The hydrodenitrogenation(HDN) of porphyrins was carried out over a series of phosphorus containing NiMo/Al 2 O 3 catalysts using a fixed‐bed flow reaction system.A method of quantitative analysis of the porphyrin and...The hydrodenitrogenation(HDN) of porphyrins was carried out over a series of phosphorus containing NiMo/Al 2 O 3 catalysts using a fixed‐bed flow reaction system.A method of quantitative analysis of the porphyrin and its derivatives produced by HDN was established.In HDN of porphyrin,four types of hydrocarbons:C8 alkanes,C 8 alkenes,C9 alkanes,and C10 alkanes,and two groups of nitrogen‐containing compounds:alkyl substituted bipyrrolidines(alkylbipyrrolidines) and alkyl substituted tripyrrolidines(alkyltripyrrolidines) were identified.The hydrogenolysis of porphyrins occurred rapidly at lower temperature but higher temperatures were required for the HDN of porphyrins.The NiMoP3 catalyst showed the highest catalytic activity for the HDN of porphyrins.Based on the characterization of the supports and catalysts,it is suggested that the dispersion of Mo is improved and the number of weak acidic sites on the NiMoP catalysts increases with the addition of phosphorus.展开更多
Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. However, there are several case reports resulted in the regression of hepatocellular carcinoma(HCC) and the accumulation of clinical ...Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. However, there are several case reports resulted in the regression of hepatocellular carcinoma(HCC) and the accumulation of clinical information and analyses of the mechanism can contribute to the development of a novel therapy. For this purpose, we have carefully reviewed 23 cases of spontaneously regressed HCC published in recent 5 years and our case. The information regarding the tumor size, tumor marker, treatments, etc., have been summarized. The mechanism of spontaneous regression has been discussed to date and presumed to be due to many factors, including hypoxia and immunological reactions. In this careful review of the 24 cases based on the clinical information, hypoxia, systemic inflammation, and both upon spontaneous regression were seen in 3, 8, and 4 cases, respectively amo ng t he 15 c as e s f or w hic h t he inf o r mat io n regarding the proposed mechanisms are available. Recent development of immunotherapeutic approaches in oncology shows promising results, therefore, accumulation of additional cases and analysis of mechanisms underlying the spontaneous regression of HCC are essential and could lead to the development of a new generation of immunotherapies including antibodies directed against immune reactions.展开更多
Hepatocellular carcinoma(HCC) is one of the most common cancers and the third highest cause of cancerassociated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the freq...Hepatocellular carcinoma(HCC) is one of the most common cancers and the third highest cause of cancerassociated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization(TOCE), and hepatic arterial infusion chemotherapy(HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.展开更多
BACKGROUND Shear wave speed has been widely applied to quantify a degree of liver fibrosis. However, there is no standardized procedure, which makes it difficult to utilize the speed universally. AIM To provide proced...BACKGROUND Shear wave speed has been widely applied to quantify a degree of liver fibrosis. However, there is no standardized procedure, which makes it difficult to utilize the speed universally. AIM To provide procedural standardization of shear wave speed measurement. METHODS Point shear wave elastography (pSWE) was measured in 781 patients, and twodimensional shear wave elastography (2dSWE) was measured on the same day in 18 cases. Regions-of-interest were placed at 12 sites, and the median and robust coefficient-of-variation (CVR) were calculated. A residual sum-of-square (Σdi2) was computed for bootstrap values of 1000 iterations in 18 cases with each assumption of 1 to 12 measurements. The proportion of the Σdi2 (%Σdi2) was calculated as the ratio of Σdi2 to pSWE after converting it based on the correlation between pSWE and 2dSWE. RESULTS The CVR showed a significantly broader distribution in the left lobe (P < 0.0001),and the smallest CVR in the right anterior segment that covered 95% cases was 40.4%. pSWE was significantly higher in the left lobe than in the right lobe (1.63 ± 0.78 m/s vs 1.61 ± 0.78 m/s, P = 0.0004), and the difference between the lobes became further discrete when the subjects were limited to the cases with a CVR less than 40.4% in any segment (1.76 ± 0.80 m/s vs 1.70 ± 0.82 m/s, P < 0.0001). The highest values of the CVR in every 0.1 m/s interval were plotted in convex upward along pSWE and peaked at 1.93 m/s. pSWE and 2dSWE were significantly correlated (P < 0.0001, r = 0.95). In 216000 resamples from 18 cases, the %Σdi2 of 12 sites was 8.0% and gradually increased as the acquisition sites decreased to reach a significant difference with a %Σdi2 of 7 sites (P = 0.027). CONCLUSION These data suggest that shear wave speed should be measured at 8 or more sites of spreading in both lobes.展开更多
The vascular diseases including aneurysm, occlusion, and thromboses in the mesenteric lesions could cause severe symptoms and appropriate diagnosis and treatment are essential for managing patients. With the developme...The vascular diseases including aneurysm, occlusion, and thromboses in the mesenteric lesions could cause severe symptoms and appropriate diagnosis and treatment are essential for managing patients. With the development and improvement of imaging modalities, diagnostic frequency of these vascular diseases in abdominal lesions is increasing even with the small changes in the vasculatures. Among various vascular diseases, fibromuscular dysplasia(FMD) and segmental arterial mediolysis(SAM) are noninflammatory, nonatherosclerotic arterial diseases which need to be diagnosed urgently because these diseases could affect various organs and be lethal if the appropriate management is not provided. However, because FMD and SAM are rare, the cause, prevalence, clinical characteristics including the symptoms, findings in the imaging studies, pathological findings, management, and prognoses have not been systematically summarized. Therefore, there have been neither standard diagnostic criteria nor therapeutic methodologies established, to date. To systematically summarize the information and to compare these disease entities, we have summarized the characteristics of FMD and SAM in the gastroenterological regions by reviewing the cases reported thus far. The information summarized will be helpful for physicians treating these patients in an emergency care unit and for the differential diagnosis of other diseases showing severe abdominal pain.展开更多
Objective To clarify whether cardiac cachexia(CC)alters the prognostic impact of other general risk factors in patients with heart failure(HF).Methods This was an observational study.CC was defined as the combination ...Objective To clarify whether cardiac cachexia(CC)alters the prognostic impact of other general risk factors in patients with heart failure(HF).Methods This was an observational study.CC was defined as the combination of a body mass index of<20 kg/m^2 and at least one of the following biochemical abnormalities:C-reactive protein>5 mg/L;hemoglobin<12 g/dL;and/or albumin<3.2 g/d L.We divided 1608 hospitalized HF patients into a CC group(n=176,10.9%)and a non-CC group(n=1432,89.1%).The primary endpoints were cardiac event and all-cause death.Results The presence of CC showed significant interactions with other risk factors including cancer,estimated glomerular filtration rate(eGFR),and sodium in predicting these endpoints.Multiple Cox proportional analysis revealed that use of a blockers[hazard ratio(HR)=1.900,95%confidence interval(CI):1.045–3.455,P=0.035]and eGFR(HR=0.989,95%CI:0.980–0.998,P=0.018)were independent predictors of cardiac event in the CC group,while age(HR=1.020,95%CI:1.002–1.039,P=0.029)and hemoglobin(HR=0.844,95%CI:0.734–0.970,P=0.017)were independent predictors of all-cause death.The survival classification and regression tree analysis showed the optimal cut-off points for cardiac event(eGFR:59.9 m L/min per 1.73 m^2)and all-cause death(age,83 years old;hemoglobin,10.1 g/dL)in the CC group.Conclusions In predicting prognosis,CC showed interactions with several risk factors.Renal function,age,and hemoglobin were pivotal markers in HF patients with CC.展开更多
Although particular chromosomal syndromes are phenotypicaUy and clinically distinct, the majority of individuals with autosomal imbalance, such as aneuploidy, manifest mental retardation. A common abnormal phenotype o...Although particular chromosomal syndromes are phenotypicaUy and clinically distinct, the majority of individuals with autosomal imbalance, such as aneuploidy, manifest mental retardation. A common abnormal phenotype of Down syndrome （DS）, the most prevalent autosomal aneuploidy, shows a reduction in both the number and the density of neurons in the brain. As a DS model, we have recently created chimeric mice from ES cells containing a single human chromosome 21. The mice mimicked the characteristic phenotypic features of DS, and ES cells showed a higher incidence of apoptosis during early neuronal differentiation in vitro. In this study, we examined the induction of anomalous early neural development by aneuploidy in mouse ES cells by transferring various human chromosomes or additional mouse chromosomes. Results showed an elevated incidence of apoptosis in all autosome-aneuploid clones examined during early neuronal differentiation in vitro. Further, cDNA microarray analysis revealed a common cluster of down-regulated genes, of which eight known genes are related to cell proliferation, neurite outgrowth and differentiation. Importantly, targeting of these genes by siRNA knockdown in normal mouse ES cells led to enhanced apoptosis during early neuronal differentiation. These findings strongly suggest that autosomal imbalance is associated with general neuronal loss through a common molecular mechanism for apoptosis.展开更多
BACKGROUND As survival has been prolonged owing to surgical and medical improvements,liver failure has become a prognostic determinant in patients with congestive heart diseases.Congestive hepatopathy,an abnormal stat...BACKGROUND As survival has been prolonged owing to surgical and medical improvements,liver failure has become a prognostic determinant in patients with congestive heart diseases.Congestive hepatopathy,an abnormal state of the liver as a result of congestion,insidiously proceed toward end-stage liver disease without effective biomarkers evaluating pathological progression.Regular measurements of shear wave elastography cannot qualify liver fibrosis,which is a prognosticator in any type of chronic liver disease,in cases of congestion because congestion makes the liver stiff without fibrosis.We hypothesized that the effects of congestion and fibrosis on liver stiffness can be dissociated by inducing architectural deformation of the liver to expose structural rigidity.To establish a strategy measuring liver stiffness as a reflection of architectural rigidity under congestion.METHODS Two-dimensional shear wave elastography(2dSWE)was measured in the supine(Sp)and left decubitus(Ld)positions in 298 consecutive cases as they were subjected to an ultrasound study for various liver diseases.Regions of interest were placed at twelve sites,and the median and robust coefficient of variation were calculated.Numerical data were compared using the Mann-Whitney U or Kruskal-Wallis test followed by Dunn's post-hoc multiple comparisons.The inferior vena cava(IVC)diameters at different body positions were compared using the Wilcoxon matched pairs signed rank test.The number of cases with cardiothoracic ratios greater than or not greater than 50%was compared using Fisher’s exact test.A correlation of 2dSWE between different body positions was evaluated by calculating Spearman correlation coefficients.RESULTS The IVC diameter was significantly reduced in Ld in subjects with higher 2dSWE values in Ld(LdSWE)than in Sp(SpSWE)(P=0.007,(average±SD)13.9±3.6 vs 13.1±3.4 mm)but not in those with lower LdSWE values(P=0.32,13.3±3.5 vs 13.0±3.5 mm).In 81 subjects,SpSWE was increased or decreased in Ld beyond the magnitude of robust coefficient of variation,which suggests that body postural changes induced an alteration of liver stiffness significantly larger than the technical dispersion.Among these subjects,all 37 with normal SpSWE had a higher LdSWE than SpSWE(Normal-to-Hard,SpSWE-LdSWE(Δ2dSWE):(minimum-maximum)-0.74--0.08 m/sec),whereas in 44 residual subjects with abnormal SpSWE,LdSWE was higher in 27 subjects(Hard-to-Hard,-0.74--0.05 m/sec)and lower in 17 subjects(Hard-to-Soft,0.04-0.52 m/sec)than SpSWE.SpSWE was significantly correlated withΔ2dSWE only in Hard-to-Soft(P<0.0001).Δ2dSWE was larger in each lobe than in the entire liver.When Hard-to-Hard and Hard-to-Soft values were examined for each lobe,fibrosis-4 or platelet counts were significantly higher or lower only for Hard-to-Soft vs Normal-to-Hard cases.CONCLUSION Gravity alters the hepatic architecture during body postural changes,causing outflow blockage in hepatic veins.A rigid liver is resistant to structural deformation.Stiff-liver softening in the Ld position suggests a fibrous liver.展开更多
基金supported by a research project of The Japan Petroleum Institute commissioned by the Japan Petroleum Cooperation Center, subsidized by the Ministry of Economy, Trade, and Industry
文摘The hydrodenitrogenation(HDN) of porphyrins was carried out over a series of phosphorus containing NiMo/Al 2 O 3 catalysts using a fixed‐bed flow reaction system.A method of quantitative analysis of the porphyrin and its derivatives produced by HDN was established.In HDN of porphyrin,four types of hydrocarbons:C8 alkanes,C 8 alkenes,C9 alkanes,and C10 alkanes,and two groups of nitrogen‐containing compounds:alkyl substituted bipyrrolidines(alkylbipyrrolidines) and alkyl substituted tripyrrolidines(alkyltripyrrolidines) were identified.The hydrogenolysis of porphyrins occurred rapidly at lower temperature but higher temperatures were required for the HDN of porphyrins.The NiMoP3 catalyst showed the highest catalytic activity for the HDN of porphyrins.Based on the characterization of the supports and catalysts,it is suggested that the dispersion of Mo is improved and the number of weak acidic sites on the NiMoP catalysts increases with the addition of phosphorus.
文摘Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. However, there are several case reports resulted in the regression of hepatocellular carcinoma(HCC) and the accumulation of clinical information and analyses of the mechanism can contribute to the development of a novel therapy. For this purpose, we have carefully reviewed 23 cases of spontaneously regressed HCC published in recent 5 years and our case. The information regarding the tumor size, tumor marker, treatments, etc., have been summarized. The mechanism of spontaneous regression has been discussed to date and presumed to be due to many factors, including hypoxia and immunological reactions. In this careful review of the 24 cases based on the clinical information, hypoxia, systemic inflammation, and both upon spontaneous regression were seen in 3, 8, and 4 cases, respectively amo ng t he 15 c as e s f or w hic h t he inf o r mat io n regarding the proposed mechanisms are available. Recent development of immunotherapeutic approaches in oncology shows promising results, therefore, accumulation of additional cases and analysis of mechanisms underlying the spontaneous regression of HCC are essential and could lead to the development of a new generation of immunotherapies including antibodies directed against immune reactions.
文摘Hepatocellular carcinoma(HCC) is one of the most common cancers and the third highest cause of cancerassociated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization(TOCE), and hepatic arterial infusion chemotherapy(HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.
文摘BACKGROUND Shear wave speed has been widely applied to quantify a degree of liver fibrosis. However, there is no standardized procedure, which makes it difficult to utilize the speed universally. AIM To provide procedural standardization of shear wave speed measurement. METHODS Point shear wave elastography (pSWE) was measured in 781 patients, and twodimensional shear wave elastography (2dSWE) was measured on the same day in 18 cases. Regions-of-interest were placed at 12 sites, and the median and robust coefficient-of-variation (CVR) were calculated. A residual sum-of-square (Σdi2) was computed for bootstrap values of 1000 iterations in 18 cases with each assumption of 1 to 12 measurements. The proportion of the Σdi2 (%Σdi2) was calculated as the ratio of Σdi2 to pSWE after converting it based on the correlation between pSWE and 2dSWE. RESULTS The CVR showed a significantly broader distribution in the left lobe (P < 0.0001),and the smallest CVR in the right anterior segment that covered 95% cases was 40.4%. pSWE was significantly higher in the left lobe than in the right lobe (1.63 ± 0.78 m/s vs 1.61 ± 0.78 m/s, P = 0.0004), and the difference between the lobes became further discrete when the subjects were limited to the cases with a CVR less than 40.4% in any segment (1.76 ± 0.80 m/s vs 1.70 ± 0.82 m/s, P < 0.0001). The highest values of the CVR in every 0.1 m/s interval were plotted in convex upward along pSWE and peaked at 1.93 m/s. pSWE and 2dSWE were significantly correlated (P < 0.0001, r = 0.95). In 216000 resamples from 18 cases, the %Σdi2 of 12 sites was 8.0% and gradually increased as the acquisition sites decreased to reach a significant difference with a %Σdi2 of 7 sites (P = 0.027). CONCLUSION These data suggest that shear wave speed should be measured at 8 or more sites of spreading in both lobes.
文摘The vascular diseases including aneurysm, occlusion, and thromboses in the mesenteric lesions could cause severe symptoms and appropriate diagnosis and treatment are essential for managing patients. With the development and improvement of imaging modalities, diagnostic frequency of these vascular diseases in abdominal lesions is increasing even with the small changes in the vasculatures. Among various vascular diseases, fibromuscular dysplasia(FMD) and segmental arterial mediolysis(SAM) are noninflammatory, nonatherosclerotic arterial diseases which need to be diagnosed urgently because these diseases could affect various organs and be lethal if the appropriate management is not provided. However, because FMD and SAM are rare, the cause, prevalence, clinical characteristics including the symptoms, findings in the imaging studies, pathological findings, management, and prognoses have not been systematically summarized. Therefore, there have been neither standard diagnostic criteria nor therapeutic methodologies established, to date. To systematically summarize the information and to compare these disease entities, we have summarized the characteristics of FMD and SAM in the gastroenterological regions by reviewing the cases reported thus far. The information summarized will be helpful for physicians treating these patients in an emergency care unit and for the differential diagnosis of other diseases showing severe abdominal pain.
基金supported in part by a Grant-in-Aid for Scientific Research (No. 16K09447) from the Japan Society for the Promotion of Sciencesupported by Fukuda-denshi Co, Ltd.
文摘Objective To clarify whether cardiac cachexia(CC)alters the prognostic impact of other general risk factors in patients with heart failure(HF).Methods This was an observational study.CC was defined as the combination of a body mass index of<20 kg/m^2 and at least one of the following biochemical abnormalities:C-reactive protein>5 mg/L;hemoglobin<12 g/dL;and/or albumin<3.2 g/d L.We divided 1608 hospitalized HF patients into a CC group(n=176,10.9%)and a non-CC group(n=1432,89.1%).The primary endpoints were cardiac event and all-cause death.Results The presence of CC showed significant interactions with other risk factors including cancer,estimated glomerular filtration rate(eGFR),and sodium in predicting these endpoints.Multiple Cox proportional analysis revealed that use of a blockers[hazard ratio(HR)=1.900,95%confidence interval(CI):1.045–3.455,P=0.035]and eGFR(HR=0.989,95%CI:0.980–0.998,P=0.018)were independent predictors of cardiac event in the CC group,while age(HR=1.020,95%CI:1.002–1.039,P=0.029)and hemoglobin(HR=0.844,95%CI:0.734–0.970,P=0.017)were independent predictors of all-cause death.The survival classification and regression tree analysis showed the optimal cut-off points for cardiac event(eGFR:59.9 m L/min per 1.73 m^2)and all-cause death(age,83 years old;hemoglobin,10.1 g/dL)in the CC group.Conclusions In predicting prognosis,CC showed interactions with several risk factors.Renal function,age,and hemoglobin were pivotal markers in HF patients with CC.
文摘Although particular chromosomal syndromes are phenotypicaUy and clinically distinct, the majority of individuals with autosomal imbalance, such as aneuploidy, manifest mental retardation. A common abnormal phenotype of Down syndrome （DS）, the most prevalent autosomal aneuploidy, shows a reduction in both the number and the density of neurons in the brain. As a DS model, we have recently created chimeric mice from ES cells containing a single human chromosome 21. The mice mimicked the characteristic phenotypic features of DS, and ES cells showed a higher incidence of apoptosis during early neuronal differentiation in vitro. In this study, we examined the induction of anomalous early neural development by aneuploidy in mouse ES cells by transferring various human chromosomes or additional mouse chromosomes. Results showed an elevated incidence of apoptosis in all autosome-aneuploid clones examined during early neuronal differentiation in vitro. Further, cDNA microarray analysis revealed a common cluster of down-regulated genes, of which eight known genes are related to cell proliferation, neurite outgrowth and differentiation. Importantly, targeting of these genes by siRNA knockdown in normal mouse ES cells led to enhanced apoptosis during early neuronal differentiation. These findings strongly suggest that autosomal imbalance is associated with general neuronal loss through a common molecular mechanism for apoptosis.
文摘BACKGROUND As survival has been prolonged owing to surgical and medical improvements,liver failure has become a prognostic determinant in patients with congestive heart diseases.Congestive hepatopathy,an abnormal state of the liver as a result of congestion,insidiously proceed toward end-stage liver disease without effective biomarkers evaluating pathological progression.Regular measurements of shear wave elastography cannot qualify liver fibrosis,which is a prognosticator in any type of chronic liver disease,in cases of congestion because congestion makes the liver stiff without fibrosis.We hypothesized that the effects of congestion and fibrosis on liver stiffness can be dissociated by inducing architectural deformation of the liver to expose structural rigidity.To establish a strategy measuring liver stiffness as a reflection of architectural rigidity under congestion.METHODS Two-dimensional shear wave elastography(2dSWE)was measured in the supine(Sp)and left decubitus(Ld)positions in 298 consecutive cases as they were subjected to an ultrasound study for various liver diseases.Regions of interest were placed at twelve sites,and the median and robust coefficient of variation were calculated.Numerical data were compared using the Mann-Whitney U or Kruskal-Wallis test followed by Dunn's post-hoc multiple comparisons.The inferior vena cava(IVC)diameters at different body positions were compared using the Wilcoxon matched pairs signed rank test.The number of cases with cardiothoracic ratios greater than or not greater than 50%was compared using Fisher’s exact test.A correlation of 2dSWE between different body positions was evaluated by calculating Spearman correlation coefficients.RESULTS The IVC diameter was significantly reduced in Ld in subjects with higher 2dSWE values in Ld(LdSWE)than in Sp(SpSWE)(P=0.007,(average±SD)13.9±3.6 vs 13.1±3.4 mm)but not in those with lower LdSWE values(P=0.32,13.3±3.5 vs 13.0±3.5 mm).In 81 subjects,SpSWE was increased or decreased in Ld beyond the magnitude of robust coefficient of variation,which suggests that body postural changes induced an alteration of liver stiffness significantly larger than the technical dispersion.Among these subjects,all 37 with normal SpSWE had a higher LdSWE than SpSWE(Normal-to-Hard,SpSWE-LdSWE(Δ2dSWE):(minimum-maximum)-0.74--0.08 m/sec),whereas in 44 residual subjects with abnormal SpSWE,LdSWE was higher in 27 subjects(Hard-to-Hard,-0.74--0.05 m/sec)and lower in 17 subjects(Hard-to-Soft,0.04-0.52 m/sec)than SpSWE.SpSWE was significantly correlated withΔ2dSWE only in Hard-to-Soft(P<0.0001).Δ2dSWE was larger in each lobe than in the entire liver.When Hard-to-Hard and Hard-to-Soft values were examined for each lobe,fibrosis-4 or platelet counts were significantly higher or lower only for Hard-to-Soft vs Normal-to-Hard cases.CONCLUSION Gravity alters the hepatic architecture during body postural changes,causing outflow blockage in hepatic veins.A rigid liver is resistant to structural deformation.Stiff-liver softening in the Ld position suggests a fibrous liver.
