Interthyr - Publications and Patents

GRAVES' AUTOANTIBODY BIOASSAYS AND NEW DIAGNOSTICS

1. Kohn, L. D., Valente, W. A., Grollman, E. F., Aloj, S. M., and Vitti, P.: Clinical determination and/or quantification of thyrotropin and a variety of thyroid stimulatory or inhibitory factors performed in vitro with an improved thyroid cell line FRTL-5, Sept. 2, 1986, U.S. Patent 4,609,622.

2. Scholl, D. S., Ambesi-Impiombato, F. S., Brown, J. L., Kohn, L. D., Jollick, J. A.: In situ growth, freezing, and testing of cultured cells. U.S. Patent 6,472,206 B1

3. Scholl, D. S., Ambesi-Impiombato, F. S., Brown, J. L., Kohn, L. D., Jollick, J. A.: In situ growth, freezing, and testing of cultured cells. U.S. Patent 6,472,206

4. Kohn, L. D., Malgor, R., Goetz, D. J., Silver, M., Schwartz, F., McCall, K. D., Kummitha, C. M., Christman, M. A., Lewis, C. J.: Wnt5a for screening, diagnosis, staging and identification of vulnerable vascular plaques.

5. Kohn, L. D., Malgor, R., Goetz, D. J., Silver, M., Schwartz, F., McCall, K. D., Kummitha, C. M., Christman, M. A., Lewis, C. J.: Wnt5a for screening, diagnosis, staging and identification of vulnerable vascular plaques.

6. Kohn, L. D., Brown, J., Scholl, D., Li, Y., and Napolitano, G.: Sensitive And Rapid Methods Of Using Chimeric Receptors To Identify Autoimmune Disease. U.S. Patent Application No. 12/206,322 ( September 8, 2008).

NOVEL THERAPEUTICS

1. Singer, D. S., Kohn, L. D, Mozes, E., Saji, M., Weissman, J., Napolitano, G., Ledley, F. D.:Methods for assessing the ability of a candidate drug to suppress MHC class I expression. U.S. Patent 5,556.754, Feb. 17, 1996.

2. Singer, D. S., Kohn, L. D, Mozes, E., Saji, M., Weissman, J., Napolitano, G., Ledley, F. D.:Methods of treating autoimmune disease and transplant rejection. U.S. Patent 5,871,950 Feb. 16, 1999.

3. Kohn, L. D., Curley, R. W. Jr., Rice, J. M.: Methimazole derivatives and tautomeric cyclic thiones to treat autoimmune disease. U.S. Patent 6,365,616 April 2, 2002.

4. Kohn, L. D., Curley, R. W. Jr., Rice, J. M.: Methimazole derivatives and tautomeric cyclic thiones to treat autoimmune disease. Australian Patent 775606 Issued November 18, 2004.

5. Kohn, L. D., Curley, R. W. Jr., Rice, J. M.: Methimazole derivatives and tautomeric cyclic thiones to treat autoimmune disease. Canadian Patent 2,339,090 Issued November 17, 2009.

6. Kohn, L.D., Suzuki, K., Mori, A., Iishi, K., Klinman, D. M., Rice, J. M.: Immune activation by double strand polynucleotides. Australian Patent 2004201249 Issued September 20, 2007.

7. Kohn, L. D., Goetz, D., Benavides-Peralta, U., Gonzalez-Murguiondo, M,. Harii, N., Lewis, C., Napolitano, G., Dagia N.: Compositions and methods for treatment of colitis using methimazole and/or cyclic thione derivatives . Canadian Patent Application 2,575,777 allowed June 11, 2010.

8. Kohn, L. D., Goetz, D., Harii, N., Lewis, C., Giuliani, C., Napolitano, G., Dagia N.: Methimazole derivatives and tautomeric cyclic thiones to inhibit cell adhesion. U.S. Patent pending, Application Serial No. 10/801,986 (2004).

9. Kohn, L. D., Goetz, D., Benavides-Peralta, U., Gonzalez-Murguiondo, M,. Harii, N., Lewis, C., Napolitano, G., Dagia N.: Compositions and methods for treatment of colitis. U.S. Patent pending, Application Serial No. 10/912,948 (2004).

10. Kohn, L. D., Harii, N., Benavides-Peralta, U., Gonzalez-Murguiondo, M., Lewis, C. J., Napolitano, G., Giuliani, C., Malgor, R., and Goetz, D. J.: Use of Phenylmethimazoles, Methimazole derivatives, and tautomeric cyclic thiones for the treatment of autoimmune/inflammatory diseases associated with Toll-like receptor overexpression. U.S. Patent Pending. Application Serial No. 11/130,922 (2005).

11. Kohn, L.D., Suzuki, K., Mori, A., Iishi, K., Klinman, D. M., Rice, J. M.: Immune activation by double strand polynucleotides. U.S. Application Publication US2005/0036993 A1 Feb. 17, 2005.

12. Kohn, L. D., Goetz, D., Benavides-Peralta, U., Gonzalez-Murguiondo, M,. Harii, N., Lewis, C., Napolitano, G., Dagia N.: Compositions and methods for treatment of colitis. Japanese patent pending, Application Serial No. 2007-524823 (2004).

13. Kohn, L.D., Suzuki, K., Mori, A., Iishi, K., Klinman, D. M., Rice, J. M.: Immune activation by double strand polynucleotides. European Patent Application No. 99969109.0 (2006).

14. Kohn, L. D., Goetz, D J., McCall, K. D., Schwartz, A., Schwartz, F., Malgor, R., Napolitano, G., Giuliani, C.: Methods and compositions for the treatment ofmelanoma, breast, prostate, colon, papillary thyroid and pancreatic cancer. U.S. Patent Application No. 12/286,880 (October 1, 2008).

15. Kohn, L. D., Curley, R. W. Jr., Rice, J. M.: Methimazole derivatives and tautomeric cyclic thiones to treat autoimmune disease. Japanese Patent Pending (2010).

RELEVANT PUBLICATIONS

1. Lytton, S., Li, Y. , Olivo, P. , Kohn, L. and Kahaly, G.: Novel Chimeric TSH-Receptor Bioassay for Thyroid-Stimulating Immunoglobulins. Clinical and Experimental Immunology, in press (2010).

2. McCall1, K. D., Holliday, D., Dickerson, E. Wallace, B., Schwartz, A. L., Schwartz, C., Lewis, C. J., Kohn, L. D., and Schwartz, F. L.: 5Phenylmethimazole Blocks Palmitate-Mediated Induction of Inflammatory Cytokine Pathways in 3T3L1 Adipocytes and RAW 264.7 Macrophages. J. Endocrinology, in press (2010).

3. Giuliani, C. Bucci, I. Montani, V. Singer, D. S. Monaco, F., Kohn, L. D. and Napolitano, D.: Regulation Of Major Histocompatibility Complex Gene Expression In Thyroid Epithelial Cells By Methimazole And Phenylmethimazole. J. Endocrinology, 204, 57-66 (2010).

4. Kummitha, C. M., Mayle, K., Christman. M. II, Deosarkar, S., Schwartz, A., McCall, K., Kohn, L. D., Malgor, R., and Goetz, D. J.: A Sandwich ELISA for the detection of Wnt5a. J. Immunol. Methods, 352, 38-44 (2010).

5. Lytton, S. D., Ponto, K. A., Kanitz, M., Matheis, N., Kohn, L. D., and Kahaly, G. J.: A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves' orbitopathy. J Clin Endocrinol Metab. 95, 2123-2131 (2010).

6. Benavides, U., Gonzalez-Murguiondo, M., Harii, N., Lewis, C. J., Sakhalkar, H. S., Deosarkar, S. P., Kurjiaka, D. T., Dagia, N. M., Goetz, D. J., and Kohn, L . D.: Phenyl methimazole suppresses DSS-induced murine colitis. European Journal of Pharmacology. 643, 129-138 (2010).

7. Schwartz, A. L., Malgor, R., Dickerson, E., Weeraratna, A. T., Slominski, A., Wortsman, J., Harii, N., Kohn, A. D., Moon, R. T., Schwartz, F. L., Goetz, D. J., Kohn, L. D.. and McCall, K. D.: Phenylmethimazole Decreases Toll-Like Receptor 3 and Noncanonical Wnt5a Expression in Pancreatic Cancer and Melanoma Together with Tumor Cell Growth and Migration. Clin. Cancer Res. 15, 4114-4122 (2009).

8. Arima, T., Shimojo, N., Yamaguchi, K-I., Tomiita, M., Kohn, L.D, and Kohno, Y.,: Enhancement of experimental Graves’ disease by intranasal administration of a T cell epitope of the thyrotropin receptor. Clinical Immunology. 127, 7-13 (2008).

9. Christman, M.A.II, Goetz, D.J. Dickerson, E. McCall, K.D., Lewis, C.J., Benencia, F. Silver, M.J., Kohn, L. D., and Malgor, R.: Wnt5a is Expressed in Murine and Human Atherosclerotic Lesions. Am. J. Physiol. – Heart Circ Physiol, 294, H2864-70 (2008).

10. Deosarkar, S. P, Malgor, R., Fu, J., Kohn, L. D., Hanes, J., and Goetz, D. J.: Polymeric particles conjugated with a ligand to VCAM-1 exhibit selective, avid, and focal adhesion to sites of atherosclerosis. Biotechnol Bioeng. 101, 400-407. (2008).

11. Grassadonia, A., Tinari, N., Fiorentino, B., Nakazato, M., Chung, H-K,, Giuliani, C., Napolitano, G., Iacobelli, S., Howcroft, T. K., Singer, D. S. and Kohn, L. D.: Upstream Stimulatory Factor (Usf) Regulates Constitutive Expression and Hormonal Suppression of the 90k (Mac-2bp) Protein. Endocrinology, 148, 3507-3517 (2007).

12. Kim, W. B., Lewis, C. J., McCall, K. D., Malgor, R., Kohn, A. D., Moon, R. T. and. Kohn, L. D.: Overexpression of Wnt-1 in Thyrocytes Enhances Cellular Growth But Suppresses Transcription of the Thyroperoxidase Gene via Different Signaling Mechanisms. J. Endocrinology, 192, 93-106 (2007).

13. McCall, K. D., Harii, N., Lewis, C. J., Malgor, R., Kim, W. B., Saji, M., Kohn, A. D., Moon, R. T., Kohn, L. D.: High Basal Levels of Functional Toll-like Receptor 3 (TLR3) and Non-Cannonical Wnt5a Are Expressed in Papillary Thyroid Cancer (PTC) and Are Coordinately Decreased by Phenylmethimazole Together with Cell Proliferation and Migration. Endocrinology, 148, 4226-4237. (2007).

14. Giuliani, C., Saji, M., Bucci, I., Fiore, G., Liberatore, M., Singer D. S., Monaco, F., Kohn, L. D., and Napolitano, G.: Transcriptional regulation of major histocompatibility class I gene by insulin and IGF-I in FRTL-5 cells. J. Endocrinol., 189, 605-615 (2006).

15. Harii, N., Lewis, C. J., Vasko, V., McCall, K., Benavides-Peralta, U., Sun, X., Ringel, M. D., Saji, M., Giuliani, C., Napolitano, G., Goetz, D. J., and Kohn, L. D.: Thyrocytes Express a Functional Toll-like Receptor 3 (TLR3): Overexpression Can Be Induced by Viral Infection, Reversed by Phenylmethimazole, and Is Associated with Hashimoto's Autoimmune Thyroiditis. Mol. Endocrinol., 19, 1231-1250 (2005).

16. Kohn, L. D., Schwartz, F., Silver, M. J., and Goetz, D. J.: Toll-like Receptors in Nonimmune Cells and Environmental Induction of the Pathologic Expression of Innate Immunity and Autoimmune Inflammatory Diseases: A New Therapeutic Opportunity. Ohio Research and Review, 15, Spring, 3-11 (2005)

17. Sakhalkar, H., S., Hanes, J., Fu, J., Benavides, U., Malgor, R., Borruso, C. L., Kohn, L. D., Kurjiaka, D. T., and Goetz, D. J.: Enhanced adhesion of ligand-conjugated biodegradable particles to colitic venules. FASEB J. 19, 792-4 (2005).

18. Kohn, L. D., Wallace, B., Schwartz, F., and McCall, K.: Is type 2 diabetes (DMII) an autoimmune-inflammatory disorder of the innate immune system? Endocrinology (News and Views), 146, 4189-4181 (2005).

19. Grassadonia, A., Tinari, N., Fiorentino, B., De Tursi, M., Suzuki, K., Nakazato, M., A., Giuliani, C., Napolitano, G., Singer, D. S., Iacobelli, S., and Kohn, L. D.: The 90K protein increases MHC class I expression and is regulated by hormones, -interferon , and double-strand polynucleotides. Endocrinology, 145, 4728-4736 (2004).

20. Dagia, N. M., Harii, N., Meli, A. E., Sun, X., Lewis C. J., Kohn, L. D., and Goetz, D. J.: Phenylmethimazole inhibits TNF- induced VCAM-1 expression in and IRF-1-dependent manner and reduces monocyte cell adhesion to endothelial cells. J. Immunology, 173, 2041-2049 (2004).

21. Kohn, L. D. And Harii, N.: Thyrotropin receptor autoantibodies (TSHYRAbs): Epitopes, Origins, and Clinical significance. Autoimmunity. 36, 331-338 (2003).

22. Kim, T. Y., Park, Y. J., Park, D. J., Chung, H.-K., Kim, W. B., Kohn, L. D. and Cho, B. Y.: Prediction of Outcome in Patients with Graves’ Disease after Antithyroid Drug Treatment According to Epitope Heterogeneity of Thyroid-Stimulating Antibodies. J. Clin. Endocrinol. Metab. 88, 117-124 (2003) .

23. Molteni, M., Kohn, L. D., Rossetti, C., Scrofani, S., Bonara, P., and Scorza, R.: Coexpression of the CD8 receptor in a human CD4(+) T-cell clone influences proliferation, cytosolic Ca (2+) release and cytokine production. Immunol. Lett. 83, 111-117 (2002)

24. Napolitano, G., Bucci, I., Giuliani, G., Massafra, C., Di Petta, C., Devangelio, E., Singer, D. S., Monaco, F., Kohn, L. D.: High glucose levels increase MHC class I gene expression in thyroid cells and amplify interferon- action. Endocrinology, 143, 1008-1017 (2002).

25. Kung, A. W. C., Lau, K. S., and Kohn, L. D.: Epitope Mapping of TSH receptor blocking antibodies in Graves' disease which appear during pregnancy. J. Clin. Endocrinol. Metab. 86, 3647-3653 (2001)

26. Shimojo, N., Arima, T., Yamaguchi, K-I., Kikuoka, S., Kohn, L. D., and Kohno, Y.: A novel mouse model of Graves’ disease: implications for a role in aberrant MHC class II expression in its pathogenesis. Int. Rev. Immunology, 19, 619-631 (2000).

27. Kohn, L. D., Napolitano, G., Singer, D. S., Moltini, M., Scorza, R., Shimojo, N., Kohno, Y., Mozes, E., Nakazato, M., Ulianich, L., Chung, H-K., Matoba, H., Saunier, B., Suzuki, K., Schuppert, F., and Saji, M.: Graves’ disease: a host defense mechanism gone awry. Int. Rev. Immunol., 19, 633-644 (2000).

28. Kung, A. W. C., Lau, K. S., and Kohn, L. D.: Characterization of thyroid-stimulating blocking antibodies which appeared during transient hypothyroidism after radioactive iodine therapy. Thyroid, 10, 909-917 (2000).

29. Kohn, L. D., Shimojo, N., Kohno, Y., Suzuki, K.: An animal model of Graves’ Disease: Understanding the cause of autoimmune hyperthyroidism. In Le Roith, D. (Ed): Rev. Endocr. Metab. Disord., 1, 59-67 (2000).

30. Kim, W. B., Chung, H. K., Park, D. J., Lee, H. K., Tahara, K., Kohn, L. D., and Cho, B. Y.: The prevalence and clinical significance of blocking TSH receptor antibodies in untreated Graves' disease. Thyroid, 10, 579-586 (2000).

31. Akamizu, T., Kohn, L. D., Saijo, M., Hatttori, Y., Moriyama, K., Tahara, K., and Nakao, K.: A Hashimoto’s patient with heterogeneous anti-thyrotropin receptor antibodies: unique epitopes may contribute to the regulation of thyroid function by the antibodies. J. Clin. Endocrinol. Metab., 85, 2116-2121 (2000).

32. Singer, D. S., Zinger, H., Kohn, L. D., and Mozes, E.: Differeing major histocompatibility class I requirements for induction and propagation of experimental systemic lupus erythematosus. Eur. J. Immunol., 29, 2259-2268 (1999).

33. Suzuki, K., Mori, A., Ishii, K. J., Saito, J., Singer, D. S., Klinman, D. M., Krause, P. R., and Kohn, L. D.: Activation of target tissue immune recognition molecules by double strand polynucleotides. Proc. Natl. Acad. Sci. U. S. A., 96, 2285-2290 (1999).