The Experts below are selected from a list of 177 Experts worldwide ranked by ideXlab platform
Robert S Lindsay - One of the best experts on this subject based on the ideXlab platform.
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daily and cyclic Parathyroid Hormone in women receiving alendronate
The New England Journal of Medicine, 2005Co-Authors: Felicia Cosman, Jeri W Nieves, Marsha Zion, Lillian Woelfert, Marjorie M Luckey, Robert S LindsayAbstract:BACKGROUND We evaluated whether patients with osteoporosis treated with long-term alendronate have a response to Parathyroid Hormone treatment and whether short, three-month cycles of Parathyroid Hormone therapy could be as effective as daily administration. METHODS We randomly assigned 126 women with osteoporosis who had been taking alendronate for at least 1 year to continued alendronate plus Parathyroid Hormone (1-34) subcutaneously daily, continued alendronate plus Parathyroid Hormone (1-34) subcutaneously daily for three 3-month cycles alternating with 3-month periods without Parathyroid Hormone, or alendronate alone for 15 months. RESULTS In both Parathyroid Hormone groups, bone formation indexes rose swiftly. Among the women who were receiving cyclic Parathyroid Hormone, bone formation declined during cycles without Parathyroid Hormone and increased again during cycles with Parathyroid Hormone. Bone resorption increased in both Parathyroid Hormone groups but increased progressively more in the daily-treatment group than in the cyclic-therapy group. Spinal bone mineral density rose 6.1 percent in the daily-treatment group and 5.4 percent in the cyclic-therapy group (P<0.001 for each Parathyroid Hormone group as compared with the alendronate group and no significant difference between Parathyroid Hormone groups). One woman in the daily-treatment group, two in the cyclic-therapy group, and four in the alendronate group had new or worsening vertebral deformities. CONCLUSIONS This study suggests that a regimen of three-month cycles of Parathyroid Hormone alternating with three-month cycles without Parathyroid Hormone causes the early phase of action of Parathyroid Hormone (characterized by pure stimulation of bone formation) to be dissociated from the later phase (activation of bone remodeling). The early phase may be more important to the increase in spinal bone mineral density. In patients with persistent osteoporosis after prior alendronate treatment, both daily treatment and cyclic treatment with Parathyroid Hormone increase spinal bone mineral density.
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Daily and Cyclic Parathyroid Hormone in Women Receiving Alendronate
The New England journal of medicine, 2005Co-Authors: Felicia Cosman, Jeri W Nieves, Marsha Zion, Lillian Woelfert, Marjorie M Luckey, Robert S LindsayAbstract:BACKGROUND We evaluated whether patients with osteoporosis treated with long-term alendronate have a response to Parathyroid Hormone treatment and whether short, three-month cycles of Parathyroid Hormone therapy could be as effective as daily administration. METHODS We randomly assigned 126 women with osteoporosis who had been taking alendronate for at least 1 year to continued alendronate plus Parathyroid Hormone (1-34) subcutaneously daily, continued alendronate plus Parathyroid Hormone (1-34) subcutaneously daily for three 3-month cycles alternating with 3-month periods without Parathyroid Hormone, or alendronate alone for 15 months. RESULTS In both Parathyroid Hormone groups, bone formation indexes rose swiftly. Among the women who were receiving cyclic Parathyroid Hormone, bone formation declined during cycles without Parathyroid Hormone and increased again during cycles with Parathyroid Hormone. Bone resorption increased in both Parathyroid Hormone groups but increased progressively more in the daily-treatment group than in the cyclic-therapy group. Spinal bone mineral density rose 6.1 percent in the daily-treatment group and 5.4 percent in the cyclic-therapy group (P
Harald Jüppner - One of the best experts on this subject based on the ideXlab platform.
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Receptors for Parathyroid Hormone and Parathyroid Hormone–related protein
Principles of Bone Biology, 2020Co-Authors: Thomas J. Gardella, Harald Jüppner, John T PottsAbstract:Abstract This chapter describes the molecular biology of the Parathyroid Hormone receptor type 1 (PTHR1), specifically at the level of ligand binding and signal activation mechanisms. It begins with the basic protein architecture of the PTHR1, viewed particularly in the light of the X-ray crystal and cryo-electron microscopy structures that have emerged for several related class B G-protein-coupled receptors. The evolutionary history of the PTHR1 and its ligands is then outlined, from ancient origins in early chordates through the gene rearrangement events that led to the diversified receptor subtypes seen in various vertebrate lineages, as well the possibility for other receptors for C-terminal portions of Parathyroid Hormone and Parathyroid Hormone–related protein. Focus then turns to specific mechanisms of binding and activation at the PTHR1, and how new developing concepts of ligand-dependent conformational selectivity, temporal bias, and endosomal signaling are suggesting unique opportunities for new therapeutic ligand development. Disease-causing mutations in the PTHR1 are then discussed in terms of their impact on basic mechanisms, and finally presented are the recent advances in small-molecule ligand discovery for the PTHR1. In all, the chapter aims to sharpen awareness of progress made in defining how the PTHR1 functions and how it might be better targeted for the treatment of bone and mineral metabolism diseases.
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receptors for Parathyroid Hormone and Parathyroid Hormone related protein
2020Co-Authors: Thomas J. Gardella, Harald Jüppner, John T PottsAbstract:Abstract This chapter describes the molecular biology of the Parathyroid Hormone receptor type 1 (PTHR1), specifically at the level of ligand binding and signal activation mechanisms. It begins with the basic protein architecture of the PTHR1, viewed particularly in the light of the X-ray crystal and cryo-electron microscopy structures that have emerged for several related class B G-protein-coupled receptors. The evolutionary history of the PTHR1 and its ligands is then outlined, from ancient origins in early chordates through the gene rearrangement events that led to the diversified receptor subtypes seen in various vertebrate lineages, as well the possibility for other receptors for C-terminal portions of Parathyroid Hormone and Parathyroid Hormone–related protein. Focus then turns to specific mechanisms of binding and activation at the PTHR1, and how new developing concepts of ligand-dependent conformational selectivity, temporal bias, and endosomal signaling are suggesting unique opportunities for new therapeutic ligand development. Disease-causing mutations in the PTHR1 are then discussed in terms of their impact on basic mechanisms, and finally presented are the recent advances in small-molecule ligand discovery for the PTHR1. In all, the chapter aims to sharpen awareness of progress made in defining how the PTHR1 functions and how it might be better targeted for the treatment of bone and mineral metabolism diseases.
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roles of Parathyroid Hormone and Parathyroid Hormone related peptide in calcium metabolism and bone biology biological actions and receptors
Comprehensive Physiology, 2011Co-Authors: Harald Jüppner, John T PottsAbstract:The sections in this article are: 1 Parathyroid Hormone 1.1 Chemistry 1.2 Peripheral Metabolism 1.3 Actions in Kidney and Bone 2 Parathyroid Hormone-Related Peptide 2.1 Chemistry: Role of the Amino-terminal Portion in Calcium Metabolism 2.2 Biological Role in Bone Development 3 Receptors That Mediate Analogous and Distinct Molecular Actions of Parathyroid Hormone and Parathyroid Hormone–Related Peptide 3.1 The Parathyroid Hormone/Parathyroid Hormone–Related Peptide Receptor 3.2 The Type 2 Parathyroid Hormone Receptor 3.3 Additional Receptors 3.4 Structure-Based Design of Analogues 4 Summary
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Comprehensive Physiology - Roles of Parathyroid Hormone and Parathyroid Hormone–Related Peptide in Calcium Metabolism and Bone Biology: Biological Actions and Receptors
Comprehensive Physiology, 2011Co-Authors: Harald Jüppner, John T PottsAbstract:The sections in this article are: 1 Parathyroid Hormone 1.1 Chemistry 1.2 Peripheral Metabolism 1.3 Actions in Kidney and Bone 2 Parathyroid Hormone-Related Peptide 2.1 Chemistry: Role of the Amino-terminal Portion in Calcium Metabolism 2.2 Biological Role in Bone Development 3 Receptors That Mediate Analogous and Distinct Molecular Actions of Parathyroid Hormone and Parathyroid Hormone–Related Peptide 3.1 The Parathyroid Hormone/Parathyroid Hormone–Related Peptide Receptor 3.2 The Type 2 Parathyroid Hormone Receptor 3.3 Additional Receptors 3.4 Structure-Based Design of Analogues 4 Summary
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Parathyroid Hormone and Parathyroid Hormone related peptide and their receptors
Biochemical and Biophysical Research Communications, 2005Co-Authors: Robert C Gensure, Thomas J. Gardella, Harald JüppnerAbstract:Parathyroid Hormone (PTH) has a central role in the regulation of serum calcium and phosphate, while Parathyroid Hormone-related peptide (PTHrP) has important developmental roles. Both peptides signal through the same receptor, the PTH/PTHrP receptor (a class B G-protein-coupled receptor). The different biological effects of these ligands result from their modes of regulation and secretion, endocrine vs. paracrine/autocrine. The importance of PTH and PTHrP is evident by the variety of clinical syndromes caused by deficiency or excess production of either peptide, and the demonstration that intermittent injection of PTH increases bone mass, and thus provides a means to treat osteoporosis. This, in turn, has triggered increased interest in understanding the mechanisms of PTH/PTHrP receptor action and the search for smaller peptide or non-peptide agonists that have efficacy at this receptor when administered non-parenterally.
Felicia Cosman - One of the best experts on this subject based on the ideXlab platform.
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daily and cyclic Parathyroid Hormone in women receiving alendronate
The New England Journal of Medicine, 2005Co-Authors: Felicia Cosman, Jeri W Nieves, Marsha Zion, Lillian Woelfert, Marjorie M Luckey, Robert S LindsayAbstract:BACKGROUND We evaluated whether patients with osteoporosis treated with long-term alendronate have a response to Parathyroid Hormone treatment and whether short, three-month cycles of Parathyroid Hormone therapy could be as effective as daily administration. METHODS We randomly assigned 126 women with osteoporosis who had been taking alendronate for at least 1 year to continued alendronate plus Parathyroid Hormone (1-34) subcutaneously daily, continued alendronate plus Parathyroid Hormone (1-34) subcutaneously daily for three 3-month cycles alternating with 3-month periods without Parathyroid Hormone, or alendronate alone for 15 months. RESULTS In both Parathyroid Hormone groups, bone formation indexes rose swiftly. Among the women who were receiving cyclic Parathyroid Hormone, bone formation declined during cycles without Parathyroid Hormone and increased again during cycles with Parathyroid Hormone. Bone resorption increased in both Parathyroid Hormone groups but increased progressively more in the daily-treatment group than in the cyclic-therapy group. Spinal bone mineral density rose 6.1 percent in the daily-treatment group and 5.4 percent in the cyclic-therapy group (P<0.001 for each Parathyroid Hormone group as compared with the alendronate group and no significant difference between Parathyroid Hormone groups). One woman in the daily-treatment group, two in the cyclic-therapy group, and four in the alendronate group had new or worsening vertebral deformities. CONCLUSIONS This study suggests that a regimen of three-month cycles of Parathyroid Hormone alternating with three-month cycles without Parathyroid Hormone causes the early phase of action of Parathyroid Hormone (characterized by pure stimulation of bone formation) to be dissociated from the later phase (activation of bone remodeling). The early phase may be more important to the increase in spinal bone mineral density. In patients with persistent osteoporosis after prior alendronate treatment, both daily treatment and cyclic treatment with Parathyroid Hormone increase spinal bone mineral density.
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Daily and Cyclic Parathyroid Hormone in Women Receiving Alendronate
The New England journal of medicine, 2005Co-Authors: Felicia Cosman, Jeri W Nieves, Marsha Zion, Lillian Woelfert, Marjorie M Luckey, Robert S LindsayAbstract:BACKGROUND We evaluated whether patients with osteoporosis treated with long-term alendronate have a response to Parathyroid Hormone treatment and whether short, three-month cycles of Parathyroid Hormone therapy could be as effective as daily administration. METHODS We randomly assigned 126 women with osteoporosis who had been taking alendronate for at least 1 year to continued alendronate plus Parathyroid Hormone (1-34) subcutaneously daily, continued alendronate plus Parathyroid Hormone (1-34) subcutaneously daily for three 3-month cycles alternating with 3-month periods without Parathyroid Hormone, or alendronate alone for 15 months. RESULTS In both Parathyroid Hormone groups, bone formation indexes rose swiftly. Among the women who were receiving cyclic Parathyroid Hormone, bone formation declined during cycles without Parathyroid Hormone and increased again during cycles with Parathyroid Hormone. Bone resorption increased in both Parathyroid Hormone groups but increased progressively more in the daily-treatment group than in the cyclic-therapy group. Spinal bone mineral density rose 6.1 percent in the daily-treatment group and 5.4 percent in the cyclic-therapy group (P
John T Potts - One of the best experts on this subject based on the ideXlab platform.
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Receptors for Parathyroid Hormone and Parathyroid Hormone–related protein
Principles of Bone Biology, 2020Co-Authors: Thomas J. Gardella, Harald Jüppner, John T PottsAbstract:Abstract This chapter describes the molecular biology of the Parathyroid Hormone receptor type 1 (PTHR1), specifically at the level of ligand binding and signal activation mechanisms. It begins with the basic protein architecture of the PTHR1, viewed particularly in the light of the X-ray crystal and cryo-electron microscopy structures that have emerged for several related class B G-protein-coupled receptors. The evolutionary history of the PTHR1 and its ligands is then outlined, from ancient origins in early chordates through the gene rearrangement events that led to the diversified receptor subtypes seen in various vertebrate lineages, as well the possibility for other receptors for C-terminal portions of Parathyroid Hormone and Parathyroid Hormone–related protein. Focus then turns to specific mechanisms of binding and activation at the PTHR1, and how new developing concepts of ligand-dependent conformational selectivity, temporal bias, and endosomal signaling are suggesting unique opportunities for new therapeutic ligand development. Disease-causing mutations in the PTHR1 are then discussed in terms of their impact on basic mechanisms, and finally presented are the recent advances in small-molecule ligand discovery for the PTHR1. In all, the chapter aims to sharpen awareness of progress made in defining how the PTHR1 functions and how it might be better targeted for the treatment of bone and mineral metabolism diseases.
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receptors for Parathyroid Hormone and Parathyroid Hormone related protein
2020Co-Authors: Thomas J. Gardella, Harald Jüppner, John T PottsAbstract:Abstract This chapter describes the molecular biology of the Parathyroid Hormone receptor type 1 (PTHR1), specifically at the level of ligand binding and signal activation mechanisms. It begins with the basic protein architecture of the PTHR1, viewed particularly in the light of the X-ray crystal and cryo-electron microscopy structures that have emerged for several related class B G-protein-coupled receptors. The evolutionary history of the PTHR1 and its ligands is then outlined, from ancient origins in early chordates through the gene rearrangement events that led to the diversified receptor subtypes seen in various vertebrate lineages, as well the possibility for other receptors for C-terminal portions of Parathyroid Hormone and Parathyroid Hormone–related protein. Focus then turns to specific mechanisms of binding and activation at the PTHR1, and how new developing concepts of ligand-dependent conformational selectivity, temporal bias, and endosomal signaling are suggesting unique opportunities for new therapeutic ligand development. Disease-causing mutations in the PTHR1 are then discussed in terms of their impact on basic mechanisms, and finally presented are the recent advances in small-molecule ligand discovery for the PTHR1. In all, the chapter aims to sharpen awareness of progress made in defining how the PTHR1 functions and how it might be better targeted for the treatment of bone and mineral metabolism diseases.
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roles of Parathyroid Hormone and Parathyroid Hormone related peptide in calcium metabolism and bone biology biological actions and receptors
Comprehensive Physiology, 2011Co-Authors: Harald Jüppner, John T PottsAbstract:The sections in this article are: 1 Parathyroid Hormone 1.1 Chemistry 1.2 Peripheral Metabolism 1.3 Actions in Kidney and Bone 2 Parathyroid Hormone-Related Peptide 2.1 Chemistry: Role of the Amino-terminal Portion in Calcium Metabolism 2.2 Biological Role in Bone Development 3 Receptors That Mediate Analogous and Distinct Molecular Actions of Parathyroid Hormone and Parathyroid Hormone–Related Peptide 3.1 The Parathyroid Hormone/Parathyroid Hormone–Related Peptide Receptor 3.2 The Type 2 Parathyroid Hormone Receptor 3.3 Additional Receptors 3.4 Structure-Based Design of Analogues 4 Summary
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Comprehensive Physiology - Roles of Parathyroid Hormone and Parathyroid Hormone–Related Peptide in Calcium Metabolism and Bone Biology: Biological Actions and Receptors
Comprehensive Physiology, 2011Co-Authors: Harald Jüppner, John T PottsAbstract:The sections in this article are: 1 Parathyroid Hormone 1.1 Chemistry 1.2 Peripheral Metabolism 1.3 Actions in Kidney and Bone 2 Parathyroid Hormone-Related Peptide 2.1 Chemistry: Role of the Amino-terminal Portion in Calcium Metabolism 2.2 Biological Role in Bone Development 3 Receptors That Mediate Analogous and Distinct Molecular Actions of Parathyroid Hormone and Parathyroid Hormone–Related Peptide 3.1 The Parathyroid Hormone/Parathyroid Hormone–Related Peptide Receptor 3.2 The Type 2 Parathyroid Hormone Receptor 3.3 Additional Receptors 3.4 Structure-Based Design of Analogues 4 Summary
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a g protein linked receptor for Parathyroid Hormone and Parathyroid Hormone related peptide
Science, 1991Co-Authors: Harald Jüppner, Ernestina Schipani, John T Potts, Abdul B Abousamra, Mason W Freeman, X F Kong, Julia E Richards, L F Kolakowski, J Hock, Henry M. KronenbergAbstract:The complementary DNA encoding a 585-amino acid Parathyroid Hormone-Parathyroid Hormone-related peptide (PTH-PTHrP) receptor with seven potential membrane-spanning domains was cloned by COS-7 expression using an opossum kidney cell complementary DNA (cDNA) library. The expressed receptor binds PTH and PTHrP with equal affinity, and both ligands equivalently stimulate adenylate cyclase. Striking homology with the calcitonin receptor and lack of homology with other G protein-linked receptors indicate that receptors for these calcium-regulating Hormones are related and represent a new family.
Marjorie M Luckey - One of the best experts on this subject based on the ideXlab platform.
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daily and cyclic Parathyroid Hormone in women receiving alendronate
The New England Journal of Medicine, 2005Co-Authors: Felicia Cosman, Jeri W Nieves, Marsha Zion, Lillian Woelfert, Marjorie M Luckey, Robert S LindsayAbstract:BACKGROUND We evaluated whether patients with osteoporosis treated with long-term alendronate have a response to Parathyroid Hormone treatment and whether short, three-month cycles of Parathyroid Hormone therapy could be as effective as daily administration. METHODS We randomly assigned 126 women with osteoporosis who had been taking alendronate for at least 1 year to continued alendronate plus Parathyroid Hormone (1-34) subcutaneously daily, continued alendronate plus Parathyroid Hormone (1-34) subcutaneously daily for three 3-month cycles alternating with 3-month periods without Parathyroid Hormone, or alendronate alone for 15 months. RESULTS In both Parathyroid Hormone groups, bone formation indexes rose swiftly. Among the women who were receiving cyclic Parathyroid Hormone, bone formation declined during cycles without Parathyroid Hormone and increased again during cycles with Parathyroid Hormone. Bone resorption increased in both Parathyroid Hormone groups but increased progressively more in the daily-treatment group than in the cyclic-therapy group. Spinal bone mineral density rose 6.1 percent in the daily-treatment group and 5.4 percent in the cyclic-therapy group (P<0.001 for each Parathyroid Hormone group as compared with the alendronate group and no significant difference between Parathyroid Hormone groups). One woman in the daily-treatment group, two in the cyclic-therapy group, and four in the alendronate group had new or worsening vertebral deformities. CONCLUSIONS This study suggests that a regimen of three-month cycles of Parathyroid Hormone alternating with three-month cycles without Parathyroid Hormone causes the early phase of action of Parathyroid Hormone (characterized by pure stimulation of bone formation) to be dissociated from the later phase (activation of bone remodeling). The early phase may be more important to the increase in spinal bone mineral density. In patients with persistent osteoporosis after prior alendronate treatment, both daily treatment and cyclic treatment with Parathyroid Hormone increase spinal bone mineral density.
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Daily and Cyclic Parathyroid Hormone in Women Receiving Alendronate
The New England journal of medicine, 2005Co-Authors: Felicia Cosman, Jeri W Nieves, Marsha Zion, Lillian Woelfert, Marjorie M Luckey, Robert S LindsayAbstract:BACKGROUND We evaluated whether patients with osteoporosis treated with long-term alendronate have a response to Parathyroid Hormone treatment and whether short, three-month cycles of Parathyroid Hormone therapy could be as effective as daily administration. METHODS We randomly assigned 126 women with osteoporosis who had been taking alendronate for at least 1 year to continued alendronate plus Parathyroid Hormone (1-34) subcutaneously daily, continued alendronate plus Parathyroid Hormone (1-34) subcutaneously daily for three 3-month cycles alternating with 3-month periods without Parathyroid Hormone, or alendronate alone for 15 months. RESULTS In both Parathyroid Hormone groups, bone formation indexes rose swiftly. Among the women who were receiving cyclic Parathyroid Hormone, bone formation declined during cycles without Parathyroid Hormone and increased again during cycles with Parathyroid Hormone. Bone resorption increased in both Parathyroid Hormone groups but increased progressively more in the daily-treatment group than in the cyclic-therapy group. Spinal bone mineral density rose 6.1 percent in the daily-treatment group and 5.4 percent in the cyclic-therapy group (P
