Additional file 1: Supplementary Table S1. Over-represented KEGG pathways. Supplementary Table S2... more Additional file 1: Supplementary Table S1. Over-represented KEGG pathways. Supplementary Table S2. Top 5 statistically significant over-represented diseases. Supplementary Table S3. Average cytokine levels (pg/mL) by matched RvE1 treatment of T2D (N = 3) and healthy (N = 3) neutrophils in cell culture. Supplementary Table S4. Average cytokine levels (pg/mL) by differing RvE1 treatment of T2D (N = 3) and healthy (N = 3) neutrophils in cell culture. Supplementary Fig. S1. Principal component analysis (PCA) plot of type 2 diabetic and healthy subjects. Supplementary Fig. S2. Neutrophil gene expression in type 2 diabetic versus healthy subjects for all 50 significant genes. Supplementary Fig. S3. Top 50 significant neutrophil genes differentially expressed in type 2 diabetic and healthy subjects by top biological pathways. Supplementary Fig. S4. Neutrophil gene expression of type 2 diabetic and healthy subjects by biologically relevant KEGG pathways.
International Journal of Research -GRANTHAALAYAH, 2015
Definitely the Internet banking services adoption (IBSA) represents a good opportunity for develo... more Definitely the Internet banking services adoption (IBSA) represents a good opportunity for developing nations to attain greater economic development and growth. This sector plays a vital role in developing numerous businesses and increasing Gross Domestic Product (GDP) in different countries, particularly in developing countries, such as the Republic of Iraq. Although a lot of research evidences the wide adoption of Internet banking in developed nations, there is still limited research in developing nations in the Middle East, specifically in Iraq on this area. There is definitely a need in this country to identify the factors that could encourage IBSA. There is also a paucity of empirical research on IBSA from the perspective of customers. Taking these into cognizance, this quantitative research aims to understand IBSA, by investigating the key factors that encourage customers to adopt Internet banking in the Iraqi context, using the Theory of Planned Behavior (TPB). In order to te...
Watershed characteristics and their hydrological responses can have severe effects on the occurre... more Watershed characteristics and their hydrological responses can have severe effects on the occurrence and extent of floods. Therefore, this study focuses on the integration of geospatial techniques and remote sensing data to identify watershed terrain characteristics and evaluate the influence of these characteristics on flood susceptibility in South Australia. Data from the Shuttle Radar Topography Mission (SRTM) and geologic and topographic maps and a geographic information system (GIS) were used to delineate drainage basins, measure morphometric parameters and link different parameters to evaluate the degree of flood vulnerability. Depending on their relations to the flood hazards, the morphometric parameters were categorized into two groups; then, a rank score was assigned to each group. Finally, the flood susceptibility of the basins was visualized, and the basins were classified into low, intermediate and high flood hazard areas. The results show that approximately 45.7, 44.7 and 9.7% of the study area is at risk of high, medium and low degrees of flooding, respectively. The results were validated through secondary data relating to historic floods. The causes of flooding were analysed using rainfall and road density data, while the consequences of flooding were verified by the population distribution across the study area. The findings of this study can be used to support decision-makers in planning and investing in mitigation measures, especially in highly susceptible areas of South Australian basins.
A generalization of the generalized inverse Weibull distribution the so-called transmuted general... more A generalization of the generalized inverse Weibull distribution the so-called transmuted generalized inverse Weibull distribution is proposed and studied. We will use the quadratic rank transmutation map (QRTM) in order to generate a flexible family of probability distributions taking the generalized inverseWeibull distribution as the base value distribution by introducing a new parameter that would offer more distributional flexibility. Various structural properties including explicit expressions for the moments, quantiles, and moment generating function of the new distribution are derived. We propose the method of maximum likelihood for estimating the model parameters and obtain the observed information matrix. A real data set are used to compare the flexibility of the transmuted version versus the generalized inverse Weibull distribution.
A pre-albumin glycoprotein that inhibits complement-mediated prevention of immune precipitation (... more A pre-albumin glycoprotein that inhibits complement-mediated prevention of immune precipitation (PIP) has been purified from normal human serum by sequential affinity chromatography on IgG-Sepharose, protein A-Sepharose and Con A-Sepharose. A total of 4.7 mg of this protein were obtained from 50 ml of serum, representing a yield of 49% and a 253-fold degree of purification. We have named this glycoprotein gp60 as it has an apparent molecular weight of 60,000 on SDS-PAGE. The addition of gp60 to normal serum produced dose-dependent inhibition of both PIP and solubilization of immune precipitates. Maximum inhibition of PIP was achieved by a concentration of 600 micrograms/ml. A monospecific antiserum was produced by the immunization of rabbits, which enabled us to develop an enzyme-linked immunosorbent assay to measure serum concentrations of gp60. In 12 normal sera the mean concentration was 205 micrograms/ml (range 132-258 micrograms/ml), while that in 15 rheumatoid arthritis sera w...
The association between inherited deficiencies of the classical pathway complement components (C1... more The association between inherited deficiencies of the classical pathway complement components (C1q, C1r, C1s, C4, C2 and C3) and immune complex disease shows that complement is involved in protection against the development of immune complex disease (ICD). This protection is conferred by the ability of the complement system to keep antigen antibody complexes (IC) small and soluble. Two mechanisms exist, prevention of immune precipitation (PIP), which inhibits the formation of large insoluble lattices when IC are formed in the presence of complement (nascent IC), and solubilisation of preformed immune precipitates (SOL). PIP is probably the more important as it is unlikely that, in vivo, IC are ever formed in the absence of complement. PIP displays an absolute dependency upon the classical pathway while SOL is alternative pathway dependent. However, for optimal efficiency SOL requires an intact classical pathway. Thus the classical pathway plays a role in both PIP and SOL. The end re...
Background: Hepatitis C virus is considered to be one of the most important devastating causes of... more Background: Hepatitis C virus is considered to be one of the most important devastating causes of chronic hepatitis, cirrhosis, and hepatic cellular carcinoma. Toll-like receptor 7 (TLR7) is a pathogen-recognition receptor that is expressed on innate immune cells. It recognizes viral RNA which induces its activation with a subsequent increase in IFN-a transcription. It has been postulated that HCV may cause down regulation of these receptors as one of immune evading mechanisms that participate in viral persistence. The aim of the work: Was to investigate the expression of TLR7 in peripheral blood of patients with chronic HCV infections and patients with HCC, comparing it with normal individuals, and correlating it with both serum levels of IFN-a and viral load. Results: The results of this study showed a significant decrease in TLR7 expression in patients with chronic HCV and no detection at all in patients with HCC, in addition a significant negative correlation was observed between levels of TLR7expression and interferon a when compared to viral load. Conclusion: Down regulation of TLR7 expression in HCV and HCC patients may contribute to the decrease of IFN-a and increase in viral load. These results raise the possibility that by targeting TLR7 with high affinity pharmacological stimulants may be able to control HCV infection by induction of IFN-a and direct activation of antiviral mechanisms in hepatocytes. Additionally, they provide insight about the potential use of TLR7 as a new set of molecular markers for prognosis and outcomes of chronic HCV infection and HCC.
Medicine & Science in Sports & Exercise, 2004
Purpose: To measure the influence of vitamin E ingestion on oxidative stress and immune changes i... more Purpose: To measure the influence of vitamin E ingestion on oxidative stress and immune changes in response to the Triathlon World Championship in Kona, Hawaii. Methods: Thirty-eight triathletes received vitamin E (VitE) (800 IU•d Ϫ1 ␣-tocopherol) or placebo (Pla) capsules in randomized, double-blind fashion for 2 months before the race event. Blood, urine, and saliva samples were collected the day before the race, 5-10 min postrace, and 1.5 h postrace. Results: Race times did not differ between VitE (N ϭ 19, 721 Ϯ 24 min) and Pla groups (N ϭ 17, 719 Ϯ 27 min, P ϭ 0.959), and both groups maintained an intensity of ϳ80% maximum heart rate during the bike and run portions. Plasma ␣-tocopherol was approximately 75% higher in the VitE versus Pla group prerace (24.1 Ϯ 1.1 and 13.8 Ϯ 1.1 mol•L Ϫ1 , P Ͻ 0.001, respectively) and postrace. Plasma F 2-isoprostanes increased 181% versus 97% postrace in the VitE versus Pla groups (P ϭ 0.044). IL-6 was 89% higher (166 Ϯ 28 and 88 Ϯ 13 pg•mL Ϫ1 , respectively, P ϭ 0.016), IL-1ra was 107% higher (4848 Ϯ 1203 and 2341 Ϯ 790 pg•mL Ϫ1 , respectively, P ϭ 0.057), and IL-8 was 41% higher postrace in the VitE versus Pla groups (26.0 Ϯ 3.6 and 18.4 Ϯ 2.4 pg•mL Ϫ1 , respectively, P ϭ 0.094). Conclusion: These data indicate that vitamin E (800 IU•d Ϫ1 for 2 months) compared with placebo ingestion before a competitive triathlon race event promotes lipid peroxidation and inflammation during exercise.
Objective: To test the clinical response of systemic lupus erythematosus (SLE) patients to intrav... more Objective: To test the clinical response of systemic lupus erythematosus (SLE) patients to intravenous immunoglobulins (IVIg), and whether the clinical response of IVIg treatment in SLE is accompanied by modification of SLE-associated autoantibodies/antibodies (Abs) and complement levels.Methods: Twenty SLE patients were treated with high-dose (2 g/kg) IVIg monthly, in a 5-d schedule. Each patient received between 1-8 treatment courses. They were evaluated for the clinical response, Systemic Lupus Activity Measure (SLAM) score before and after IVIg, levels of antinuclear antibody (ANA), dsDNA (double-stranded DNA), SS-A or SS-B, ENA (extractable nuclear antigens), C3and C4levels before and after the treatment, and before and after each treatment course.Results: A beneficial clinical response following IVIg treatment was noted in 17 out of 20 patients (85%). Few clinical manifestations responded more to treatment: arthritis, fever, thrombocytopenia, and neuropsychiatric lupus. In 9 p...
Twenty-nine patients with clinically defined Takayasu arteritis and 26 healthy control volunteers... more Twenty-nine patients with clinically defined Takayasu arteritis and 26 healthy control volunteers were recruited by INSSYS investigators from their clinical practices. Patients with Takayasu arteritis were divided into those with clear-cut clinically active or inactive disease based on Birmingham Vasculitis Activity Scores. Multiple serological tests were performed including ESR, C-reactive protein, tissue factor, von Willebrand factor, thrombomodulin, tissue plasminogen activator, ICAM-1, VCAM-1, E-selectin and PECAM-1. No test was reliably able to distinguish between healthy volunteers and patients with active Takayasu arteritis. At present there is no known serological test which can consistently supplant vascular histopathology in determining the activity of Takayasu arteritis.
International Archives of Allergy and Immunology, 1999
Background: Autoimmune vasculitides cannot always be controlled by steroids and immunosuppressive... more Background: Autoimmune vasculitides cannot always be controlled by steroids and immunosuppressive drugs. Intravenous immunoglobulin (IVIg) treatment was found beneficial in several vasculitides including systemic and organ–specific diseases. In this article we tested whether the beneficial clinical response of IVIg treatment in vasculitides was accompanied by a decrease in vasculitis–associated autoantibody levels. Methods: Ten patients diagnosed as having vasculitis were treated with high–dose (2 g/kg) IVIg monthly, in a 5–day schedule. In all the patients, other therapeutic measures failed to control disease progression prior to IVIg treatment. Each patient received between 1 and 6 treatment courses. All patients were evaluated for the levels of 5 autoantibodies (Abs) related to vasculitis before and after each treatment course. Results: In 6 out of the 10 patients, a beneficial clinical response followed IVIg treatment. Moreover, no treatment–related adverse effects were observed...
The aim of this study was to examine the presence of antibodies to GM1 and sulfatide in various I... more The aim of this study was to examine the presence of antibodies to GM1 and sulfatide in various IVIg preparations. Five brands of commercially available human IVIg (Sandoglobulin, Isiven, Cytogam, Omrigam and Cutter) were examined and compared. Serial dilutions of each of the above preparations were prepared at a working range of 0.009 to 25.0 mg/ml IVIg, and screened by a standard 96-well microplate EIA for autoantibodies to the ganglioside GM1 and to the glycolipid sulfatide. The various IVIg preparations (Omrigam, Cytogam, Sandoglobulin, Isiven), except for Cutter IVIg, contained low to medium titers of the autoantibodies tested. Omrigam and Cytogam IVIg contained low titer of antibodies to GM1, and medium-titer of antibodies to sulfatide, whereas Sandoglobulin and Isiven contained only low-titer of autoantibodies to sulfatide. The presence of natural autoantibodies to myelin in human sera may explain the presence of the tested antibodies within IVIg preparations. Measurements of antibodies to ganglioside and glycolipid in sera of Guillain-Barré patients immediately following IVIg, would probably not reveal antibody decrease. Alternatively, long-term (several weeks) follow-up of titers might result in their modification due to inhibition of antibodies production by IVIg.
Primary bilary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the presen... more Primary bilary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in the serum. The major antigens recognized by the antibodies are the E2 components of the 2-oxo acid dehydrogenase complexes, all of which possess covalently attached lipoic acid cofactors. A bacterial etiology has been proposed for the disease, and patients' antibodies are known to recognize the E2 subunits (E2p) of both mammalian and bacterial pyruvate dehydrogenase complexes. Immunoblotting and ELISA inhibition techniques using extracts of Escherichia coli deletion strains, genetically restructured E2 polypeptides, and isolated lipoyl domains demonstrate that (i) the E2o subunit of the E. coli 2-oxoglutarate dehydrogenase complex is recognized by patients' antibodies; (ii) the main immunogenic region of E2p lies within the lipoyl domains; (ii) the presence of a lipoyl residue within the domain is crucial for effective recognition by the antibodies; and (iv) octanoylated E2p, octanoylated E2o, and octanoylated lipoyl domain, produced by a mutant deficient in lipoate biosynthesis, are recognized by patients' antibodies but not as effectively as their lipoylated counterparts. These rmdings indicate that antibodies in PBC patients' sera bind to a unique peptide-cofactor conformation within the lipoyl domains of the E2 polypeptides and that this epitope is partially mimicked by substituting the lipoyl cofactor with an octanoyl group.
Additional file 1: Supplementary Table S1. Over-represented KEGG pathways. Supplementary Table S2... more Additional file 1: Supplementary Table S1. Over-represented KEGG pathways. Supplementary Table S2. Top 5 statistically significant over-represented diseases. Supplementary Table S3. Average cytokine levels (pg/mL) by matched RvE1 treatment of T2D (N = 3) and healthy (N = 3) neutrophils in cell culture. Supplementary Table S4. Average cytokine levels (pg/mL) by differing RvE1 treatment of T2D (N = 3) and healthy (N = 3) neutrophils in cell culture. Supplementary Fig. S1. Principal component analysis (PCA) plot of type 2 diabetic and healthy subjects. Supplementary Fig. S2. Neutrophil gene expression in type 2 diabetic versus healthy subjects for all 50 significant genes. Supplementary Fig. S3. Top 50 significant neutrophil genes differentially expressed in type 2 diabetic and healthy subjects by top biological pathways. Supplementary Fig. S4. Neutrophil gene expression of type 2 diabetic and healthy subjects by biologically relevant KEGG pathways.
International Journal of Research -GRANTHAALAYAH, 2015
Definitely the Internet banking services adoption (IBSA) represents a good opportunity for develo... more Definitely the Internet banking services adoption (IBSA) represents a good opportunity for developing nations to attain greater economic development and growth. This sector plays a vital role in developing numerous businesses and increasing Gross Domestic Product (GDP) in different countries, particularly in developing countries, such as the Republic of Iraq. Although a lot of research evidences the wide adoption of Internet banking in developed nations, there is still limited research in developing nations in the Middle East, specifically in Iraq on this area. There is definitely a need in this country to identify the factors that could encourage IBSA. There is also a paucity of empirical research on IBSA from the perspective of customers. Taking these into cognizance, this quantitative research aims to understand IBSA, by investigating the key factors that encourage customers to adopt Internet banking in the Iraqi context, using the Theory of Planned Behavior (TPB). In order to te...
Watershed characteristics and their hydrological responses can have severe effects on the occurre... more Watershed characteristics and their hydrological responses can have severe effects on the occurrence and extent of floods. Therefore, this study focuses on the integration of geospatial techniques and remote sensing data to identify watershed terrain characteristics and evaluate the influence of these characteristics on flood susceptibility in South Australia. Data from the Shuttle Radar Topography Mission (SRTM) and geologic and topographic maps and a geographic information system (GIS) were used to delineate drainage basins, measure morphometric parameters and link different parameters to evaluate the degree of flood vulnerability. Depending on their relations to the flood hazards, the morphometric parameters were categorized into two groups; then, a rank score was assigned to each group. Finally, the flood susceptibility of the basins was visualized, and the basins were classified into low, intermediate and high flood hazard areas. The results show that approximately 45.7, 44.7 and 9.7% of the study area is at risk of high, medium and low degrees of flooding, respectively. The results were validated through secondary data relating to historic floods. The causes of flooding were analysed using rainfall and road density data, while the consequences of flooding were verified by the population distribution across the study area. The findings of this study can be used to support decision-makers in planning and investing in mitigation measures, especially in highly susceptible areas of South Australian basins.
A generalization of the generalized inverse Weibull distribution the so-called transmuted general... more A generalization of the generalized inverse Weibull distribution the so-called transmuted generalized inverse Weibull distribution is proposed and studied. We will use the quadratic rank transmutation map (QRTM) in order to generate a flexible family of probability distributions taking the generalized inverseWeibull distribution as the base value distribution by introducing a new parameter that would offer more distributional flexibility. Various structural properties including explicit expressions for the moments, quantiles, and moment generating function of the new distribution are derived. We propose the method of maximum likelihood for estimating the model parameters and obtain the observed information matrix. A real data set are used to compare the flexibility of the transmuted version versus the generalized inverse Weibull distribution.
A pre-albumin glycoprotein that inhibits complement-mediated prevention of immune precipitation (... more A pre-albumin glycoprotein that inhibits complement-mediated prevention of immune precipitation (PIP) has been purified from normal human serum by sequential affinity chromatography on IgG-Sepharose, protein A-Sepharose and Con A-Sepharose. A total of 4.7 mg of this protein were obtained from 50 ml of serum, representing a yield of 49% and a 253-fold degree of purification. We have named this glycoprotein gp60 as it has an apparent molecular weight of 60,000 on SDS-PAGE. The addition of gp60 to normal serum produced dose-dependent inhibition of both PIP and solubilization of immune precipitates. Maximum inhibition of PIP was achieved by a concentration of 600 micrograms/ml. A monospecific antiserum was produced by the immunization of rabbits, which enabled us to develop an enzyme-linked immunosorbent assay to measure serum concentrations of gp60. In 12 normal sera the mean concentration was 205 micrograms/ml (range 132-258 micrograms/ml), while that in 15 rheumatoid arthritis sera w...
The association between inherited deficiencies of the classical pathway complement components (C1... more The association between inherited deficiencies of the classical pathway complement components (C1q, C1r, C1s, C4, C2 and C3) and immune complex disease shows that complement is involved in protection against the development of immune complex disease (ICD). This protection is conferred by the ability of the complement system to keep antigen antibody complexes (IC) small and soluble. Two mechanisms exist, prevention of immune precipitation (PIP), which inhibits the formation of large insoluble lattices when IC are formed in the presence of complement (nascent IC), and solubilisation of preformed immune precipitates (SOL). PIP is probably the more important as it is unlikely that, in vivo, IC are ever formed in the absence of complement. PIP displays an absolute dependency upon the classical pathway while SOL is alternative pathway dependent. However, for optimal efficiency SOL requires an intact classical pathway. Thus the classical pathway plays a role in both PIP and SOL. The end re...
Background: Hepatitis C virus is considered to be one of the most important devastating causes of... more Background: Hepatitis C virus is considered to be one of the most important devastating causes of chronic hepatitis, cirrhosis, and hepatic cellular carcinoma. Toll-like receptor 7 (TLR7) is a pathogen-recognition receptor that is expressed on innate immune cells. It recognizes viral RNA which induces its activation with a subsequent increase in IFN-a transcription. It has been postulated that HCV may cause down regulation of these receptors as one of immune evading mechanisms that participate in viral persistence. The aim of the work: Was to investigate the expression of TLR7 in peripheral blood of patients with chronic HCV infections and patients with HCC, comparing it with normal individuals, and correlating it with both serum levels of IFN-a and viral load. Results: The results of this study showed a significant decrease in TLR7 expression in patients with chronic HCV and no detection at all in patients with HCC, in addition a significant negative correlation was observed between levels of TLR7expression and interferon a when compared to viral load. Conclusion: Down regulation of TLR7 expression in HCV and HCC patients may contribute to the decrease of IFN-a and increase in viral load. These results raise the possibility that by targeting TLR7 with high affinity pharmacological stimulants may be able to control HCV infection by induction of IFN-a and direct activation of antiviral mechanisms in hepatocytes. Additionally, they provide insight about the potential use of TLR7 as a new set of molecular markers for prognosis and outcomes of chronic HCV infection and HCC.
Medicine & Science in Sports & Exercise, 2004
Purpose: To measure the influence of vitamin E ingestion on oxidative stress and immune changes i... more Purpose: To measure the influence of vitamin E ingestion on oxidative stress and immune changes in response to the Triathlon World Championship in Kona, Hawaii. Methods: Thirty-eight triathletes received vitamin E (VitE) (800 IU•d Ϫ1 ␣-tocopherol) or placebo (Pla) capsules in randomized, double-blind fashion for 2 months before the race event. Blood, urine, and saliva samples were collected the day before the race, 5-10 min postrace, and 1.5 h postrace. Results: Race times did not differ between VitE (N ϭ 19, 721 Ϯ 24 min) and Pla groups (N ϭ 17, 719 Ϯ 27 min, P ϭ 0.959), and both groups maintained an intensity of ϳ80% maximum heart rate during the bike and run portions. Plasma ␣-tocopherol was approximately 75% higher in the VitE versus Pla group prerace (24.1 Ϯ 1.1 and 13.8 Ϯ 1.1 mol•L Ϫ1 , P Ͻ 0.001, respectively) and postrace. Plasma F 2-isoprostanes increased 181% versus 97% postrace in the VitE versus Pla groups (P ϭ 0.044). IL-6 was 89% higher (166 Ϯ 28 and 88 Ϯ 13 pg•mL Ϫ1 , respectively, P ϭ 0.016), IL-1ra was 107% higher (4848 Ϯ 1203 and 2341 Ϯ 790 pg•mL Ϫ1 , respectively, P ϭ 0.057), and IL-8 was 41% higher postrace in the VitE versus Pla groups (26.0 Ϯ 3.6 and 18.4 Ϯ 2.4 pg•mL Ϫ1 , respectively, P ϭ 0.094). Conclusion: These data indicate that vitamin E (800 IU•d Ϫ1 for 2 months) compared with placebo ingestion before a competitive triathlon race event promotes lipid peroxidation and inflammation during exercise.
Objective: To test the clinical response of systemic lupus erythematosus (SLE) patients to intrav... more Objective: To test the clinical response of systemic lupus erythematosus (SLE) patients to intravenous immunoglobulins (IVIg), and whether the clinical response of IVIg treatment in SLE is accompanied by modification of SLE-associated autoantibodies/antibodies (Abs) and complement levels.Methods: Twenty SLE patients were treated with high-dose (2 g/kg) IVIg monthly, in a 5-d schedule. Each patient received between 1-8 treatment courses. They were evaluated for the clinical response, Systemic Lupus Activity Measure (SLAM) score before and after IVIg, levels of antinuclear antibody (ANA), dsDNA (double-stranded DNA), SS-A or SS-B, ENA (extractable nuclear antigens), C3and C4levels before and after the treatment, and before and after each treatment course.Results: A beneficial clinical response following IVIg treatment was noted in 17 out of 20 patients (85%). Few clinical manifestations responded more to treatment: arthritis, fever, thrombocytopenia, and neuropsychiatric lupus. In 9 p...
Twenty-nine patients with clinically defined Takayasu arteritis and 26 healthy control volunteers... more Twenty-nine patients with clinically defined Takayasu arteritis and 26 healthy control volunteers were recruited by INSSYS investigators from their clinical practices. Patients with Takayasu arteritis were divided into those with clear-cut clinically active or inactive disease based on Birmingham Vasculitis Activity Scores. Multiple serological tests were performed including ESR, C-reactive protein, tissue factor, von Willebrand factor, thrombomodulin, tissue plasminogen activator, ICAM-1, VCAM-1, E-selectin and PECAM-1. No test was reliably able to distinguish between healthy volunteers and patients with active Takayasu arteritis. At present there is no known serological test which can consistently supplant vascular histopathology in determining the activity of Takayasu arteritis.
International Archives of Allergy and Immunology, 1999
Background: Autoimmune vasculitides cannot always be controlled by steroids and immunosuppressive... more Background: Autoimmune vasculitides cannot always be controlled by steroids and immunosuppressive drugs. Intravenous immunoglobulin (IVIg) treatment was found beneficial in several vasculitides including systemic and organ–specific diseases. In this article we tested whether the beneficial clinical response of IVIg treatment in vasculitides was accompanied by a decrease in vasculitis–associated autoantibody levels. Methods: Ten patients diagnosed as having vasculitis were treated with high–dose (2 g/kg) IVIg monthly, in a 5–day schedule. In all the patients, other therapeutic measures failed to control disease progression prior to IVIg treatment. Each patient received between 1 and 6 treatment courses. All patients were evaluated for the levels of 5 autoantibodies (Abs) related to vasculitis before and after each treatment course. Results: In 6 out of the 10 patients, a beneficial clinical response followed IVIg treatment. Moreover, no treatment–related adverse effects were observed...
The aim of this study was to examine the presence of antibodies to GM1 and sulfatide in various I... more The aim of this study was to examine the presence of antibodies to GM1 and sulfatide in various IVIg preparations. Five brands of commercially available human IVIg (Sandoglobulin, Isiven, Cytogam, Omrigam and Cutter) were examined and compared. Serial dilutions of each of the above preparations were prepared at a working range of 0.009 to 25.0 mg/ml IVIg, and screened by a standard 96-well microplate EIA for autoantibodies to the ganglioside GM1 and to the glycolipid sulfatide. The various IVIg preparations (Omrigam, Cytogam, Sandoglobulin, Isiven), except for Cutter IVIg, contained low to medium titers of the autoantibodies tested. Omrigam and Cytogam IVIg contained low titer of antibodies to GM1, and medium-titer of antibodies to sulfatide, whereas Sandoglobulin and Isiven contained only low-titer of autoantibodies to sulfatide. The presence of natural autoantibodies to myelin in human sera may explain the presence of the tested antibodies within IVIg preparations. Measurements of antibodies to ganglioside and glycolipid in sera of Guillain-Barré patients immediately following IVIg, would probably not reveal antibody decrease. Alternatively, long-term (several weeks) follow-up of titers might result in their modification due to inhibition of antibodies production by IVIg.
Primary bilary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the presen... more Primary bilary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in the serum. The major antigens recognized by the antibodies are the E2 components of the 2-oxo acid dehydrogenase complexes, all of which possess covalently attached lipoic acid cofactors. A bacterial etiology has been proposed for the disease, and patients' antibodies are known to recognize the E2 subunits (E2p) of both mammalian and bacterial pyruvate dehydrogenase complexes. Immunoblotting and ELISA inhibition techniques using extracts of Escherichia coli deletion strains, genetically restructured E2 polypeptides, and isolated lipoyl domains demonstrate that (i) the E2o subunit of the E. coli 2-oxoglutarate dehydrogenase complex is recognized by patients' antibodies; (ii) the main immunogenic region of E2p lies within the lipoyl domains; (ii) the presence of a lipoyl residue within the domain is crucial for effective recognition by the antibodies; and (iv) octanoylated E2p, octanoylated E2o, and octanoylated lipoyl domain, produced by a mutant deficient in lipoate biosynthesis, are recognized by patients' antibodies but not as effectively as their lipoylated counterparts. These rmdings indicate that antibodies in PBC patients' sera bind to a unique peptide-cofactor conformation within the lipoyl domains of the E2 polypeptides and that this epitope is partially mimicked by substituting the lipoyl cofactor with an octanoyl group.
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Papers by Alaa Ahmed