Mutation of the p53 gene is a key event in the carcinogenesis of many different types of tumours. These can occur throughout the length of the p53 gene. Anti-p53 auto-antibodies are commonly produced in response to th...Mutation of the p53 gene is a key event in the carcinogenesis of many different types of tumours. These can occur throughout the length of the p53 gene. Anti-p53 auto-antibodies are commonly produced in response to these p53 mutations. This review firstly describes the various mechanisms of p53 dysfunction and their association with subsequent carcinogenesis. Following this, the mechanisms of induction of anti-p53 auto-antibody production are shown, with various hypotheses for the discrepancies between the presence of p53 mutation and the presence/absence of anti-p53 auto-antibodies. A systematic review was performed with a descriptive summary of key findings of each anti-p53 auto-antibody study in all cancers published in the last 30 years. Using this, the cumulative frequency of anti-p53 autoantibody in each cancer type is calculated and then compared with the incidence of p53 mutation in each cancer to provide the largest sample calculation and correlation between mutation and anti-p53 auto-antibody published to date. Finally, the review focuses onthe data of anti-p53 auto-antibody in colorectal cancer studies, and discusses future strategies including the potentially promising role using anti-p53 auto-antibody presence in screening and surveillance.展开更多
Objective The study will explore effects of the autoantibodies against AT1 receptor and angiotensin Ⅱ on the refractory hypertension. Methods Seventy-seven patients (46 men and 31 women) with essential hypertension w...Objective The study will explore effects of the autoantibodies against AT1 receptor and angiotensin Ⅱ on the refractory hypertension. Methods Seventy-seven patients (46 men and 31 women) with essential hypertension were divided into groups of refractory hypertension (RH) and hypertension (HT) according to the 1999 WHO-ISH Guidelines for the Management of Hypertension. Forty normotensives (22 men) were recruited as controls. The mean age was 54. 3±13 years old in RH group, 53. 5±9 years old in HT group and 51. 2±11. 9 years old in normotensives (NT) group. The mean blood pressure was 154. 2±9. 4/98. 4± 8. 2 mmHg in RH group and 130. 1±7. 6/80. 5±6. 7 mmHg in HT group after combination drug therapy of hypertension for 4 weeks. Blood pressure in NT group was 120. 8±11. 7/76. 4 ± 7. 2 mmHg. The epitope of the 2nd extracellular loops of AT1 receptor was synthesized and used as antigens to screen the autoantibodies by ELISA. Plasma angiotensin (Ang) II were examined by a radioimmunoassay. Results The autoantibodies against AT1 receptor were positive in 18 (46. 15 %) patients with RH, in 4 (10. 5 % ) hypertension and in 3 (7. 5 % ) normotensives, P < 0. 01. Ang Ⅱwas 57. 01±52. 63 pmol/L in patients with RH. Both the autoantibodies positive and the Ang Ⅱ increasing were 4 (10. 3 % ) cases, both normal were 7 (17. 9 % ) cases, the autoantibodies positive or Ang II increasing was all of 14 (35. 9 % ) cases (x2 = 0. 09, P>0. 05) . There was no relationship between the autoantibodies against AT1 receptor and the angiotensin Ⅱ in refractory hypertension. Conclusion The autoantibodies against AT1 receptor and Ang Ⅱ might be two independent factors in developing of refractory hypertension. The findings suggest that AT1 receptor an-tagnist used in the treatment of refractory hypertension might have an important value.展开更多
Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of e...Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients.The genetic basis,biological functions,and epitopes of the obtained Bn Abs were assessed and modeled.Results Two Bn Abs,2-12 D5,and 3-37 G7.1,were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset.Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity(ADCC)activity.Albeit derived from distinct Ab lineages,i.e.,V^H1-69-D2-15-JH^4(2-12D5)and V^H1-2-D3-9-JH^5(3-32 G7.1),the Bn Abs were directed toward CR6261-like epitopes in the HA stem,and HA2 I45 in the hydrophobic pocket was the critical residue for their binding.Signature motifs for binding with the HA stem,namely,IFY in VH1-69-encoded Abs and LXYFXW in D3-9-encoded Abs,were also observed in 2-12D5 and 3-32 G7.1,respectively.Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus.The HA stem epitopes targeted by the Bn Abs,and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.展开更多
The method of immunohistochemistry assay for the detection of scrapie in Chinese Short-tailed Han sheep was established using monoclonal antibody. Genomic DNA was isolated from Chinese Short-tailed Hart sheep blood. U...The method of immunohistochemistry assay for the detection of scrapie in Chinese Short-tailed Han sheep was established using monoclonal antibody. Genomic DNA was isolated from Chinese Short-tailed Hart sheep blood. Using the polymerase chain reaction technique, PrP27-30 gene sequence was amplified from Chinese Short-tailed Han sheep genomic DNA. By recombinant DNA technology, the recombinant protein of Chinese Short-tailed Han sheep PrP27-30 was obtained. Then, using standard methodology of myeloma cell fusion, a panel of monoclonal antibodies was generated. With mAbs, scrapie in Chinese Short-tailed Han sheep was detected by immunohistochemistry assay. The recombinant protein of Chinese Short-tailed Han sheep PrP27-30 was obtained and a panel of six hybridoma cell lines secreting specific antibodies to Chinese Short-tailed Han sheep PrP27-30 related to scrapie was obtained with one fusion between myeloma Sp2/0 and spleen ceils from mice immunized with the purified recombinant protein. Four hybridoma cell lines can be used in immunohistochemistry assay for the detection of scrapie in Chinese Short-tailed Han sheep. So that the special monoclonal antibody developed in author＇s institute can be used to detect PrP^sc of scrapie in Chinese Short-tailed Han sheep by immunohistochemistry in China.展开更多
The expression of an auto-antibody in patients with edematous acute pancreatitis and its possible clinical significance was investiaged. Eighteen cases of acute pancreatitis were chosen as experimental group and 25 su...The expression of an auto-antibody in patients with edematous acute pancreatitis and its possible clinical significance was investiaged. Eighteen cases of acute pancreatitis were chosen as experimental group and 25 subjects served as control group. Venous blood samples were taken in both groups at 4 time points: at the day of admission, the 2nd, 4th and 7th day of hospitalization. By using indirect immuno-fluorescence tests the expression of auto-antibody in the samples was semiquantitatively detected. Other biochemical indexes, such as serum amylase, urine amylase, were determined simultaneously. As well, the clinical signs or symptoms were mornitored. It was found that the expression of the auto-antibody was gradually enhanced with the development of acute pancreatitis. The inceased positive expression of auto-antibody showed a correlationship with the improvement of biochemical indexes (r=0.951) and clinical manifestations (r=0.996). There was significant difference between experimental and control groups (P<0.05). During the recovery period of acute pancreatitis, gradually increased auto-antibody expression was detectable. This antibody is against the interstitial structure of the pancreas.展开更多
Based on the structure of chute - feed and autoleveHer, an analysis of their working principle and the verification of their practical production results have been carried out. Finally, the future investigation direet...Based on the structure of chute - feed and autoleveHer, an analysis of their working principle and the verification of their practical production results have been carried out. Finally, the future investigation direetiom of chute - feed and card autuleveller are put forward.展开更多
Hepatocellular carcinoma(HCC)is rarely associated with autoimmune paraneoplastic syndromes.We report a case of anti-transcriptional intermediary factor-1 gamma(TIF1-γ)-positive dermatomyositis(DM)as clinical presenta...Hepatocellular carcinoma(HCC)is rarely associated with autoimmune paraneoplastic syndromes.We report a case of anti-transcriptional intermediary factor-1 gamma(TIF1-γ)-positive dermatomyositis(DM)as clinical presentation of HCC recurrence in a 72-year-old male patient admitted to our hospital due to fatigue,myalgia,and typical skin rash.His medical history was notable for hepatitis C-related cirrhosis,successful treatment with direct-acting antiviral agents,and previously efficacious treatment of HCC.Laboratory testing showed significant rhabdomyolysis with antiTIF1-γantibodies at high titer,and DM was diagnosed.After a careful diagnostic workup,HCC recurrence was diagnosed.After first-line corticosteroid treatment,azathioprine and intravenous immunoglobulin treatments were administered;unfortunately,he mounted only partial response.Owing to the compromised performance status,no HCC treatment was feasible,and,according to international guidelines,he received only best supportive care.Here,we discuss the diagnostic,prognostic,and pathogenic roles of anti-TIF1-γantibodies associated with paraneoplastic DM and the scant literature data on its occurrence in HCC patients.Considering the TIF1 gene family’s established role in oncogenesis,we also review the role of TIF1-γas a tumor-related neoantigen,leading to the development of clinically overt antiTIF1-γantibodies-positive DM.展开更多
Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseas-es(AiLD),namely autoimmune hepatitis types 1 and 2(AIH-1 and 2),primary biliary cirrhosis(PBC),and the s...Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseas-es(AiLD),namely autoimmune hepatitis types 1 and 2(AIH-1 and 2),primary biliary cirrhosis(PBC),and the sclerosing cholangitis variants in adults and children.AIH-1 is specified by anti-nuclear antibody(ANA) and smooth muscle antibody(SMA).AIH-2 is specified by antibody to liver kidney microsomal antigen type-1(anti-LKM1) and anti-liver cytosol type 1(anti-LC1).SMA,ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation.PBC is specified by antimitochondrial antibodies(AMA) react-ing with enzymes of the 2-oxo-acid dehydrogenase complexes(chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly react-ing with nuclear pore gp210 and nuclear body sp100.Sclerosing cholangitis presents as at least two variants,first the classical primary sclerosing cholangitis(PSC) mostly affecting adult men wherein the only(and non-specific) reactivity is an atypical perinuclear antineutro-phil cytoplasmic antibody(p-ANCA),also termed peri-nuclear anti-neutrophil nuclear antibodies(p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis(ASC) with serological features resembling those of type 1 AIH.Liver diagnostic serol-ogy is a fast-expanding area of investigation as new purified and recombinant autoantigens,and automatedtechnologies such as ELISAs and bead assays,become available to complement(or even compete with) tradi-tional immunofluorescence procedures.We survey for the first time global trends in quality assurance impact-ing as it does on(1) manufacturers/purveyors of kits and reagents,(2) diagnostic service laboratories that fulfill clinicians' requirements,and(3) the end-user,the physician providing patient care,who must properly interpret test results in the overall clinical context.展开更多
Objective To study the potential role of tumor necrosis factor-α (TNF-α) induction in the development of mucosal barrier dysfunction in rats caused by acute intestinal ischemia-reperfusion injury, and to examine whe...Objective To study the potential role of tumor necrosis factor-α (TNF-α) induction in the development of mucosal barrier dysfunction in rats caused by acute intestinal ischemia-reperfusion injury, and to examine whether pretreatment with monoclonal antibody against TNF-α (TNF-α MoAb) would affect the release of D(-)-lactate after local gut ischemia followed by reperfusion. Methods Anesthetized Sprague-Dawley rats underwent superior mesenteric artery occlusion for 75 min followed by reperfusion for 6 hr. The rats were treated intravenously with either TNF-α MoAb (20 mg/kg) or albumin (20 mg/kg) 30 min prior to the onset of ischemia. Plasma D(-)-lactate levels were measured in both the portal and systemic blood by an enzymatic spectrophotometric assay. Intestinal TNF-αmRNA expression as well as protein levels were also measured at various intervals. In addition, a postmortem examination was performed together with a macropathological evaluation based on a four-grade scoring system.Results Intestinal ischemia resulted in a significant elevation in D(-)-lactate levels in the portal vein blood in both the control and treatment groups ( P ＜0.05). However, animals pretreated with TNF-α MoAb at 6 hr after reperfusion showed significant attenuation of an increase in both portal and systemic D(-)-lactate levels when compared with those only receiving albumin (P ＜ 0.05). In the control animals, a remarkable rise in intestinal TNF-α level was measured at 0.5 hr after clamp release ( P ＜ 0.01); however, prophylactic treatment with TNF-α MoAb completely annulled the increase of local TNF-α levels seen in the control animals. Similarly, after anti-TNF-α MoAb administration, intestinal TNF-α mRNA expression was markedly inhibited, which showed significant differences when compared with the control group at 0.5 hr, 2 hr and 6 hr after the release of occlusion ( P ＜ 0.05-0.01 ). In addition, the pathological examination showed marked intestinal lesions that formed during ischemia, which were much worse upon reperfusion,particularly at the 6 hr time point. These acute injuries were obviously attenuated in animals receiving TNF-α MoAb.Conclusions It appeared that acute intestinal ischemia was associated with failure of the mucosal barrier, resulting in increased plasma D(-)-lactate levels in both portal and systemic blood. These results suggest that TNF-α appears to be involved in the development of local damage associated with intestinal ischemic injury. Moreover, prophylactic treatment with TNF-α MoAb exerts preventive effects on ischemia/ reperfusion-induced circulating D (-)-lactate elevation and gut injury. ( J Geriatr Cardiol 2004;1(2):119-124. )展开更多
Aggregate amyloid beta protein1-42 (Aβ1-42) can typically be found in the early stage of Alzheimer’s disease (AD). Aβ1-42 self-assembles and is highly toxic to neurons. Thus, recognizing aggregated Aβ1-42 is very ...Aggregate amyloid beta protein1-42 (Aβ1-42) can typically be found in the early stage of Alzheimer’s disease (AD). Aβ1-42 self-assembles and is highly toxic to neurons. Thus, recognizing aggregated Aβ1-42 is very important for elucidation of Aβ1-42 structure and for the diagnosis of AD. In this study, the specificity of the 79-3 monoclonal antibody against soluble aggre- gate Aβ1-42 was measured by sandwich Enzyme-Linked Immuno Sorbent Assay (ELISA). Eight monoclonal antibodies against both soluble aggregates and amorphous aggregates were used as primary antibodies. Soluble aggregates and amorphous aggregates were used as antigen. As secondary antibody, HRP was labeled with the 79-3 monoclonal antibody. The reactivity of the 79-3 monoclonal antibody against soluble aggregates was confirmed in all combinations, but little reactivity against amorphous aggregates was found. Furthermore, we performed the above sandwich ELISA using the 37-11 antibody, which is reactive against large oval aggregates (LOA) that occur in micro aggregates, instead of the 79-3 antibody. The 77-3 antibody is 1 of the 8 monoclonal antibodies against soluble aggregates;amorphous aggregates also reacted with the 37-11 antibody. These results indicated that soluble aggregates are specifically recognized by a combination of different antibodies. The combined use of these antibodies can be applied to the diagnosis of AD and to defining the structure of the Aβ1-42.展开更多
Uric acid is reduced in demyelinating diseases, including multiple sclerosis and neuromyelitis optica （NMO）. Longitudinally extensive transverse myelitis （LETM） is often an early manifestation of NMO. Whether uric...Uric acid is reduced in demyelinating diseases, including multiple sclerosis and neuromyelitis optica （NMO）. Longitudinally extensive transverse myelitis （LETM） is often an early manifestation of NMO. Whether uric acid levels are reduced at presentation of LETM remains unknown. The present study investigated serum uric acid levels by evaluating 35 patients with LETM, 64 with NMO, 62 with multiple sclerosis, 63 with other neurological diseases and 65 healthy controls. In addition, we tested the correlation between serum uric acid and the clinical characteristics of LETM. All patients were in the acute phase, defined as less than 1 month from onset or relapse. The results revealed that serum uric acid levels in LETM were significantly lower than in multiple sclerosis, other neurological diseases and healthy controls, but no difference was found between LETM and NMO. A negative correlation between uric acid levels and Expanded Disability Status Scale scores was found in LETM patients （r = -0.545, P 〈 0.05）. The results suggest that uric acid levels are reduced in patients with LETM, raising the possibility that lower uric acid levels are an indicator of disease disability. Moreover, reduced uric acid levels may be a risk factor in NMO.展开更多
文摘Mutation of the p53 gene is a key event in the carcinogenesis of many different types of tumours. These can occur throughout the length of the p53 gene. Anti-p53 auto-antibodies are commonly produced in response to these p53 mutations. This review firstly describes the various mechanisms of p53 dysfunction and their association with subsequent carcinogenesis. Following this, the mechanisms of induction of anti-p53 auto-antibody production are shown, with various hypotheses for the discrepancies between the presence of p53 mutation and the presence/absence of anti-p53 auto-antibodies. A systematic review was performed with a descriptive summary of key findings of each anti-p53 auto-antibody study in all cancers published in the last 30 years. Using this, the cumulative frequency of anti-p53 autoantibody in each cancer type is calculated and then compared with the incidence of p53 mutation in each cancer to provide the largest sample calculation and correlation between mutation and anti-p53 auto-antibody published to date. Finally, the review focuses onthe data of anti-p53 auto-antibody in colorectal cancer studies, and discusses future strategies including the potentially promising role using anti-p53 auto-antibody presence in screening and surveillance.
文摘Objective The study will explore effects of the autoantibodies against AT1 receptor and angiotensin Ⅱ on the refractory hypertension. Methods Seventy-seven patients (46 men and 31 women) with essential hypertension were divided into groups of refractory hypertension (RH) and hypertension (HT) according to the 1999 WHO-ISH Guidelines for the Management of Hypertension. Forty normotensives (22 men) were recruited as controls. The mean age was 54. 3±13 years old in RH group, 53. 5±9 years old in HT group and 51. 2±11. 9 years old in normotensives (NT) group. The mean blood pressure was 154. 2±9. 4/98. 4± 8. 2 mmHg in RH group and 130. 1±7. 6/80. 5±6. 7 mmHg in HT group after combination drug therapy of hypertension for 4 weeks. Blood pressure in NT group was 120. 8±11. 7/76. 4 ± 7. 2 mmHg. The epitope of the 2nd extracellular loops of AT1 receptor was synthesized and used as antigens to screen the autoantibodies by ELISA. Plasma angiotensin (Ang) II were examined by a radioimmunoassay. Results The autoantibodies against AT1 receptor were positive in 18 (46. 15 %) patients with RH, in 4 (10. 5 % ) hypertension and in 3 (7. 5 % ) normotensives, P < 0. 01. Ang Ⅱwas 57. 01±52. 63 pmol/L in patients with RH. Both the autoantibodies positive and the Ang Ⅱ increasing were 4 (10. 3 % ) cases, both normal were 7 (17. 9 % ) cases, the autoantibodies positive or Ang II increasing was all of 14 (35. 9 % ) cases (x2 = 0. 09, P>0. 05) . There was no relationship between the autoantibodies against AT1 receptor and the angiotensin Ⅱ in refractory hypertension. Conclusion The autoantibodies against AT1 receptor and Ang Ⅱ might be two independent factors in developing of refractory hypertension. The findings suggest that AT1 receptor an-tagnist used in the treatment of refractory hypertension might have an important value.
基金supported by the General Program of the National Natural Science Foundation of China[No.31570162]the National Key Research Program[No.2016YFC1200200].
文摘Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients.The genetic basis,biological functions,and epitopes of the obtained Bn Abs were assessed and modeled.Results Two Bn Abs,2-12 D5,and 3-37 G7.1,were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset.Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity(ADCC)activity.Albeit derived from distinct Ab lineages,i.e.,V^H1-69-D2-15-JH^4(2-12D5)and V^H1-2-D3-9-JH^5(3-32 G7.1),the Bn Abs were directed toward CR6261-like epitopes in the HA stem,and HA2 I45 in the hydrophobic pocket was the critical residue for their binding.Signature motifs for binding with the HA stem,namely,IFY in VH1-69-encoded Abs and LXYFXW in D3-9-encoded Abs,were also observed in 2-12D5 and 3-32 G7.1,respectively.Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus.The HA stem epitopes targeted by the Bn Abs,and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.
基金the National Natural Sci-ence Foundation of China (C02030606)948 Project from Agriculture Ministry of China (2001-366)
文摘The method of immunohistochemistry assay for the detection of scrapie in Chinese Short-tailed Han sheep was established using monoclonal antibody. Genomic DNA was isolated from Chinese Short-tailed Hart sheep blood. Using the polymerase chain reaction technique, PrP27-30 gene sequence was amplified from Chinese Short-tailed Han sheep genomic DNA. By recombinant DNA technology, the recombinant protein of Chinese Short-tailed Han sheep PrP27-30 was obtained. Then, using standard methodology of myeloma cell fusion, a panel of monoclonal antibodies was generated. With mAbs, scrapie in Chinese Short-tailed Han sheep was detected by immunohistochemistry assay. The recombinant protein of Chinese Short-tailed Han sheep PrP27-30 was obtained and a panel of six hybridoma cell lines secreting specific antibodies to Chinese Short-tailed Han sheep PrP27-30 related to scrapie was obtained with one fusion between myeloma Sp2/0 and spleen ceils from mice immunized with the purified recombinant protein. Four hybridoma cell lines can be used in immunohistochemistry assay for the detection of scrapie in Chinese Short-tailed Han sheep. So that the special monoclonal antibody developed in author＇s institute can be used to detect PrP^sc of scrapie in Chinese Short-tailed Han sheep by immunohistochemistry in China.
文摘The expression of an auto-antibody in patients with edematous acute pancreatitis and its possible clinical significance was investiaged. Eighteen cases of acute pancreatitis were chosen as experimental group and 25 subjects served as control group. Venous blood samples were taken in both groups at 4 time points: at the day of admission, the 2nd, 4th and 7th day of hospitalization. By using indirect immuno-fluorescence tests the expression of auto-antibody in the samples was semiquantitatively detected. Other biochemical indexes, such as serum amylase, urine amylase, were determined simultaneously. As well, the clinical signs or symptoms were mornitored. It was found that the expression of the auto-antibody was gradually enhanced with the development of acute pancreatitis. The inceased positive expression of auto-antibody showed a correlationship with the improvement of biochemical indexes (r=0.951) and clinical manifestations (r=0.996). There was significant difference between experimental and control groups (P<0.05). During the recovery period of acute pancreatitis, gradually increased auto-antibody expression was detectable. This antibody is against the interstitial structure of the pancreas.
文摘Based on the structure of chute - feed and autoleveHer, an analysis of their working principle and the verification of their practical production results have been carried out. Finally, the future investigation direetiom of chute - feed and card autuleveller are put forward.
文摘Hepatocellular carcinoma(HCC)is rarely associated with autoimmune paraneoplastic syndromes.We report a case of anti-transcriptional intermediary factor-1 gamma(TIF1-γ)-positive dermatomyositis(DM)as clinical presentation of HCC recurrence in a 72-year-old male patient admitted to our hospital due to fatigue,myalgia,and typical skin rash.His medical history was notable for hepatitis C-related cirrhosis,successful treatment with direct-acting antiviral agents,and previously efficacious treatment of HCC.Laboratory testing showed significant rhabdomyolysis with antiTIF1-γantibodies at high titer,and DM was diagnosed.After a careful diagnostic workup,HCC recurrence was diagnosed.After first-line corticosteroid treatment,azathioprine and intravenous immunoglobulin treatments were administered;unfortunately,he mounted only partial response.Owing to the compromised performance status,no HCC treatment was feasible,and,according to international guidelines,he received only best supportive care.Here,we discuss the diagnostic,prognostic,and pathogenic roles of anti-TIF1-γantibodies associated with paraneoplastic DM and the scant literature data on its occurrence in HCC patients.Considering the TIF1 gene family’s established role in oncogenesis,we also review the role of TIF1-γas a tumor-related neoantigen,leading to the development of clinically overt antiTIF1-γantibodies-positive DM.
文摘Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseas-es(AiLD),namely autoimmune hepatitis types 1 and 2(AIH-1 and 2),primary biliary cirrhosis(PBC),and the sclerosing cholangitis variants in adults and children.AIH-1 is specified by anti-nuclear antibody(ANA) and smooth muscle antibody(SMA).AIH-2 is specified by antibody to liver kidney microsomal antigen type-1(anti-LKM1) and anti-liver cytosol type 1(anti-LC1).SMA,ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation.PBC is specified by antimitochondrial antibodies(AMA) react-ing with enzymes of the 2-oxo-acid dehydrogenase complexes(chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly react-ing with nuclear pore gp210 and nuclear body sp100.Sclerosing cholangitis presents as at least two variants,first the classical primary sclerosing cholangitis(PSC) mostly affecting adult men wherein the only(and non-specific) reactivity is an atypical perinuclear antineutro-phil cytoplasmic antibody(p-ANCA),also termed peri-nuclear anti-neutrophil nuclear antibodies(p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis(ASC) with serological features resembling those of type 1 AIH.Liver diagnostic serol-ogy is a fast-expanding area of investigation as new purified and recombinant autoantigens,and automatedtechnologies such as ELISAs and bead assays,become available to complement(or even compete with) tradi-tional immunofluorescence procedures.We survey for the first time global trends in quality assurance impact-ing as it does on(1) manufacturers/purveyors of kits and reagents,(2) diagnostic service laboratories that fulfill clinicians' requirements,and(3) the end-user,the physician providing patient care,who must properly interpret test results in the overall clinical context.
基金supported in part by grants from the National Key Program for Fundamental Research and Development(973 Project,Grant No.G1999054203)National Natural Science Outstanding Youth Foundation(Grant No.30125020)the National Natural Science Foundation(Grant No.39870286,30200293)of China.
文摘Objective To study the potential role of tumor necrosis factor-α (TNF-α) induction in the development of mucosal barrier dysfunction in rats caused by acute intestinal ischemia-reperfusion injury, and to examine whether pretreatment with monoclonal antibody against TNF-α (TNF-α MoAb) would affect the release of D(-)-lactate after local gut ischemia followed by reperfusion. Methods Anesthetized Sprague-Dawley rats underwent superior mesenteric artery occlusion for 75 min followed by reperfusion for 6 hr. The rats were treated intravenously with either TNF-α MoAb (20 mg/kg) or albumin (20 mg/kg) 30 min prior to the onset of ischemia. Plasma D(-)-lactate levels were measured in both the portal and systemic blood by an enzymatic spectrophotometric assay. Intestinal TNF-αmRNA expression as well as protein levels were also measured at various intervals. In addition, a postmortem examination was performed together with a macropathological evaluation based on a four-grade scoring system.Results Intestinal ischemia resulted in a significant elevation in D(-)-lactate levels in the portal vein blood in both the control and treatment groups ( P ＜0.05). However, animals pretreated with TNF-α MoAb at 6 hr after reperfusion showed significant attenuation of an increase in both portal and systemic D(-)-lactate levels when compared with those only receiving albumin (P ＜ 0.05). In the control animals, a remarkable rise in intestinal TNF-α level was measured at 0.5 hr after clamp release ( P ＜ 0.01); however, prophylactic treatment with TNF-α MoAb completely annulled the increase of local TNF-α levels seen in the control animals. Similarly, after anti-TNF-α MoAb administration, intestinal TNF-α mRNA expression was markedly inhibited, which showed significant differences when compared with the control group at 0.5 hr, 2 hr and 6 hr after the release of occlusion ( P ＜ 0.05-0.01 ). In addition, the pathological examination showed marked intestinal lesions that formed during ischemia, which were much worse upon reperfusion,particularly at the 6 hr time point. These acute injuries were obviously attenuated in animals receiving TNF-α MoAb.Conclusions It appeared that acute intestinal ischemia was associated with failure of the mucosal barrier, resulting in increased plasma D(-)-lactate levels in both portal and systemic blood. These results suggest that TNF-α appears to be involved in the development of local damage associated with intestinal ischemic injury. Moreover, prophylactic treatment with TNF-α MoAb exerts preventive effects on ischemia/ reperfusion-induced circulating D (-)-lactate elevation and gut injury. ( J Geriatr Cardiol 2004;1(2):119-124. )
文摘Aggregate amyloid beta protein1-42 (Aβ1-42) can typically be found in the early stage of Alzheimer’s disease (AD). Aβ1-42 self-assembles and is highly toxic to neurons. Thus, recognizing aggregated Aβ1-42 is very important for elucidation of Aβ1-42 structure and for the diagnosis of AD. In this study, the specificity of the 79-3 monoclonal antibody against soluble aggre- gate Aβ1-42 was measured by sandwich Enzyme-Linked Immuno Sorbent Assay (ELISA). Eight monoclonal antibodies against both soluble aggregates and amorphous aggregates were used as primary antibodies. Soluble aggregates and amorphous aggregates were used as antigen. As secondary antibody, HRP was labeled with the 79-3 monoclonal antibody. The reactivity of the 79-3 monoclonal antibody against soluble aggregates was confirmed in all combinations, but little reactivity against amorphous aggregates was found. Furthermore, we performed the above sandwich ELISA using the 37-11 antibody, which is reactive against large oval aggregates (LOA) that occur in micro aggregates, instead of the 79-3 antibody. The 77-3 antibody is 1 of the 8 monoclonal antibodies against soluble aggregates;amorphous aggregates also reacted with the 37-11 antibody. These results indicated that soluble aggregates are specifically recognized by a combination of different antibodies. The combined use of these antibodies can be applied to the diagnosis of AD and to defining the structure of the Aβ1-42.
基金the National Natural Science Foundation of China,No. 30971037
文摘Uric acid is reduced in demyelinating diseases, including multiple sclerosis and neuromyelitis optica （NMO）. Longitudinally extensive transverse myelitis （LETM） is often an early manifestation of NMO. Whether uric acid levels are reduced at presentation of LETM remains unknown. The present study investigated serum uric acid levels by evaluating 35 patients with LETM, 64 with NMO, 62 with multiple sclerosis, 63 with other neurological diseases and 65 healthy controls. In addition, we tested the correlation between serum uric acid and the clinical characteristics of LETM. All patients were in the acute phase, defined as less than 1 month from onset or relapse. The results revealed that serum uric acid levels in LETM were significantly lower than in multiple sclerosis, other neurological diseases and healthy controls, but no difference was found between LETM and NMO. A negative correlation between uric acid levels and Expanded Disability Status Scale scores was found in LETM patients （r = -0.545, P 〈 0.05）. The results suggest that uric acid levels are reduced in patients with LETM, raising the possibility that lower uric acid levels are an indicator of disease disability. Moreover, reduced uric acid levels may be a risk factor in NMO.
