7 results on '"Tashjian AH Jr"'
Search Results
2. Teriparatide [human PTH(1-34)]: 2.5 years of experience on the use and safety of the drug for the treatment of osteoporosis.
- Author
-
Tashjian AH Jr and Gagel RF
- Subjects
- Bone Density Conservation Agents administration & dosage, Bone Density Conservation Agents adverse effects, Humans, Teriparatide administration & dosage, Teriparatide adverse effects, Bone Density Conservation Agents therapeutic use, Osteoporosis drug therapy, Teriparatide therapeutic use
- Published
- 2006
- Full Text
- View/download PDF
3. Commentary on clinical safety of recombinant human parathyroid hormone 1-34 in the treatment of osteoporosis in men and postmenopausal women.
- Author
-
Tashjian AH Jr and Chabner BA
- Subjects
- Animals, Biological Assay, Consumer Product Safety, Disease Models, Animal, Female, Humans, Male, Recombinant Proteins therapeutic use, Risk Assessment, Osteoporosis drug therapy, Osteoporosis, Postmenopausal drug therapy, Parathyroid Hormone therapeutic use, Peptide Fragments therapeutic use
- Published
- 2002
- Full Text
- View/download PDF
4. Direct measurement of hormone-induced acidification in intact bone.
- Author
-
Belinsky GS and Tashjian AH Jr
- Subjects
- 1-Methyl-3-isobutylxanthine pharmacology, Adenylyl Cyclases physiology, Animals, Animals, Newborn, Bone Neoplasms pathology, Bone and Bones chemistry, Bucladesine pharmacology, Calcium Signaling drug effects, Carbonic Anhydrases physiology, Colforsin pharmacology, Cyclic AMP-Dependent Protein Kinases physiology, Enzyme Activation drug effects, Extracellular Space chemistry, Extracellular Space drug effects, Humans, Mice, Organ Culture Techniques, Organ Specificity, Osteoblasts metabolism, Osteosarcoma pathology, Protein Kinase C antagonists & inhibitors, Protein Kinase C physiology, Second Messenger Systems drug effects, Skull chemistry, Skull drug effects, Tetradecanoylphorbol Acetate pharmacology, Thapsigargin pharmacology, Tumor Cells, Cultured chemistry, Tumor Cells, Cultured drug effects, Bone and Bones drug effects, Hydrogen-Ion Concentration drug effects, Osteoblasts drug effects, Parathyroid Hormone pharmacology
- Abstract
Previous findings have shown that osteoblasts respond to parathyroid hormone (PTH) with an increase in extracellular acidification rate (ECAR) in addition to the known effect of PTH to increase local acidification by osteoclasts. We, therefore, investigated use of the Cytosensor to measure the ECAR response of whole intact bone to PTH employing microphysiometry. The Cytosensor measures a generic metabolic increase of cells to various agents. Using neonatal mouse calvaria, we found that the area surrounding the sagittal suture was particularly responsive to PTH. In this bone, the increase in ECAR was slower to develop (6 minutes) and more persistent than in cultured human osteoblast-like SaOS-2 cells and was preceded by a brief decrease in ECAR. Salmon calcitonin also produced an increase in ECAR in this tissue but with a different pattern than that elicited by PTH. Because PTH stimulates osteoclastic bone resorption in mouse calvaria via a cyclic adenosine monophosphate (cAMP)-mediated mechanism, we showed that the adenylyl cyclase activator forskolin also stimulated ECAR in this tissue. When the protein kinase A (PKA) pathway was activated by maintaining a high intracellular concentration of cAMP using N6-2'-0-dibutyryladenosine-cAMP (db-cAMP), there was a reduction of PTH-induced acidification, while isobutylmethylxanthine pretreatment potentiated the PTH-induced acidification, consistent with a PKA-mediated pathway. Thapsigargin and the protein kinase C (PKC) activator phorbol myristate acetate had no effect on the PTH-induced increase in ECAR in calvaria, indicating that PKC does not play a major role in the ECAR response in intact bone. These results indicate the utility of using microphysiometry to study ECAR responses in intact tissue and should enable elucidation of the relative importance of extracellular acidification by osteoblasts and osteoclasts to the anabolic and catabolic activities of PTH, respectively.
- Published
- 2000
- Full Text
- View/download PDF
5. Comparison of recombinant human PTH(1-34) (LY333334) with a C-terminally substituted analog of human PTH-related protein(1-34) (RS-66271): In vitro activity and in vivo pharmacological effects in rats.
- Author
-
Frolik CA, Cain RL, Sato M, Harvey AK, Chandrasekhar S, Black EC, Tashjian AH Jr, and Hock JM
- Subjects
- Animals, Binding, Competitive, Bone Resorption chemically induced, Calcium metabolism, Cattle, Cell Line, Humans, Male, Mice, Organ Culture Techniques, Rats, Rats, Inbred F344, Receptor, Parathyroid Hormone, Type 1, Receptors, Parathyroid Hormone metabolism, Signal Transduction, Teriparatide metabolism, Bone Density drug effects, Teriparatide analogs & derivatives, Teriparatide pharmacology
- Abstract
Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are believed to exert their biological actions through binding and activation of a common cell surface receptor. Recently, an analog of PTHrP (RS-66271), was described that demonstrated reduced binding affinity for the PTH/PTHrP receptor compared with bovine PTH(1-34) but retained equal biological activity. The present study investigated the receptor binding affinities of synthetic RS-66271 and recombinant human PTH(1-34) (LY333334) and compared their in vitro and in vivo pharmacological effects. RS-66271 had one hundredth the activity of PTH(1-34) in competing for the binding of [125I] [Nle8,18, Tyr34]human PTH(1-34) to the human PTH/PTHrP receptor stably expressed in a human kidney cell line. Despite this reduced binding affinity, RS-66271 had equivalent activity in increasing both cAMP production in osteoblast-like cells and bone resorption in neonatal mouse calvariae. However, RS-66271 was 7. 6-fold less active in stimulating inositol phosphate production. For in vivo studies, young, male Fisher rats received a daily subcutaneous dose of either 10 or 40 microg/kg of peptide for 1, 2, or 4 weeks. Volumetric bone mineral density and total bone mineral content of the proximal tibia were determined by peripheral quantitative computerized tomography. Trabecular and cortical bone of the distal femur were analyzed for calcium and dry weight. Lumbar vertebrae (L4-L6) were analyzed by histomorphometry. Trabecular and cortical bone mass showed a dose- and time-dependent increase in the treated animals compared with the controls. These increases were evident as early as 1 week after initiation of dosing. There were no consistent significant differences in the comparative effects of PTH(1-34) and RS-66271 on the measured bone parameters. In conclusion, despite the reduced binding affinity of RS-66271 for the PTH/PTHrP receptor compared with human PTH(1-34), both peptides displayed similar in vitro and in vivo pharmacological effects.
- Published
- 1999
- Full Text
- View/download PDF
6. Structure-activity studies of the s-echistatin inhibition of bone resorption.
- Author
-
Sato M, Garsky V, Majeska RJ, Einhorn TA, Murray J, Tashjian AH Jr, and Gould RJ
- Subjects
- Amino Acid Sequence, Animals, Bone Neoplasms pathology, Cell Adhesion drug effects, Cells, Cultured, Dose-Response Relationship, Drug, Endothelium, Vascular cytology, Endothelium, Vascular drug effects, Female, Giant Cell Tumor of Bone pathology, Humans, Intercellular Signaling Peptides and Proteins, Mice, Microscopy, Confocal, Microscopy, Electron, Scanning, Microscopy, Fluorescence, Molecular Sequence Data, Organ Culture Techniques, Osteoclasts cytology, Osteoclasts ultrastructure, Platelet Aggregation drug effects, Platelet Aggregation Inhibitors pharmacology, Rats, Rats, Sprague-Dawley, Structure-Activity Relationship, Viper Venoms chemistry, Viper Venoms pharmacology, Bone Resorption drug therapy, Oligopeptides chemistry, Osteoclasts drug effects, Peptides, Platelet Aggregation Inhibitors therapeutic use, Viper Venoms therapeutic use
- Abstract
Synthetic Arg-Gly-Asp (RGD)-containing peptides were examined in bone resorption or attachment and detachment assays with isolated mammalian osteoclasts in an effort to elucidate the mechanistic and structural basis for the inhibition of bone resorption by s-echistatin. Bone resorption was the process most sensitive to inhibition by s-echistatin, with IC50 = 0.3 nM; inhibition of attachment to bone or detachment (lamellipodial retraction) was 30- to 70-fold less sensitive, with IC50 = 10 or 20 nM, respectively. Single amino acid substitutions within the 49-residue sequence of s-echistatin showed that although the efficacy of s-echistatin is dependent on the Arg24-Gly25-Asp26 sequence, additional residues, including Asp27, Met28, and Cys39, are also critical for potent inhibition of the resorbing activity of isolated rat osteoclasts. Because of the identification of the av beta 3 as the primary integrin on rat osteoclasts interacting the RGD peptides (Helfrich et al.), we examined the possibility of modeling bone resorption with other beta 3-mediated processes. Specifically, av beta 3 endothelial cell (human or rat) attachment to vitronectin and aIIb beta 3 platelet aggregation were compared with bone resorption for sensitivity to s-echistatin analogs, linear RGD peptides, and cyclic RGD peptides. Essentially no similarity in sensitivity to RGD peptides were observed between bone resorption, platelet aggregation, or endothelial cell attachment. Because rat osteoclasts and human giant cell tumors (osteoclastomas) shared similar sensitivity to s-echistatin and rat and human endothelial cells showed a similar sensitivity profile to RGD peptides, the dissimilarity of bone resorption to other beta 3-mediated processes cannot be explained in terms of species differences.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
- Full Text
- View/download PDF
7. Actions of rat growth hormone-releasing factor and norepinephrine on cytosolic free calcium and inositol trisphosphate in rat C-cells.
- Author
-
Fried RM and Tashjian AH Jr
- Subjects
- Animals, Cytosol drug effects, Rats, Calcium metabolism, Carcinoma metabolism, Cytosol metabolism, Growth Hormone-Releasing Hormone pharmacology, Inositol Phosphates metabolism, Norepinephrine pharmacology, Sugar Phosphates metabolism
- Abstract
Rat growth hormone-releasing factor (rGRF) and norepinephrine (NE) stimulate secretion of calcitonin (CT) and neurotensin (NT) from cultured C-cells. The mechanism by which these agents cause secretion has not been well studied. We have examined the actions of the CT and NT secretagogues rGRF and NE on cytosolic free calcium concentrations ([Ca2+]i) in the rat C-cell line rMTC 44-2. Because inositol trisphosphate (IP3) has been shown to cause release of intracellular calcium stores in several cell types, we have also examined the effects of rat GRF, NE, and increases in extracellular calcium on IP3 accumulation in rMTC 44-2 cells. Stimulation by 10(-6) M rGRF caused a biphasic response in [Ca2+]i consisting of a rapid spike to 136 +/- 4% (mean +/- SE) of basal [Ca2+]i. This increase in [Ca2+]i decayed to base line and then gradually increased to 173 +/- 13% of basal [Ca2+]i. Stimulation by 10(-6) M NE gave a similar biphasic increase in [Ca2+]i. The increases in [Ca2+]i induced by both rGRF and NE were inhibited by pretreatment with EGTA or verapamil. rGRF, NE, and increasing concentrations of extracellular calcium, which all caused rapid increases in [Ca2+]i, failed to increase IP3 accumulation in rMTC 44-2 cells. These results suggest that rGRF- and NE-induced secretion in C-cells are mediated by changes in [Ca2+]i. These increases in [Ca2+]i appear to be generated by extracellular calcium influx rather than by release of intracellular calcium stores.
- Published
- 1987
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.