Pharmacokinetic study of busulfan in an AML patient treated with regular hemodialysis.
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Busulfan↗
Biomedical subjects
M Ogasawara
Publications and source records attributed to M Ogasawara.
Activated partial thromboplastin time is a predictive parameter for further miscarriages in cases of recurrent fetal loss.
OBJECTIVE: To determine whether clinically routine clotting tests such as activated partial thromboplastin time (aPTT), prothrombin time (PT), or fibrinogen can be used to predict further miscarriages. DESIGN: Prospective study. SETTING: Nagoya City University Hospital, Nagoya, Japan. PATIENT(S): A total of 261 patients with a history of two consecutive first-trimester spontaneous abortions who had no antiphospholipid antibodies or other autoimmune diseases and no anatomic anomalies were examined for aPTT, PT, and fibrinogen before becoming pregnant again. INTERVENTION(S): Blood tests were performed before pregnancy. Patients then were followed up during subsequent pregnancy and their outcomes were compared with their previous blood test results. MAIN OUTCOME MEASURE(S): Activated partial thromboplastin time, PT, and fibrinogen were measured by coagulation time methods. RESULT(S): Fifty-eight of 261 patients (22.2%) had a subsequent miscarriage. Mean (+/-SD) values for preconception aPTT in individuals whose subsequent pregnancies ended in success and failure were 88.2%+/-23.4% and 99.3%+/-26.4%, respectively. The difference was statistically significant. Respective values were 106.8%+/-22.8% and 106.3%+/-21.4% for PT and 245+/-61.1 mg/dL and 259.1+/-57 mg/dL for fibrinogen. These findings were not significantly different. CONCLUSION(S): A shortened aPTT before conception is associated with further miscarriages in patients with a history of recurrent spontaneous abortions who have no antiphospholipid antibodies.
Abortion, Habitual↗
Recurrent abortion and moderate or strong antiphospholipid antibody production.
OBJECTIVE: To investigate the treatment outcome for women suffering recurrent miscarriages associated with strong or moderate antiphospholipid antibody (aPL) production. METHODS: Sixty-seven pregnancies in 61 women demonstrating at least one kind of aPL with a history of recurrent miscarriages were treated with: (1) aspirin (ASA) alone; (2) prednisolone (PSL) and ASA; and (3) PSL, ASA, heparin and/or immunoglobulin (IgG). For comparison purposes the aPL-positive patients were divided into two groups, strongly and moderately-positive. IgG and IgM antibodies against PE and five negatively-charged phospholipids were measured by ELISA between 1987 and 1993. Beta2-glycoprotein I (beta2GPI) dependent anticardiolipin antibodies were measured by ELISA since 1993. Lupus anticoagulant was measured by a diluted aPTT method since 1993. RESULTS: Out of a total of 16 (50%) patients strongly-positive for aPL and 47 out of 51 (92.2%) moderately-positive demonstrated a successful outcome. The live birth rate moderate group was significantly higher than in the strongly-positive cases (P < 0.0005). In the cases exhibiting moderate aPL production, 28 out of 30 (93.3%) receiving PSL and ASA and 14 out of 15 (93.3%) treated with ASA alone successfully gave birth. None of the 14 given ASA alone suffered preterm delivery or IUGR. In contrast 12 (36.4%) and 6 (18.2%) of the 33 patients treated with the PSL combination therapy suffered from preterm delivery and IUGR, respectively. CONCLUSIONS: The live birth rate in patients strongly positive for aPL is lower than that in patients with moderate aPL production even if treatment is performed during pregnancy. However, ASA is useful to treat cases with moderate aPL so that distinction of the two groups is warranted.
Abortion, Habitual↗
Establishment of a novel cell line (TS-2) of pre-B acute lymphoblastic leukemia with a t(1;19) not involving the E2A gene.
The t(1;19)(q23;p13) translocation involving the E2A gene on chromosome 19p13.3 is a nonrandom translocation that is often seen in childhood pre-B-cell acute lymphoblastic leukemia (ALL). However, recent studies have demonstrated the presence of immunophenotypic and molecular heterogeneity among patients with the cytogenetically identical chromosome translocation. Here we report a novel pre-B ALL cell line, TS-2, with t(1;19) translocation not involving the E2A gene. The breakpoint of t(1;19) in TS-2 was demonstrated to be at 19p13.3, a region indistinguishable from the locus of the E2A gene, by cytogenetic study and fluorescence in situ hybridization. However, rearrangement of the E2A gene was not detected in TS-2 by Southern blot analysis. Moreover, the expressions of PBX1 or E2A/PBX1 fusion genes were not detected by an extensive study with Northern blot analysis and reverse transcription-polymerase chain reaction. These findings suggest that TS-2 may have a genetic abnormality involving uncharacterized gene(s) at 19p13.3 distinct from the E2A gene and, therefore, may be useful for investigating the heterogeneity of molecular pathogenesis in leukemias with t(1;19)(q23;p13) translocation.
Adenovirus E2 Proteins↗
Maternally localized RNA encoding a serine/threonine protein kinase in the ascidian, Halocynthia roretzi.
Maternally localized cytoplasmic determinants play important roles in the embryogenesis of many animals, including ascidians. Cytoplasmic determinants are particularly important in the determination of cell fates, and in the establishment of the embryonic axes. Ascidians, which show mosaic development, are good models for the study of maternal cytoplasmic determinants. Here we report the isolation and characterization of HrPOPK-1 (Halocynthia roretzi posterior protein kinase-1), a putative protein serine/threonine kinase. HrPOPK-1 cDNA was obtained from a Halocynthia roretzi fertilized egg cDNA library by screening for localized RNAs using whole-mount in situ hybridization. HrPOPK-1 mRNA is strongly localized at the posterior pole of embryos. The pattern of HrPOPK-1 mRNA localization during early embryogenesis is identical to that of HrWnt-5 in Halocynthia roretzi, and to those of the posterior end mark (pem) transcripts of Ciona savignyi. In addition, HrPOPK-1 shows zygotic expression in neural tissues at the tailbud stage. These results show that the temporal regulation of HrPOPK-1 transcription is complex.
Amino Acid Sequence↗
Effect of N-methyl-D-aspartate and potassium on striatal monoamine metabolism in immature rat: an in vivo microdialysis study.
Effects of N-methyl-D-aspartate (NMDA) and potassium on 5-day-old rat's brain were examined. We measured extracellular striatal monoamines such as dopamine (DA), 3,4 dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole-3-acetic acid (5-HIAA) using intracerebral microdialysis. After 3 h stabilization, pups received varying concentrations of NMDA (1-3 mM) and potassium (200-800 mM) by intrastriatal perfusion for 32 minutes. Increasing the concentration of NMDA and potassium induced a dose related DA increase (p < 0.001), whereas DOPAC, HVA, and 5-HIAA decreased significantly. Five days later the same animals were sacrificed and the weight reduction of their cerebral hemispheres was measured. The weight of the drug perfused side was significantly reduced compared with that of the contralateral one. We examined next the relationship between the level of maximum DA and the relative hemisphere weight reduction. The DA peak was highly correlated with the hemisphere weight reduction (r = 0.70, n = 52, p < 0.001 in the NMDA group, r = 0.83, n = 30, p < 0.001 in the potassium group, respectively). These data show that each treatment alter striatal monoamine metabolism in immature rat brain and that the extracellular DA peak is a potential early indicator to estimate brain injury.
3,4-Dihydroxyphenylacetic Acid↗
Isolation and characterization of endostyle-specific genes in the ascidian Ciona intestinalis.
The endostyle is a special organ in the pharynx of Urochordata, Cephalochordata, and Cyclostomata. It may have arisen in the common ancestor of these taxa, along with a shift to internal feeding for extracting suspended food from the water. In addition, the endostyle has a functional homology to the vertebrate thyroid gland. The endostyle is therefore one of the structures key to the understanding of the origin and evolution of chordates. In the present study, we isolated and characterized cDNA clones for four endostyle-specific genes, CiEnds1, CiEnds2, CiEnds3, and CiEnds4, of the ascidian Ciona intestinalis. Although the predicted amino acid sequences of the gene products CiENDS1, CiENDS2, and CiENDS3 showed no similarity to known proteins, their mean hydropathy profiles suggest that they are secretory proteins. In addition, CiENDS3 contained a unique repeat of 10 amino acids [R(QPCI)-(RRPC)I]. CiEnds1 and CiEnds2 were expressed in zone 6, a protein-secreting glandular element of the endostyle, and CiEnds3 was expressed in zone 2, another secretory zone. CiEnds4, a cytoplasmic actin gene, was predominantly expressed in zones 3 and 5, which are supporting elements of the endostyle. The amino acid sequences of CiENDS1 and CiENDS2 resembled each other. In addition, they resembled a zone-6-specific gene product (HrENDS2) of another ascidian, Halocynthia roretzi. The results suggest that these genes are conserved among ascidian species, and therefore they (as well as CiEnds3 for the protein with a unique motif) may be useful probes for further analyses of molecular mechanisms involved in endostyle development.
Amino Acid Sequence↗
Postpartum thrombosis after a successful pregnancy in a recurrent aborter strongly positive for antiphospholipid antibodies.
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Abortion, Habitual↗
Psychosocial factors in recurrent miscarriages.
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Abortion, Habitual↗
HrWnt-5: a maternally expressed ascidian Wnt gene with posterior localization in early embryos.
Ascidians show a highly determinate mode of development. In particular, components of the posterior-vegetal cytoplasm of fertilized eggs are responsible for the establishment of the embryonic axis. Recent studies have, however, also revealed significant roles of cell-cell interactions during embryogenesis. Proteins encoded by the Wnt family of genes act as signals and have been shown to play important roles in a wide range of developmental processes. Here we have isolated and characterized an ascidian Wnt gene, HrWnt-5, from Halocynthia roretzi. HrWnt-5 mRNA is present in the vegetal cortex in unfertilized eggs. After fertilization, HrWnt-5 mRNA moves to the equatorial region to form a crescent-like structure, after which the mRNA is concentrated in the posteriormost region of the embryo. This early pattern of HrWnt-5 mRNA localization coincides with another posterior-vegetally localized mRNA, pem, isolated from Ciona savignyi. In the gastrula, the zygotic HrWnt-5 mRNA is found in a variety of blastomeres, suggesting multiple roles of the gene.
Amino Acid Sequence↗
[Unilateral gustatory disturbance by pontine infarction].
We reported a case of pontine infarction presenting as diminished taste on the contralateral side. A 67-year-old man was hospitalized with a sudden onset of right hypogeusia. No neurological abnormalities were found except diminished taste in the areas innervated by the chorda tympani, greater petrosal and glossopharyngeal nerves on the right side. Brain MRI demonstrated a lesion with low-intensity on T1-weighted images and high-intensity on T2-weighted images in the left suprapontine tegmentum. Cases of pontine disease presenting as contralateral dysgeusia have rarely been reported. In the present case, we considered that infarction occurred superior to the pontine taste are (PTA). It is suggested that the gustatory pathway superior to PTA takes a chiasmal tract ascending in the brainstem.
Cerebral Infarction↗
[Treatment of aplastic anemia with anti-thymocyte globulin and cyclosporine].
Antithymocyte globulin (ATG) is an effective immunosuppressive therapy for aplastic anemia (AA). We administered ATG combined with cyclosporine (CyA), to 9 patients (4 men and 5 women; median age, 55 years). AA was severe in 8 patients and moderate in 1. The ATG and CyA regimen was the initial treatment for 3 patients, but sequential treatment for the other 6, who were refractory to other agents. Peripheral T lymphocytes, including CD4-positive and CD8-positive cells, decreased rapidly after treatment. Although 1 patient died of pulmonary hemorrhage during the 6-month period following treatment with this combined regimen, 3 showed a favorable response, 2 moderate response, and 3 no response at all. Adverse drug reactions, including transient fever and rash, were not severe. These findings suggested that ATG and CyA in combination are a safe and effective immunosuppressive regimen for initial and refractory patients with AA.
Adult↗
[Case of hepatocellular carcinoma due to interferon therapy of chronic hepatitis C].
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Aged↗
Differential effect of intestinal neuropeptides on invasion and migration of colon carcinoma cells in vitro.
We investigated the effect of neuropeptides, which are vasoactive intestinal polypeptide (VIP), substance P, (SP), neuropeptide Y (NPY), neurokinin A (NKA), somatostatin (SOM), calcitonin gene-related peptide (CGRP), and leucine-enkephalin (L-ENK), on the invasion of murine Colon 26-L5 adenocarcinoma cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. VIP, SP, NPY, and L-ENK reduced invasive potential of tumor cells in a concentration-dependent manner, whereas SOM, CGRP, and NKA had no effect. Especially, VIP showed the most effective in inhibiting tumor invasion, and achieved 50% reduction at 10(-6) M. A similar effect by VIP was also observed in cell migration to fibronectin. VIP had no effect on the growth of tumor cells at the concentrations ranging from 10(-10) to 10(-6) M. The suppressed ability of the tumor cell motility by VIP (10(-6) M) was practically recovered by co-treatment with 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor. These results indicate that VIP, among the neuropeptides used, could inhibit Matrigel invasion of Colon 26-L5 carcinoma cells through partial suppression of their motility, and the reduction was associated with an intracellular cAMP-mediated pathway.
Adenocarcinoma↗
Are serum progesterone levels predictive of recurrent miscarriage in future pregnancies?
OBJECTIVE: To examine the predictive value of midluteal serum P as a marker of a luteal phase defect (LPD) in future pregnancies of recurrent aborters. DESIGN: Prospective analysis. SETTING: Nagoya City University Hospital. PATIENT(S): One hundred ninety-seven women with a history of two consecutive first trimester abortions, none of whom had any other medical problems or an identifiable cause of recurrent miscarriages, such as uterine anomalies or evidence of antiphospholipid antibodies. None of the study subjects received any medication for miscarriage or infertility. MAIN OUTCOME MEASURE(S): A midluteal phase single serum P level < 10 ng/mL was used as the criterion for a potential LPD: those whose subsequent pregnancy was successful and those in which failure was the end result. RESULT(S): Of the 197 patients, 46 (23.4%) demonstrated LPD without other endocrine abnormalities and 38 (19.3%) recurrent aborters suffered another abortion, with figures for LPD-negative and LPD-positive patients of 20.5% (31/151) and 15.2% (7/46), respectively. There was no statistically significant difference between the two groups. CONCLUSION(S): Progesterone, E2, and the P/E2 ratio may not predict future pregnancy loss in recurrent aborters.
Abortion, Habitual↗
Clinical trial of immunostimulation with a biological response modifier in unexplained recurrent spontaneous abortion patients.
We determined clinically whether a killed streptococcal preparation (KSP), a biological response modifier, is as effective as paternal lymphocyte immunotherapy for unexplained recurrent pregnancy abortion (RSA) therapy. The success rate of adverse pregnancy in the study group of 23 RSA cases, who were administered low doses of KSP before and during early pregnancy, was statistically compared with that in a control group of 205 women who received paternal lymphocyte immunotherapy. The association of natural killer (NK) cell activity in the peripheral blood with pregnancy outcome was also assessed. The success rate in the study group was 73.9% (17/23), compared to 75.1% (154/ 205) observed for the controls (not significant). Most of the successful cases exhibited low levels of NK cell activity in the peripheral blood. Immunotherapy with low doses of KSP is as effective as that with paternal lymphocytes, providing a simple and safe alternative therapy for unexplained RSA. Suppression of NK cell activity by some immunoregulatory mechanism was also found to have potential benefit in terms of a successful pregnancy outcome.
Abortion, Habitual↗
Low serum M-CSF levels are associated with unexplained recurrent abortion.
PROBLEM: The purpose of this study was to determine whether the serum macrophage-colony stimulating factor (M-CSF) level is associated with early pregnancy loss in unexplained recurrent spontaneous abortion (RSA) patients. METHOD: We therefore compared preconceptional serum M-CSF levels between unexplained RSA patients and controls. The former comprised 44 bed-rest therapy patients and 43 intradermal immunization (IDI) patients receiving paternal lymphocyte therapy, who had experienced two and three or more consecutive first-trimester pregnancy losses, respectively. The controls were 46 healthy non-pregnant women. We also prospectively studied the association between M-CSF levels during pregnancy and adverse pregnancy outcomes. Sera from a total of 31 pregnant women, including 16 of the bed-rest therapy group and 15 of the IDI therapy group, were collected at the 4th, 6th, and 8th gestational weeks and were measured for M-CSF levels, using the enzyme-linked immunoadsorbent assay (ELISA) method established by Hanamura et al. RESULTS: Serum M-CSF levels were significantly lower in the non-pregnant RSA patients (460.0 +/- 185.6 U/ml; mean +/- SD) than in the control group (726.5 +/- 134.0 U/ml) and also were lower at the 8th, but not the 4th or 6th gestational week in those patients of both the bed-rest and IDI therapy groups whose outcome was pregnancy failure. CONCLUSION: Thus a low level of serum M-CSF was found to be associated with unexplained recurrent pregnancy loss in both the preconceptional and conceptional phases. These results raise the possibility that M-CSF may play an important role in the maintenance of pregnancy and that it can be used as a parameter for determining individuals at risk.
Abortion, Habitual↗
Platelet-derived growth factor blocks the cell-cycle transition from the G0 to G1 phase in subcultured angiogenic endothelial cells in rat thoracic aorta.
Platelet-derived growth factor (PDGF)-BB induces tube formation by the differentiating (tube-forming) endothelial cells (EC) of rat thoracic aorta, although PDGF-BB does not affect the proliferative EC (increasing the cell numbers) at the progression phase. These changes in the responses to PDGF-BB were due to the phenotype-dependent expression of PDGF beta-receptor (PDGFR-beta) on EC because PDGFR-beta-like immunoreactivity was observed in the angiogenic EC forming a tube-like structure in 35-day culture with 10% fetal bovine serum, but not in the proliferative EC in 5-day culture. To elucidate the functional role of PDGFR-beta in the alteration of EC phenotype, the influence of PDGF-BB on the cell cycle of EC was investigated by flow cytometry. This analysis demonstrates that PDGF-BB blocks the transition from the G0 to G1 phase in the 35-day cultured EC, although no effect was observed on any phases of the cell cycle in 5-day culture. We conclude that 1) PDGFR-beta is expressed in mature angiogenic EC of rat aorta, and 2) PDGF-BB may contribute to promotion of the EC differentiation with tubular morphogenesis by inhibiting cell growth.
Animals↗