Background:The neuropsychiatric disorders due to post-streptococcal autoimmune complications such as Sydenham's chorea(SC)are associated with acute rheumatic fever and rheumatic heart disease(ARF/RHD).An animal mo...Background:The neuropsychiatric disorders due to post-streptococcal autoimmune complications such as Sydenham's chorea(SC)are associated with acute rheumatic fever and rheumatic heart disease(ARF/RHD).An animal model that exhibits char-acteristics of both cardiac and neurobehavioral defects in ARF/RHD would be an important adjunct for future studies.Since age,gender,strain differences,and geno-types impact on the development of autoimmunity,we investigated the behavior of male and female Wistar and Lewis rat strains in two age cohorts(6 weeks and 12 weeks)under normal husbandry conditions and following exposure to group A streptococcus(GAS).Methods:Standard behavioral assessments were performed to determine the impair-ments in fine motor control(food manipulation test),gait and balance(beam walk-ing test),and obsessive-compulsive behavior(grooming and marble burying tests).Furthermore,electrocardiography,histology,and behavioral assessments were per-formed on male and female Lewis rats injected with GAS antigens.Results:For control Lewis rats there were no significant age and gender dependent differences in marble burying,food manipulation,beam walking and grooming be-haviors.In contrast significant age-dependent differences were observed in Wistar rats in all the behavioral tests except for food manipulation.Therefore,Lewis rats were selected for further experiments to determine the effect of GAS.After ex-posure to GAS,Lewis rats demonstrated neurobehavioral abnormalities and cardiac pathology akin to SC and ARF/RHD,respectively.Conclusion:We have characterised a new model that provides longitudinal stability of age-dependent behavior,to simultaneously investigate both neurobehavioral and cardiac abnormalities associated with post-streptococcal complications.展开更多
BACKGROUND Common autoimmune diseases(AID)tend to occur together in the same individual and families.Type 1 diabetes(T1D)is caused by an autoimmuneinduced inflammatory destruction of the pancreatic tissue and clusters...BACKGROUND Common autoimmune diseases(AID)tend to occur together in the same individual and families.Type 1 diabetes(T1D)is caused by an autoimmuneinduced inflammatory destruction of the pancreatic tissue and clusters with several other AID.AIM To compare the demographic,clinical,and serological features of patients with single T1D vs those with T1D and associated AID.METHODS From October 1999 to February 2020,a total of 665 patients with T1D and their first-degree relatives were evaluated.RESULTS Compared to patients with isolated T1D,those with T1D+AID were older and had a higher female:male ratio.Average patient age and age at disease onset were higher in T1D+AID vs T1D only.The average time interval between T1D onset and the onset of a second glandular AID was markedly shorter than the time interval between T1D and the occurrence of a non-endocrine AID.T1Dspecific autoantibodies were more frequent in patients with T1D+AID and relatives vs those with T1D only.However,the prevalence of AID and autoantibodies against various tissues were found to be higher in relatives of patients with T1D only compared to relatives of patients with T1D+AID.CONCLUSION Annual serological and subsequent functional screening for AID in patients with T1D and their first-degree relatives is recommended.展开更多
Alternative splicing is the process of producing variably spliced mRNAs by choosing distinct combinations of splice sites within a messenger RNA precursor.This splicing enables mRNA from a single gene to synthesize di...Alternative splicing is the process of producing variably spliced mRNAs by choosing distinct combinations of splice sites within a messenger RNA precursor.This splicing enables mRNA from a single gene to synthesize different proteins,which have different cellular properties and functions and yet arise from the same single gene.A family of splicing factors,Serine-arginine rich proteins,are needed to initiate the assembly and activation of the spliceosome.Serine and arginine rich splicing factor 1,part of the arginine/serine-rich splicing factor protein family,can either activate or inhibit the splicing of mRNAs,depending on the phosphorylation status of the protein and its interaction partners.Considering that serine and arginine rich splicing factor 1 is either an activator or an inhibitor,this protein has been studied widely to identify its various roles in different diseases.Research has found that serine and arginine rich splicing factor 1 is a key target for neuroprotection,showing its promising potential use in therapeutics for neurodegenerative disorders.Furthermore,serine and arginine rich splicing factor 1 might be used to regulate cancer development and autoimmune diseases.In this review,we highlight how serine and arginine rich splicing factor 1 has been studied concerning neuroprotection.In addition,we draw attention to how serine and arginine rich splicing factor 1 is being studied in cancer and immunological disorders,as well as how serine and arginine rich splicing factor 1 acts outside the central or peripheral nervous system.展开更多
In this paper</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> we present a thorough review of one of the most</span><span style...In this paper</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> we present a thorough review of one of the most</span><span style="font-family:Verdana;"> life-threatening autoimmune diseases, Systemic lupus erythematosus (lupus). Symptoms, risk factors, including genetic and epidemiological factors are discussed. Treatment, life expectancies, and Health Related Quality of Life of patients with SLE will be discussed as well. Special attention will be given to Lupus Nephritis.展开更多
BACKGROUND: Dubin-Johnson syndrome (DJS) is a rare clinical entity. We describe a case of DJS complicated by systemic lupus erythematosus (SLE). METHODS: A case of congenital hyperbilirubinemia with SLE was evaluated ...BACKGROUND: Dubin-Johnson syndrome (DJS) is a rare clinical entity. We describe a case of DJS complicated by systemic lupus erythematosus (SLE). METHODS: A case of congenital hyperbilirubinemia with SLE was evaluated systematically including review of history, physical examination for the stigmata of chronic liver disease, and other investigations. RESULT: Liver biopsy revealed a black liver with preserved architecture suggestive of DJS. CONCLUSIONS: SLE may develop in DJS. The relationship between DJS and SLE in this case is most likely a chance occurrence.展开更多
Anti-acetylcholine receptor antibodies (AAR) are considered pathognomonic and pathogenetic for myasthenia gravis (MG). AAR detection confirms clinical diagnosis of MG. However, AAR is rarely detected in patients w...Anti-acetylcholine receptor antibodies (AAR) are considered pathognomonic and pathogenetic for myasthenia gravis (MG). AAR detection confirms clinical diagnosis of MG. However, AAR is rarely detected in patients without MG. The underlying pathophysiological mechanisms in a normal subject without MG have not been adequately addressed in previous studies. The present study reports on a case study of a healthy, elderly man with high AAR titers for 14 years. Pathophysiological mechanisms could be due to AAR heterogeneity in specificity, affinity, and multiform, and to muscle variability in response to AAR.展开更多
It is well known that the treatment of Dampness-heat falling into the lowerburner(DHFLB) is very difficult to deal with by both traditional Chinese medicine(TCM) and western medicine.After TCM system of Epidemic Febri...It is well known that the treatment of Dampness-heat falling into the lowerburner(DHFLB) is very difficult to deal with by both traditional Chinese medicine(TCM) and western medicine.After TCM system of Epidemic Febril Disease(composed of three parts,Shanghan,exogenous febril disease;)展开更多
Myasthenia gravis(MG)is an autoimmune antibody-mediated disorder which causes fluctuating weakness in ocular,bulbar and limb skeletal muscles.There are two major clinical types of MG.Ocular MG(OMG)affects extra ocular...Myasthenia gravis(MG)is an autoimmune antibody-mediated disorder which causes fluctuating weakness in ocular,bulbar and limb skeletal muscles.There are two major clinical types of MG.Ocular MG(OMG)affects extra ocular muscles associated with eye movement and eyelid function and generalized MG results in muscle weakness throughout the body.Patients with OMG have painless fluctuating extra ocular muscles weakness,diplopia and ptosis accompanied by normal visual acuity and pupillary function.Frequently,patients with OMG develop generalized MG over 24 months.Pure OMG is more often earlier in onset(<45 years)than generalized MG.It can also occur as part of an immune-genetic disorder or paraneoplastic syndrome related to thymus tumors.Diagnosis is based on clinical manifestations,laboratory findings,electrophysiological evaluation and pharmacologic tests.Therapeutic strategies for MG consist of symptom relieving medications(e.g.,acetylcholine esterase inhibitors),immunosuppressive agents,and surgical intervention(e.g.,thymectomy).展开更多
CD4^(+)T cells are critical to the development of autoimmune disorders.Glucose,fatty acids,and glutamine metabolisms are the primary metabolic pathways in immune cells,including CD4^(+)T cells.The distinct metabolic p...CD4^(+)T cells are critical to the development of autoimmune disorders.Glucose,fatty acids,and glutamine metabolisms are the primary metabolic pathways in immune cells,including CD4^(+)T cells.The distinct metabolic programs in CD4^(+)T cell subsets are recognized to reflect the bioenergetic requirements,which are compatible with their functional demands.Gut microbiota affects T cell responses by providing a series of antigens and metabolites.Accumulating data indicate that CD4^(+)T cell metabolic pathways underlie aberrant T cell functions,thereby regulating the pathogenesis of autoimmune disorders,including inflammatory bowel diseases,systemic lupus erythematosus,and rheumatoid arthritis.Here,we summarize the current progress of CD4^(+)T cell metabolic programs,gut microbiota regulation of T cell metabolism,and T cell metabolic adaptions to autoimmune disorders to shed light on potential metabolic therapeutics for autoimmune diseases.展开更多
In recent years,studying the role of myeloid-derived suppressor cells(MDSCs)in many pathological inflammatory conditions has become a very active research area.Although the role of MDSCs in cancer is relatively well e...In recent years,studying the role of myeloid-derived suppressor cells(MDSCs)in many pathological inflammatory conditions has become a very active research area.Although the role of MDSCs in cancer is relatively well established,their role in non-cancerous pathological conditions remains in its infancy resulting in much confusion.Our objectives in this review are to address some recent advances in MDSC research in order to minimize such confusion and to provide an insight into their function in the context of other diseases.The following topics will be specifically focused upon:(1)definition and characterization of MDSCs;(2)whether all MDSC populations consist of immature cells;(3)technical issues in MDSC isolation,estimation and characterization;(4)the origin of MDSCs and their anatomical distribution in health and disease;(5)mediators of MDSC expansion and accumulation;(6)factors that determine the expansion of one MDSC population over the other;(7)the Yin and Yang roles of MDSCs.Moreover,the functions of MDSCs will be addressed throughout the text.展开更多
基金RAM Rafeek is recipient of International Postgraduate Research Award(IPRA)from University of New England.CM Lobbe and E.Wilkinson are recipients of student scholarship from the Royal College of Pathologists of Australasia(RCPA).
文摘Background:The neuropsychiatric disorders due to post-streptococcal autoimmune complications such as Sydenham's chorea(SC)are associated with acute rheumatic fever and rheumatic heart disease(ARF/RHD).An animal model that exhibits char-acteristics of both cardiac and neurobehavioral defects in ARF/RHD would be an important adjunct for future studies.Since age,gender,strain differences,and geno-types impact on the development of autoimmunity,we investigated the behavior of male and female Wistar and Lewis rat strains in two age cohorts(6 weeks and 12 weeks)under normal husbandry conditions and following exposure to group A streptococcus(GAS).Methods:Standard behavioral assessments were performed to determine the impair-ments in fine motor control(food manipulation test),gait and balance(beam walk-ing test),and obsessive-compulsive behavior(grooming and marble burying tests).Furthermore,electrocardiography,histology,and behavioral assessments were per-formed on male and female Lewis rats injected with GAS antigens.Results:For control Lewis rats there were no significant age and gender dependent differences in marble burying,food manipulation,beam walking and grooming be-haviors.In contrast significant age-dependent differences were observed in Wistar rats in all the behavioral tests except for food manipulation.Therefore,Lewis rats were selected for further experiments to determine the effect of GAS.After ex-posure to GAS,Lewis rats demonstrated neurobehavioral abnormalities and cardiac pathology akin to SC and ARF/RHD,respectively.Conclusion:We have characterised a new model that provides longitudinal stability of age-dependent behavior,to simultaneously investigate both neurobehavioral and cardiac abnormalities associated with post-streptococcal complications.
文摘BACKGROUND Common autoimmune diseases(AID)tend to occur together in the same individual and families.Type 1 diabetes(T1D)is caused by an autoimmuneinduced inflammatory destruction of the pancreatic tissue and clusters with several other AID.AIM To compare the demographic,clinical,and serological features of patients with single T1D vs those with T1D and associated AID.METHODS From October 1999 to February 2020,a total of 665 patients with T1D and their first-degree relatives were evaluated.RESULTS Compared to patients with isolated T1D,those with T1D+AID were older and had a higher female:male ratio.Average patient age and age at disease onset were higher in T1D+AID vs T1D only.The average time interval between T1D onset and the onset of a second glandular AID was markedly shorter than the time interval between T1D and the occurrence of a non-endocrine AID.T1Dspecific autoantibodies were more frequent in patients with T1D+AID and relatives vs those with T1D only.However,the prevalence of AID and autoantibodies against various tissues were found to be higher in relatives of patients with T1D only compared to relatives of patients with T1D+AID.CONCLUSION Annual serological and subsequent functional screening for AID in patients with T1D and their first-degree relatives is recommended.
文摘Alternative splicing is the process of producing variably spliced mRNAs by choosing distinct combinations of splice sites within a messenger RNA precursor.This splicing enables mRNA from a single gene to synthesize different proteins,which have different cellular properties and functions and yet arise from the same single gene.A family of splicing factors,Serine-arginine rich proteins,are needed to initiate the assembly and activation of the spliceosome.Serine and arginine rich splicing factor 1,part of the arginine/serine-rich splicing factor protein family,can either activate or inhibit the splicing of mRNAs,depending on the phosphorylation status of the protein and its interaction partners.Considering that serine and arginine rich splicing factor 1 is either an activator or an inhibitor,this protein has been studied widely to identify its various roles in different diseases.Research has found that serine and arginine rich splicing factor 1 is a key target for neuroprotection,showing its promising potential use in therapeutics for neurodegenerative disorders.Furthermore,serine and arginine rich splicing factor 1 might be used to regulate cancer development and autoimmune diseases.In this review,we highlight how serine and arginine rich splicing factor 1 has been studied concerning neuroprotection.In addition,we draw attention to how serine and arginine rich splicing factor 1 is being studied in cancer and immunological disorders,as well as how serine and arginine rich splicing factor 1 acts outside the central or peripheral nervous system.
文摘In this paper</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> we present a thorough review of one of the most</span><span style="font-family:Verdana;"> life-threatening autoimmune diseases, Systemic lupus erythematosus (lupus). Symptoms, risk factors, including genetic and epidemiological factors are discussed. Treatment, life expectancies, and Health Related Quality of Life of patients with SLE will be discussed as well. Special attention will be given to Lupus Nephritis.
文摘BACKGROUND: Dubin-Johnson syndrome (DJS) is a rare clinical entity. We describe a case of DJS complicated by systemic lupus erythematosus (SLE). METHODS: A case of congenital hyperbilirubinemia with SLE was evaluated systematically including review of history, physical examination for the stigmata of chronic liver disease, and other investigations. RESULT: Liver biopsy revealed a black liver with preserved architecture suggestive of DJS. CONCLUSIONS: SLE may develop in DJS. The relationship between DJS and SLE in this case is most likely a chance occurrence.
文摘Anti-acetylcholine receptor antibodies (AAR) are considered pathognomonic and pathogenetic for myasthenia gravis (MG). AAR detection confirms clinical diagnosis of MG. However, AAR is rarely detected in patients without MG. The underlying pathophysiological mechanisms in a normal subject without MG have not been adequately addressed in previous studies. The present study reports on a case study of a healthy, elderly man with high AAR titers for 14 years. Pathophysiological mechanisms could be due to AAR heterogeneity in specificity, affinity, and multiform, and to muscle variability in response to AAR.
文摘It is well known that the treatment of Dampness-heat falling into the lowerburner(DHFLB) is very difficult to deal with by both traditional Chinese medicine(TCM) and western medicine.After TCM system of Epidemic Febril Disease(composed of three parts,Shanghan,exogenous febril disease;)
文摘Myasthenia gravis(MG)is an autoimmune antibody-mediated disorder which causes fluctuating weakness in ocular,bulbar and limb skeletal muscles.There are two major clinical types of MG.Ocular MG(OMG)affects extra ocular muscles associated with eye movement and eyelid function and generalized MG results in muscle weakness throughout the body.Patients with OMG have painless fluctuating extra ocular muscles weakness,diplopia and ptosis accompanied by normal visual acuity and pupillary function.Frequently,patients with OMG develop generalized MG over 24 months.Pure OMG is more often earlier in onset(<45 years)than generalized MG.It can also occur as part of an immune-genetic disorder or paraneoplastic syndrome related to thymus tumors.Diagnosis is based on clinical manifestations,laboratory findings,electrophysiological evaluation and pharmacologic tests.Therapeutic strategies for MG consist of symptom relieving medications(e.g.,acetylcholine esterase inhibitors),immunosuppressive agents,and surgical intervention(e.g.,thymectomy).
基金supported by National Institutes of Health(Grants No.DK105585,DK112436,DK125011,AI150210,and DK124132)。
文摘CD4^(+)T cells are critical to the development of autoimmune disorders.Glucose,fatty acids,and glutamine metabolisms are the primary metabolic pathways in immune cells,including CD4^(+)T cells.The distinct metabolic programs in CD4^(+)T cell subsets are recognized to reflect the bioenergetic requirements,which are compatible with their functional demands.Gut microbiota affects T cell responses by providing a series of antigens and metabolites.Accumulating data indicate that CD4^(+)T cell metabolic pathways underlie aberrant T cell functions,thereby regulating the pathogenesis of autoimmune disorders,including inflammatory bowel diseases,systemic lupus erythematosus,and rheumatoid arthritis.Here,we summarize the current progress of CD4^(+)T cell metabolic programs,gut microbiota regulation of T cell metabolism,and T cell metabolic adaptions to autoimmune disorders to shed light on potential metabolic therapeutics for autoimmune diseases.
文摘In recent years,studying the role of myeloid-derived suppressor cells(MDSCs)in many pathological inflammatory conditions has become a very active research area.Although the role of MDSCs in cancer is relatively well established,their role in non-cancerous pathological conditions remains in its infancy resulting in much confusion.Our objectives in this review are to address some recent advances in MDSC research in order to minimize such confusion and to provide an insight into their function in the context of other diseases.The following topics will be specifically focused upon:(1)definition and characterization of MDSCs;(2)whether all MDSC populations consist of immature cells;(3)technical issues in MDSC isolation,estimation and characterization;(4)the origin of MDSCs and their anatomical distribution in health and disease;(5)mediators of MDSC expansion and accumulation;(6)factors that determine the expansion of one MDSC population over the other;(7)the Yin and Yang roles of MDSCs.Moreover,the functions of MDSCs will be addressed throughout the text.