20-dicyanomethylene-5,8,11,14-tetraoxa-2,17-dithiabicyclo
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Journal Article↗
Biomedical subjects
A Mori
Publications and source records attributed to A Mori.
Fetal haemodynamic changes in fetuses during fetal development evaluated by arterial pressure pulse and blood flow velocity waveforms.
OBJECTIVE: To study the relation between diameter pulse (pressure pulse) and flow velocity waveforms in the fetal descending aorta in fetuses with intrauterine growth retardation and acceleration. DESIGN: Blood flow through a tubular system can be expressed by the ratio of blood pressure to vascular resistance. Doppler ultrasound and a phase locked loop echo tracking system coupled to a B-mode ultrasonic imager (central frequency 3.5 MHz) were used to assess downstream resistance and change in blood pressure, respectively. SETTING: Tertiary referral unit in a teaching hospital PARTICIPANTS: Serial study between 21 and 40 weeks of 22 women with normally grown fetuses at intervals of four weeks; 25 women with small for gestational age fetuses with uteroplacental insufficiency (high umbilical artery pulsatility index); and six women with large for gestational age fetuses. MAIN OUTCOME MEASURES: We measured the maximum systolic and minimum diastolic diameter of the fetal descending aorta (the pulse amplitude) and then calculated the pulsatile waveform time integral above the least diastolic diameter (pulsatile area) and total waveform time integral (perfusion area). RESULTS: Normal fetal growth was associated with an increase in systolic and diastolic diameters in the fetal descending aorta with advancing gestational age. Pulse amplitude, pulsatile and perfusion areas increased with gestational age. The increased pulse amplitude and increased pulsatile area in association with a decrease of the pulsatility index in the descending aorta during the second trimester suggested that pulse pressure and stroke volume were increased. In the group with intrauterine growth retardation, systolic and diastolic diameters of the descending aorta and perfusion area were within the normal range. Moreover, there was an increase in the diastolic diameter per unit fetal weight and a decrease in the pulsatile area. In the large for gestational age fetuses, there was an increase in the pulse amplitude and pulsatile area. CONCLUSION: These findings suggest that in growth restricted fetuses there is an increase in diastolic pressure and a reduction in stroke volume, while in large for gestational age fetuses there is an increase in the pulse pressure and stroke volume. It is possible that measurement of pressure pulse waveform in relation to Doppler velocity waveform may be used to infer changes of blood flow.
Blood Flow Velocity↗
Long-term administration of oral low-dose topoisomerase II inhibitors, MST-16 and VP-16, for refractory or relapsed non-Hodgkin's lymphoma.
It is known that the topoisomerase II inhibitors, MST-16 (sobuzoxane) and VP-16 (etoposide), are effective for the treatment of lymphoma. Five patients with refractory or relapsed non-Hodgkin's lymphoma (NHL) were treated with a combination of oral MST-16 and VP-16 over a long period. Two patients had severely refractory NHL. The remaining 3 patients could not be treated with intensive chemotherapy because of severe organ dysfunction or a poor hematopoietic reserve. All 5 are alive and well after MST-16 and VP-16 treatment. MST-16 and VP-16 are effective for NHL when intensive chemotherapy is ineffective or contraindicated.
Administration, Oral↗
Acute promyelocytic leukemia with marrow fibrosis at initial presentation: possible involvement of transforming growth factor-beta(1).
Although the occurrence of marrow fibrosis in acute myeloid leukemia has been described, there have been no reports of acute promyelocytic leukemia (APL) associated with marrow fibrosis. Here we describe an APL patient with severe marrow fibrosis at initial presentation. He had the typical manifestations of APL, except for marrow fibrosis. Complete remission was achieved by treatment with all-trans retinoic acid plus chemotherapy, and his marrow fibrosis gradually improved concomitantly with the decrease in leukemic cells. To clarify the mechanism of marrow fibrosis in this patient, we investigated the expression of genes for several cytokines promoting fibrosis by the reverse transcriptase polymerase chain reaction methods. An overexpression of transforming growth factor-beta(1) was noted in his leukemic cells at initial presentation, whereas no increase in expression was observed at the time of relapse when he no longer had marrow fibrosis. These findings suggest that overexpression of transforming growth factor-beta(1) was involved in the development of marrow fibrosis in this APL patient.
Adult↗
Evolution to acute myeloblastic leukemia from chronic neutrophilic leukemia with dysplastic features in granulocytic lineage.
We experienced the case of an 82-year-old man with chronic neutrophilic leukemia (CNL) with dysplastic features in the granulocytic lineage which subsequently progressed to acute myeloblastic leukemia (AML) with myelofibrosis. The patient had hepatosplenomegaly, but there was no evident cause of neutrophilic leukocytosis. The cytogenetic study showed that he had a normal karyotype. Concentrations of the serum granulocyte colony-stimulating factor (G-CSF) were not detectable. Two years after the diagnosis of CNL, blastic transformation to AML occurred with myelofibrosis and significant morphological abnormalities in neutrophils. The blasts were positive for myeloperoxidase, CD33, CD34, and HLA-DR, and the presence of dysplasia within the granulocytic lineage suggested that he had an abnormality at the level of the granulocyte-committed progenitors. Heterogeneous origins of CNL might lead to various clinicopathological features in each case.
Aged↗
IL-5 synthesis by T cells of allergic subjects is regulated at the transcriptional level.
BACKGROUND: IL-5 plays a central role in allergic diseases associated with eosinophilic inflammation. We have previously reported that IL-5 production by peripheral blood mononuclear cells (PBMC) is greatly enhanced in both atopic and nonatopic asthmatics compared to control subjects. METHOD: Concanavalin A (Con A) blast lymphocytes were derived from PBMC of allergic and control subjects. Transcriptional regulation of the IL-5 gene was investigated by transient transfection assay. RESULTS: A significant amount of IL-5 was produced by Con A blast lymphocytes derived from allergic subjects upon stimulation with phorbol ester and Ca(2+) ionophore, whereas the cells derived from control subjects did not produce a detectable amount of IL-5. Production of IL-2 and IL-4 was not significantly different between the two groups. A luciferase reporter plasmid containing the human IL-5 promoter/enhancer region was transcribed by Con A blast lymphocytes derived from allergic subjects, but not by the cells from control subjects, upon activation. CONCLUSION: IL-5 synthesis by nontransformed T cells of allergic subjects is enhanced at the level of gene transcription. Elucidation of the molecular mechanism of IL-5 gene transcription by allergic T cells may delineate the pathogenesis of allergic disease for the future therapeutic intervention.
Adult↗
Pendrin, the protein encoded by the Pendred syndrome gene (PDS), is an apical porter of iodide in the thyroid and is regulated by thyroglobulin in FRTL-5 cells.
Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and thyroid goiter. The thyroid disease typically develops around puberty and is associated with a mild organification defect, characterized by an inappropriate discharge of iodide upon perchlorate stimulation (a positive perchlorate discharge test). The gene (PDS) mutated in Pendred syndrome is expressed in thyroid and encodes a 780-amino acid protein (pendrin) that has recently been shown to function as an iodide/chloride transporter. We sought to establish the location of pendrin in the thyroid and to examine the regulatory network controlling its synthesis. Using peptide-specific antibodies for immunolocalization studies, pendrin was detected in a limited subset of cells within the thyroid follicles, exclusively at the apical membrane of the follicular epithelium. Interestingly, significantly greater amounts of pendrin were encountered in thyroid tissue from patients with Graves' disease. Using a cultured rat thyroid cell line (FRTL-5), PDS expression was found to be significantly induced by low concentrations of thyroglobulin (TG), but not by TSH, sodium iodide, or insulin. This is different from the established effect of TG, more typically a potent suppressor of thyroid-specific gene expression. Together, these results suggest that pendrin is an apical porter of iodide in the thyroid and that the expression and function of both the apical and basal iodide porters are coordinately regulated by follicular TG.
Amino Acid Sequence↗
[Pre-and postoperative arthroscopic and MRI findings in arthroscopic anterior cruciate ligament reconstruction of the knee].
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Anterior Cruciate Ligament↗
Knee functions and a return to sports activity in competitive athletes following anterior cruciate ligament reconstruction.
We investigated knee functions and a return to sports in 50 competitive athlete patients treated with arthroscopic anterior cruciate ligament reconstruction using double-looped STG augmented by woven polyester at a 1-year follow-up. There were 25 males and 25 females with a mean age of 24.3 years (range: 19-39 years). The majority of preinjury sports were basketball, volleyball and soccer. Athletic rehabilitation including agility training and sports-specific training was started at 12 weeks. Fourty patients (80%) was rated as normal or nearly normal on the assessment of International Knee Documentation Commitee postoperatively. Fourty-eight patients (96%) obtained full range of motion, and the mean quadriceps muscle strength of the injured side was 91.3%of that of the uninjured side. As for a return to sports, 46 patients (92%) were able to do fully competitive sports at a mean of 8.1 postoperative months. These results suggest that arthroscopic reconstruction using augmented double-looped STG allows early athletic rehabilitation, and lead satisfactory outcome as well as a reliable and early return to preinjury level of sport activity for the majority of the competitive athlete patients.
Adult↗
Transcriptional regulation of IL-5 gene by nontransformed human T cells through the proximal promoter element.
OBJECTIVE: IL-5 is strongly involved in the eosinophilic inflammation in bronchial asthma and atopic dermatitis. We have previously reported that IL-5 synthesis in atopic and nonatopic asthmatics is significantly enhanced compared to control subjects. T cell IL-5 synthesis is regulated through several transcriptional elements, one of which is the proximal human IL-5 promoter (-62 to -46). The present study was undertaken to delineate the transcriptional regulation through this element using nontransformed human T cells. METHODS: Con A blast lymphocytes which tolerate electroporation were derived from peripheral blood lymphocytes. Luciferase reporter analysis and gel shift analysis were performed. RESULTS: The proximal promoter element is the overlapping binding site for the constitutive binding factor, Oct-1, and the inducible one, AP-1. The transcriptional induction was ascribed to the inducible binding, while the constitutive binding was rather inhibitory. A mutant element which lost the constitutive binding but retained the inducible binding exerted 3 times more transcriptional activity compared to the wild type element. In contrast, another mutant element which lost the inducible binding and retained the constitutive binding exhibited no transcriptional induction. Gel shift analysis clarified that the inducible binding was more prominent and the constitutive binding was less in IL-5-producing T cells derived from asthma patients compared to IL-5-nonproducing cells derived from control subjects. CONCLUSIONS: The ratio of the inducible/constitutive binding to the proximal promoter element may determine the capacity of human Th cells to transcribe IL-5 gene, and its regulation may control eosinophilic inflammation.
Adult↗
Stabilized plasmid-lipid particles: pharmacokinetics and plasmid delivery to distal tumors following intravenous injection.
A previous study has shown that plasmid DNA can be encapsulated in lipid particles (SPLP, "stabilized plasmid lipid particles") of approximately 70 nm diameter composed of 1,2-dioleoyl-3-phosphatidyl-ethanolamine (DOPE), the cationic lipid N,N-dioleoyl-N,N-dimethylammonium chloride (DODAC) and poly(ethylene glycol) conjugated to ceramide (PEG-Cer) using a detergent dialysis process (Wheeler et al. (1999) Gene Therapy 6, 271-281). In this work we evaluated the potential of these SPLPs as systemic gene therapy vectors, determining their pharmacokinetics and the biodistribution of the plasmid and lipid components. It is shown that the blood clearance and the biodistribution of the SPLPs can be modulated by varying the acyl chain length of the ceramide group used as lipid anchor for the PEG polymer. Circulation lifetimes observed for SPLPs with PEG-CerC14 and PEG-CerC20 were t(1/2) = approximately 1 and approximately 10 h, respectively. The SPLPs are stable while circulating in the blood and the encapsulated DNA is fully protected from degradation by serum nucleases. The accelerated clearance of SPLPs with PEG-CerC14 is accompanied by increased accumulation in liver and spleen as compared to PEG-CerC20 SPLPs. Delivery of intact plasmid to liver and spleen was detected. Significant accumulation (approximately 10% of injected dose) of the long circulating SPLPs with PEG-CerC20 in a distal tumor (Lewis lung tumor in the mouse flank) was observed following i.v. application and delivery of intact plasmid to tumor tissue at approximately 6% injected dose/g tissue is demonstrated.
Animals↗
TGF-alpha as well as VEGF, PD-ECGF and bFGF contribute to angiogenesis of esophageal squamous cell carcinoma.
It has been demonstrated that vascular endothelial growth factor (VEGF) is associated with tumor progression as an angiogenic factor in esophageal squamous cell carcinoma (SCC)s. However, the role of other angiogenic factors such as transforming growth factor-alpha (TGF-alpha), platelet-derived endothelial cell growth factor (PD-ECGF), and basic fibroblast growth factor (bFGF) are still unknown in esophageal SCCs. In this study, we detected the expression of VEGF, TGF-alpha, PD-ECGF and bFGF in tissue specimens from 96 patients with SCC of the esophagus by immunohistochemical staining. To evaluate angiogenesis, endothelial cells were stained immunohistochemically and microvessel density (MVD) was counted in 24 cases. The positive rates for VEGF, TGF-alpha, PD-ECGF and bFGF were 65% (62/96), 67% (64/96), 66% (63/96), and 49% (47/96), respectively. Only TGF-alpha expression had a strong correlation with the average MVD (p=0.0059). However, the MVD increased as the number of positive factors for these 4 factors increased (p=0.0023). The expression of all of these factors significantly correlated to the depth of tumor invasion, and lymph node metastasis. Finally, survival analysis of the patients revealed that VEGF, TGF-alpha, and PD-ECGF were significant prognostic factors. However, multivariate analysis revealed that these factors were not prognostic. Thus, we suggest that TGF-alpha as well as VEGF, PD-ECGF and bFGF may be associated with angiogenesis, and the progression and metastasis of esophageal squamous cell carcinoma.
Adult↗
Enhancement of angiogenesis, tumor growth, and metastasis by transfection of vascular endothelial growth factor into LoVo human colon cancer cell line.
The expression of vascular endothelial growth factor (VEGF), a highly potent angiogenic molecule, is thought to be correlated with the development of colon cancer; however, direct evidence for a role of VEGF in metastasis is lacking. This study was designed to more directly establish the role of VEGF in the growth and metastasis of human colon cancer using a genetically engineered cancer cell line. A stable VEGF gene-transfected human colon cancer cell line, LoVo, was made by genetic manipulation using eukaryotic expression constructs designed to express the complete VEGF121 cDNA in the sense orientation. Transfected clones were screened for VEGF121 mRNA expression by Northern blot analysis and for VEGF121 protein expression by Western blot analysis. Consequently, we obtained S17 cells that expressed a high level of both VEGF mRNA and VEGF protein. A vector-transfected clone (V7 cell) was used as a control. The experiment with the dorsal air sac method revealed that S17 cells elicited a stronger directional out-growth of capillaries than V7 cells. S17 cells formed faster-growing tumors than did V7 cells when xenografted s.c. into nude mice, although there was no significant difference in their in vitro proliferation. Tumors derived from S17 cells had more vascularity, as assessed by counting capillary vessels after staining with factor VIII, than did tumors derived from V7 cells (P < 0.05). With regard to the metastatic potential, S17 cells exhibited a higher capacity for both hepatic metastasis after the splenic portal inoculation and peritoneal dissemination after i.p. injection than did V7 cells. However, S17 cells showed no apparent metastasis, despite their rapid growth after orthotopic implantation. In conclusion, the present study showed clearly that VEGF plays an important role in cancer growth due to stimulation of angiogenesis by accelerating cell growth after reaching the target organs.
Animals↗
Mouse macrophage metalloelastase gene transfer into a murine melanoma suppresses primary tumor growth by halting angiogenesis.
Mouse macrophage metalloelastase (MME) has been associated with the generation of angiostatin, an internal fragment of plasminogen, which inhibits angiogenesis. To clarify whether tumor cells that consistently generate MME can suppress angiogenesis and, therefore, inhibit the growth of primary tumors in vivo, we transfected a cDNA coding for MME into murine B16-BL6 melanoma cells that grow rapidly and are MME deficient. The generation of active MME in MME-transfected clones was confirmed by immunoprecipitation followed by in vitro cleavage of plasminogen. Subcutaneous implantation of these stable clones in C57BL/6 mice inhibited primary tumor growth by an average of 73% (P = 0.00002), which directly correlated with a significant reduction of blood vessel formation (approximately 76%) in such tumors. Microangiography revealed massive angiogenesis in control tumors (mock and vector); however, in MME-transfected primary tumors it demonstrated a decreased and disrupted vascular network. Western blot analysis using a specific anti-mouse angiostatin antibody demonstrated a strong 38-kDa immunoreactive band in MME-transfected tumors and in the serum of mice bearing those tumor cells. These results show that placing MME gene directly into B16-BL6 melanoma cells is an effective approach to suppress primary tumor growth in vivo because it halts angiogenesis. Our data provide a feasible and promising strategy for gene therapy of cancer by targeting tumor vasculature.
Angiostatins↗
Effects of docarpamine on hemodynamics after open heart surgery in children.
Docarpamine is a dopamine prodrug which has been selected from a large number of dopamine derivatives in order to develop an orally effective dopamine. The pharmacokinetics after oral administration of docarpamine have not yet been studied in children undergoing open heart surgery. This study examined the effects of docarpamine on hemodynamics and evaluated its safety in 11 children undergoing open heart surgery for congenital heart disease. This study began when the patientOs postoperative condition was stabilized by continuous dopamine infusion into the vein at a rate of 5 micro g/kg/min. The patients were administered 40 mg/kg of docarpamine every 8 hours, and hemodynamics were measured every 4 hours for 16 hours after the initial docarpamine administration. Immediately after the initial docarpamine administration, the dose of dopamine was reduced to 3 micro g/kg/min. Infusion of dopamine was stopped 8 hours after the initial docarpamine administration. Systemic systolic and diastolic blood pressure and heart rate showed no significant changes. Mean right atrial pressure decreased 4 hours after docarpamine administration. Mixed venous oxygen saturation and mean velocity of circumferential fiber shortening increased significantly after docarpamine administration. No significant changes were observed in urine volume. All patients could be weaned from dopamine within 8 hours. No changes were observed in ECG, and no arrhythmia-inducing action was noted. Our study indicates that 40 mg/kg oral doses of docarpamine produce plasma dopamine concentration equivalent to those of a 3 to 5 micro g/kg/min dopamine infusion. Our data suggest that docarpamine is a safe and effective drug for children who have undergone open heart surgery.
Cardiac Surgical Procedures↗
Treatment with low-dose cytosine arabinoside followed by administration of macrophage colony-stimulating factor prolongs the survival of patients with RAEB, RAEB-T, or leukemic phase myelodysplastic syndrome: a pilot study.
The treatment of patients with aggressive subclasses of myelodysplastic syndrome (MDS) remains a challenge. In an effort to improve the survival of patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-t), or acute myelogenous leukemia transformed from MDS (MDS-AML), we conducted a small trial in which 28 such patients were treated with low-dose cytosine arabinoside (LDAraC) followed by administration of macrophage colony-stimulating factor (M-CSF). The overall rate of response to the treatment was 61%, including 39% with a complete response, which is higher than rates obtained in previous studies in which LDAraC alone was administered to patients with MDS. Median survival was 23.5 months in cases of RAEB, 16.7 months in cases of RAEB-t, and 19.7 months in cases of MDS-AML. The overall survival of the study group appeared to be prolonged in comparison with a historical control group of patients treated with LDAraC alone. It is suggested that M-CSF added to the administration of LDAraC plays an active role in the therapy. No therapy-related death occurred. Some unique actions of M-CSF were suggested in this trial. It is concluded that therapy with LDAraC + M-CSF is a useful treatment option for patients with aggressive subclasses of MDS and MDS-AML to provide better response and survival.
Adult↗
Proliferation of CD4+ lymphocytes in a patient with chronic graft-versus-host disease after allogeneic bone marrow transplantation.
Expansion of donor-derived lymphocytes after allogeneic stem cell transplantation is a serious and sometimes fatal complication. Lymphoproliferative disorders are reportedly caused mainly by reactivation of Epstein-Barr virus (EBV) and non-EBV-associated secondary lymphoma or leukemia. In this paper, we report massive proliferation of CD4+ lymphocytes in peripheral blood of a patient with chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation (alloBMT) from an HLA-identical sibling donor. The abnormal lymphocytes showed CD3low, CD4+, CD8-, CD2+, CD5+, CD7+, CD25-, CD19-, CD20-, CD21-, CD16-, CD56low, T-cell receptor (TCR)-alpha/beta- and TCR-gamma/delta- phenotypes, and no rearrangement of either TCR-C beta 1 or IG(H)JH was detected from the lymphocytes by Southern blot analysis. EBV was not found in the nuclei of lymphocytes by an immunofluorescence antibody. The lymphoproliferation was resistant against immunosuppressive drugs, administered for the treatment of chronic GVHD, and it effectively inhibited aggravation of the chronic GVHD. Although antithymocyte globulin and cytosine arabinoside were administered later, the patient died of respiratory failure with bilateral pleural effusion and interstitial pneumonia. Because we found no evidence of monoclonality of the abnormal lymphocytes, we could not conclude that this patient had suffered from malignant lymphoproliferation. To our knowledge, this is the first case report of proliferation of CD4+ lymphocytes in a patient with chronic GVHD following alloBMT. In this paper, we discuss the possible pathophysiology of the patient.
Adult↗
The role of screening bronchoalveolar lavage in BMT patients.
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Adolescent↗