[Randomized controlled study of very low-dose Ara-C versus low-dose aclarubicin for the treatment of myelodysplastic syndrome].
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Aclarubicin↗
Biomedical subjects
M Harada
Publications and source records attributed to M Harada.
[Quantitative measurements of cerebral blood flow using 99mTc-ECD radionuclide angiography, SPECT and one-point arterial sampling].
We quantified regional cerebral blood flow using 99mTc-bicisate ethyl cysteinate dimer (ECD) radionuclide (RN) angiography, one-point arterial sampling and static SPECT in 12 patients. The tracer was injected as a bolus into the right antecubital vein, and time-activity curves over the cerebrum and the aortic arch were sequentially recorded for 300 s with 3 s intervals in a 128 x 128 format with a large-field of view gamma camera equipped with a low-energy collimator. Blood was obtained from the femoral artery immediately after stopping the RN angiography and the arterial concentration of 99mTc-ECD was calculated. Thereafter, the SPECT data acquisition was started with the subject's head immobilized. We applied a three-compartment kinetic model: The influx constant of 99mTc-ECD from blood to brain (K1) and the transfer of ECD from diffusible compartment to nondiffusible one in the blood (k5). The K1 value was compared with the global cerebral blood flow value (Fa) measured by the 133Xe clearance technique. From the kinetic analysis, the following parameter values could be calculated: K1 = 0.21 +/- 0.05 (ml/ml/min), k5 = 0.66 +/- 0.15 (/min), Fa = 0.32 +/- 0.09 (ml/ml/min) and the extraction fraction E = K1/Fa = 0.65 +/- 0.05. There was a strong correlation between K1 and Fa (Y = 0.53X + 3.7; rs = 0.91). By combining the K1 and E values in the whole-brain, we can obtain the absolute global flow value and regional 99mTc-ECD CBF maps if the average concentration of the tracer in the whole-brain is used as a reference. Our method is less invasive and suitable for quantitation of cerebral blood flow in patients with brain disorders.
Aged↗
[Myocardial metastasis in the right ventricle from uterine cervical carcinoma with high 67Ga-citrate accumulation: a case report].
We report a case of high 67Ga-citrate accumulation with myocardial metastasis in the right ventricle from uterine cervical carcinoma. A 41-year-old woman was admitted to our hospital because of acute abdomen after operation and radiotherapy for uterine cervical carcinoma. On performing 67Ga-scintigraphy for differentiation from fever of unknown origin, we found significant 67Ga-citrate accumulation in the right ventricle. To the best of our knowledge, this is a rare case.
Adult↗
[Phase I study on DMDC].
Phase I study on antimetabolic carcinostatic DMDC was conducted at 16 medical institutions nationwide for patients with various types of malignant tumors. DMDC was administered by intravenous infusion as per the following three schedules: single administration, single repeated administration, and 5-consecutive-day administration. The safety of the compound was examined single administration in 16 patients, by the single repeated administration in 5 patients, and by the 5 consecutive-day administration in 7 patients, for a total of 28 patients. In the single administration trial, 200 mg/m2 (1 n) was given as an initial dose, then increased stepwise to 450 mg/m2 (2.25 n). The single repeated administration trial was conducted at a single dose of 300 mg/m2. One treatment course lasts until recovery from side effects and abnormalities in laboratory test values. As a general rule, the administration was repeated for 2 treatment courses or more. In the 5-consecutive-day administration trial, an initial dose was 30 mg/m2/day (1 n), and increased to 40 mg/m2/day (1.3 n). The dose-limiting factors for both the single and 5-consecutive-day administration trials were decreases in the numbers of leukocytes and neutrophils. The maximum tolerated dose for single administration trial was over 400 mg/m2 (2 n), and for the 5-consecutive-day administration trial 40 mg/m2 (1.3 n). The decrease in the number of leukocytes and neutrophils for both the single administration and 5-consecutive-day administration trial reached its nadir one to two weeks after administration, and recovered in about one week. In the single repeated administration trial, the administration interval for patients who had completed 2 courses was 2 approximately 3 weeks. The plasma half-life of DMDC in the final phase of elimination in the single administration trial was 5.2 approximately 6.3 hours, and no differences were seen among dose levels. The urinary excretion rate was between 32.0 approximately 61.5% until 48 hours after administration. No accumulation was seen in the 5-consecutive-day administration trial. There were no findings to suggest an antitumor effect in the present study. Given the recovery pattern for suppression of marrow, the above mentioned results led us to decide that an recommended method of administration and dosage in an early phase II trial would be 300 mg/m2 per administration by an intravenous infusion every 2 approximately 3 weeks.
Aged↗
[Allogeneic peripheral blood stem cell transplantation].
Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) has been increasingly used as an alternative to allogeneic bone marrow transplantation (allo-BMT). In comparison with allo-BMT, preliminary results indicate that rapid hematopoietic engraftment can be obtained, and there is no increase in the incidence and severity of acute GVHD after allo-PBSCT. Furthermore, general anesthesia is not required to collect a sufficient number of PBSCT, which are usually mobilized by G-CSF administration. Therefore, allo-BMT will be replaced by allo-PBSCT in near future.
Adult↗
[Chemotherapy for small-cell lung cancer].
Here we review the current treatments for small-cell lung cancer. Cisplatin and etoposide, combined with concurrent or alternating thoracic irradiation, have been considered to be the standard therapy for patients with limited disease. Dose-intensive weekly chemotherapy and high-dose chemotherapy with autologous stem cell transplantation have failed to increase survival in patients with extensive disease. Promising new drugs such as irinotecan and taxol may improve survival in patients with extensive disease.
Antineoplastic Combined Chemotherapy Protocols↗
Prognostic significance of p53 and ras p21 expression in nonsmall cell lung cancer.
BACKGROUND: Alterations of the p53 gene are one of the most common genetic changes in various types of cancer, including lung cancer. Abnormalities in the ras genes, including point mutations and overexpression, are another common feature in the molecular biology of lung cancer and are associated with a poorer prognosis. The authors' purpose was to determine expression of the mutated p53 gene in nonsmall cell lung cancer (NSCLC) specimens that were studied for expression of ras p21 and to document whether altered p53 expression was also an important factor for survival. METHODS: Ninety-six patients with NSCLC underwent surgical resection between 1977 and 1985, 63 of whom received postoperative combination chemotherapy. None received radiation therapy. Tumor specimens were analyzed for altered p53 expression by immunohistochemistry. Univariate and multivariate analyses were performed to assess the association between p53 expression and survival. RESULTS: Fifty-six (58%) of 96 tumor specimens showed altered p53 expression, and 91 patients were analyzed for survival. Altered p53 expression did not correlate with clinicopathologic characteristics except for postsurgical pathologic tumor (pT) classification. The patients with altered p53 expression survived for a significantly shorter period after surgery than those without p53 expression, including all patients who underwent resection and potentially curative resection (P = 0.02 and P = 0.048, respectively, generalized Wilcoxon test). Multivariate analysis showed independent prognostic significance for altered p53 expression (hazard ratio [HR] = 1.72, P = 0.04) and surgical cure (HR = 4.69, P < 0.001). The combined analysis of mutated p53 and ras p21 expression in the same tumor specimens revealed that patients with p53- and ras p21-negative tumors survived the longest among those with different p53 and ras p21 features (P = 0.005, generalized Wilcoxon test). CONCLUSION: Altered p53 expression is a significant and independent negative prognostic factor for patients with surgically resected NSCLC: Combined immunohistochemical analysis of mutated p53 and ras p21 expression can divide patients with NSCLC into more accurate prognostic groups. If the current findings can be confirmed in larger prospective studies, combined immunohistochemical analysis of mutated p53 and ras p21 expression can be a useful clinical tool for stratifying patients with NSCLC into accurate prognostic groups and for identifying the population with a different risk of recurrence.
Aged↗
The involvement of transforming growth factor beta in the impaired antitumor T-cell response at the gut-associated lymphoid tissue (GALT).
We studied the antitumor immune response in gut-associated lymphoid tissue (GALT), which is the tolerance-inducing site for numerous dietary antigens. The mice inoculated with colon 26 carcinoma (C-26) into the subserosal space of the cecum (i.c.) showed a more rapid tumor growth than did the mice inoculated s.c. with C-26 into the flank. In addition, the serum of the i.c. C-26-inoculated mice showed a more potent suppressive activity, and their plasma contained a higher level of transforming growth factor than the s.c. C-26-inoculated mice. We also evaluated the tumor-specific T-cell response in the GALT by utilizing B7-transfected P815 mastocytoma (B7/P815). The rejection of i.c. inoculated B7/P815 was delayed compared to that of the s.c. inoculated B7/P815. The draining axillary lymph node (LN) cells of the s.c. B7/P815-inoculated mice exhibited a CD4+ T-cell-dependent proliferative response to in vitro restimulation, whereas the draining mesenteric LN cells of the i.c. B7/P815-inoculated mice exhibited no apparent response even with the addition of interleukin 2. However, such draining mesenteric LN cells did produce higher levels of interleukin 2 and transforming growth factor beta than the draining axillary LN without any stimulation, and their production of such cytokines depend on the CD4+ and CD8+ cells, respectively. Collectively, our results suggest the possibility that the impaired antitumor T-cell response in the GALT may be attributed to "bystander suppression" by TGF-beta-producing CD8+ T cells.
Animals↗
Mercury and methylmercury in fish and human hair from the Tapajós river basin, Brazil.
Mercury is being released in the Amazon in an abusive way due to goldmining activities. The Tapajós river basin was the first to be intensively exploited in the modern Amazon gold rush. Fish and hair samples as the best indicators of human methylmercury contamination were investigated in the main cities and villages along the Tapajós river basin. The upper basin has typical fish fauna with much larger carnivorous fish with higher mercury levels reaching an average value of 0.69 microgram.g-1 wet wt. in 43 fish. This was accompanied by high levels in hair of the human population living in the same area. The maximum hair value reach 151 micrograms.g-1 dry wt. with two villages presenting an average value close to 25 micrograms.g-1 dry wt. An analytical laboratory intercalibration exercise was performed between Japanese and Brazilian laboratories for total mercury analysis. Critical fish, areas, and more exposed human groups are identified.
Animals↗
Differential expression of transforming growth factor-alpha and epidermal growth factor during postnatal development of rat submandibular gland.
The concentration and the localization of transforming growth factor (TGF)-alpha and epidermal growth factor (EGF) in the submandibular glands (SMGs) of male Wistar rats of different ages (postnatal 0 to 10 weeks of age) were examined. Highest levels of TGF-alpha were seen early, at postnatal day 0; the levels dropped thereafter in an age-dependent manner, while EGF was not detectable before the third postnatal week. Immunoreactive localization of EGF was restricted to the granules of the granular convoluted tubule (GCT) cells in the mature SMGs, whereas TGF-alpha was observed throughout postnatal development over the entire duct system. TGF-alpha was demonstrated in the cytoplasm at early stages when the GCT granules were not observed and was also located on the granules at the late stage, as was the case for EGF, indicating that TGF-alpha is colocated with EGF in the mature SMG. These results demonstrate the differences between the expression of TGF-alpha and that of EGF in the developing rat SMG.
Age Factors↗
Development of TCR-gamma delta CD4-CD8+ alpha alpha but not TCR-alpha beta CD4-CD8+ alpha alpha i-IEL is resistant to cyclosporin A.
Present evidence suggests that cyclosporin A (CSA) inhibits the development of both alpha beta and gamma delta T cells in the thymus. However, whether CSA can inhibit the development of murine intestinal intraepithelial lymphocytes (i-IEL) is unknown as most i-IEL are clearly derived from a different lineage than the conventional thymus-derived T cells found in the periphery. Using the adult thymectomized, lethally irradiated bone-marrow reconstituted chimera (ATXBM mice) as a model for the development of extrathymically derived i-IEL and the fetal thymus-grafted (FTG) nude mice as a model for the development of thymically derived i-IEL, we demonstrate that CSA nearly completely inhibited the development of extrathymically, and possibly thymically, derived TCR-alpha beta i-IEL. Most of the TCR-alpha beta i-IEL whose development was inhibited by CSA belonged to the CD4-CD8+ alpha alpha subset. In contrast, the development of extrathymically and thymically derived TCR-gamma delta i-IEL was completely resistant to CSA. The phenotype of CSA-resistant TCR-gamma delta i-IEL in these models was not different from those in control mice, and the TCR-gamma delta i-IEL in CSA-treated mice appear to be mature and activated as most were large, granular, and CD69+. Lastly, we demonstrate that CSA does not affect the extrathymic positive selection of V delta 4 i-IEL in C3H hosts. These results suggest that despite their similarity, the intracellular activation cascade involved after TCR stimulation between TCR-alpha beta CD4-CD8+ alpha alpha and TCR-gamma delta CD4-CD8+ alpha alpha i-IEL are markedly different.
Animals↗
A maize DNA-binding factor with a bZIP motif is induced by low temperature.
We have isolated a low temperature-induced maize gene, mlip15, via cross hybridization using rice lip19. The longest cDNA isolated comprised 1179 bp and coded for a 135 amino acid bZIP (basic region/leucine zipper) protein. The gene showed 61.4% and 68.9% identity with the rice gene at the DNA and amino acid sequence levels, respectively, and is distinct from other maize genes that code for bZIP proteins. The level of mlip15 transcript was positively regulated by low temperature in the same way as the lip19 transcript. The levels of the transcript were also strongly increased by salt stress and exogenous abscisic acid, and slightly increased by anaerobiosis, but were not affected by heat shock and drought. The mLIP15 protein and truncated derivatives, produced in rabbit reticulocyte lysates or in an Escherichia coli expression system, were able to bind to a fragment of the wheat histone H3 gene promoter. This binding was diminished by addition of a molar excess of the hexamer sequence 5'-ACGTCA-3' found in the promoter and of the G-box-like sequence, but not by the addition of the ocs sequence or a mutated hexamer sequence. The factor bound to a promoter region of the maize Adh1 gene, expression of which is also induced by low temperature. These results lead to the conclusion that mlip15 is a strong candidate for a low temperature-induced transcription factor in maize.
Amino Acid Sequence↗
Priming with donor spleen cells and activated B cells can induce prolonged survival of class I-disparate skin allografts in cyclophosphamide-treated mice.
We have previously reported a method for inducing tolerance using cyclophosphamide (CP) in a murine model, in which 200 mg/kg of CP is administered intraperitoneally 2 days after intravenous priming with donor spleen cells. The CP-induced tolerance method, however, cannot induce long-lasting skin allograft survival in an MHC class I-disparate combination. In this study, we tried to explain this phenomenon based on a costimulatory theory. That is, allo-class I-reactive host CD8+ helper T cells may receive insufficient costimulatory signals from donor spleen cells and, therefore, they are resistant to subsequently administered CP. We demonstrated that activated donor B cells, which can deliver sufficient costimulatory signals, induce a more efficient proliferation of allo-class I-reactive host CD8+ helper T cells than naive B cells in vitro. In addition, we also demonstrated that our idea can also be applied to the CP-induced skin allograft tolerance in an MHC class I-disparate combination.
Animals↗
[Peripheral blood stem cell transplantation].
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Blood Preservation↗
High-performance liquid chromatographic determination of prolylcarboxypeptidase activity in monkey kidney.
A simple HPLC procedure for the determination of prolylcarboxypeptidase activity in monkey kidney was established with Cbz-Pro-Ala used as substrate. Decrease of the substrate and increase of the product were stoichiometrically related to each other. Heat treatment at 60 degrees C freed the enzyme preparation of contaminating activities. Data on substrate specificity and influence of inhibitors suggested this method was sensitive for the determination of prolylcarboxypeptidase without the use of a radioactive substrate.
Animals↗
Functional expression of Fas antigen (CD95) on hematopoietic progenitor cells.
We investigated the expression of an apoptosis-associated antigen (Fas) (CD95) on hematopoietic progenitor cells in the presence or absence of interferon-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha). CD34+ cells freshly isolated from bone marrow did not express Fas. However, IFN-gamma and/or TNF-alpha induced the expression of both the mRNA of Fas and Fas itself in a dose-dependent fashion on the surface of CD34+ cells after 48 hours of serum-free culture. IFN-gamma and TNF-alpha had a synergistic effect on the induction of Fas, when both cytokines were added to the culture. The TNF-alpha-induced Fas expression is mediated by p55 TNF-alpha receptor. CD34+ cells cultured in medium alone or with stem cell factor (SCF) showed some slight expression of Fas. When anti-Fas antibody (IgM) was added to CD34+ cells after the induction of Fas expression, CD34+ cells underwent apoptosis, as shown by a decrease in the number of viable cells, morphologic changes, the induction of DNA fragmentation, and a decrease in the number of colony-forming cells (CFC) including colony-forming unit granulocytes/macrophages (CFU-GM) and burst-forming unit erythroids (BFU-E). These observations indicate that IFN-gamma and/or TNF-alpha, well known as negative hematopoietic regulators, induce functional Fas on hematopoietic progenitor cells. The suppression of hematopoiesis by negative hematopoietic regulators may be mediated in part by Fas induction.
Antigens, Surface↗
Transforming growth factor-beta 1 levels are elevated in the striatum and in ventricular cerebrospinal fluid in Parkinson's disease.
Transforming growth factor (TGF)-beta 1 content was measured for the first time in the brain (caudate nucleus, putamen, and cerebral cortex) and in ventricular cerebrospinal fluid (VCSF) from control and parkinsonian patients by a sandwich enzyme immunoassay. The concentrations of TGF-beta 1 were significantly higher in the dopaminergic striatal regions in parkinsonian patients than those in controls, but were not significantly different in the cerebral cortex between parkinsonian and control patients. Furthermore, the concentrations of TGF-beta 1 in VCSF were significantly higher in parkinsonian patients than those in non-parkinsonian control patients. Since TGF-beta 1 has potent regulatory activity on cell growth, these results suggest that TGF-beta 1 may have some significant modulatory role in the process of neurodegeneration in Parkinson's disease.
Aged↗
Selective removal of immunoglobulin E from rat blood by membrane-immobilized antibody.
We examined the suitability of an immunoaffinity membrane [rabbit IgG specific for rat immunoglobulin E (IgE) immobilized on a cellulose membrane] for removing IgE from rat blood passed through a simple extracorporeal circulatory system. To determine the concentration of IgE in the blood, we also developed a highly sensitive chemiluminescence enzyme immunoassay for rat IgE. The IgE levels in the outlet blood from the immunoaffinity membrane module decreased to 30% of the initial concentration within 30 min.
Animals↗