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Science 21 August 1987:
Vol. 237. no. 4817, pp. 893 - 896
DOI: 10.1126/science.3616618

Articles

Science, Vol 237, Issue 4817, 893-896
Copyright © 1987 by American Association for the Advancement of Science


articles

A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression

LJ Suva, GA Winslow, RE Wettenhall, RG Hammonds, JM Moseley, H Diefenbach-Jagger, CP Rodda, BE Kemp, H Rodriguez, EY Chen, and al. et

Humoral hypercalcemia of malignancy is a common complication of lung and certain other cancers. The hypercalcemia results from the actions of tumor factors on bone and kidney. We report here the isolation of full-length complementary DNA clones of a putative hypercalcemia factor, and the expression from the cloned DNA of the active protein in mammalian cells. The clones encode a prepro peptide of 36 amino acids and a mature protein of 141 amino acids that has significant homology with parathyroid hormone in the amino-terminal region. This previously unrecognized hormone may be important in normal as well as abnormal calcium metabolism.


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Parathyroid Hormone-Related Protein Induces Cachectic Syndromes without Directly Modulating the Expression of Hypothalamic Feeding-Regulating Peptides.
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Parathyroid Hormone-related Protein Regulates Tumor-relevant Genes in Breast Cancer Cells.
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Effects of calcium-sensing receptor on the secretion of parathyroid hormone-related peptide and its impact on humoral hypercalcemia of malignancy.
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PTHrP stimulated by the calcium-sensing receptor requires MAP kinase activation.
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Involvement of Prostaglandin E2 in Interleukin-1{{alpha}}-Induced Parathyroid Hormone-Related Peptide Production in Synovial Fibroblasts of Patients with Rheumatoid Arthritis.
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Humoral Hypercalcemia of Malignancy : Severe Combined Immunodeficient/Beige Mouse Model of Adult T-Cell Lymphoma Independent of Human T-Cell Lymphotropic Virus Type-1 Tax Expression.
V. Richard, M. D. Lairmore, P. L. Green, G. Feuer, R. S. Erbe, B. Albrecht, C. D'Souza, E. T. Keller, J. Dai, and T. J. Rosol (2001)
Am. J. Pathol. 158, 2219-2228
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Human Pancreatic Adenocarcinomas Express Parathyroid Hormone-Related Protein.
M. Bouvet, S. R. Nardin, D. W. Burton, C. Behling, J. M. Carethers, A. R. Moossa, and L. J. Deftos (2001)
J. Clin. Endocrinol. Metab. 86, 310-316
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Parathyroid Hormone-Related Protein Down-Regulates Bone Sialoprotein Gene Expression in Cementoblasts: Role of the Protein Kinase A Pathway.
H. Ouyang, R. T. Franceschi, L. K. McCauley, D. Wang, and M. J. Somerman (2000)
Endocrinology 141, 4671-4680
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Effects of Alendronate on Bone Metastases and Hypercalcemia After Surgery for Hepatocellular Carcinoma.
T. Ohnishi, E. Takeda, S. Yogita, H. Miyake, T. Kinoshita, Y. Terashima, T. Matsumoto, and S. Tashiro (2000)
Jpn. J. Clin. Oncol. 30, 410-413
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Regulation of secretion of PTHrP by Ca2+-sensing receptor in human astrocytes, astrocytomas, and meningiomas.
N. Chattopadhyay, C. Evliyaoglu, O. Heese, R. Carroll, J. Sanders, P. Black, and E. M. Brown (2000)
Am J Physiol Cell Physiol 279, C691-C699
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CC Chemokine I-309 Is the Principal Monocyte Chemoattractant Induced by Apolipoprotein(a) in Human Vascular Endothelial Cells.
N. S. Haque, X. Zhang, D. L. French, J. Li, M. Poon, J. T. Fallon, B. R. Gabel, M. B. Taubman, M. Koschinsky, and P. C. Harpel (2000)
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Dissection of Differentially Regulated (G+C)-Rich Promoters of the Human Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Gene.
M. Minagawa, M. Y. Kwan, J. D. Bettoun, F. W. Mansour, J. Dassa, G. N. Hendy, D. Goltzman, and J. H. White (2000)
Endocrinology 141, 2410-2421
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Calcium metabolism in sarcoidosis and its clinical implications.
M. Conron, C. Young, and H. L. C. Beynon (2000)
Rheumatology 39, 707-713
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Evaluation of Keratinocyte Proliferation and Differentiation in Vitamin D Receptor Knockout Mice.
Y. Sakai and M. B. Demay (2000)
Endocrinology 141, 2043-2049
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Enhanced Growth of MCF-7 Breast Cancer Cells Overexpressing Parathyroid Hormone-Related Peptide.
M. Falzon and P. Du (2000)
Endocrinology 141, 1882-1892
   Abstract »    Full Text »    PDF »
Expression of Parathyroid Hormone-Related Peptide (PTH-rp) and Its Receptorin the Porcine Ovary: Regulation by Transforming Growth Factor-{beta} and Possible Paracrine Effects of Granulosa Cell PTH-rp Secretion on Theca Cells.
J. C. Garmey, J. A. Schnorr, M. E. Bruns, D. E. Bruns, R. M. Seaner, J. E. Ferguson II, F. C. Luking Jayes, C. Aguirre, and J. D. Veldhuis (2000)
Biol Reprod 62, 334-339
   Abstract »    Full Text »
Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways.
S. Karp, E Schipani, B St-Jacques, J Hunzelman, H Kronenberg, and A. McMahon (2000)
Development 127, 543-548
   Abstract »    PDF »
Parathyroid Hormone-related Protein as a Growth Regulator of Prostate Carcinoma.
K. M. Dougherty, E. A. G. Blomme, A. J. Koh, J. E. Henderson, K. J. Pienta, T. J. Rosol, and L. K. McCauley (1999)
Cancer Res. 59, 6015-6022
   Abstract »    Full Text »    PDF »
Immediate Causes of Death in Thyroid Carcinoma: Clinicopathological Analysis of 161 Fatal Cases.
Y. Kitamura, K. Shimizu, M. Nagahama, K. Sugino, O. Ozaki, T. Mimura, K. Ito, K. Ito, and S. Tanaka (1999)
J. Clin. Endocrinol. Metab. 84, 4043-4049
   Abstract »    Full Text »
Elastase substrate specificity tailored through substrate-assisted catalysis and phage display.
W. Dall'Acqua, C. Halin, M. L. Rodrigues, and P. Carter (1999)
Protein Eng. Des. Sel. 12, 981-987
   Abstract »    Full Text »    PDF »
Receptors for PTH and PTHrP: their biological importance and functional properties.
M. Mannstadt, H. Juppner, and T. J. Gardella (1999)
Am J Physiol Renal Physiol 277, F665-F675
   Abstract »    Full Text »    PDF »
A G Protein-coupled Receptor from Zebrafish Is Activated by Human Parathyroid Hormone and Not by Human or Teleost Parathyroid Hormone-related Peptide. IMPLICATIONS FOR THE EVOLUTIONARY CONSERVATION OF CALCIUM-REGULATING PEPTIDE HORMONES.
D. A. Rubin, P. Hellman, L. I. Zon, C. J. Lobb, C. Bergwitz, and H. Juppner (1999)
J. Biol. Chem. 274, 23035-23042
   Abstract »    Full Text »    PDF »
Phosphorylation at the Cyclin-dependent Kinases Site (Thr85) of Parathyroid Hormone-related Protein Negatively Regulates Its Nuclear Localization.
M. H. C. Lam, C. M. House, T. Tiganis, K. I. Mitchelhill, B. Sarcevic, A. Cures, R. Ramsay, B. E. Kemp, T. J. Martin, and M. T. Gillespie (1999)
J. Biol. Chem. 274, 18559-18566
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Identification of a Human Anti-CD55 Single-Chain Fv by Subtractive Panning of a Phage Library Using Tumor and Nontumor Cell Lines.
J. B. B. Ridgway, E. Ng, J. A. Kern, J. Lee, J. Brush, A. Goddard, and P. Carter (1999)
Cancer Res. 59, 2718-2723
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Increased Serum and Urinary Levels of a Parathyroid Hormone-related Protein COOH Terminus in Non-Small Cell Lung Cancer Patients.
Y. Nishigaki, Y. Ohsaki, E. Toyoshima, and K. Kikuchi (1999)
Clin. Cancer Res. 5, 1473-1481
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Targeted Overexpression of Parathyroid Hormone-Related Protein (PTHrP) to Vascular Smooth Muscle in Transgenic Mice Lowers Blood Pressure and Alters Vascular Contractility.
S. Maeda, R. L. Sutliff, J. Qian, J. N. Lorenz, J. Wang, H. Tang, T. Nakayama, C. Weber, D. Witte, A. R. Strauch, et al. (1999)
Endocrinology 140, 1815-1825
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Reduced Blood Pressure and Increased Sensitivity of the Vasculature to Parathyroid Hormone-Related Protein (PTHrP) in Transgenic Mice Overexpressing the PTH/PTHrP Receptor in Vascular Smooth Muscle.
J. Qian, J. N. Lorenz, S. Maeda, R. L. Sutliff, C. Weber, T. Nakayama, M. C. Colbert, R. J. Paul, J. A. Fagin, and T. L. Clemens (1999)
Endocrinology 140, 1826-1833
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Walker 256/S Carcinosarcoma Causes Osteoporosis-like Changes through Ectopical Secretion of Luteinizing Hormone-releasing Hormone.
Y. Waki, M. Nomura, S. Kasugai, K. Ohya, and K.-i. Miyamoto (1999)
Cancer Res. 59, 1219-1224
   Abstract »    Full Text »    PDF »
Transforming Growth Factor-ß Stimulates Mouse Blastocyst Outgrowth through a Mechanism Involving Parathyroid Hormone-Related Protein.
R. A. Nowak, F. Haimovici, J. D. Biggers, and G. T. Erbach (1999)
Biol Reprod 60, 85-93
   Abstract »    Full Text »
Editorial: Parathyroid Hormone (PTH)/PTHrP Receptor Mutations in Human Chondrodysplasia.
R. A. Nissenson (1998)
Endocrinology 139, 4753-4755
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Hypercalcemia Caused by Ectopic Production of Parathyroid Hormone in a Patient with Papillary Adenocarcinoma of the Thyroid Gland.
H. Iguchi, C. Miyagi, K. Tomita, S. Kawauchi, Y. Nozuka, M. Tsuneyoshi, and H. Wakasugi (1998)
J. Clin. Endocrinol. Metab. 83, 2653-2657
   Abstract »    Full Text »
Parathyroid Hormone-Related Protein-Induced Hypercalcemia in SCID Mice Engrafted With Adult T-Cell Leukemia Cells.
A. Takaori-Kondo, K. Imada, I. Yamamoto, A. Kunitomi, Y. Numata, H. Sawada, and T. Uchiyama (1998)
Blood 91, 4747-4751
   Abstract »    Full Text »    PDF »
The Effects of Calcium Supplementation, Duration of Lactation, and Time of Day on Concentrations of Parathyroid Hormone-Related Protein in Human Milk: A Pilot Study.
N. A. Cross, L. S. Hillman, and L. R. Forte (1998)
J Hum Lact 14, 111-117
   Abstract »    PDF »
In Vitro Cleavage of Internally Quenched Fluorogenic Human Proparathyroid Hormone and Proparathyroid-related Peptide Substrates by Furin. GENERATION OF A POTENT INHIBITOR.
C. Lazure, D. Gauthier, F. Jean, A. Boudreault, N. G. Seidah, H. P. J. Bennett, and G. N. Hendy (1998)
J. Biol. Chem. 273, 8572-8580
   Abstract »    Full Text »    PDF »
Cancer and Bone.
T. A. Guise and G. R. Mundy (1998)
Endocr. Rev. 19, 18-54
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New insights into interactions between the human PTH/PTHrP receptor and agonist/antagonist binding.
S. Fukayama, M. Royo, M. Sugita, A. Imrich, M. Chorev, L. J. Suva, M. Rosenblatt, and A. H. Tashjian Jr. (1998)
Am J Physiol Endocrinol Metab 274, E297-E303
   Abstract »    Full Text »    PDF »
Maternal-Fetal Calcium and Bone Metabolism During Pregnancy, Puerperium, and Lactation.
C. S. Kovacs and H. M. Kronenberg (1997)
Endocr. Rev. 18, 832-872
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Solution Structure of Parathyroid Hormone Related Protein (Residues 1-34) Containing an Ala Substituted for an Ile in Position 15 (PTHrP[Ala15]-(1-34)).
J. A. Barden, R. M. Cuthbertson, W. Jia-Zhen, J. M. Moseley, and B. E. Kemp (1997)
J. Biol. Chem. 272, 29572-29578
   Abstract »    Full Text »    PDF »
Residues in the Membrane-spanning and Extracellular Loop Regions of the Parathyroid Hormone (PTH)-2 Receptor Determine Signaling Selectivity for PTH and PTH-related Peptide.
C. Bergwitz, S. A. Jusseaume, M. D. Luck, H. Juppner, and T. J. Gardella (1997)
J. Biol. Chem. 272, 28861-28868
   Abstract »    Full Text »    PDF »
Increased Expression of Parathyroid Hormone–Related Peptide Gene in Blood Vessels of Spontaneously Hypertensive Rats.
M. Noda, T. Katoh, K. Kurokawa, and Y. Takuwa (1997)
Hypertension 30, 1284-1288
   Abstract »    Full Text »
Expression of the Parathyroid Hormone-Related Peptide Gene in Retinoic Acid-Induced Differentiation: Involvement of ETS and Sp1.
M. Karperien, H. Farih-Sips, C. W.G.M. Löwik, S. W. de Laat, J. Boonstra, and L. H.K. Defize (1997)
Mol. Endocrinol. 11, 1435-1448
   Abstract »    Full Text »
Parathyroid Hormone–Related Peptide as a Local Regulator of Vascular Calcification: Its Inhibitory Action on In Vitro Calcification by Bovine Vascular Smooth Muscle Cells.
S. Jono, Y. Nishizawa, A. Shioi, and H. Morii (1997)
Arterioscler. Thromb. Vasc. Biol. 17, 1135-1142
   Abstract »    Full Text »
Cloning and Characterization of the Promoter Regions of the Human Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Gene: Analysis of Deoxyribonucleic Acid from Normal Subjects and Patients with Pseudohypoparathyroidism Type 1b.
J. D. Bettoun, M. Minagawa, M. Y. Kwan, H. S. Lee, T. Yasuda, G. N. Hendy, D. Goltzman, and J. H. White (1997)
J. Clin. Endocrinol. Metab. 82, 1031-1040
   Abstract »    Full Text »    PDF »
Parathyroid Hormone-Related Protein-(107-139) Inhibits Bone Resorption in Vivo.
J. Cornish, K. E. Callon, G. C. Nicholson, and I. R. Reid (1997)
Endocrinology 138, 1299-1304
   Abstract »    Full Text »    PDF »
Bcl-2 Lies Downstream of Parathyroid Hormone-related Peptide in a Signaling Pathway That Regulates Chondrocyte Maturation during Skeletal Development.
M. Amling, L. Neff, S. Tanaka, D. Inoue, K. Kuida, E. Weir, W. M. Philbrick, A. E. Broadus, and R. Baron (1997)
J. Cell Biol. 136, 205-213
   Abstract »    Full Text »    PDF »
Cell-Specific Expression of the Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Gene in Kidney from Kidney-Specific and Ubiquitous Promoters.
N. Amizuka, H. S. Lee, M. Y. Kwan, A. Arazani, H. Warshawsky, G. N. Hendy, H. Ozawa, J. H. White, and D. Goltzman (1997)
Endocrinology 138, 469-481
   Abstract »    Full Text »    PDF »
The Binding Activity of the Macrophage Lipoprotein(a)/Apolipoprotein(a) Receptor Is Induced by Cholesterol via a Post-translational Mechanism and Recognizes Distinct Kringle Domains on Apolipoprotein(a).
G. A. Keesler, B. R. Gabel, C. M. Devlin, M. L. Koschinsky, and I. Tabas (1996)
J. Biol. Chem. 271, 32096-32104
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Parathyroid Hormone-related Peptide Is Produced by Cultured Cerebellar Granule Cells in Response to L-type Voltage-sensitive Ca2+ Channel Flux via a Ca2+/Calmodulin-dependent Kinase Pathway.
E. H. Holt, A. E. Broadus, and M. L. Brines (1996)
J. Biol. Chem. 271, 28105-28111
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Evidence That Implicates the Parathyroid Hormone–Related Peptide in Vascular Stenosis : Increased Gene Expression in the Intima of Injured Rat Carotid Arteries and Human Restenotic Coronary Lesions.
S.-i. Ozeki, A. Ohtsuru, S. Seto, S. Takeshita, H. Yano, T. Nakayama, M. Ito, T. Yokota, M. Nobuyoshi, G. V. Segre, et al. (1996)
Arterioscler. Thromb. Vasc. Biol. 16, 565-575
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Molecular Cloning and Expression of Megakaryocyte Potentiating Factor cDNA.
T. Kojima, M. Oh-eda, K. Hattori, Y. Taniguchi, M. Tamura, N. Ochi, and N. Yamaguchi (1995)
J. Biol. Chem. 270, 21984-21990
   Abstract »    Full Text »    PDF »
Cardiotrophin-1.
D. Pennica, K. J. Shaw, T. A. Swanson, M. W. Moore, D. L. Shelton, K. A. Zioncheck, A. Rosenthal, T. Taga, N. F. Paoni, and W. I. Wood (1995)
J. Biol. Chem. 270, 10915-10922
   Abstract »    Full Text »    PDF »
Parathyroid Hormone (PTH)-PTH-related Peptide Hybrid Peptides Reveal Functional Interactions between the 1-14 and 15-34 Domains of the Ligand.
T. J. Gardella, M. D. Luck, A. K. Wilson, H. T. Keutmann, S. R. Nussbaum, J. T. Potts Jr., and H. M. Kronenberg (1995)
J. Biol. Chem. 270, 6584-6588
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A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide.
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Science 254, 1024-1026
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Structure and functional expression of a human interleukin-8 receptor.
W. Holmes, J Lee, W. Kuang, G. Rice, and W. Wood (1991)
Science 253, 1278-1280
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Increased Serum Levels of a Parathyroid Hormone-like Protein in Malignancy-Associated Hypercalcemia.
A. A. Budayr, R. A. Nissenson, R. F. Klein, K.K. Pun, O. H. Clark, D. Diep, C. D. Arnaud, and G. J. Strewler (1989)
Ann Intern Med 111, 807-812
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Parathyroid Hormone-Related Protein in Adult T-Cell Leukemia-Lymphoma.
T. Motokura, S. Fukumoto, T. Matsumoto, S. Takahashi, A. Fujita, T. Yamashita, T. Igarashi, and E. Ogata (1989)
Ann Intern Med 111, 484-488
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Tumors of the Parathyroid Gland and Circulating Parathyroid Hormone-Related Protein Associated with Persistent Hypercalcemia.
T. J. Rosol and C. C. Capen (1989)
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Review article : Hypercalcaemia of malignancy.
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Palliative Medicine 3, 1-11
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Expression of a calcium-mobilizing parathyroid hormone-like peptide in lactating mammary tissue.
M. Thiede and G. Rodan (1988)
Science 242, 278-280
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Gallium Nitrate for Acute Treatment of Cancer-Related Hypercalcemia: A Randomized, Double-Blind Comparison to Calcitonin.
R. P. WARRELL Jr., R. ISRAEL, M. FRISONE, T. SNYDER, J. J. GAYNOR, and R. S. BOCKMAN (1988)
Ann Intern Med 108, 669-674
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Humoral Hypercalcemia of Malignancy.
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Ann Intern Med 108, 454-457
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Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro.
N Horiuchi, M. Caulfield, J. Fisher, M. Goldman, R. McKee, J. Reagan, J. Levy, R. Nutt, S. Rodan, T. Schofield, et al. (1987)
Science 238, 1566-1568
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Parathyroid hormone-related protein of malignancy: active synthetic fragments.
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Science 238, 1568-1570
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The chondrogenic transcription factor Sox9 is a target of signaling by the parathyroid hormone-related peptide in the growth plate of endochondral bones.
W. Huang, U.-i. Chung, H. M. Kronenberg, and B. de Crombrugghe (2001)
PNAS 98, 160-165
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