacteric symptoms in post-menopausal women who do not need medication for osteoporosis or coronary artery disease.

Adult↗
PubMed2000

Pleomorphic angioleiomyoma.

We describe two cases of pleomorphic angioleiomyoma. In one case, a 46-year-old man presented with a single nodule on his scrotum of 1 year's duration, and in another, a 38-year-old woman presented with a single nodule on her right knee of 1 year's duration. In both cases, histopathologic examination showed a well-circumscribed nodule composed of smooth muscle and numerous veins and capillaries. Contrary to the ordinary angioleiomyoma, marked nuclear pleomorphism was noted. Although mitoses were rare, immunohistochemistry revealed many tumor cells that were positive for proliferating cell nuclear antigen, Ki-67, and p53, indicating that the pleomorphic appearance does not simply represent a degenerative change of some tumor cells.

Adult↗
PubMed2000

Subclassification of small-for-gestational-age fetus using fetal Doppler velocimetry.

Our purpose was to determine whether small-for-gestational-age (SGA) fetus can be divided to subclassified groups using fetal Doppler velocimetry. Fifty-four pregnant women with SGA infant delivered after 37 weeks of gestation were studied. After 24 weeks of gestation, fetal middle cerebral artery puslatility index (MCAPI) and umbilical artery pulsatility index (UAPI) were measured at 2- to 3-week intervals using Doppler ultrasound. Perinatal outcomes [operative delivery due to fetal distress, abnormal fetal heart rate (FHR) pattern, meconium staining, low Apgar score (<7), neonatal acidosis (umbilical artery blood pH <7.15), neonatal intensive care unit (NICU) admission due to neonatal asphyxia, and decreased amniotic fluid] were compared in subclassified SGA groups using fetal Doppler velocimetry. The number of SGA fetuses with normal MCAPI and UAPI (normal SGA group) was 39, and those with significantly low MCAPI but normal UAPI (eventful SGA group) 15, respectively. Birth age and birth weights in the eventful SGA group were significantly earlier and lower than those in the normal SGA group, respectively (p < 0.05, and p < 0.005). There were significant increases in operative deliveries, abnormal FHR patterns and decreased amniotic fluid in eventful SGA group, when compared with events related to normal SGA group. However, there were no significant differences in meconium staining of amniotic fluid, low Apgar score, neonatal acidosis, and NICU admission between the two groups. These results suggest that SGA fetus with abnormally low MCAPI but normal UAPI has more poor perinatal outcomes, compared with that with normal MCAPI and UAPI.

Adult↗
PubMed2000

Expansion of human NOD/SCID-repopulating cells by stem cell factor, Flk2/Flt3 ligand, thrombopoietin, IL-6, and soluble IL-6 receptor.

Here, we demonstrate a significant ex vivo expansion of human hematopoietic stem cells capable of repopulating in NOD/SCID mice. Using a combination of stem cell factor (SCF), Flk2/Flt3 ligand (FL), thrombopoietin (TPO), and a complex of IL-6 and soluble IL-6 receptor (IL-6/sIL-6R), we cultured cord blood CD34(+) cells for 7 days and transplanted these cells into NOD/SCID mice. Bone marrow engraftment was judged successful when recipient animals contained measurable numbers of human CD45(+) cells 10-12 weeks after transplantation. When cells were cultured with SCF+FL+TPO+IL-6/sIL-6R, 13 of 16 recipients were successfully engrafted, and CD45(+) cells represented 11.5% of bone marrow cells in engrafted recipients. Cells cultured with a subset of these factors were less efficiently engrafted, both as measured by frequency of successful transplantations and prevalence of CD45(+) cells. In animals receiving cells cultured with all 4 factors, human CD45(+) cells represented various lineages, including a large number of CD34(+) cells. The proportion of CD45(+) cells in recipient marrow was 10 times higher in animals receiving these cultured cells than in those receiving comparable numbers of fresh CD34(+) cells, and the expansion rate was estimated at 4.2-fold by a limiting dilution method. Addition of IL-3 to the cytokine combination abrogated the repopulating ability of the expanded cells. The present study may provide a novel culture method for the expansion of human transplantable hematopoietic stem cells suitable for clinical applications.

Animals↗
PubMed2000

Six months of maintenance chemotherapy after intensified treatment for acute lymphoblastic leukemia of childhood.

PURPOSE: We postulated that intensification of chemotherapy immediately after remission induction might reduce the leukemic cell burden sufficiently to allow an abbreviated period of antimetabolite therapy. PATIENTS AND METHODS: Three hundred forty-seven children (ages 1 to 15 years) with previously untreated acute lymphoblastic leukemia (ALL) were enrolled onto the Tokyo L92-13 study, which excluded patients with mature B-cell ALL and patients less than 1 year old. One hundred twenty-four patients were classified as standard risk, 122 as high risk, and 101 as extremely high risk, according to age, peripheral-blood leukocyte count, selected genetic abnormalities, and immunophenotype. All subjects received four drugs for remission induction, followed by a risk-directed multidrug intensification phase and therapy for presymptomatic leukemia in the CNS. Maintenance chemotherapy with oral mercaptopurine and methotrexate was administered for 6 months, with all treatment stopped by 1 year after diagnosis. RESULTS: The mean (+/- SD) event-free survival (EFS) and overall survival rates for all patients were 59.5% +/- 3.4% and 81.5% +/- 2.2%, respectively, at 5. 5 years after diagnosis. EFS rates by risk category were similar (60. 2% +/- 6.0% for standard risk, 57.7% +/- 5.6% for high risk, and 62. 5% +/- 5.7% for extremely high risk), whereas overall survival rates differed significantly (91.2% +/- 2.7%, 80.0% +/- 4.1%, and 72.1% +/- 4.5%, respectively, P <.0001 by the log-rank test). There were 107 relapses. Eighty-five (79.4%) of these 107 patients achieved second complete remissions, with subsequent EFS rates of 61.5% +/- 7. 9% (standard risk), 42.6% +/- 8.1% (high risk), and 9.6% +/- 6.4% (extremely high risk). Of the five risk factors analyzed, only the response to prednisolone monotherapy among extremely high-risk patients proved important. CONCLUSION: Early treatment intensification did not compensate for a truncated phase of maintenance chemotherapy in children with standard- or high-risk ALL. However, 6 months of antimetabolite treatment seemed adequate for extremely high-risk patients who were good responders to prednisolone and received intensified chemotherapy that included high-dose cytarabine early in the clinical course.

Adolescent↗
PubMed2000

Detection of bisphenol-A in dental materials by gas chromatography-mass spectrometry.

The xenoestrogenic substance bisphenol-A is widely used as a synthetic precursor of resin monomers, such as bisphenol-A diglycidyl methacrylate. Reports describing the release of bisphenol-A from polymerized resin into saliva have aroused considerable concern regarding exposure to xenoestrogen by dental treatment. The purpose of the present study was to demonstrate a reliable methodology of detecting the trace amounts of bisphenol-A in dental materials. Bisphenol-A was separable from bisphenol-A diglycidyl methacrylate, which is often employed as the principal dimethacrylate monomer, by selective extraction with a Sep-Pak C18 cartridge. Using this extraction method in combination with a gas-chromatography mass-spectrometry, we have obtained evidence that all unpolymerized materials used in this study were contaminated with bisphenol-A. Quantitative analysis using a deuterium-labeled compound as an internal standard revealed bisphenol-A contents in commercial dental materials ranging from < 1 microgram/g material to about 20 micrograms/g material. The polymerized dental materials released up to 91.4 ng bisphenol-A/g material into phosphate buffered saline during 24-h incubation. These results indicate that bisphenol-A can be released from dental materials, however the leachable amount would be less than 1/1000 of the reported dose (2 micrograms/kg body weight/day) required for xenoestrogenisity in vivo.

Benzhydryl Compounds↗
PubMed2000

Massive pericardial and pleural effusion with anasarca following allogeneic bone marrow transplantation.

A 10-year-old girl presented with massive pericardial/pleural effusion with anasarca 216 days after an allogeneic bone marrow transplantation from her HLA-matched sibling for relapsed acute lymphoblastic leukemia. She did not show any other symptoms of chronic graft-versus-host disease (GVHD). The antinucleolar antibody was elevated in the blood and the pleural fluid. The lymphocytes in the fluid were mostly CD8+/HLA-DR+, and a majority of CD8+ cells in the blood expressed CD57. These data suggested that she had chronic GVHD. Immunosuppressive therapy including prednisolone, cyclosporin A, high-dose methylprednisolone, tacrolimus (FK506), and methotrexate had no effect, and the patient died of Aspergillus pneumonia 183 days after the presentation of the disease. Although it has not been described before, isolated serositis with edema should be recognized as a clinical feature of chronic GVHD.

Antigens, CD↗
PubMed2000

Second International Symposium on Myelodysplastic Syndromes in Childhood.

This article summarizes presentations from the Second International Symposium on Myelodysplastic Syndromes in Childhood, May 11 to 14, 2000, in Funen, Denmark. Topics included epidemiology, pathology, pathophysiology, cytogenetics, congenital neutropenia, transplantation, and classification. Dr. Henrik Hasle was the Meeting Chair and Dr. Gitte Kerndrup was the Co-Chair.

Adolescent↗
PubMed1999

Differential effects of human granulocyte colony-stimulating factor (hG-CSF) and thrombopoietin on megakaryopoiesis and platelet function in hG-CSF receptor-transgenic mice.

Granulocyte-colony stimulating factor (G-CSF) has been found to act on the neutrophilic lineage. We recently showed that human G-CSF (hG-CSF) has effects similar to early-acting cytokines such as interleukin-3 (IL-3) in the development of multipotential hematopoietic progenitors in transgenic (Tg) mice expressing receptors (R) for hG-CSF. In the present study, we examined the effects of hG-CSF on more mature hematopoietic cells committed to megakaryocytic lineage in these Tg mice. The administration of hG-CSF to the Tg mice increased the numbers of both platelets in peripheral blood and megakaryocytes in the spleen, indicating that hG-CSF stimulates megakaryopoiesis in the Tg mice in vivo. The stimulatory effect of hG-CSF was also supported by the results of studies in vitro. hG-CSF supported megakaryocyte colony formation in a dose-dependent fashion in clonal cultures of bone marrow cells derived from the Tg mice. Direct effects of hG-CSF on megakaryocytic progenitors in the Tg mice were confirmed by culture of single-cell sorted from bone marrow cells. hG-CSF showed a stronger effect on maturation of megakaryocytes in the Tg mice than that of IL-3 alone, but weaker than that of TPO alone. In addition, hG-CSF induced phosphorylation of STAT3 but not Jak2 or STAT5, while TPO induced phosphorylation of both. In contrast to TPO, hG-CSF did not enhance ADP-induced aggregation. Thus, hG-CSF has a wide variety of functions in megakaryopoiesis of hG-CSFR-Tg mice, as compared with other megakaryopoietic cytokines, but the activity of hG-CSF in megakaryocytes and platelets does not stand up to a comparison with that of TPO. Specific signals may be required for the full maturation and activation of platelets.

Animals↗