Tamer Hadi - Academia.edu (original) (raw)
Papers by Tamer Hadi
Bone, Mar 1, 2007
Evidence suggests that osteocyte apoptosis is involved in the adaptive response of bone, although... more Evidence suggests that osteocyte apoptosis is involved in the adaptive response of bone, although the specific role of osteocytes in the signaling mechanism is unknown. Here, we examined and correlated regional variability in indices of remodeling, modeling, osteocyte apoptosis, and osteocyte density in rabbit tibia midshafts. Histomorphometric analysis indicated that remodeling parameters (BMU activation frequency, osteon density, forming osteon density, and resorption cavity density) were lower in the cranial region compared to other quadrants. In addition, pericortical subregions displayed less remodeling relative to intracortical and endocortical ones. Modeling indices also demonstrated regional variability in that periosteal surfaces exhibited a greater extent of bone forming surface than endosteal ones across all anatomic quadrants. In contrast, endosteal surfaces demonstrated significantly greater surface mineral apposition rates compared to periosteal surfaces in caudal, medial, and lateral but not cranial quadrants. Using TUNEL analysis to detect osteocytes undergoing apoptosis, the density of apoptotic osteocytes was found to be lower in cranial quadrants relative to medial ones. In addition, the densities of osteocyte lacunae, empty lacunae, and total osteocytes were higher in lateral fields relative to caudal quadrants. There was a strong, statistically significant linear correlation between the remodeling indices and apoptotic osteocyte density, supporting the theory that osteocytes undergoing apoptosis produce signals that attract or direct bone remodeling. In contrast, the modeling parameters did not exhibit a correlation with apoptotic osteocytes, although there was a strong correlation between the modeling indices and the density of empty osteocyte lacunae, corroborating previous studies that have found that osteocytes inhibit bone formation. It was found that osteocyte density and osteocyte lacunar density did not significantly correlate with modeling or remodeling parameters, suggesting that cell viability should be examined in studies correlating bone turnover parameters with the functional role of osteocytes in bone adaptation.
Osteoporosis International, Aug 5, 2005
Recently, basic fibroblast growth factor (bFGF) has been found to increase trabecular bone mass a... more Recently, basic fibroblast growth factor (bFGF) has been found to increase trabecular bone mass and connectivity in the proximal tibial metaphyses (PTM) in osteopenic rats. The purpose of this study was to determine the bone anabolic effects of bFGF in the lumbar vertebral body (LVB), a less loaded skeletal site with a lower rate of bone turnover than the PTM. Six-month old female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated and untreated for 8 weeks to induce osteopenia. Then group 1 (sham) and group 2 (OVX) were treated subcutaneously (SC) with vehicle, and OVXed groups 3 and 4 were treated SC with PTH [hPTH (1-34) at 40 μg/kg, 5×/week] and bFGF (1 mg/kg, 5×/week), respectively, for 8 weeks. At sacrifice, the fifth LVB was removed, subjected to micro-CT for determination of trabecular bone structure and then processed N.E. Lane,
Investigative Ophthalmology & Visual Science, Jul 22, 2019
European Spine Journal, Sep 20, 2005
The Spine Journal, Sep 1, 2004
Investigative Ophthalmology & Visual Science, Jul 22, 2019
Abstract: Three English ophthalmic texts of the 1580s were frequently republished: 1) Walter Bail... more Abstract: Three English ophthalmic texts of the 1580s were frequently republished: 1) Walter Bailey’s A Briefe Treatise Touching the Preseruation of the Eie Sight, 2) The Method of Phisicke, an adaptation of the medieval treatise of Benevenutus Grassus, and 3) A Worthy Treatise of the Eyes, a translation of Jacques Guillemeau’s treatise. Their history is intertwined through composite publications, some of which lacked clear attribution. At least 21 editions incorporated these texts. Although not previously realized, major elements of all 3 works are found in Two Treatises Concerning the Preseruation of Eie-sight, first published in 1616. To preserve eyesight, Bailey recommended eyebright (Euphrasia officinalis), fennel (Fæniculum vulgare), and a moderate lifestyle incorporating wine. In the works of Grassus and Guillemeau, cataracts were believed to lie anterior to the ‘crystalline humor, ’ and were treated by the ‘art of the needle,’ or couching. Links are found between Grassus, Gu...
To effectively reduce vision loss due to age-related macular generation (AMD) on a global scale, ... more To effectively reduce vision loss due to age-related macular generation (AMD) on a global scale, knowledge of its genetic architecture in diverse populations is necessary. A critical element, AMD risk profiles in African and Hispanic/Latino ancestries, remains largely unknown due to lower lifetime prevalence. We combined genetic and clinical data in the Million Veteran Program with five other cohorts to conduct the first multi-ancestry genome-wide association study of AMD and discovered 63 loci (30 novel). We observe marked cross-ancestry heterogeneity at major risk loci, especially in African-ancestry populations which demonstrate a primary signal in a Major Histocompatibility Complex Class II haplotype and reduced risk at the established CFH and ARMS2/HTRA1 loci. Broadening efforts to include ancestrally-distinct populations helped uncover genes and pathways which boost risk in an ancestry-dependent manner, and are potential targets for corrective therapies.One Sentence Summaryrob...
Investigative Ophthalmology & Visual Science, 2018
AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science, 2019
Electronic health records (EHRs) linked to extensive biorepositories and supplemented with lifest... more Electronic health records (EHRs) linked to extensive biorepositories and supplemented with lifestyle, behavioral, and environmental exposure data, have enormous potential to contribute to genomic discovery, a necessary step in the pathway towards translational or precision medicine. A major bottleneck in incorporating EHRs into genomic studies is the extraction of research-grade variables for analysis, particularly when gold-standard measurements are not available or accessible. Here we develop algorithms for age-related macular degeneration (AMD), a common cause of blindness among the elderly, and controls free of AMD. These computable phenotypes were developed using billing codes (ICD-9-CM and ICD-10-CM) and Current Procedural Terminology (CPT) codes and evaluated in two study sites of the Veterans Affairs Million Veteran Program: Louis Stokes Cleveland VA Medical Center and the Providence VA Medical Center. After establishing a high overall positive and negative predictive values...
THE ROLE OF p62 IN OSTEOCLASTOGENESIS AND PAGET’S DISEASE OF BONE by Tamer M. A. Hadi, M.S., Ph.D... more THE ROLE OF p62 IN OSTEOCLASTOGENESIS AND PAGET’S DISEASE OF BONE by Tamer M. A. Hadi, M.S., Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University, 2014 Director: Jolene J. Windle, Ph.D. Irene Shaw Grigg Distinguished Professor, Department of Molecular and Human Genetics Director, VCU Transgenic/Knock-out Mouse Core Cancer Molecular Genetics Program Co-leader, Massey Cancer Center Paget’s disease (PDB) is the second most common metabolic bone disease after osteoporosis, affecting up to 3% of adults over age 55. It is characterized by focal lesions of bone resorbed by hyperactive osteoclasts coupled with rapid formation of highly disorganized, low quality bone formed by osteoblasts. Such lesions cause skeletal deformity, fractures, and other symptoms that significantly decrease quality of life. In 2001, mutations in the SQSTM1/p62 gene were found in a subset of Paget’s patients. The work su...
International Ophthalmology Clinics
Clinical Ophthalmology, 2016
Objective: To determine whether, as most modern historians have written, ancient Greco-Roman auth... more Objective: To determine whether, as most modern historians have written, ancient Greco-Roman authors believed the crystalline lens is positioned in the center of the eye. Background: Historians have written that statements about cataract couching by Celsus, or perhaps Galen of Pergamon, suggested a centrally located lens. Celsus specifically wrote that a couching needle placed intermediate between the corneal limbus and the lateral canthus enters an empty space, presumed to represent the posterior chamber. Methods: Ancient ophthalmic literature was analyzed to understand where these authors believed the crystalline lens was positioned. In order to estimate where Celsus proposed entering the eye during couching, we prospectively measured the distance from the temporal corneal limbus to the lateral canthus in 30 healthy adults. Results: Rufus of Ephesus and Galen wrote that the lens is anterior enough to contact the iris. Galen wrote that the lens equator joins other ocular structures at the corneoscleral junction. In 30 subjects, half the distance from the temporal corneal limbus to the lateral canthus was a mean of 4.5 mm (range: 3.3-5.3 mm). Descriptions of couching by Celsus and others are consistent with pars plana entry of the couching needle. Anterior angulation of the needle would permit contact of the needle with the lens. Conclusion: Ancient descriptions of anatomy and couching do not establish the microanatomic relationships of the ciliary region with any modern degree of accuracy. Nonetheless, ancient authors, such as Galen and Rufus, clearly understood that the lens is located anteriorly. There is little reason to believe that Celsus or other ancient authors held a variant understanding of the anatomy of a healthy eye. The notion of the central location of the lens seems to have arisen with Arabic authors in 9th century Mesopotamia, and lasted for over 7 centuries.
European Spine Journal, 2006
Because the disc and facets work together to constrain spinal kinematics, changes in the instant ... more Because the disc and facets work together to constrain spinal kinematics, changes in the instant axis of rotation associated with disc degeneration or disc replacement may adversely influence risk for facet overloading and arthritis. The relationships between L5/S1 segmental kinematics and facet forces are not well defined, since previous studies have separated investigations of spinal motion and facet force. The
Osteoporosis International, 2005
Recently, basic fibroblast growth factor (bFGF) has been found to increase trabecular bone mass a... more Recently, basic fibroblast growth factor (bFGF) has been found to increase trabecular bone mass and connectivity in the proximal tibial metaphyses (PTM) in osteopenic rats. The purpose of this study was to determine the bone anabolic effects of bFGF in the lumbar vertebral body (LVB), a less loaded skeletal site with a lower rate of bone turnover than the PTM. Sixmonth old female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated and untreated for 8 weeks to induce osteopenia. Then group 1 (sham) and group 2 (OVX) were treated subcutaneously (SC) with vehicle, and OVXed groups 3 and 4 were treated SC with PTH [hPTH (1-34) at 40 lg/kg, 5•/week] and bFGF (1 mg/kg, 5•/week), respectively, for 8 weeks. At sacrifice, the fifth LVB was removed, subjected to micro-CT for determination of trabecular bone structure and then processed for histomorphometry to assess bone turnover. The sixth LVB was used for mechanical compression testing (MTS, Bionix 858). The data were analyzed with the Kruskal-Wallis test followed by posthoc testing as needed. After 16 weeks of estrogen deficiency, there were significant reductions in vertebral trabecular bone volume and trabecular thickness. Treatment with either bFGF or hPTH (1-34) increased BV/TV in OVX animals. Human PTH (1-34)-treated animals had significant increases in trabecular (48%) and cortical thickness (30%) and bone strength [maximum load (53%) and work to failure (175%)] compared to OVX + Vehicle animals. Treatment of osteopenic rats with bFGF increased bone volume (15%), trabecular thickness (13%), maximum load (45%) and work to failure (140%) compared to OVX + Vehicle animals (all P <0.05). Basic FGF increased trabecular bone volume in the lumbar vertebral body of osteopenic rats by restoring trabecular number, thickness and connectivity density. Also, bFGF improved bone mechanical properties (maximum force and work to failure) compared to the OVX + Vehicle group. Therefore, increasing the number, thickness and connections of the trabeculae contributes to increased bone strength in this small animal model of osteoporosis. Keywords Biomechanical properties AE Bone structure AE bFGF AE Lumber vertebrae AE Ovariectomy AE Rat
Bone, Mar 1, 2007
Evidence suggests that osteocyte apoptosis is involved in the adaptive response of bone, although... more Evidence suggests that osteocyte apoptosis is involved in the adaptive response of bone, although the specific role of osteocytes in the signaling mechanism is unknown. Here, we examined and correlated regional variability in indices of remodeling, modeling, osteocyte apoptosis, and osteocyte density in rabbit tibia midshafts. Histomorphometric analysis indicated that remodeling parameters (BMU activation frequency, osteon density, forming osteon density, and resorption cavity density) were lower in the cranial region compared to other quadrants. In addition, pericortical subregions displayed less remodeling relative to intracortical and endocortical ones. Modeling indices also demonstrated regional variability in that periosteal surfaces exhibited a greater extent of bone forming surface than endosteal ones across all anatomic quadrants. In contrast, endosteal surfaces demonstrated significantly greater surface mineral apposition rates compared to periosteal surfaces in caudal, medial, and lateral but not cranial quadrants. Using TUNEL analysis to detect osteocytes undergoing apoptosis, the density of apoptotic osteocytes was found to be lower in cranial quadrants relative to medial ones. In addition, the densities of osteocyte lacunae, empty lacunae, and total osteocytes were higher in lateral fields relative to caudal quadrants. There was a strong, statistically significant linear correlation between the remodeling indices and apoptotic osteocyte density, supporting the theory that osteocytes undergoing apoptosis produce signals that attract or direct bone remodeling. In contrast, the modeling parameters did not exhibit a correlation with apoptotic osteocytes, although there was a strong correlation between the modeling indices and the density of empty osteocyte lacunae, corroborating previous studies that have found that osteocytes inhibit bone formation. It was found that osteocyte density and osteocyte lacunar density did not significantly correlate with modeling or remodeling parameters, suggesting that cell viability should be examined in studies correlating bone turnover parameters with the functional role of osteocytes in bone adaptation.
Osteoporosis International, Aug 5, 2005
Recently, basic fibroblast growth factor (bFGF) has been found to increase trabecular bone mass a... more Recently, basic fibroblast growth factor (bFGF) has been found to increase trabecular bone mass and connectivity in the proximal tibial metaphyses (PTM) in osteopenic rats. The purpose of this study was to determine the bone anabolic effects of bFGF in the lumbar vertebral body (LVB), a less loaded skeletal site with a lower rate of bone turnover than the PTM. Six-month old female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated and untreated for 8 weeks to induce osteopenia. Then group 1 (sham) and group 2 (OVX) were treated subcutaneously (SC) with vehicle, and OVXed groups 3 and 4 were treated SC with PTH [hPTH (1-34) at 40 μg/kg, 5×/week] and bFGF (1 mg/kg, 5×/week), respectively, for 8 weeks. At sacrifice, the fifth LVB was removed, subjected to micro-CT for determination of trabecular bone structure and then processed N.E. Lane,
Investigative Ophthalmology & Visual Science, Jul 22, 2019
European Spine Journal, Sep 20, 2005
The Spine Journal, Sep 1, 2004
Investigative Ophthalmology & Visual Science, Jul 22, 2019
Abstract: Three English ophthalmic texts of the 1580s were frequently republished: 1) Walter Bail... more Abstract: Three English ophthalmic texts of the 1580s were frequently republished: 1) Walter Bailey’s A Briefe Treatise Touching the Preseruation of the Eie Sight, 2) The Method of Phisicke, an adaptation of the medieval treatise of Benevenutus Grassus, and 3) A Worthy Treatise of the Eyes, a translation of Jacques Guillemeau’s treatise. Their history is intertwined through composite publications, some of which lacked clear attribution. At least 21 editions incorporated these texts. Although not previously realized, major elements of all 3 works are found in Two Treatises Concerning the Preseruation of Eie-sight, first published in 1616. To preserve eyesight, Bailey recommended eyebright (Euphrasia officinalis), fennel (Fæniculum vulgare), and a moderate lifestyle incorporating wine. In the works of Grassus and Guillemeau, cataracts were believed to lie anterior to the ‘crystalline humor, ’ and were treated by the ‘art of the needle,’ or couching. Links are found between Grassus, Gu...
To effectively reduce vision loss due to age-related macular generation (AMD) on a global scale, ... more To effectively reduce vision loss due to age-related macular generation (AMD) on a global scale, knowledge of its genetic architecture in diverse populations is necessary. A critical element, AMD risk profiles in African and Hispanic/Latino ancestries, remains largely unknown due to lower lifetime prevalence. We combined genetic and clinical data in the Million Veteran Program with five other cohorts to conduct the first multi-ancestry genome-wide association study of AMD and discovered 63 loci (30 novel). We observe marked cross-ancestry heterogeneity at major risk loci, especially in African-ancestry populations which demonstrate a primary signal in a Major Histocompatibility Complex Class II haplotype and reduced risk at the established CFH and ARMS2/HTRA1 loci. Broadening efforts to include ancestrally-distinct populations helped uncover genes and pathways which boost risk in an ancestry-dependent manner, and are potential targets for corrective therapies.One Sentence Summaryrob...
Investigative Ophthalmology & Visual Science, 2018
AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science, 2019
Electronic health records (EHRs) linked to extensive biorepositories and supplemented with lifest... more Electronic health records (EHRs) linked to extensive biorepositories and supplemented with lifestyle, behavioral, and environmental exposure data, have enormous potential to contribute to genomic discovery, a necessary step in the pathway towards translational or precision medicine. A major bottleneck in incorporating EHRs into genomic studies is the extraction of research-grade variables for analysis, particularly when gold-standard measurements are not available or accessible. Here we develop algorithms for age-related macular degeneration (AMD), a common cause of blindness among the elderly, and controls free of AMD. These computable phenotypes were developed using billing codes (ICD-9-CM and ICD-10-CM) and Current Procedural Terminology (CPT) codes and evaluated in two study sites of the Veterans Affairs Million Veteran Program: Louis Stokes Cleveland VA Medical Center and the Providence VA Medical Center. After establishing a high overall positive and negative predictive values...
THE ROLE OF p62 IN OSTEOCLASTOGENESIS AND PAGET’S DISEASE OF BONE by Tamer M. A. Hadi, M.S., Ph.D... more THE ROLE OF p62 IN OSTEOCLASTOGENESIS AND PAGET’S DISEASE OF BONE by Tamer M. A. Hadi, M.S., Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University, 2014 Director: Jolene J. Windle, Ph.D. Irene Shaw Grigg Distinguished Professor, Department of Molecular and Human Genetics Director, VCU Transgenic/Knock-out Mouse Core Cancer Molecular Genetics Program Co-leader, Massey Cancer Center Paget’s disease (PDB) is the second most common metabolic bone disease after osteoporosis, affecting up to 3% of adults over age 55. It is characterized by focal lesions of bone resorbed by hyperactive osteoclasts coupled with rapid formation of highly disorganized, low quality bone formed by osteoblasts. Such lesions cause skeletal deformity, fractures, and other symptoms that significantly decrease quality of life. In 2001, mutations in the SQSTM1/p62 gene were found in a subset of Paget’s patients. The work su...
International Ophthalmology Clinics
Clinical Ophthalmology, 2016
Objective: To determine whether, as most modern historians have written, ancient Greco-Roman auth... more Objective: To determine whether, as most modern historians have written, ancient Greco-Roman authors believed the crystalline lens is positioned in the center of the eye. Background: Historians have written that statements about cataract couching by Celsus, or perhaps Galen of Pergamon, suggested a centrally located lens. Celsus specifically wrote that a couching needle placed intermediate between the corneal limbus and the lateral canthus enters an empty space, presumed to represent the posterior chamber. Methods: Ancient ophthalmic literature was analyzed to understand where these authors believed the crystalline lens was positioned. In order to estimate where Celsus proposed entering the eye during couching, we prospectively measured the distance from the temporal corneal limbus to the lateral canthus in 30 healthy adults. Results: Rufus of Ephesus and Galen wrote that the lens is anterior enough to contact the iris. Galen wrote that the lens equator joins other ocular structures at the corneoscleral junction. In 30 subjects, half the distance from the temporal corneal limbus to the lateral canthus was a mean of 4.5 mm (range: 3.3-5.3 mm). Descriptions of couching by Celsus and others are consistent with pars plana entry of the couching needle. Anterior angulation of the needle would permit contact of the needle with the lens. Conclusion: Ancient descriptions of anatomy and couching do not establish the microanatomic relationships of the ciliary region with any modern degree of accuracy. Nonetheless, ancient authors, such as Galen and Rufus, clearly understood that the lens is located anteriorly. There is little reason to believe that Celsus or other ancient authors held a variant understanding of the anatomy of a healthy eye. The notion of the central location of the lens seems to have arisen with Arabic authors in 9th century Mesopotamia, and lasted for over 7 centuries.
European Spine Journal, 2006
Because the disc and facets work together to constrain spinal kinematics, changes in the instant ... more Because the disc and facets work together to constrain spinal kinematics, changes in the instant axis of rotation associated with disc degeneration or disc replacement may adversely influence risk for facet overloading and arthritis. The relationships between L5/S1 segmental kinematics and facet forces are not well defined, since previous studies have separated investigations of spinal motion and facet force. The
Osteoporosis International, 2005
Recently, basic fibroblast growth factor (bFGF) has been found to increase trabecular bone mass a... more Recently, basic fibroblast growth factor (bFGF) has been found to increase trabecular bone mass and connectivity in the proximal tibial metaphyses (PTM) in osteopenic rats. The purpose of this study was to determine the bone anabolic effects of bFGF in the lumbar vertebral body (LVB), a less loaded skeletal site with a lower rate of bone turnover than the PTM. Sixmonth old female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated and untreated for 8 weeks to induce osteopenia. Then group 1 (sham) and group 2 (OVX) were treated subcutaneously (SC) with vehicle, and OVXed groups 3 and 4 were treated SC with PTH [hPTH (1-34) at 40 lg/kg, 5•/week] and bFGF (1 mg/kg, 5•/week), respectively, for 8 weeks. At sacrifice, the fifth LVB was removed, subjected to micro-CT for determination of trabecular bone structure and then processed for histomorphometry to assess bone turnover. The sixth LVB was used for mechanical compression testing (MTS, Bionix 858). The data were analyzed with the Kruskal-Wallis test followed by posthoc testing as needed. After 16 weeks of estrogen deficiency, there were significant reductions in vertebral trabecular bone volume and trabecular thickness. Treatment with either bFGF or hPTH (1-34) increased BV/TV in OVX animals. Human PTH (1-34)-treated animals had significant increases in trabecular (48%) and cortical thickness (30%) and bone strength [maximum load (53%) and work to failure (175%)] compared to OVX + Vehicle animals. Treatment of osteopenic rats with bFGF increased bone volume (15%), trabecular thickness (13%), maximum load (45%) and work to failure (140%) compared to OVX + Vehicle animals (all P <0.05). Basic FGF increased trabecular bone volume in the lumbar vertebral body of osteopenic rats by restoring trabecular number, thickness and connectivity density. Also, bFGF improved bone mechanical properties (maximum force and work to failure) compared to the OVX + Vehicle group. Therefore, increasing the number, thickness and connections of the trabeculae contributes to increased bone strength in this small animal model of osteoporosis. Keywords Biomechanical properties AE Bone structure AE bFGF AE Lumber vertebrae AE Ovariectomy AE Rat