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Showing papers by "Kumamoto University published in 1993"


Journal ArticleDOI
TL;DR: It is concluded that plasma levels of BNP mainly reflect the degree of ventricular overload and that the secretion patterns of ANP and BNP vary with underlying cardiac disorders of CHF with different degrees of overload in atria and ventricles.
Abstract: BACKGROUNDThe plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are increased in relation to the severity of congestive heart failure (CHF). This study was designed to examine whether the secretion patterns of ANP and BNP vary with underlying cardiac disorders of CHF with different degrees of overload in atria and ventricles.METHODS AND RESULTSWe measured plasma levels of ANP and BNP in the aorta in 20 patients with mitral stenosis (MS) in whom atria are mainly overloaded, 30 patients with dilated cardiomyopathy (DCM) in whom both atria and ventricles are overloaded, and 20 control subjects during cardiac catheterization. Pulmonary capillary wedge pressure (PCWP) was significantly higher in the MS and DCM groups (16.7 +/- 4.7 mm Hg and 15.1 +/- 7.7 mm Hg, respectively) than in the control group (7.2 +/- 1.1 mm Hg, p < 0.01), whereas there was no significant difference between the MS and DCM groups. Left ventricular end-diastolic pressure (LVEDP) was significantly higher...

617 citations


Journal ArticleDOI
TL;DR: It is concluded that the plasma level of brain natriuretic peptide is increased markedly in patients with acute myocardial infarction and may reflect the degree of left ventricular dysfunction in these patients.
Abstract: BACKGROUNDBrain natriuretic peptide is a novel natriuretic peptide that is secreted predominantly from the ventricles, and its plasma levels have been shown to be markedly increased in patients with chronic congestive heart failure This study was designed to examine the plasma levels of brain natriuretic peptide as well as atrial natriuretic peptide in patients with acute myocardial infarctionMETHODS AND RESULTSWe examined the plasma levels of brain natriuretic peptide as well as atrial natriuretic peptide in 50 consecutive patients (36 men and 14 women; mean age, 66 years) with acute myocardial infarction over the time course of 4 weeks The plasma level of brain natriuretic peptide was significantly increased on admission in patients with acute myocardial infarction compared with controls (92 +/- 28 versus 52 +/- 05 pg/mL, P < 01) and reached the peak level of 319 +/- 58 pg/mL at 164 +/- 07 hours after admission Thereafter, the level decreased and then again increased, forming the second peak of

586 citations


Journal ArticleDOI
TL;DR: It was clarified that imidazolineoxyl N-oxide antagonize EDRF/.NO via a unique radical-radical reaction with .NO.
Abstract: A labile inorganic free radical, nitric oxide (.NO), is produced by nitric oxide synthase from the substrate L-arginine in various cells and tissues. It acts as an endothelium-derived relaxing factor (EDRF) or as a neurotransmitter in vivo. We investigated the reactivity of stable radical compounds, imidazolineoxyl N-oxides such as 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO), carboxy-PTIO, and carboxymethoxy-PTIO against .NO/EDRF in both chemical and biological systems. By using electron spin resonance (ESR) spectroscopy, imidazolineoxyl N-oxides were found to react with .NO in a stoichiometric manner (PTIO/.NO = 1.0) in a neutral solution (sodium phosphate buffer, pH 7.4) with rate constants of approximately 10(4) M-1 s-1, resulting in the generation of NO2-/NO3- and imidazolineoxyls such as 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl (PTI), carboxy-PTI, or carboxymethoxy-PTI. Furthermore, the effects of imidazolineoxyl N-oxides on acetylcholine- or ATP-induced relaxation of the smooth muscle of rabbit aorta were tested. The vasorelaxations were inhibited by all three imidazolineoxyl N-oxides markedly. The inhibitory effects of carboxy-PTIO was almost 2-fold stronger than those of .NO synthesis inhibitors, N omega-nitro-L-arginine and N omega-monomethyl-L-arginine. Generation of EDRF/.NO was identified by reacting the PTIO in aortic strips and quantitating the reaction product with ESR spectroscopy. Thus, it was clarified that imidazolineoxyl N-oxide antagonize EDRF/.NO via a unique radical-radical reaction with .NO.

569 citations


Journal ArticleDOI
TL;DR: Evidence is provided that AGE-modified beta 2M is a dominant constituent of the amyloid deposits in hemodialysis-associated amyloidsosis.
Abstract: beta 2-Microglobulin (beta 2M) is a major constituent of amyloid fibrils in hemodialysis-associated amyloidosis, a complication of long-term hemodialysis patients. Amyloid fibril proteins were isolated from connective tissues forming carpal tunnels in hemodialysis patients with carpal tunnel syndrome. Two-dimensional polyacrylamide gel electrophoresis and Western blotting demonstrated that most of the beta 2M forming amyloid fibrils exhibited a more acidic pI value than normal beta 2M. This acidic beta 2M was also found in a small fraction of beta 2M in sera and urine from these patients, whereas heterogeneity was not observed in healthy individuals. We purified acidic and normal beta 2M from the urine of long-term hemodialysis patients and compared their physicochemical and immunochemical properties. Acidic beta 2M, but not normal beta 2M, was brown in color and fluoresced, both of which are characteristics of advanced glycation end products (AGEs) of the Maillard reaction. Immunochemical studies showed that acidic beta 2M reacted with anti-AGE antibody and also with an antibody against an Amadori product, an early product of the Maillard reaction, but normal beta 2M did not react with either antibody. Incubating normal beta 2M with glucose in vitro resulted in a shift to a more acidic pI, generation of fluorescence, and immunoreactivity to the anti-AGE antibody. The beta 2M forming amyloid fibrils also reacted with anti-AGE antibody. These data provided evidence that AGE-modified beta 2M is a dominant constituent of the amyloid deposits in hemodialysis-associated amyloidosis.

423 citations


Journal ArticleDOI
TL;DR: It is reported that high, but not low frequency stimulation applied to two groups of CA1 afferents resulted in a long lasting increase in the Ca(2+)-independent and total activities of the enzyme as well as an increased in the ratio of Ca( 2+)- independent to total activity.

395 citations


Journal ArticleDOI
TL;DR: It is concluded that the cell populations positive for MCP-1 are different in early and advanced atherosclerotic lesions, and that the endothelial cells and subendothelial macrophages are considered to be the major sources of M CP-1 in early atheroscerotic lesions.

282 citations


Journal ArticleDOI
TL;DR: Homology search revealed that an approximately 200-amino-acid domain in the ftsH1(Ts) gene is highly homologous to the domain found in members of a novel, eukaryotic family of putative ATPases, e.g., Sec18p, Pas1p, CDC48p, and TBP-1, which function in protein transport pathways, peroxisome assembly, cell division cycle, and gene expression, respectively.
Abstract: The ftsH gene is essential for cell viability in Escherichia coli. We cloned and sequenced the wild-type ftsH gene and the temperature-sensitive ftsH1(Ts) gene. It was suggested that FtsH protein was an integral membrane protein of 70.7 kDa (644 amino acid residues) with a putative ATP-binding domain. The ftsH1(Ts) gene was found to have two base substitutions within the coding sequence corresponding to the amino acid substitutions Glu-463 by Lys and Pro-587 by Ala. Homology search revealed that an approximately 200-amino-acid domain, including the putative ATP-binding sequence, is highly homologous (35 to 48% identical) to the domain found in members of a novel, eukaryotic family of putative ATPases, e.g., Sec18p, Pas1p, CDC48p, and TBP-1, which function in protein transport pathways, peroxisome assembly, cell division cycle, and gene expression, respectively. Possible implications of these observations are discussed.

230 citations


Journal ArticleDOI
TL;DR: Characterization of two novel genes of their full-length cDNA sequences revealed that they were mouse homologues of the endothelial cell RTK genes, TIE and TEK, which shared a unique structural property of coexistent immunoglobulin-like domain, epidermal growth factor-like repeats, and fibronectin type III repeats in their extracellular domains.

227 citations


Journal ArticleDOI
TL;DR: In this paper, the extraction of essential oil from peppermint leaves with supercritical carbon dioxide was studied in a semibatch-flow extraction apparatus, and the extraction rates of the major components, l-menthol and menthone, were measured at various conditions: 313-353 K, 8.83-19.6 MPa.
Abstract: The extraction of essential oil from peppermint leaves with supercritical carbon dioxide was studied in a semibatch-flow extraction apparatus. The extraction rates of the major components, l-menthol and menthone, were measured at various conditions: 313–353 K, 8.83–19.6 MPa. The exit concentration of l-menthol extracted from peppermint leaves was much smaller than the solubility of l-menthol. The extraction curves at various flow rates coincide in the plot of yield versus quantity of CO2 consumed. A mathematical model based on the local adsorption equilibrium of essential oil on lipid in leaves and mass transfer well described the extraction results. The adsorption equilibrium constant determined by filling the theoretical extraction curve to the experimental data increased with temperature and decreased with pressure.

212 citations


Journal ArticleDOI
TL;DR: The binding of carprofen, a nonsteroidal anti-inflammatory drug of the aryl propionic acid class [2-(6-chlorocarbazole)propionic acid], and its enantiomers to human serum albumin (HSA) has been studied by dialysis and spectroscopic methods as discussed by the authors.

199 citations


Journal ArticleDOI
TL;DR: The plasma IL-6 level is increased over a time course of 4 weeks in patients with AMI, and there was a significant positive linear correlation between the peak level of plasmaIL-6 minus the level on admission and the peaklevel of plasma C-reactive protein in patientswith AMI.

Journal ArticleDOI
TL;DR: It is concluded that a ferrocene-mediated needle-type glucose sensor covered with an MPC membrane is stable and reliable, as compared to any other glucose sensors already developed, and can thus be applied for continuous glucose monitoring and for glycaemic control with a wearable artificial endocrine pancreas.
Abstract: A ferrocene-mediated needle-type glucose sensor covered with a newly designed biocompatible membrane of 2-methacryloyloxyethyl phosphorylcholine (MPC) has been developed and its characteristics examined in vitro and in vivo. Application of ferrocene derivatives to the glucose sensor could solve the oxygen-limitation problems, and also compensate the sensor decay due to an insufficient microconvection and diffusion of oxygen resulting from protein fixation on the sensor surface during continuous subcutaneous tissue glucose monitoring. The MPC membrane, a hydrophobic polymer surface covered with a grafted hydrophilic phosphorylcholine chain, has the potential for supressing adsorption of biochemical molecules due to the mobility of the grafted polymer chain. With this glucose sensor covered with an MPC membrane, subcutaneous tissue glucose concentrations can be monitored for up to seven days without any in situ calibrations, followed by 14 days with one-point in situ calibrations. Therefore, we conclude that a ferrocene-mediated needle-type glucose sensor covered with an MPC membrane is stable and reliable, as compared to any other glucose sensors already developed, and can thus be applied for continuous glucose monitoring and for glycaemic control with a wearable artificial endocrine pancreas.

Journal ArticleDOI
TL;DR: In this paper, Ficoll density gradient centrifugation was used to separate the Primordial Germ Cells (PGC) from blood cells by Ficll density gradient gradient centrifuge and transferred them to the blood stream of White Leghorn embryos.

Journal ArticleDOI
TL;DR: In this paper, the effects of the molecular weights of chitosan hydrolysates on the release and absorption rates of indomethacin from gel beads were examined.

Journal ArticleDOI
TL;DR: Evaluation of signal intensity at T2-weighted imaging and degree of contrast enhancement at dynamic enhanced MR imaging provide useful information on the nature of leiomyomas.
Abstract: PURPOSE: To evaluate the role of dynamic enhanced magnetic resonance (MR) imaging in differentiating leiomyomas with high signal intensity at T2-weighted imaging. MATERIALS AND METHODS: Histologic features of 34 uterine leiomyomas that showed hyperintensity on T2-weighted images were compared with those of ordinary hypointense leiomyomas (n = 74). The results of treatment with gonadotropin-releasing hormone analogue were also analyzed in relation to pretreatment signal intensity. RESULTS: Degenerated leiomyomas (n = 13) had higher signal intensity and heterogeneous architecture, but there was considerable overlap in signal intensity with cellular leiomyomas (n = 21). At dynamic enhanced MR imaging, cellular leiomyomas had marked contrast enhancement in the early phase, while degenerated leiomyomas showed slight or irregular enhancement. Cellular leiomyomas were reduced significantly in size after treatment (P = .02). The response in degenerated leiomyomas was minimal. CONCLUSION: Evaluation of signal inte...

Journal ArticleDOI
TL;DR: It is concluded that FtsH protein is an integral cytoplasmic membrane protein spanning the membrane twice and that it has a large cytopLasmic carboxy-terminal part with a putative ATP-binding domain.
Abstract: FtsH protein in Escherichia coli is an essential protein of 70.7 kDa (644 amino acid residues) with a putative ATP-binding sequence. Western blots (immunoblots) of proteins from fractionated cell extracts and immunoelectron microscopy of the FtsH-overproducing strain showed exclusive localization of the FtsH protein in the cytoplasmic membrane. Most of the FtsH-specific labeling with gold particles was observed in the cytoplasmic membrane and the adjacent cytoplasm; much less was observed in the outer membrane and in the bulk cytoplasm. Genetic analysis by TnphoA insertions into ftsH revealed that the 25- to 95-amino-acid region, which is flanked by two hydrophobic stretchs, protrudes into the periplasmic space. From these results, we concluded that FtsH protein is an integral cytoplasmic membrane protein spanning the membrane twice and that it has a large cytoplasmic carboxy-terminal part with a putative ATP-binding domain. The average number of FtsH molecules per cell was estimated to be approximately 400.

Journal ArticleDOI
TL;DR: Contrast-enhanced MR imaging is significantly superior to transvaginal sonography and unenhanced T2-weighted MR imaging for detecting myometrial invasion in patients with early-stage endometrial carcinoma.
Abstract: A prospective study was designed to compare transvaginal sonography with contrast-enhanced MR imaging to determine preoperatively the depth of myometrial invasion in patients with early-stage endometrial carcinoma.In 40 patients, findings on transvaginal sonograms, unenhanced T2-weighted MR images, and contrast-enhanced T1-weighted Mr images were compared with histologic findings. The depth of myometrial invasion was classified as stage E (tumor limited to endometrium, n = 12), stage S (superficial invasion: tumor invades up to 50% of the myometrium, n = 15), or stage D (deep invasion: tumor invades more than 50% of the myometrium, n = 13).Findings on transvaginal sonograms were accurate in 27 of 40 patients (accuracy, 68%); the depth of invasion was overestimated in five patients and underestimated in eight patients. The results of unenhanced T2-weighted MR images were accurate in 27 patients (accuracy, 68%), with four overestimations and nine underestimations. The results of contrast-enhanced T1-weighte...

Journal ArticleDOI
01 May 1993-Geology
TL;DR: In this paper, a tectonic model is proposed to explain how diamond-facies rocks were, emplaced into the crust on both sides of an orogen, by a method other than kimberlitic volcanism.
Abstract: Octahedral graphite aggregates are present in garnet pyroxenites from the Ronda peridotite massif, southern Spain. In the aggregates, basal {0001} planes of graphite are parallel to {111} of the octahedra, demonstrating that the graphite is pseudomorphic after a cubic mineral. The aggregates contain clinopyroxene inclusions that have a morphology atypical of a monoclinic phase, demonstrating that the precursor diamond has imposed a cubic symmetry. Graphitized diamonds at Ronda and Beni Bousera (northern Morocco) establish that mantle-derived material is brought to the surface from great depths by a method other than kimberlitic volcanism. A tectonic model is proposed to explain how diamond-facies rocks were, emplaced into the crust on both sides of an orogen.

Journal ArticleDOI
TL;DR: To determine whether oxidized low- density lipoprotein (Ox-LDL), which accumulates in atherosclerotic arteries, modulates the endothelial fibrinolytic system, cultures of human umbilical vein endothelial cells were incubated with low-density lipoproteins or lipids.
Abstract: Decreased fibrinolytic activity has been reported in atherosclerotic cardiovascular diseases. To determine whether oxidized low-density lipoprotein (Ox-LDL), which accumulates in atherosclerotic arteries, modulates the endothelial fibrinolytic system, cultures of human umbilical vein endothelial cells were incubated with low-density lipoproteins or lipids, and levels of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) antigens in the conditioned medium were measured by enzyme-linked immunosorbent assay. Ox-LDL (30 micrograms protein/mL) and its extracted lipid (50 micrograms cholesterol/mL) stimulated PAI-1 release by 42 +/- 3% and 29 +/- 3% of control cultures, respectively, whereas Ox-LDL and its lipid inhibited t-PA release by 42 +/- 4% and 53 +/- 3% of control cultures, respectively. Native LDL and its lipid were inactive on their release. Ox-LDL depleted of hydrophilic lipids, which was prepared by the incubation with defatted albumin (an acceptor for hydrophilic lipids), lost both the stimulatory action on PAI-1 and the inhibitory action on t-PA. The extracted lipid from the incubated albumin, which has been found to accept the hydrophilic lipids from Ox-LDL, gained the stimulatory action on PAI-1 and the inhibitory action on t-PA. Ox-LDL depleted of lysophosphatidylcholine (LPC), which was prepared by the incubation with phospholipase B, lost the stimulatory effect on PAI-1, whereas the inhibitory effect on t-PA remained present in the Ox-LDL depleted of LPC. The incubation with synthetic palmitoyl LPC (10 microM) stimulated PAI-1 release by 85 +/- 7% of control.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: The results provide evidence that there are two waves of hemopoiesis in murine embryos relative to c-Kit dependency, and an antagonistic anti-c-Kit monoclonal antibody, ACK2, which can block the function of c- Kit.
Abstract: The protooncogene c-kit encodes a receptor type tyrosine kinase and is allelic with the W locus of mice. SLF, the c-Kit ligand which is encoded by the Sl locus, has growth promoting activity for hemopoietic stem cells. Previous studies demonstrated that c-Kit is functionally required for the proliferation of hemopoietic progenitor cells at various differentiation stages in adult bone marrow. However, the absence of functional SLF and c-Kit in fetuses with mutant alleles of Sl and W loci produces only minor effects on the myeloid and early erythroid progenitor cells in the fetal liver, although the level of the late erythroid progenitor cells is significantly affected. We used an anti-c-Kit monoclonal antibody to investigate the expression and function of c-Kit in murine fetal hemopoietic progenitor cells. Flow-cytometric analysis showed that hemopoiesis in the yolk sac and fetal liver started from cells that express c-Kit. The c-Kit expression decreased upon maturation into erythrocytes in each organ. By fluorescence activated cell sorting, the c-Kit+ cell population was enriched with the hemopoietic progenitor cells clonable in vitro (CFU-E, BFU-E and GM-CFC). To elucidate whether c-Kit functions in these progenitor cells in vivo, we took advantage of the antagonistic anti-c-Kit monoclonal antibody, ACK2, which can block the function of c-Kit. Administration of ACK2 after 12.5 days of gestation rapidly eliminated BFU-E and GM-CFC as well as CFU-E from the fetal liver. However, the number of these progenitor cells in the yolk sac and fetal liver was less affected when the fetuses were given ACK2 before 12.5 days of gestation. Our results provide evidence that there are two waves of hemopoiesis in murine embryos relative to c-Kit dependency. The c-Kit has an essential role on the growth of hemopoietic progenitor cells in the fetal liver after 12.5 days of gestation, whereas the progenitor cells in the liver and yolk sac of the earlier embryo do not depend on c-Kit and its ligand SLF.

Book ChapterDOI
TL;DR: Following further research, practicable new processes for production of ethylene will be established and will herald a new age free from the threat of shortages of petroleum resources.
Abstract: Publisher Summary Ethylene is the simplest of unsaturated hydrocarbons and the most important starting material in petroleum chemistry. It is also a plant hormone involved in a number of physiological processes, such as fruit ripening and plant senescence. The chapter summarizes the biosynthetic pathways to ethylene found in micro-organisms and compares them with results from higher plants. The chapter discusses the characteristics of the reaction catalyzed by the ethylene-forming enzyme. Micro-organisms and higher plants synthesize ethylene by different biochemical pathways. In micro-organisms, there are two biosynthetic pathways for ethylene formation—namely, the KMBA and the 2-oxoglutarate pathways. Using the purified enzyme, the ethylene-forming reactions were surveyed and it was found that the purified enzyme simultaneously catalyzes two reactions— namely, formation of ethylene and of succinate from 2-oxoglutarate. In a comparison with the ethylene-forming enzymes of higher plants, the homology score for the entire amino acid-residue sequence of the enzyme from Ps. syringae compared with the enzymes from plants, or with 2-oxoglutarate-dependent dioxygenases, was low. However, functionally significant regions appear to be conserved. The chapter also discusses the genes for the ethylene-forming enzyme of Ps. syringae and higher plants from the evolutionary point of view. It is expected that the gene in Ps. syringae will be very useful for production of ethylene, and following further research, practicable new processes for production of ethylene will be established and will herald a new age free from the threat of shortages of petroleum resources.

Journal ArticleDOI
TL;DR: The finding that large deletions or rearrangements spanning more than 10 kb were found in the 3'-flanking region of the trap vector introduced by electroporation suggests that phenotypes observed in homozygotes with a mutated allele could be due to the disruption of a gene adjacent to the trapped gene, but not of the trapped genes.
Abstract: New trap vectors (U1 and U2) have been developed to trap genes in murine embryonic stem (ES) cells. The polyA addition signal of the neomycin phosphotransferase II (neo) gene was removed from these vectors so that they needed to trap an endogenous polyA signal for expression of the neo gene. The frequency of gene-trap events of these vectors was about five times higher than with the vector containing the polyA signal, and only one copy of the trap vector was integrated in most cases. Four out of five 5'-flanking regions of the integrated vector in ES cell lines were found to be novel endogenous promoters, suggesting that this method is efficient for trapping genes in ES cells. In two cases analyzed, large deletions or rearrangements spanning more than 10 kb were found in the 3'-flanking region of the trap vector introduced by electroporation. This result suggests that phenotypes observed in homozygotes with a mutated allele could be due to the disruption of a gene adjacent to the trapped gene, but not of the trapped gene.

Journal ArticleDOI
TL;DR: A co-operative study for patients with intracranial germ cell tumours was performed to analyze their prognosis and the effectiveness of Cisplatin/Etoposide (CDDP/VP-16) chemotherapy, finding a high response rate could be achieved in both the primary and the recurrent cases except in those cases of immature teratoma.
Abstract: A co-operative study for patients with intracranial germ cell tumours was performed to analyze their prognosis and the effectiveness of Cisplatin/Etoposide (CDDP/VP-16) chemotherapy.

Journal ArticleDOI
TL;DR: Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) and hepatocyte nuclear factor-4 (HNF-4) are orphan members of the steroid/thyroid receptor superfamily and exhibit ubiquitous and liver-enriched tissue distribution, respectively.

Journal ArticleDOI
TL;DR: It is concluded that zinc supplementation is effective for inducing growth in short children with zinc deficiency, and that body zinc clearance tests facilitate detection of marginal zinc deficiency.

Journal ArticleDOI
TL;DR: In vivo administration of a monoclonal antibody specific for the receptor for SCF (c‐kit) was found to completely prevent the generation of intestinal mastocytosis normally observed following T. spiralis infection.
Abstract: SUMMARY The role of stem cell factor (SCF) in the generation of intestinal mast cell hyperplasia and host protective immunity following helminth infection was investigated using the Trichinella spiralis/mouse model. In vivo administration of a monoclonal antibody specific for the receptor for SCF (c-kit) was found to completely prevent the generation of intestinal mastocytosis normally observed following T. spiralis infection. This was reflected by markedly reduced intestinal mast cell protease (IMCP) levels in both tissue and serum. Moreover, animals treated with anti-c-kit antibody failed to show any evidence of worm expulsion from the gut. The data demonstrate for the first time, a critical role for the SCF in the generation of mucosal mastocytosis and host protective immunity following an intestinal helminth infection.


Journal ArticleDOI
15 Jun 1993-Cancer
TL;DR: It was assessed whether addition of vincristine to remission induction therapy would increase the complete remission (CR) rate, and whether 12 courses of maintenance—intensification therapy would produce longer survival than 4 courses in adult acute myeloid leukemia (AML).
Abstract: Background. It was assessed whether addition of vincristine (VCR) to remission induction therapy would increase the complete remission (CR) rate, and, secondarily, whether 12 courses of maintenance—intensification therapy would produce longer survival than 4 courses in adult acute myeloid leukemia (AML). Methods. A randomized comparison of individualized induction therapy was conducted between daunorubicin, behenoyl cytarabine, 6-mercaptopurine, and prednisolone with or without VCR. After 3 courses of intensive consolidation therapy, maintenance—intensification therapy was randomized to 4 or 12 courses given every 6 weeks. Results. Of 265 patients registered, 252 were evaluable. CR was obtained in 78%; 80% in 205 patients of age younger than 60 years, and 65% in 47 of age 60 years or older. Addition of VCR reduced the CR rate significantly (84% to 70%, P = 0.007). Predicted 4-year survival, continuing CR, and disease-free survival (DFS) rates of 196 CR patients are 45%, 41%, and 35%, respectively. Patients receiving 12 courses of maintenance—intensification showed better DFS. By multivariate analyses, significant factors for achievement of CR were performance status 0 to 2, age younger than 60 years, and no VCR; and those for longer DFS were achievement of CR by one course, age younger than 50 years, and French—American—British (FAB) classification M3 or M5. Among 131 patients randomized to the maintenance, the administration of 12 courses was the most important factor (P = 0.0040) for longer DFS, followed by FAB M3 or M5, and by achievement of CR by one course. Conclusions. Addition of VCR in remission induction therapy was harmful, and longer intensive maintenance therapy prolonged DFS in adult AML.

Journal ArticleDOI
T Doi1, Masayuki Ando1, Takaaki Akaike1, Moritaka Suga1, Keizo Sato1, Hiroshi Maeda1 
TL;DR: The results indicate that the intracellular growth of MAC is not always inhibited by NO generated by immunologically activated M phi; rather, NO generation induced by infection with an NO-resistant MAC strain suppresses phagocytosis of the Mphi, which may allow extracellular spreading of such NO- resistant mycobacteria.
Abstract: Susceptibility of three different strains of Mycobacterium avium complex (MAC), i.e., one strain of M. avium (Mino) and two strains of M. intracellulare (31F093T and KUMS 9007), to nitric oxide (NO) generated by rat alveolar macrophages (M phi) or NO generated chemically by acidification of NO2- was examined in vitro. We also investigated the effects of NO on phagocytosis and superoxide anion (O2-) generation by M phi. The intracellular growth of M. avium Mino was significantly suppressed by NO generated by gamma interferon (IFN-gamma)-stimulated M phi, whereas that of two strains of M. intracellulare (31F093T and KUMS 9007) was not. M. avium Mino was also more susceptible to NO generated chemically by acidification of NO2- than the two M. intracellulare strains. In L-arginine (1 mM)-containing medium, NO release from the M phi assessed by measuring NO2- increased as the concentration of IFN-gamma increased. The enhancing potential of IFN-gamma for NO release became more pronounced when M phi were infected with 31F093T, an NO-resistant strain. A large amount of NO generated by IFN-gamma-stimulated M phi suppressed both phagocytosis and O2- generation by the M phi, especially after infection of the M phi with strain 31F093T. These results indicate that the intracellular growth of MAC is not always inhibited by NO generated by immunologically activated M phi; rather, NO generation induced by infection with an NO-resistant MAC strain suppresses phagocytosis of the M phi, which may allow extracellular spreading of such NO-resistant mycobacteria. Therefore, the pathogenic potential of MAC may be partly attributed to its resistance to NO.

Journal ArticleDOI
15 May 1993-Cancer
TL;DR: It is confirmed that membrane‐associated phospholipase A2 (M‐PLA2) was one of the acute phase reactants and increased in serum of patients with various malignant tumors.
Abstract: Background. Recently, the authors reported that membrane-associated phospholipase A2 (M-PLA2) was one of the acute phase reactants and increased in serum of patients with various malignant tumors. Methods. M-PLA2 concentrations in tissue specimens from 78 breast cancers, 16 benign breast tumors, and 10 normal breast tissues were determined by a specific radioimmunoassay recently developed. Immunohistochemical staining was performed on all specimens by the avidin-biotin-peroxidase method. Results. Tissue levels of M-PLA2 concentration were significantly higher in breast cancer than in benign breast tumor or normal breast tissue (P < 0.01). Correlation analyses between the tissue concentration of M-PLA2 and clinicopathologic factors showed that tissue M-PLA2 levels were significantly higher in patients with skin or muscle invasion, vessel involvement, and distant metastasis than in those without. In addition, this enzyme concentration was significantly greater in scirrhous carcinoma than in papillotubular or solid-tubular carcinoma. No association was found between M-PLA2 concentration and steroid hormone receptor status. Immunohistochemically, M-PLA2 was preferentially stained in the invading zone of breast cancer tissues, especially in scirrhous carcinoma. Patients with breast cancer with low levels of M-PLA2 showed significantly longer overall survival and disease-free survival compared with those with high levels of this enzyme at the cutoff point of 50 ng/100 mg protein. The combination of estrogen receptor status with M-PLA2 concentration could be a powerful prognostic factor in predicting such survival rates. Conclusions. M-PLA2 is closely related to the malignant potential of breast cancers, and the M-PLA2 contents in breast cancer tissues could be a new valuable prognostic factor, other than the hormone receptor, in delineating the status of human breast cancer.