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Papers by Homayoun Sadeghi

Research paper thumbnail of Correspondence: Homayoun Sadeghi

Neuropsychiatric Disease and Treatment OPLS statistical model versus linear regression to assess ... more Neuropsychiatric Disease and Treatment OPLS statistical model versus linear regression to assess sonographic predictors of stroke prognosis

Research paper thumbnail of Efficacy of Tadalafil on Ureteral Stent Symptoms: A Randomized Controlled Trial

Nephro-Urology Monthly, 2019

Objectives: To determine whether tadalafil, a PDE5i, is effective on stent-associated symptoms. M... more Objectives: To determine whether tadalafil, a PDE5i, is effective on stent-associated symptoms. Methods: In this double-blind randomized clinical trial, 80 consecutive male patients with unilateral double J stents were randomly assigned to intervention and placebo groups (n = 40 per group). The patients received 10 mg of tadalafil or placebo once a day for four weeks. The Ureteral Stent Symptom Questionnaire (USSQ) was selected as the primary outcome assessment tool. Complications were recorded as secondary outcomes. Data were analyzed using STATA 11 statistical software. Relative risk (RR) and risk difference (RD) were calculated for appropriately dichotomized endpoints. Results: Of the 80 patients who provided consent, 72 patients successfully completed the study. The mean urinary symptom index score was 30.94 in the placebo group and 26.59 in the tadalafil group (P = 0.0003). Stent-related pain was reported by 80% of the patients in the placebo group and by 67.6% of the patients in the tadalafil group. The mean pain index score was 20.77 in the placebo group and 16.41 in the tadalafil group (P = 0.039). The mean sexual matters score in the placebo and tadalafil groups was 6.20 and 3.73, respectively (P = 0.0007). There was no significant difference in other domains between the groups. The tadalafil group showed no increase in major side effects compared to the placebo group. Conclusions: Tadalafil improved stent-related urinary symptoms, pain, sexual status, and overall score; it can also be used as a novel treatment modality in the alleviation of lower urinary tract symptoms and improve the quality of life in these patients.

Research paper thumbnail of Prognostic factors in patients with acute ischemic stroke treated with intravenous tissue plasminogen activator: The first study among Iranian patients

Iranian Journal of Neurology, 2018

Background: Tissue plasminogen activator (tPA) has been long approved as an efficacious treatment... more Background: Tissue plasminogen activator (tPA) has been long approved as an efficacious treatment in patients with acute ischemic stroke (AIS); however, due to some serious complications, particularly intracranial hemorrhage (ICH), many physicians are still reluctant to use it liberally. This study sought to find potential prognostic factors in patients with AIS treated with tPA. Methods: A retrospective, hospital-bases observational study was conducted. Consecutively, a total of 132 patients with AIS treated with intravenous tPA, form June 2011 to July 2015 were enrolled. Inclusion and exclusion criteria were based on updated guidelines. Probable prognostic variables were examined separately in three distinct groups; the occurrence of ICH within 24 hours after treatment, poor 3-month outcome on the basis of modified Rankin Scale (mRS) and 3-month mortality. Results: Patients were 83 men (62.9%) and 49 women (37.1%) with a median age of 66 years [interquartile range (IQR)of 55-72]. ...

Research paper thumbnail of Modified transferrin fusion proteins comprising duplicate transferrin amino or carboxy terminal domains

Research paper thumbnail of Fusion protein of exendin-4 to a transferrin (Tf) polypeptide

Research paper thumbnail of Therapeutic polypeptide with prolonged shelf-life and increased half life for use in treatment of cell proliferative, cardiovascular, inflammatory and autoimmune disorders

Research paper thumbnail of Modified transferrin-antibody fusion proteins

Research paper thumbnail of Combination therapy using transferrin fusion proteins comprising glp-1

The present invention provides combination therapy comprising transferrin fusion protein and DPP-... more The present invention provides combination therapy comprising transferrin fusion protein and DPP-IV inhibitors and/or neutral endopeptidase (NEP) inhibitors. The transferrin fusion protein comprises therapeutic polypeptides or peptides useful in the treatment of diseases such as diabetes.

Research paper thumbnail of Modified transferin-antibody fusion proteins

Research paper thumbnail of Therapeutic fusion protein with enhanced for use in prevention and treatment of cell proliferative, blood and nervous system disorders

Research paper thumbnail of Transferrin fusion protein libraries

Research paper thumbnail of Modified Transferrin Fusion Proteins

Research paper thumbnail of Natriuretic Peptide Modified Transferrin Fusion Proteins

Research paper thumbnail of Modified Vasoactive Intestinal Peptides

Research paper thumbnail of C30 Validity and Reliability ICIQ-OAB questionnaire in the Persian version

European Urology Supplements, 2013

Research paper thumbnail of Generation of Heterohybridomas Capable of Releasing Swine Monoclonal Antibody Specific to Porcine Growth Hormone

Hybridoma, 1994

An effort was made to generate stable swine hybridomas capable of releasing monoclonal antibodies... more An effort was made to generate stable swine hybridomas capable of releasing monoclonal antibodies (MAb) with antigenic specificity. Crossbred pigs were immunized with recombinant porcine growth hormone (r-pGH) and the splenic cells were harvested from these animals. B lymphocytes enriched by gradient centrifugation and nylon wool adherence were briefly stimulated in vitro with r-pGH prior to hybridization with murine SP2/0 myeloma cells. The fused hybrids were screened for their ability to produce anti-pGH antibody and the positive ones were subcloned by a limiting dilution procedure. The stable cell lines were maintained by serial passages in cultures for further analysis. One such hybridoma, designated PM20/20, was found to secrete swine IgM. It recognized not only the immunizing r-pGH but also the native pGH extracted from the swine pituitary glands, as demonstrated by Western analysis. It also recognized two smaller fragments with m.w. of 10 kD and 5 kD of r-pGH following trypsin digestion. In addition to pGH, PM20/20 immunoreacted with several other GH species including bovine, chicken, and human origins, but not with ovine prolactin nor rat GH binding protein. The binding association rate constant and dissociation rate constant of PM20/20 to pGH were 5.3 x 10(4) M-1 s-1 and 1.0 x 10(-4) s-1, respectively, thus producing a dissociation constant of 1.9 x 10(-9) M. Therefore, stable swine-mouse heterohybridoma lines have been established and shown to continuously release swine mAb in cultures. These mAb may serve as useful alternatives to murine mAb in certain areas of research.

Research paper thumbnail of Inhibitory effect of growth-enhancing antibody on the interaction between growth hormone and growth hormone binding protein

Molecular and Cellular Endocrinology, 1993

A monoclonal antibody (mAb), designated PS-7.6, was generated in mice by immunizing these animals... more A monoclonal antibody (mAb), designated PS-7.6, was generated in mice by immunizing these animals with recombinant porcine growth hormone (pGH). This antibody has been previously shown to enhance the growth-promoting activity of pGH in an experimental rat model. An effort was made in this report to further characterize the immunologic properties of this antibody and its effect on the interaction between pGH and GH binding protein (GHBP). This antibody was classified as IgG, isotype and found to be highly specific to pGH in a competition radioimmunoassay (RIA). It did not recognize several other GHs including those of bovine, chicken and human origins, nor several growth related factors including prolactin, insulin, somatostatin and growth hormone releasing factor. In Western analysis, PS-7.6 mAb identified not only the 22.5 kDa recombinant pGH, but also the native pGH in swine pituitary gland. An additional 45 kDa protein was also detected in the gland by the antibody, presumably a dimer form of pGH. The association and dissociation rate constants of the antibody as determined by biospecific interaction analysis (BIA) were 2.43 X lo4 M-' s-l and 1.29 X 1O-3 s-l, respectively and its affinity (K,) was 4.85 x lo-' M. Furthermore, PS-7.6 mAb prevented pGH from interacting with GHBP in RIA and BIA, indicating that the antibody epitope closely associated with the pGH binding region for GHBP. Therefore, present findings suggest that a possible mechanism of action of PS-7.6 mAb in enhancing animal growth is to prevent pGH from being bound to GHBP in circulation, thus making more pGH available to tissue receptors.

Research paper thumbnail of Transferrin Fusion Technology: A Novel Approach to Prolonging Biological Half-Life of Insulinotropic Peptides

Journal of Pharmacology and Experimental Therapeutics, 2010

Fusion proteins made up of glucagon-like peptide 1 (GLP-1) and exendin-4 (EX-4) fused to a nongly... more Fusion proteins made up of glucagon-like peptide 1 (GLP-1) and exendin-4 (EX-4) fused to a nonglycosylated form of human transferrin (GLP-1-Tf or EX-4-Tf) were produced and characterized. GLP-1-Tf activated the GLP-1 receptor, was resistant to inactivation by peptidases, and had a half-life of approximately 2 days, compared with 1 to 2 min for native GLP-1. GLP-1-Tf retained the acute, glucose-dependent insulin-secretory properties of native GLP-1 in diabetic animals and had a profound effect on proliferation of pancreatic ␤-cells. In addition, Tf and the fusion proteins did not cross the blood-brain-barrier but still reduced food intake after peripheral administration. EX-4-Tf proved to be as effective as EX-4 but had longer lived effects on blood glucose and food intake. This novel transferrin fusion technology could improve the pharmacology of various peptides.

Research paper thumbnail of Proliferation of Nb2 lymphoma cells in vitro in response to interleukin-7

Immunology Letters, 1992

An attempt was made to investigate the proliferative effect of interleukin-7 (IL-7) on a rat Nb2 ... more An attempt was made to investigate the proliferative effect of interleukin-7 (IL-7) on a rat Nb2 T-cell lymphoma line. It was demonstrated that both human and mouse IL-7 stimulated these cells to proliferate in a dose dependent fashion in culture medium containing 10% horse serum. The maximum activities of mIL-7 and hIL-7 were observed at 100 and 1000 units/ml with their half-maximal response of 10 and 50 units/ml, respectively. In a totally serum-free culture condition, mIL-7 produced a similar cellular proliferation, whereas hIL-7 was much less effective. The effectiveness of IL-7 on Nb2 cells was completely abolished by antibody to IL-7, but not by antibody to IL-2. Therefore, Nb2 cells may serve as a simple, convenient and sensitive assay for monitoring the biological activity of IL-7 in vitro. In addition, these cells are also useful for studying the lymphopoiesis of T-cell lineage regulated by IL-7.

Research paper thumbnail of Biosynthesis of 117 antigen: A cell cohesion molecule inDictyostelium discoideum

Developmental Genetics, 1988

117 antigen is involved in the process of intercellular cohesion in Dictyostelium discoideum [Bro... more 117 antigen is involved in the process of intercellular cohesion in Dictyostelium discoideum [Brodie et al., 1983]. The antigen, a 69- and 72-kDa doublet, was found to arise from a 60- and 62-kDa precursor. The mature antigen contains N-linked oligosaccharides that are sulfated and fucosylated [Sadeghi et al., 1987]. These oligosaccharide chains are resistant to endoglycosidase H digestion. 117 antigen also contains a post-translationally added carbohydrate-containing modification(s). Unlike the N-linked oligosaccharide, this carbohydrate moiety is sensitive to periodate oxidation. 117 antigen is developmentally regulated, and the changes in rate of 117 antigen synthesis reflect changes in the cellular levels of its mRNA. 117 mRNA accumulates in starving cells and reaches its maximum when cells become aggregation competent. The mRNA levels then decline, and by the time the slug structure is formed, no 117 mRNA is present. 117 mRNA reaccumulates for a brief period during early culmination and then returns to an undetectable level.

Research paper thumbnail of Correspondence: Homayoun Sadeghi

Neuropsychiatric Disease and Treatment OPLS statistical model versus linear regression to assess ... more Neuropsychiatric Disease and Treatment OPLS statistical model versus linear regression to assess sonographic predictors of stroke prognosis

Research paper thumbnail of Efficacy of Tadalafil on Ureteral Stent Symptoms: A Randomized Controlled Trial

Nephro-Urology Monthly, 2019

Objectives: To determine whether tadalafil, a PDE5i, is effective on stent-associated symptoms. M... more Objectives: To determine whether tadalafil, a PDE5i, is effective on stent-associated symptoms. Methods: In this double-blind randomized clinical trial, 80 consecutive male patients with unilateral double J stents were randomly assigned to intervention and placebo groups (n = 40 per group). The patients received 10 mg of tadalafil or placebo once a day for four weeks. The Ureteral Stent Symptom Questionnaire (USSQ) was selected as the primary outcome assessment tool. Complications were recorded as secondary outcomes. Data were analyzed using STATA 11 statistical software. Relative risk (RR) and risk difference (RD) were calculated for appropriately dichotomized endpoints. Results: Of the 80 patients who provided consent, 72 patients successfully completed the study. The mean urinary symptom index score was 30.94 in the placebo group and 26.59 in the tadalafil group (P = 0.0003). Stent-related pain was reported by 80% of the patients in the placebo group and by 67.6% of the patients in the tadalafil group. The mean pain index score was 20.77 in the placebo group and 16.41 in the tadalafil group (P = 0.039). The mean sexual matters score in the placebo and tadalafil groups was 6.20 and 3.73, respectively (P = 0.0007). There was no significant difference in other domains between the groups. The tadalafil group showed no increase in major side effects compared to the placebo group. Conclusions: Tadalafil improved stent-related urinary symptoms, pain, sexual status, and overall score; it can also be used as a novel treatment modality in the alleviation of lower urinary tract symptoms and improve the quality of life in these patients.

Research paper thumbnail of Prognostic factors in patients with acute ischemic stroke treated with intravenous tissue plasminogen activator: The first study among Iranian patients

Iranian Journal of Neurology, 2018

Background: Tissue plasminogen activator (tPA) has been long approved as an efficacious treatment... more Background: Tissue plasminogen activator (tPA) has been long approved as an efficacious treatment in patients with acute ischemic stroke (AIS); however, due to some serious complications, particularly intracranial hemorrhage (ICH), many physicians are still reluctant to use it liberally. This study sought to find potential prognostic factors in patients with AIS treated with tPA. Methods: A retrospective, hospital-bases observational study was conducted. Consecutively, a total of 132 patients with AIS treated with intravenous tPA, form June 2011 to July 2015 were enrolled. Inclusion and exclusion criteria were based on updated guidelines. Probable prognostic variables were examined separately in three distinct groups; the occurrence of ICH within 24 hours after treatment, poor 3-month outcome on the basis of modified Rankin Scale (mRS) and 3-month mortality. Results: Patients were 83 men (62.9%) and 49 women (37.1%) with a median age of 66 years [interquartile range (IQR)of 55-72]. ...

Research paper thumbnail of Modified transferrin fusion proteins comprising duplicate transferrin amino or carboxy terminal domains

Research paper thumbnail of Fusion protein of exendin-4 to a transferrin (Tf) polypeptide

Research paper thumbnail of Therapeutic polypeptide with prolonged shelf-life and increased half life for use in treatment of cell proliferative, cardiovascular, inflammatory and autoimmune disorders

Research paper thumbnail of Modified transferrin-antibody fusion proteins

Research paper thumbnail of Combination therapy using transferrin fusion proteins comprising glp-1

The present invention provides combination therapy comprising transferrin fusion protein and DPP-... more The present invention provides combination therapy comprising transferrin fusion protein and DPP-IV inhibitors and/or neutral endopeptidase (NEP) inhibitors. The transferrin fusion protein comprises therapeutic polypeptides or peptides useful in the treatment of diseases such as diabetes.

Research paper thumbnail of Modified transferin-antibody fusion proteins

Research paper thumbnail of Therapeutic fusion protein with enhanced for use in prevention and treatment of cell proliferative, blood and nervous system disorders

Research paper thumbnail of Transferrin fusion protein libraries

Research paper thumbnail of Modified Transferrin Fusion Proteins

Research paper thumbnail of Natriuretic Peptide Modified Transferrin Fusion Proteins

Research paper thumbnail of Modified Vasoactive Intestinal Peptides

Research paper thumbnail of C30 Validity and Reliability ICIQ-OAB questionnaire in the Persian version

European Urology Supplements, 2013

Research paper thumbnail of Generation of Heterohybridomas Capable of Releasing Swine Monoclonal Antibody Specific to Porcine Growth Hormone

Hybridoma, 1994

An effort was made to generate stable swine hybridomas capable of releasing monoclonal antibodies... more An effort was made to generate stable swine hybridomas capable of releasing monoclonal antibodies (MAb) with antigenic specificity. Crossbred pigs were immunized with recombinant porcine growth hormone (r-pGH) and the splenic cells were harvested from these animals. B lymphocytes enriched by gradient centrifugation and nylon wool adherence were briefly stimulated in vitro with r-pGH prior to hybridization with murine SP2/0 myeloma cells. The fused hybrids were screened for their ability to produce anti-pGH antibody and the positive ones were subcloned by a limiting dilution procedure. The stable cell lines were maintained by serial passages in cultures for further analysis. One such hybridoma, designated PM20/20, was found to secrete swine IgM. It recognized not only the immunizing r-pGH but also the native pGH extracted from the swine pituitary glands, as demonstrated by Western analysis. It also recognized two smaller fragments with m.w. of 10 kD and 5 kD of r-pGH following trypsin digestion. In addition to pGH, PM20/20 immunoreacted with several other GH species including bovine, chicken, and human origins, but not with ovine prolactin nor rat GH binding protein. The binding association rate constant and dissociation rate constant of PM20/20 to pGH were 5.3 x 10(4) M-1 s-1 and 1.0 x 10(-4) s-1, respectively, thus producing a dissociation constant of 1.9 x 10(-9) M. Therefore, stable swine-mouse heterohybridoma lines have been established and shown to continuously release swine mAb in cultures. These mAb may serve as useful alternatives to murine mAb in certain areas of research.

Research paper thumbnail of Inhibitory effect of growth-enhancing antibody on the interaction between growth hormone and growth hormone binding protein

Molecular and Cellular Endocrinology, 1993

A monoclonal antibody (mAb), designated PS-7.6, was generated in mice by immunizing these animals... more A monoclonal antibody (mAb), designated PS-7.6, was generated in mice by immunizing these animals with recombinant porcine growth hormone (pGH). This antibody has been previously shown to enhance the growth-promoting activity of pGH in an experimental rat model. An effort was made in this report to further characterize the immunologic properties of this antibody and its effect on the interaction between pGH and GH binding protein (GHBP). This antibody was classified as IgG, isotype and found to be highly specific to pGH in a competition radioimmunoassay (RIA). It did not recognize several other GHs including those of bovine, chicken and human origins, nor several growth related factors including prolactin, insulin, somatostatin and growth hormone releasing factor. In Western analysis, PS-7.6 mAb identified not only the 22.5 kDa recombinant pGH, but also the native pGH in swine pituitary gland. An additional 45 kDa protein was also detected in the gland by the antibody, presumably a dimer form of pGH. The association and dissociation rate constants of the antibody as determined by biospecific interaction analysis (BIA) were 2.43 X lo4 M-' s-l and 1.29 X 1O-3 s-l, respectively and its affinity (K,) was 4.85 x lo-' M. Furthermore, PS-7.6 mAb prevented pGH from interacting with GHBP in RIA and BIA, indicating that the antibody epitope closely associated with the pGH binding region for GHBP. Therefore, present findings suggest that a possible mechanism of action of PS-7.6 mAb in enhancing animal growth is to prevent pGH from being bound to GHBP in circulation, thus making more pGH available to tissue receptors.

Research paper thumbnail of Transferrin Fusion Technology: A Novel Approach to Prolonging Biological Half-Life of Insulinotropic Peptides

Journal of Pharmacology and Experimental Therapeutics, 2010

Fusion proteins made up of glucagon-like peptide 1 (GLP-1) and exendin-4 (EX-4) fused to a nongly... more Fusion proteins made up of glucagon-like peptide 1 (GLP-1) and exendin-4 (EX-4) fused to a nonglycosylated form of human transferrin (GLP-1-Tf or EX-4-Tf) were produced and characterized. GLP-1-Tf activated the GLP-1 receptor, was resistant to inactivation by peptidases, and had a half-life of approximately 2 days, compared with 1 to 2 min for native GLP-1. GLP-1-Tf retained the acute, glucose-dependent insulin-secretory properties of native GLP-1 in diabetic animals and had a profound effect on proliferation of pancreatic ␤-cells. In addition, Tf and the fusion proteins did not cross the blood-brain-barrier but still reduced food intake after peripheral administration. EX-4-Tf proved to be as effective as EX-4 but had longer lived effects on blood glucose and food intake. This novel transferrin fusion technology could improve the pharmacology of various peptides.

Research paper thumbnail of Proliferation of Nb2 lymphoma cells in vitro in response to interleukin-7

Immunology Letters, 1992

An attempt was made to investigate the proliferative effect of interleukin-7 (IL-7) on a rat Nb2 ... more An attempt was made to investigate the proliferative effect of interleukin-7 (IL-7) on a rat Nb2 T-cell lymphoma line. It was demonstrated that both human and mouse IL-7 stimulated these cells to proliferate in a dose dependent fashion in culture medium containing 10% horse serum. The maximum activities of mIL-7 and hIL-7 were observed at 100 and 1000 units/ml with their half-maximal response of 10 and 50 units/ml, respectively. In a totally serum-free culture condition, mIL-7 produced a similar cellular proliferation, whereas hIL-7 was much less effective. The effectiveness of IL-7 on Nb2 cells was completely abolished by antibody to IL-7, but not by antibody to IL-2. Therefore, Nb2 cells may serve as a simple, convenient and sensitive assay for monitoring the biological activity of IL-7 in vitro. In addition, these cells are also useful for studying the lymphopoiesis of T-cell lineage regulated by IL-7.

Research paper thumbnail of Biosynthesis of 117 antigen: A cell cohesion molecule inDictyostelium discoideum

Developmental Genetics, 1988

117 antigen is involved in the process of intercellular cohesion in Dictyostelium discoideum [Bro... more 117 antigen is involved in the process of intercellular cohesion in Dictyostelium discoideum [Brodie et al., 1983]. The antigen, a 69- and 72-kDa doublet, was found to arise from a 60- and 62-kDa precursor. The mature antigen contains N-linked oligosaccharides that are sulfated and fucosylated [Sadeghi et al., 1987]. These oligosaccharide chains are resistant to endoglycosidase H digestion. 117 antigen also contains a post-translationally added carbohydrate-containing modification(s). Unlike the N-linked oligosaccharide, this carbohydrate moiety is sensitive to periodate oxidation. 117 antigen is developmentally regulated, and the changes in rate of 117 antigen synthesis reflect changes in the cellular levels of its mRNA. 117 mRNA accumulates in starving cells and reaches its maximum when cells become aggregation competent. The mRNA levels then decline, and by the time the slug structure is formed, no 117 mRNA is present. 117 mRNA reaccumulates for a brief period during early culmination and then returns to an undetectable level.