Monitoring sialyl lewis x (CD15s) on peripheral lymphocytes for the diagnosis of acute rejection.
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Acute Disease↗
Biomedical subjects
K Utsumi
Publications and source records attributed to K Utsumi.
Interrelation between oxygen tension and nitric oxide in the respiratory system.
To understand the relationship between oxygen tension and nitric oxide (NO) function, one animal and two human studies were designed. In the animal study, the effect of NO in inducing the relaxation of aortic specimens was significantly lower by 68% under 480 mm Hg of oxygen tension than under 28 mm Hg, indicating that oxygen tension has an important role in determining the biological effects of NO. In a clinical analysis with nonsmokers (n = 23), the alveolar-to-arterial difference for oxygen (A-aDO(2)) was reciprocally correlated with exhaled NO concentrations (r = 0.53). Because NO concentration in the lower respiratory zone depends partly on the amount of inspirable NO originating in the upper airway, a well-ventilated area, requiring much perfusion, could receive greater amounts of NO than a poorly ventilated one. Thus, the reciprocal relation of A-aDO(2) with the concentration of exhaled NO is not necessarily incompatible with the effect of hypoxic pulmonary vasoconstriction in ventilation-to-perfusion (V'A/Q') imbalance. In our third experiment, with nonsmokers (n = 21), pure oxygen inhalation during mechanical ventilation significantly decreased the concentration of exhaled NO and enhanced A-aDO(2), indicating a relationship between NO and oxygen similar to that observed in the animal experiment. These findings led us to conclude that a positive relation between exhaled NO and blood oxygenation efficiency exists in the respiratory system, and further, that oxygen might affect this relationship. Thus, the relative balance of NO and oxygen concentrations may be another factor for consideration in respiratory function.
Adult↗
Circulating and tumor-infiltrating gamma delta T Cells in patients with B-cell lymphomas.
In order to analyze the involvement of gamma delta T cells in the immune surveillance against B cell lymphomas (BCL), we investigated the proportion of circulating gamma delta T cells in 52 BCL patients using two-color flow cytometry, together with tumor-infiltrating gamma delta T cells in 22 of those patients. We found that the proportion of tumor-infiltrating gamma delta T cells in BCL patients was not different from that of lymph node gamma delta T cells in reactive hyperplasia patients. However, a decreased percentage of circulating gamma delta T cells were observed in indolent lymphoma (IL) and limited aggressive lymphoma (AL) patients when compared with normal controls. In contrast, as a result of a histogram, advanced AL patients were divided into two subgroups: the patients with increased circulating gamma delta T cells and those without any increase. However, there was no difference in the clinical features of between the two AL subgroups.
Adult↗
[A case of amebic colitis with liver abscess].
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Adult↗
[The mental health of school children after the Great Hanshin-Awaji Earthquake: I. Epidemiological study and risk factors for mental distress].
UNLABELLED: We conducted surveys to study the magnitude and nature of psychological consequences of school children affected by the Great Hanshin Awaji Earthquake, which occurred in Kobe on January 17th, 1995. It measured 7.2 in magnitude, killed more than 6000 people and destroyed at least 170,000 buildings and houses. The investigations were carried out 4 months following of the disaster. SUBJECTS: About 9000 school children in the 3rd grade, the 5th grade, the 8th grade living in the disaster areas. About 2000 children living in distant areas were also surveyed as control subjects. METHOD: The questionnaire was in a self-descriptive format and consisted of 10 items regarding situation and behavior when the earthquake occurred and 22 items about mental health condition. The responses were rated from 1 to 4 depending on the frequency of the symptoms, and statistically analyzed. RESULT: By factor analysis, three factors were elicited. Factor 1 was interpreted as being related to fear and anxiety, factor 2 as related to depression and physical symptoms, and factor 3 as related to pro-social tendencies. The highest mean score of factor 1 was associated with the most heavily damaged areas. Less severe damage was associated with a lower mean score, and the control areas showed the lowest score. These results show that the children in the damaged areas were strongly affected. Factor 2 shows a different pattern from factor 1. The score of heavily damaged areas is conspicuously high. However, the differences between the other areas were not significant, the control areas had scores almost the same as these of the slightly damaged areas. These results may mean that in less damaged areas than in more heavily damaged areas, there was a more remarkable "heroic phase" after the disaster, which hid depressive moods and lasted longer than in the more severely damaged areas, where people had to face stern reality in the early stages. Factor 3 shows the reverse pattern of factor 2. The slightly damaged areas had the highest score. This result also shows the influence of the "heroic stage". As for the mean scores of factors 1 and 2, younger children showed higher scores. There were no differences in the scores of factor 3 between students in the 3rd grade and 5th grade. The score of the students in the 8th grade was the lowest among all. It can be seen that adolescents generally lessen their consideration for society as a developmental stage in their growth. All of the mean scores of factors 1, 2 and 3 of females are higher than those of males. In the heavily damaged areas, factor 1 is associated with an experience of being rescued and injuries of the children themselves. Factor 2 is associated with injuries of the children themselves. In the moderately damaged areas, factors 1 and 2 are associated with injuries of the children themselves and taking in victims in the children's homes. In the slightly damaged areas, factor 1 is associated with injuries within families. Factor 2 is associated with injuries within families and taking in victims in the childrens' homes. CONCLUSIONS: School-aged children exposed to a high-magnitude natural disaster had 3 categories of emotions: "fear and anxiety," "depressive mood and physical symptoms" and "pro-social tendency." The severity of disaster, younger age, and female gender were high risk factors for distress. In the heavily damaged areas, an experience of being rescued and injuries of the children themselves had a great influence on the mental health of children. In lesser damaged areas, taking in victims in the childrens' homes and injuries within families had an influence.
Adolescent↗
Midgut malrotation in adulthood.
A 29-year-old man was admitted to our hospital with a history of recurrent right upper quadrant abdominal pain and vomiting. These symptoms appeared intermittently for 7 years. Various examinations revealed a diagnosis of midgut malrotation. Laparotomy was performed and revealed reverse rotation of the duodenum with paraduodenal hernia and a normal rotating colon. This case suggests that recurrent abdominal complaints in an adult should arouse suspicion of midgut malrotation.
Abdominal Pain↗
[Evaluation of bronchial arterial infusion (BAI) for high risk lung cancer].
MATERIALS AND METHODS: Seventeen lung cancer patients with advanced age, complications or severe symptoms from the tumor were examined. Standard systemic chemotherapy, irradiation or operation was not indicated in these cases due the patients' systemic condition. BAI was performed using CDDP (40-50 mg/m2) + ETP (70 mg/m2) or CPT-11 (40 mg/m2). The therapeutic effects and side effects were examined. A pharmacokinetic/pharmacodynamic study was done in thirteen cases. RESULTS: Two patient (12%) revealed partial response and fifteen revealed minor response or no change. BAI was effective especially in six cases of malignant pleural effusion. Clinical effects were recognized in thirteen patient with severe chest symptoms (cough in 8, hemosputum in 2 and chest pain in 3). Side effects of over grade II were vomiting in 2 and leukopenia in one. The median survival was 240 days and the cumulative 2-year survival rate was 19.2%. The results of pharmacokinetic studies showed BAI was similar to standard systemic chemotherapy. COMMENT: BAI using low-dose anti-cancer agents was safe and effective and provided improved quality of life in cases of high risk lung cancer.
Adenocarcinoma↗
GM2 gangliosidosis AB variant: clinical and biochemical studies of a Japanese patient.
OBJECTIVE: To determine the clinical features and biochemical basis of the first Japanese patient with the GM2 gangliosidosis AB variant. METHODS: The clinical manifestations and laboratory findings in the patient were investigated. Cultured fibroblasts from the patient were analyzed by means of immunofluorescence staining with an anti-GM2 ganglioside monoclonal antibody and thin-layer chromatography and immunostaining. GM1 ganglioside catabolism in cultured cells was analyzed by pulse labeling, and the amount of GM2 activator in cells was determined by Western blot analysis. Gene analysis was performed according to standard protocols. RESULTS: The patient showed progressive neurologic manifestations of quite early onset. Muscular weakness and hypotonia became evident by 1 month of age, and the patient then developed a startle reaction, severe psychomotor retardation, and myoclonic seizures. Immunocytochemical analysis clearly revealed the accumulation of GM2 ganglioside in cultured fibroblasts from the patient, and thin-layer chromatography confirmed it. Western blot and metabolic studies showed a complete deficiency of GM2 activator. Gene analysis did not reveal any mutations in the protein coding region of the GM2 activator gene. CONCLUSION: The clinical features and biochemical basis of this Japanese patient with GM2 gangliosidosis AB variant were determined. Immunocytochemical analysis using cultured fibroblasts as samples is available for the diagnosis of this disease.
Anticonvulsants↗
Urinary excretion of the vitronectin receptor (integrin alpha V beta 3) in patients with Fabry disease.
A renal disorder is one of the important manifestations of Fabry disease, but the details of the pathogenesis have not been clarified yet. We examined the possibility that the vitronectin receptor (VNR, integrin alpha V beta 3), one of the integrins, is involved in the progression of the renal injury in Fabry disease. We measured the urinary excretion of beta 3 originating from VNR in Fabry patients by immunoblotting analysis and enzyme-linked immunosorbent assay (ELISA). Immunofluorescent microscopic analyses for VNR and globotriaosylceramide were performed on urinary sediments from Fabry patients. Furthermore, beta 3 and vitronectin in kidney tissues were analyzed immunohistochemically. Immunoblotting analysis and ELISA showed that the urinary excretion of beta 3 originating from VNR was significantly increased in the Fabry group compared with both the pathological and healthy control groups. Immunofluorescent microscopy revealed the expression of VNR and accumulation of globotriaosylceramide in urinary sediments from the Fabry patients. Increased expression of beta 3 was observed in glomerular epithelial cells, and in Bowman's capsular epithelial layer and tubular cells, and the amount of vitronectin was moderately increased in the kidney tissues from the Fabry patients. The urinary excretion of VNR was increased, and the expression of VNR was observed in Fabry kidney tissues. The expression of VNR may be involved in the progression of the renal injury in this disease.
Adolescent↗
Oral vs intravenous tacrolimus-based induction therapy in renal transplantation.
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Administration, Oral↗
Resistance to nitric oxide-mediated apoptosis in HL-60 variant cells is associated with increased activities of Cu,Zn-superoxide dismutase and catalase.
Nitric oxide (NO) released from (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1- ium-1,2-diolate (DETA/NO or NOC-18) induces apoptosis in human leukemia HL-60 cells. In this study, we isolated a HL-60 variant cell line, HL-NR6, that is resistant to DETA/NO toxicity as assessed by DNA fragmentation, morphology, and colony forming ability. The variant cells also showed resistance to reactive oxygen species (ROS) such as superoxide and hydrogen peroxide as well as NO donors, but not to anti-tumor drugs. We found that HL-NR6 cells when compared with HL-60 cells possessed twice the activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and catalase, but no change in Mn-SOD nor in glutathione peroxidase. Immunoblotting confirmed the high levels of both enzymes in the variant cell. We also observed that ROS generation following DETA/NO exposure was substantially higher in HL-60 cells than in HL-NR6 cells, using the 2',7'-dichlorofluorescein fluorometric method. Moreover, the SOD mimetic Mn(III) tetrakis(1-methyl-4-pyridyl) porphyrin and exogenous catalase effectively attenuated DETA/NO-elicited DNA fragmentation in HL-60 cells. Taken together, these data suggested that the NO resistance in HL-NR6 cells is associated with the increased Cu,Zn-SOD/catalase and that NO-mediated apoptosis in HL-60 cells is correlated with the generation of ROS and derived molecules like peroxynitrite.
Apoptosis↗
Thyroxine enhancement and the role of reactive oxygen species in tadpole tail apoptosis.
Our objective is to clarify the role of reactive oxygen species (ROS) in the atrophying tail of anuran tadpoles (tail apoptosis). Changes in catalase, superoxide dismutase (SOD) and caspase activity, genomic DNA, and nitric oxide (NO) generation were investigated biochemically using Rana japonica tadpole tails undergoing regression during thyroid hormone enhancement. DNA fragmentation and ladder formation with concomitant shortening of tadpole tail were induced by DL-thyroxine (T4) in culture medium. Catalase activity was also decreased by T4 treatment. T4 was also found to increase NO synthase (NOS) activity in cultured tadpole tail with concomitant increase in the concentration of NO2- plus NO3- (NOx) in the culture medium. Additional treatment with N-monomethyl-L-arginine (NMMA), a potent inhibitor of NOS, suppressed the enhancing effects of T4 on tail shortening and catalase activity reduction. It was also found that treatment with isosorbide dinitrate (ISDN), a NO generating drug, alone also had an enhancing effect on tail shortening and catalase activity reduction similar to that seen with T4. Both NO and an NO donor (ISDN) strongly suppressed catalase activity. Kinetic analysis revealed that catalase activity decreased and caspase-3-like activity increased during normal tadpole tail atrophy (apoptosis). These results suggested that T4 enhances NO generation, thereby strongly inhibiting catalase activity, resulting in an increase in hydrogen peroxide, and that the oxidative stress elicited by excess hydrogen peroxide might activate cysteine-dependent aspartate-directed protease-3 (caspase-3-like protease), which is thought to cause DNA fragmentation, leading to apoptosis.
Animals↗
Oxygen concentration regulates NO-dependent relaxation of aortic smooth muscles.
Nitric oxide (NO) functions as an endothelium-derived relaxation factor and regulates vascular resistance. Recent studies in this laboratory(Arch.Biochem.Biophys.323, 27-32, 1995) revealed that the lifetime of NO significantly increased at physiologically low levels of oxygen concentrations and, hence, this gaseous radical strongly inhibited mitochondrial electron transport for a fairly long duration at low oxygen concentrations. The present work describes the effect of oxygen concentration on NO-induced relaxation and guanylate cyclase (GC) activity of endothelium-denuded aorta of the rat. Both NO and 2,2 '-(hydroxynitrosohydrazono)bis-ethanamine (NOC18), an NO donor, induced the relaxation of endothelium-denuded helical segments of rat aorta which were contracted by norepinephrine. NO-dependent relaxation of arterial specimens was enhanced by lowering oxygen concentration in the medium with concomitant increase in their cGMP levels. Anoxia induced the relaxation of the aorta by some NO-enhanceable and methylene blue-insensitive mechanism. These results suggested that local concentrations of oxygen might play important roles in the regulation of NO-dependent GC activity and vascular tonus of resistance arteries.
Animals↗
Cross-talk of NO, superoxide and molecular oxygen, a majesty of aerobic life.
Because nitric oxide (NO) reacts with various molecules, such as hemeproteins, superoxide and thiols including glutathione (GSH) and cysteine residues in proteins, biological effects and metabolic fate of this gaseous radical are affected by these reactants. Although the lifetime of NO is short particularly under air atmospheric conditions (where the oxygen tension is unphysiologically high), it increases significantly under physiologically low oxygen concentrations. Because oxygen tensions in human body differ from one tissue to another and change depending on their metabolism, biological activity of NO in various tissues might be affected by local oxygen tensions. To elucidate the role of NO and related radicals in the regulation of circulation and energy metabolism, their effects on arterial resistance and energy metabolism in mitochondria, mammalian cells and enteric bacteria were studied under different oxygen tensions. Kinetic analysis revealed that NO-dependent generation of cGMP in resistance arteries and their relaxation were strongly enhanced by lowering oxygen tensions in the medium. NO reversibly suppressed the respiration and ATP synthesis of isolated mitochondria and intact cells particularly under low oxygen tensions. Kinetic analysis revealed that cross-talk between NO and superoxide generated in and around endothelial cells regulates arterial resistance particularly under physiologically low oxygen tensions. NO also inhibited the respiration and ATP synthesis of E. coli particularly under low oxygen tensions. Because concentrations of NO and H+ in gastric juice are high, most ingested bacteria are effectively killed in the stomach. However, the inhibitory effects of NO on the respiration and ATP synthesis of H. pylori are extremely small. Kinetic analysis revealed that H. pylori generates the superoxide radical thereby inhibiting the bactericidal action of NO in gastric juice. Based on such observations, critical roles of the cross-talk of NO, superoxide and molecular oxygen in the regulation of energy metabolism and survival of aerobic and microaerophilic organisms are discussed.
Aerobiosis↗
Geranylgeranylacetone induces apoptosis in HL-60 cells.
Geranylgeranylacetone (GGA) induces apoptosis in human leukemia HL-60 cells in a dose- and time-dependent manner. This effect was completely prevented by the pan-caspase inhibitor z-Val-Ala-Asp(OMe) fluoromethylketone, thereby implicating the caspase cascade in the process. Prior to DNA fragmentation, GGA treatment markedly activated caspase-3(-like) proteases, which might be responsible for the observed apoptosis. In addition, GGA treatment interfered with the processing and membrane localization of Rap1 and Ras, and these changes may be a result of apoptosis. Moreover, nitric oxide donors significantly accentuated the GGA-induced apoptosis, suggesting that the apoptotic pathway induced by GGA might be regulated by a redox-sensitive mechanism. Taken together, these data suggest that the isoprenoid, GGA, is an effective inducer of apoptotic cell death in HL-60 cells.
Amino Acid Chloromethyl Ketones↗
Participation of a cathepsin L-type protease in the activation of caspase-3.
A previous paper from this laboratory reported the activation of a caspase-3-like protease by a digitonin-treated lysosomal fraction [FEBS Lett. 435, 233-236, 1998]. In this study, we examined the effects of specific inhibitors of lysosomal cysteine proteases, such as cathepsins B, S, and L, on the activation of caspase-3 to find out which cathepsin is responsible for the activation. Pro-caspase-3 in the cytosol was cleaved by a lysosomal protease(s) contained in the supernatant of a digitonin-treated crude mitochondrial fraction containing lysosomes (ML) and the cleaved product was detected by Western blotting using anti-caspase-3 antibody. The activation of caspase-3 by the lysosomal protease(s) was pH dependent and the optimum pH for activation was pH 6.6-6.8. This activation was not inhibited by CA-074, a specific inhibitor of cathepsin B, but was strongly inhibited by CLIK-066 and CLIK-181, specific inhibitors of cathepsin L. The inhibitory effect of CLIK-060, a specific inhibitor of cathepsin S, was very weak. Furthermore, the activation of caspase-3 was enhanced by addition of purified cathepsin L only in the presence of the supernatant of the digitonin-treated ML. These results suggested that a cathepsin L-type protease activity might participate in the activation mechanism of caspase-3 in the presence of the supernatnat from the ML.
Adenosine Triphosphate↗
X-irradiation enhances the expression of Bcl-2 in HL-60 cells: the resulting effects on apoptosis and radiosensitivity.
Although p53 has been shown to directly activate transcriptional bax gene and to inhibit expression of bcl-2 gene during radiation-induced apoptosis, it is poorly understood how the Bcl-2 family changes in p53-deficient cells during radiation-induced apoptosis. The present work describes the effect of X-irradiation on the apoptosis of p53-deficient HL-60 cells as assessed by means of several methods. Apoptosis of HL-60 cells was induced by X-irradiation in a dose- and time-dependent manner. 18 h after 5 Gy irradiation, G2 cells underwent apoptosis, while 15 Gy X-irradiation induced the death of G1/S cells by 6 h. After X-irradiation, expression of Bcl-2 was elevated, while Bax expression was unchanged. We have isolated a clonal HL-60 variant following twice 5 Gy irradiation of HL-XR3 cells. These cells highly expressed Bcl-2 (about 2-fold), showed a reduced activation of caspase-3, and were not only more resistant to X-irradiation-induced apoptosis but also more radioresistant. These results suggest that HL-60 cells may resist apoptosis and radiation by increasing Bcl-2 expression, and that this elevated Bcl-2 expression might be one of the causes of the phenomenon, often seen clinically, that tumor cells gradually acquire radioresistance during fractionated radiation therapy.
Apoptosis↗
Role of nuclear lamins in nuclear segmentation of human neutrophils.
Nuclear breakdown leading to the formation of apoptotic bodies has been postulated to involve degradation of nuclear structural proteins, such as lamins A/C and B. Although nuclear segmentation occurs during the maturation of polymorphonuclear leukocytes (neutrophils), its mechanism is not known. We found that human neutrophils have lamin B but lack lamins A/C while mononuclear cells possess all three types of lamin as assessed by immunoblotting. Differentiation of human promyelocytic HL-60 cells into neutrophil-like cells was also accompanied by the down-regulation of lamins A/C but not of lamin B. Moreover, when compared with normal cells, neutrophils with the Pelger-Huët anomaly of nuclear hyposegmentation exhibited significantly lower activity of caspase-6, a lamin A/C-cleaving enzyme. Differentiated HL-60 cells showed higher activity of caspase-6 than that of untreated cells. These observations allow us to speculate that remodeling of nuclear lamins might underlie the mechanism for nuclear segmentation of neutrophils.
Apoptosis↗