The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes P-4...The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes P-450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients' health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider.展开更多
Primary malignant melanoma of the liver is an exceedingly rare tumor. Only 12 cases have been reported in the worldwide literature. We present a case of isolated malignant melanoma of the liver occurring in a 36-year-...Primary malignant melanoma of the liver is an exceedingly rare tumor. Only 12 cases have been reported in the worldwide literature. We present a case of isolated malignant melanoma of the liver occurring in a 36-year-old Chinese male patient. Comprehensive dermatologic and ophthalmologic examinations revealed no evidence of a cutaneous or ocular primary lesion. Other lesions in brain, respiratory tract, lung, gastrointestinal tract and anus, were not demonstrated by serial position emission tomography (PET). Microscopic examination of the resected specimen revealed a malignant melanoma, which was confi rmed by immunohistochemical staining for HMB-45, S-100 protein, melanoma-pan and vimentin. Moreover, electron microscopy demonstrated melanosomes in tumor cell cytoplasm. Our case shows that primary malignant melanoma may occur in the liver and should be considered when the histopathological appearance is not typical for other hepatic neoplasm.展开更多
AIM:To evaluate the glycated hemoglobin(HbA_(1c)) determination methods and to determine fructosamine in patients with chronic hepatitis,compensated cirrhosis and in patients with chronic hepatitis treated with ribavi...AIM:To evaluate the glycated hemoglobin(HbA_(1c)) determination methods and to determine fructosamine in patients with chronic hepatitis,compensated cirrhosis and in patients with chronic hepatitis treated with ribavirin. METHODS:HbA_(1c) values were determined in 15 patients with compensated liver cirrhosis and in 20 patients with chronic hepatitis using the ion-exchange high performance liquid chromatography and the immunoassay methods. Fructosamine was determined using nitroblue tetrazolium. RESULTS:Forty percent of patients with liver cirrhosis had HbA_(1c) results below the non-diabetic reference range by at least one HbA_(1c)method,while fructosamine results were either within the reference range or elevated.Twenty percent of patients with chronic hepatitis(hepatic fibrosis) had HbA_(1c)results below the non-diabetic reference range by at least one HbA_(1c)method.In patients with chronic hepatitis treated with ribavirin,50% of HbA_(1c)results were below the non-diabetic reference using at least one of the HbA_(1c)methods. CONCLUSION:Only evaluated in context with all liver function parameters as well as a red blood count including reticulocytes,HbA_(1c)results should be used in patients with advanced liver disease.HbA_(1c)and fructosamine measurements should be used with caution when evaluating long-term glucose control in patients with hepatic cirrhosis or in patients with chronic hepatitis and dbavidn treatment.展开更多
AIM： To cost-effectively express the 23-ku pE2, the most promising subunit vaccine encoded by the E2 fragment comprising of the 3＇-portion of hepatitis E virus （HEV） open reading frame 2 （ORF2） in plastids of to...AIM： To cost-effectively express the 23-ku pE2, the most promising subunit vaccine encoded by the E2 fragment comprising of the 3＇-portion of hepatitis E virus （HEV） open reading frame 2 （ORF2） in plastids of tobacco （Nicotiana tabacum cv. SR1）, to investigate the transgene expression and pE2 accumulation in plastids, and to evaluate the antigenic effect of the plastid-derived pE2 in mice. METHODS： Plastid-targeting vector pRB94-E2 containing the E2 fragment driven by rice psbA promoter was constructed. Upon delivery into tobacco plastids, this construct could initiate homologous recombination in psaB-trnfM and trnG-psbC fragments in plastid genome, and result in transgene inserted between the two fragments. The pRB94-E2 was delivered with a biolistic particle bombardment method, and the plastid-transformed plants were obtained following the regeneration of the bombarded leaf tissues on a spectinomycin-supplemented medium. Transplastomic status of the regenerated plants was confirmed by PCR and Southern blot analysis, transgene expression was investigated by Northern blot analysis, and accumulation of pE2 was measured by ELISA. Furthermore, protein extracts were used to immunize mice, and the presence of the pE2-reactive antibodies in serum samples of the immunized mice was studied by ELISA. RESULTS： Transplastomic lines confirmed by PCR and Southern blot analysis could actively transcribe the E2 mRNA. The pE2 polypeptide was accumulated to a level as high as 13.27 μg/g fresh leaves. The pE2 could stimulate the immunized mice to generate pE2-specific antibodies. CONCLUSION： HEV-E2 fragment can be inserted into the plastid genome and the recombinant pE2 antigen derived is antigenic in mice. Hence, plastids may be a novel source for cost-effective production of HEV vaccines.展开更多
AIM： To examine the serum from black African patients with acute hepatitis B to ascertain if integrants of viral DNA can be detected in fragments of cellular DNA leaking from damaged hepatocytes into the circulation....AIM： To examine the serum from black African patients with acute hepatitis B to ascertain if integrants of viral DNA can be detected in fragments of cellular DNA leaking from damaged hepatocytes into the circulation. METHODS： DNA was extracted from the sera of five patients with uncomplicated acute hepatitis B and one with fulminant disease. Two subgenomic PCRs designed to amplify the complete genome of HBV were used and the resulting amplicons were cloned and sequenced. RESULTS： HBV and chromosomal DNA were amplified from the sera of all the patients. In one patient with uncomplicated disease, HBV DNA was integrated into host chromosome 7 q11.23 in the WBSCR1 gene. The viral DNA comprised 200 nucleotides covering the S and X genes in opposite orientation, with a 1 169 nucleotide deletion. The right virus/host junction was situated at nucleotide 1 774 in the cohesive overlap region of the viral genome, at a preferred topoisomerase I cleavage motif. The chromosomal DNA was not rearranged. The patient made a full recovery and seroconverted to anti-HBs- and anti-HBe-positivity. Neither HBV nor chromosomal DNA could be amplified from his serum at that time. CONCLUSION： Integration of viral DNA into chromosomal DNA may occur rarely during acute hepatitis B and, with clonal propagation of the integrant, might play a role in hepatocarcinogenesis.展开更多
The treatment of metastic melanoma has rapidly evolved in the last 5 years, giving clinicians and patients the hope for long lasting responses. In the field of modern immunotherapy, we are reaching the point of an exp...The treatment of metastic melanoma has rapidly evolved in the last 5 years, giving clinicians and patients the hope for long lasting responses. In the field of modern immunotherapy, we are reaching the point of an expressive percentage of patients achieving long term survival with anti-CTLA4 and anti-PD1 checkpoint inhibitors. Of note, there is a considerable amount of patients excluded from the checkpoint blockade trials because of comorbidities like chronic viral infections. A precaution to avoid autoimmune induced hepatitis rendered HBV （hepatitis B virus） and HCV （hepatitis C virus） infected patients usually ineligible, but real life data in those patients, who are getting treatment despite of that, is pointing toward the feasibility and safety of immunotherapy in this context. To ilustrate that, we report the case of a metastatic non-BRAF mutated melanoma patient with HCV chronic infection and a surprising benefit derived from ipilimumab and pembrolizumab for his latter condition.展开更多
文摘The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes P-450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients' health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider.
文摘Primary malignant melanoma of the liver is an exceedingly rare tumor. Only 12 cases have been reported in the worldwide literature. We present a case of isolated malignant melanoma of the liver occurring in a 36-year-old Chinese male patient. Comprehensive dermatologic and ophthalmologic examinations revealed no evidence of a cutaneous or ocular primary lesion. Other lesions in brain, respiratory tract, lung, gastrointestinal tract and anus, were not demonstrated by serial position emission tomography (PET). Microscopic examination of the resected specimen revealed a malignant melanoma, which was confi rmed by immunohistochemical staining for HMB-45, S-100 protein, melanoma-pan and vimentin. Moreover, electron microscopy demonstrated melanosomes in tumor cell cytoplasm. Our case shows that primary malignant melanoma may occur in the liver and should be considered when the histopathological appearance is not typical for other hepatic neoplasm.
文摘AIM:To evaluate the glycated hemoglobin(HbA_(1c)) determination methods and to determine fructosamine in patients with chronic hepatitis,compensated cirrhosis and in patients with chronic hepatitis treated with ribavirin. METHODS:HbA_(1c) values were determined in 15 patients with compensated liver cirrhosis and in 20 patients with chronic hepatitis using the ion-exchange high performance liquid chromatography and the immunoassay methods. Fructosamine was determined using nitroblue tetrazolium. RESULTS:Forty percent of patients with liver cirrhosis had HbA_(1c) results below the non-diabetic reference range by at least one HbA_(1c)method,while fructosamine results were either within the reference range or elevated.Twenty percent of patients with chronic hepatitis(hepatic fibrosis) had HbA_(1c)results below the non-diabetic reference range by at least one HbA_(1c)method.In patients with chronic hepatitis treated with ribavirin,50% of HbA_(1c)results were below the non-diabetic reference using at least one of the HbA_(1c)methods. CONCLUSION:Only evaluated in context with all liver function parameters as well as a red blood count including reticulocytes,HbA_(1c)results should be used in patients with advanced liver disease.HbA_(1c)and fructosamine measurements should be used with caution when evaluating long-term glucose control in patients with hepatic cirrhosis or in patients with chronic hepatitis and dbavidn treatment.
基金Supported by a grant from the Hong Kong Research Grant Council, No. 7342/03M to YX Zhou and E Lam
文摘AIM： To cost-effectively express the 23-ku pE2, the most promising subunit vaccine encoded by the E2 fragment comprising of the 3＇-portion of hepatitis E virus （HEV） open reading frame 2 （ORF2） in plastids of tobacco （Nicotiana tabacum cv. SR1）, to investigate the transgene expression and pE2 accumulation in plastids, and to evaluate the antigenic effect of the plastid-derived pE2 in mice. METHODS： Plastid-targeting vector pRB94-E2 containing the E2 fragment driven by rice psbA promoter was constructed. Upon delivery into tobacco plastids, this construct could initiate homologous recombination in psaB-trnfM and trnG-psbC fragments in plastid genome, and result in transgene inserted between the two fragments. The pRB94-E2 was delivered with a biolistic particle bombardment method, and the plastid-transformed plants were obtained following the regeneration of the bombarded leaf tissues on a spectinomycin-supplemented medium. Transplastomic status of the regenerated plants was confirmed by PCR and Southern blot analysis, transgene expression was investigated by Northern blot analysis, and accumulation of pE2 was measured by ELISA. Furthermore, protein extracts were used to immunize mice, and the presence of the pE2-reactive antibodies in serum samples of the immunized mice was studied by ELISA. RESULTS： Transplastomic lines confirmed by PCR and Southern blot analysis could actively transcribe the E2 mRNA. The pE2 polypeptide was accumulated to a level as high as 13.27 μg/g fresh leaves. The pE2 could stimulate the immunized mice to generate pE2-specific antibodies. CONCLUSION： HEV-E2 fragment can be inserted into the plastid genome and the recombinant pE2 antigen derived is antigenic in mice. Hence, plastids may be a novel source for cost-effective production of HEV vaccines.
基金Supported by grants from the Poliomyelitis Research Foundation of South African and the HE Griffin Cancer Trust
文摘AIM： To examine the serum from black African patients with acute hepatitis B to ascertain if integrants of viral DNA can be detected in fragments of cellular DNA leaking from damaged hepatocytes into the circulation. METHODS： DNA was extracted from the sera of five patients with uncomplicated acute hepatitis B and one with fulminant disease. Two subgenomic PCRs designed to amplify the complete genome of HBV were used and the resulting amplicons were cloned and sequenced. RESULTS： HBV and chromosomal DNA were amplified from the sera of all the patients. In one patient with uncomplicated disease, HBV DNA was integrated into host chromosome 7 q11.23 in the WBSCR1 gene. The viral DNA comprised 200 nucleotides covering the S and X genes in opposite orientation, with a 1 169 nucleotide deletion. The right virus/host junction was situated at nucleotide 1 774 in the cohesive overlap region of the viral genome, at a preferred topoisomerase I cleavage motif. The chromosomal DNA was not rearranged. The patient made a full recovery and seroconverted to anti-HBs- and anti-HBe-positivity. Neither HBV nor chromosomal DNA could be amplified from his serum at that time. CONCLUSION： Integration of viral DNA into chromosomal DNA may occur rarely during acute hepatitis B and, with clonal propagation of the integrant, might play a role in hepatocarcinogenesis.
文摘The treatment of metastic melanoma has rapidly evolved in the last 5 years, giving clinicians and patients the hope for long lasting responses. In the field of modern immunotherapy, we are reaching the point of an expressive percentage of patients achieving long term survival with anti-CTLA4 and anti-PD1 checkpoint inhibitors. Of note, there is a considerable amount of patients excluded from the checkpoint blockade trials because of comorbidities like chronic viral infections. A precaution to avoid autoimmune induced hepatitis rendered HBV （hepatitis B virus） and HCV （hepatitis C virus） infected patients usually ineligible, but real life data in those patients, who are getting treatment despite of that, is pointing toward the feasibility and safety of immunotherapy in this context. To ilustrate that, we report the case of a metastatic non-BRAF mutated melanoma patient with HCV chronic infection and a surprising benefit derived from ipilimumab and pembrolizumab for his latter condition.
