The aetiology of primary sclerosing cholangitis (PSC) is not known and controversy exists as to whether PSC should be denominated an autoimmune disease. A large number of autoantibodies have been detected in PSC patie...The aetiology of primary sclerosing cholangitis (PSC) is not known and controversy exists as to whether PSC should be denominated an autoimmune disease. A large number of autoantibodies have been detected in PSC patients,but the specifi city of these antibodies is generally low,and the frequencies vary largely between different studies. The presence of autoantibodies in PSC may be the result of a nonspecifi c dysregulation of the immune system,but the literature in PSC points to the possible presence of specifi c antibody targets in the biliary epithelium and in neutrophil granulocytes. The present review aims to give an overview of the studies of autoantibodies in PSC,with a particular emphasis on the prevalence,clinical relevance and possible pathogenetic importance of each individual marker.展开更多
Neutrophils are the first cell type to arrive at the in-jury sites and play a critical role in host defense, by virtueof its ability to adhere and transmigrate through endothe-lium, to phagocytose foreign pathogens, a...Neutrophils are the first cell type to arrive at the in-jury sites and play a critical role in host defense, by virtueof its ability to adhere and transmigrate through endothe-lium, to phagocytose foreign pathogens, and to producefree oxygen radicals and proteolytic enzymes. Yet, inap-propriate neutrophil activation causes tissue damage andvarious inflammatory diseases. These physiological andpathological functions of neutrophils depend on the en-gagement of certain surface receptors, especially αMβ2,the ma jor β2 integrin receptor present on neutrophil sur-face. Understanding of the molecular mechanisms under-lying ligand binding by αMβ2, as well as the roles of αMβ2-ligand interactions in neutrophil functions will enable usto regulate more precisely neutrophil activities: that is,to promote their host defense functions, and at the sametime to minimize their deleterious effects on normal cells.展开更多
Helicobacter pylori(H.pylori) infection is among the most common human infections and the major risk factor for peptic ulcer disease and gastric cancer.With-in this work we present the implication of C-terminal region...Helicobacter pylori(H.pylori) infection is among the most common human infections and the major risk factor for peptic ulcer disease and gastric cancer.With-in this work we present the implication of C-terminal region of H.pylori neutrophil activating protein in the stimulation of neutrophil activation as well as the evi-dence that the C-terminal region of H.pylori activating protein is indispensable for neutrophil adhesion to endothelial cells,a step necessary to H.pylori inflammation.In addition we show that arabino galactan proteins derived from chios mastic gum,the natural resin of the plant Pistacia lentiscus var.Chia inhibit neutrophil activation in vitro.展开更多
Helicobacter pylori （H. pylori） virulence factors pro- mote the release of various chemoattractants/inflam- matory mediators, including mainly the neutrophil- attractant chemokine interleukin-8 and neutrophil- activ...Helicobacter pylori （H. pylori） virulence factors pro- mote the release of various chemoattractants/inflam- matory mediators, including mainly the neutrophil- attractant chemokine interleukin-8 and neutrophil- activating protein （NAP）, involved in H. pylor/-induced gastric pathologies. Co-administration of Chios mastic gum （CMG）, which inhibits H. pylor/NAP, with an H. pylori eradication regimen might add clinical benefits against H. pylori-related gastric pathologies, but pos- sibly not CMG as main therapy. Although H. pylori NAP and other H. pylori-related cytotoxins [i.e., vaculating cytotoxin （VacA）] appear to play a major role in gener- ating and maintaining the H. pylori-associated gastric inflammatory response and H. pylor/NAP is a promising vaccine candidate against H. pylori infection （H. pylori-1）, concerns regarding its potential drawbacks, particularly neurogenic ones, due to possible cross- mimicry, should be considered. Possible cross-mimicry between H. p, vlor/ NAP and/or bacterial aquaporin （AQP） and neural tissues may be associated with the anti-AQP-4 antibody-related neural damage in multiple sclerosis （MS）/neuromyelitis optica patients. Moreover, the sequence homology found between H. pylori VacA and human Na＋/K＋-ATPase A subunit suggests that antibodies to VacA involve ion channels in abaxonal Schwann cell plasmalemma resulting in demyelination in some patients. A series of factors have been im- plicated in inducing blood-brain barrier （BBB） disrup- tion, including inflammatory mediators （e.g., cytokines and chemokines induced by H. pylor/-I） and oxidative stress. BBB disruption permits access of AQP4-specific antibodies and T lymphocytes to the central nervous system, thereby playing a major role in multiple sclero- sis pathogenesis. Relative studies show a strong asso- ciation between H. pylori-I and MS. H. pylor/-I induces humoral and cellular immune responses that, owing to the sharing of homologous epitopes （molecular mim- icry）, cross-react with components of nerves, thereby contributing and perpetuating neural tissue damage. Finally, H. pylori NAP also plays a possible pathoge- netic role in both gastric and colon oncogenesis.展开更多
AIM： To detect and evaluate the antibodies against Helicobacter pylori （H pylori） neutrophil-activating protein （HP-NAP） in patients with gastric cancer and other gastroduodenal diseases.METHODS： Recombinant HP-...AIM： To detect and evaluate the antibodies against Helicobacter pylori （H pylori） neutrophil-activating protein （HP-NAP） in patients with gastric cancer and other gastroduodenal diseases.METHODS： Recombinant HP-NAP was prepared from a prokaryotic expression system in Escherichia coll. Serum positivity and level of HP-NAP-specific antibodies in sera from 43 patients with gastric cancer, 28 with chronic gastritis, 28 with peptic ulcer, and 89 healthy controls were measured by rHP-NAP-based ELISA. rHP-NAP-stimulated production of interleukin-8 （IL-8） and growth-related oncogene （GROα） cytokines in the culture supernatant of SGC7901 gastric epithelial cells was also detected.RESULTS： The serum positivity and mean absorbancevalue of HP-NAP-specific antibodies in the gastriccancer group （97.7% and 1.01 ± 0.24） were significantly higher than those in the chronic gastritisgroup （85.7% and 0.89 ± 0.14, P 〈 0.005） and healthy control group （27.7% and 0.65 ± 0.18, P 〈 0.001）. The sensitivity and specificity of ELISA for the detection of HP-NAP-specific antibodies were 95.5% and 91.5%, respectively. HP-NAP could slightly upregulate IL-8 production in gastric epithelial cell lines but had no effect on GROα production.CONCLUSION： Infection with virulent H py/ori strains secreting HP-NAP is associated with severe gastroduodenal diseases, and HP-NAP may play a role in the development of gastric carcinoma, rHP-NAP- based ELISA can be used as a new method to detect H pylori infection. The direct effect of HP-NAP on gastric epithelial cells may be limited, but HP-NAP may contribute to inflammatory response or carcinogenesis by activating neutrophils.展开更多
The aim of this study was to evaluate morphometric and hematological parameters of juveniles Piracanjubas treated with two distinct photoperiod. Twenty nine fish with 100 g, in a factorial design were performed in 18 ...The aim of this study was to evaluate morphometric and hematological parameters of juveniles Piracanjubas treated with two distinct photoperiod. Twenty nine fish with 100 g, in a factorial design were performed in 18 h light：6 h dark （18L：6D） and 6L：lSD two different photoperiod, and morphometric and hematological parameters were evaluated at 45 d and 90 d after photoperiod treatment. Benzocaine 1% was used for euthanasia. Fish were weighed and measured, so as visceral fat, liver and gonads. Hematocrit, total count of white cells, lymphocytes and neutrophils were counted. Results showed that there was no significant relationship between bodyweight and standard length. Significant interaction （P = 0.00018） had been found between the fat index （FI） and gonado-somatic index （GSI） and the photoperiod and time. At 90 d, the fish kept in 18L：6D had a lower rate of fat than the fish kept in 6L：18D （P 〈 0.05）. The GSI was higher in the group 6L.＇18D compared with the 18L：6D （P 〈 0.005）. There was no interaction between photoperiod and period of treatment for total leukocyte count, however with 90 d, the total leukocyte count was decreased （P 〈 0.05）. Moreover, decrease of the hematocrit from 58.1% to 46.9% and an increase of lymphocytes from 31.5% to 43.5% had been found in fish kept in 18L：6D after 90 d （P 〈 0.05）. Fish kept in 6L：ISD presented an increase in segmented neutrophils and lymphocytes （P 〈 0.05）. It is concluded that photoperiod maintained at 6L： 18D for Piracanjubas permits a greater gonadal development and an amount of immune cells over the photoperiod maintained in 18L： 6D.展开更多
Abstract:Objective To map the epitopes on Wegener's granulomatosis autoantigen proteinase 3.Methods Antigenicity of proteinase 3 was studied with Western blot analysis in which proteinase 3 was prepared under redu...Abstract:Objective To map the epitopes on Wegener's granulomatosis autoantigen proteinase 3.Methods Antigenicity of proteinase 3 was studied with Western blot analysis in which proteinase 3 was prepared under reducing and non-reducing conditions. Two anti-proteinase 3 monoclonal antibodies, HZ1F12 and HZ1H3, were used to inhibit each other and to inhibit 22 anti-proteinase 3 positive sera from patients with Wegener's granulomatosis in competitive inhibition enzyme-linked immunosorbent assays (ELISA) and Western blot analysis. Results All monoclonal antibodies and patient sera recognized proteinase 3 under non-reducing conditions in Western blot analysis. HZ1F12 was inhibited 74% by HZ1H3. 10/22 (46%) sera were completely or partially inhibited by HZ1F12; 9/22 (41%) sera were partially inhibited by HZ1H3; and 6/22 (27%) were inhibited by both monoclonal antibodies. In inhibition Western blot analysis, the binding of patient sera to proteinase 3 could be inhibited by HZ1F12. Conclusions The epitopes of Wegener's granulomatosis autoantigen were conformational. Anti-proteinase 3 monoclonal HZ1F12 and HZ1H3 recognized similar or overlapping epitopes on the proteinase 3 molecule. Epitopes of proteinase 3 recognized by anti-proteinase 3 positive sera were not restricted.展开更多
文摘The aetiology of primary sclerosing cholangitis (PSC) is not known and controversy exists as to whether PSC should be denominated an autoimmune disease. A large number of autoantibodies have been detected in PSC patients,but the specifi city of these antibodies is generally low,and the frequencies vary largely between different studies. The presence of autoantibodies in PSC may be the result of a nonspecifi c dysregulation of the immune system,but the literature in PSC points to the possible presence of specifi c antibody targets in the biliary epithelium and in neutrophil granulocytes. The present review aims to give an overview of the studies of autoantibodies in PSC,with a particular emphasis on the prevalence,clinical relevance and possible pathogenetic importance of each individual marker.
文摘Neutrophils are the first cell type to arrive at the in-jury sites and play a critical role in host defense, by virtueof its ability to adhere and transmigrate through endothe-lium, to phagocytose foreign pathogens, and to producefree oxygen radicals and proteolytic enzymes. Yet, inap-propriate neutrophil activation causes tissue damage andvarious inflammatory diseases. These physiological andpathological functions of neutrophils depend on the en-gagement of certain surface receptors, especially αMβ2,the ma jor β2 integrin receptor present on neutrophil sur-face. Understanding of the molecular mechanisms under-lying ligand binding by αMβ2, as well as the roles of αMβ2-ligand interactions in neutrophil functions will enable usto regulate more precisely neutrophil activities: that is,to promote their host defense functions, and at the sametime to minimize their deleterious effects on normal cells.
基金Supported by A Grant from the General Secretariat of Research and Technology, Ministry of Development of Greece, by the Program HERAKLITOS I as well as by Chios Gum Mastic Growers Association
文摘Helicobacter pylori(H.pylori) infection is among the most common human infections and the major risk factor for peptic ulcer disease and gastric cancer.With-in this work we present the implication of C-terminal region of H.pylori neutrophil activating protein in the stimulation of neutrophil activation as well as the evi-dence that the C-terminal region of H.pylori activating protein is indispensable for neutrophil adhesion to endothelial cells,a step necessary to H.pylori inflammation.In addition we show that arabino galactan proteins derived from chios mastic gum,the natural resin of the plant Pistacia lentiscus var.Chia inhibit neutrophil activation in vitro.
文摘Helicobacter pylori （H. pylori） virulence factors pro- mote the release of various chemoattractants/inflam- matory mediators, including mainly the neutrophil- attractant chemokine interleukin-8 and neutrophil- activating protein （NAP）, involved in H. pylor/-induced gastric pathologies. Co-administration of Chios mastic gum （CMG）, which inhibits H. pylor/NAP, with an H. pylori eradication regimen might add clinical benefits against H. pylori-related gastric pathologies, but pos- sibly not CMG as main therapy. Although H. pylori NAP and other H. pylori-related cytotoxins [i.e., vaculating cytotoxin （VacA）] appear to play a major role in gener- ating and maintaining the H. pylori-associated gastric inflammatory response and H. pylor/NAP is a promising vaccine candidate against H. pylori infection （H. pylori-1）, concerns regarding its potential drawbacks, particularly neurogenic ones, due to possible cross- mimicry, should be considered. Possible cross-mimicry between H. p, vlor/ NAP and/or bacterial aquaporin （AQP） and neural tissues may be associated with the anti-AQP-4 antibody-related neural damage in multiple sclerosis （MS）/neuromyelitis optica patients. Moreover, the sequence homology found between H. pylori VacA and human Na＋/K＋-ATPase A subunit suggests that antibodies to VacA involve ion channels in abaxonal Schwann cell plasmalemma resulting in demyelination in some patients. A series of factors have been im- plicated in inducing blood-brain barrier （BBB） disrup- tion, including inflammatory mediators （e.g., cytokines and chemokines induced by H. pylor/-I） and oxidative stress. BBB disruption permits access of AQP4-specific antibodies and T lymphocytes to the central nervous system, thereby playing a major role in multiple sclero- sis pathogenesis. Relative studies show a strong asso- ciation between H. pylori-I and MS. H. pylor/-I induces humoral and cellular immune responses that, owing to the sharing of homologous epitopes （molecular mim- icry）, cross-react with components of nerves, thereby contributing and perpetuating neural tissue damage. Finally, H. pylori NAP also plays a possible pathoge- netic role in both gastric and colon oncogenesis.
基金Supported by Grants from Guangdong Natural Science Foundation Project,5004750National Key Development Project,973 Program 2002CB513206
文摘AIM： To detect and evaluate the antibodies against Helicobacter pylori （H pylori） neutrophil-activating protein （HP-NAP） in patients with gastric cancer and other gastroduodenal diseases.METHODS： Recombinant HP-NAP was prepared from a prokaryotic expression system in Escherichia coll. Serum positivity and level of HP-NAP-specific antibodies in sera from 43 patients with gastric cancer, 28 with chronic gastritis, 28 with peptic ulcer, and 89 healthy controls were measured by rHP-NAP-based ELISA. rHP-NAP-stimulated production of interleukin-8 （IL-8） and growth-related oncogene （GROα） cytokines in the culture supernatant of SGC7901 gastric epithelial cells was also detected.RESULTS： The serum positivity and mean absorbancevalue of HP-NAP-specific antibodies in the gastriccancer group （97.7% and 1.01 ± 0.24） were significantly higher than those in the chronic gastritisgroup （85.7% and 0.89 ± 0.14, P 〈 0.005） and healthy control group （27.7% and 0.65 ± 0.18, P 〈 0.001）. The sensitivity and specificity of ELISA for the detection of HP-NAP-specific antibodies were 95.5% and 91.5%, respectively. HP-NAP could slightly upregulate IL-8 production in gastric epithelial cell lines but had no effect on GROα production.CONCLUSION： Infection with virulent H py/ori strains secreting HP-NAP is associated with severe gastroduodenal diseases, and HP-NAP may play a role in the development of gastric carcinoma, rHP-NAP- based ELISA can be used as a new method to detect H pylori infection. The direct effect of HP-NAP on gastric epithelial cells may be limited, but HP-NAP may contribute to inflammatory response or carcinogenesis by activating neutrophils.
文摘The aim of this study was to evaluate morphometric and hematological parameters of juveniles Piracanjubas treated with two distinct photoperiod. Twenty nine fish with 100 g, in a factorial design were performed in 18 h light：6 h dark （18L：6D） and 6L：lSD two different photoperiod, and morphometric and hematological parameters were evaluated at 45 d and 90 d after photoperiod treatment. Benzocaine 1% was used for euthanasia. Fish were weighed and measured, so as visceral fat, liver and gonads. Hematocrit, total count of white cells, lymphocytes and neutrophils were counted. Results showed that there was no significant relationship between bodyweight and standard length. Significant interaction （P = 0.00018） had been found between the fat index （FI） and gonado-somatic index （GSI） and the photoperiod and time. At 90 d, the fish kept in 18L：6D had a lower rate of fat than the fish kept in 6L：18D （P 〈 0.05）. The GSI was higher in the group 6L.＇18D compared with the 18L：6D （P 〈 0.005）. There was no interaction between photoperiod and period of treatment for total leukocyte count, however with 90 d, the total leukocyte count was decreased （P 〈 0.05）. Moreover, decrease of the hematocrit from 58.1% to 46.9% and an increase of lymphocytes from 31.5% to 43.5% had been found in fish kept in 18L：6D after 90 d （P 〈 0.05）. Fish kept in 6L：ISD presented an increase in segmented neutrophils and lymphocytes （P 〈 0.05）. It is concluded that photoperiod maintained at 6L： 18D for Piracanjubas permits a greater gonadal development and an amount of immune cells over the photoperiod maintained in 18L： 6D.
文摘Abstract:Objective To map the epitopes on Wegener's granulomatosis autoantigen proteinase 3.Methods Antigenicity of proteinase 3 was studied with Western blot analysis in which proteinase 3 was prepared under reducing and non-reducing conditions. Two anti-proteinase 3 monoclonal antibodies, HZ1F12 and HZ1H3, were used to inhibit each other and to inhibit 22 anti-proteinase 3 positive sera from patients with Wegener's granulomatosis in competitive inhibition enzyme-linked immunosorbent assays (ELISA) and Western blot analysis. Results All monoclonal antibodies and patient sera recognized proteinase 3 under non-reducing conditions in Western blot analysis. HZ1F12 was inhibited 74% by HZ1H3. 10/22 (46%) sera were completely or partially inhibited by HZ1F12; 9/22 (41%) sera were partially inhibited by HZ1H3; and 6/22 (27%) were inhibited by both monoclonal antibodies. In inhibition Western blot analysis, the binding of patient sera to proteinase 3 could be inhibited by HZ1F12. Conclusions The epitopes of Wegener's granulomatosis autoantigen were conformational. Anti-proteinase 3 monoclonal HZ1F12 and HZ1H3 recognized similar or overlapping epitopes on the proteinase 3 molecule. Epitopes of proteinase 3 recognized by anti-proteinase 3 positive sera were not restricted.
