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Review

Pharmacological peroxisome proliferator-activated receptorγ ligands: emerging clinical indications beyond diabetes

Pages 1859-1872 | Published online: 23 Feb 2005

Bibliography

  • MANGELSDORF DJ, THUMMEL C, BEATO M et al: The receptor superfamily: the second decade. Cell (1995) 83(6)835–839.
  • ••Overview of the molecular biology of nuclear transcriptionfactors, best for new-comers to the area.
  • BRAISSANT 0, FOUFELLE F, SCOTTO C, DAUCA M, WAHLI W: Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distri-bution of PPAR-a, -6, and -y in the adult rat. Endocri-nology (1996) 137(0:354–366.
  • VAMECQ J, LATRUFFE N: Medical significance of peroxi-some proliferator-activated receptors. Lancet (1999) 354(9173):141–148.
  • •The most recent general review of the medical significance of PPARs.
  • KLIEWER SA, WILLSON TM: The nuclear receptor PPARy
  • - bigger than fat. Curr. Opin. Genet. Dev. (1998) 8(5):576–581.
  • •Review of PPARs focusing on their ligands and their potential clinical significance.
  • SPIEGELMAN BM: PPAR-y: adipogenic regulator and receptor. Diabetes (1 9 9 8) 47 (4):507–514.
  • •Review on importance of PPARy in insulin resistance.
  • KLIEWER SA, LEHMANN JM, WILLSON TM: Orphan receptors: shifting endocrinology into reverse. Science (1999) 284 (5415) :757–760.
  • SCHULMAN IG, SHAO G, HEYMAN RA: Transactivation by retinoid X receptor-peroxisome proliferator-activated receptor-y (PPARy) heterodimers: intermo-lecular synergy requires only the PPARy hormone-dependent activation function. Mol. Cell. Biol. (1998) 18(6)3483–3494.
  • MUKHERJEE R, DAVIES PJ, CROMBIE DL et al.: Sensitiza-tion of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature (1997) 386 (6623) 407–410.
  • ELSTNER E, MULLER C, KOSHIZUKA K et al.: Ligands for peroxisome proliferator-activated receptor-y and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc. Natl. Acad. Sci. USA (1 9 9 8) 95(15)8806–8811.
  • ••Provides evidence for potential efficacy of a thiazolidinedi-one in the treatment of breast cancer in humans.
  • WARRELL RP JR, DE THE H, WANG ZY, DEGOS L: Acute promyelocytic leukemia. New Engl. J. Med. (1993) 329(3)177–189.
  • ELBRECHT A, CHEN Y, CULLINAN CA et al.: Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors yl and y2. Biochem. Biophys. Res. Commun. (1996) 224(2):431–437.
  • GUAN Y, ZHANG Y, DAVIS L, BREYER MD: Expression of peroxisome proliferator-activated receptors in urinary tract of rabbits and humans. Am. J. Physiol (1997) 273(6 Pt 2):F1013–F1022.
  • VIDAL-PUIG AJ, CONSIDINE RV, JIMENEZ-LINAN M et al.: Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weightand regulation by insulin and glucocorticoids. J. Clin. Invest. (1997) 99(102416–2422.
  • FAJAS L, AUBOEUF D, RASPE E, SCHOONJANS K etal.: The, promoter analysis, and expression of the human PPARy gene. J. Biol. Chem. (1997) 272(30)18779–18789.
  • ••Good paper on variability of PPARy expression in humans.
  • ELLIS CN, VARANI J, PERSHADSINGH HA et al.: Troglita- improves psoriasis and normalizes models of proliferative skin disease: Ligands for peroxisome proliferator-activated receptor-y (PPARy) inhibit keratinocyte proliferation. Arch. Dermatol. (In press.).
  • ••First demonstration of a therapeutic effect of a thiazolidine-dione on psoriasis in non-diabetic subjects.
  • PERSHADSINGH HA, BENSON SC, MARSHALL B et al.:Ocular diseases and peroxisome proliferator-activated receptor-y (PPARy) in mammalian eye. Proc. Soc. Neurosci. (1999) (In Press).
  • FAJAS L, FRUCHART JC, AUWERX J: PPARy3 mRNA: a distinct PPARy mRNA subtype transcribed from an independent promoter. FEBS Lett (1998) 438:55–60.
  • HENRY RR: Thiazolidinediones. Endocrinol. Metab. North Am. (1997) 26(3):553–573.
  • KURTZ TW, GARDNER DG: Transcription-modulating drugs: a new frontier in the treatment of essential hypertension. Hypertension (1998) 32 (3) 380–386.
  • ••Excellent recent review on control of gene transcription andPPARy activation as a new approach to treating hypertension.
  • HAIGH D, ALLEN G, BIRRELL HC et al.: Non-thiazolidinedione antihyperglycaemic agents. Part 3: The effects of stereochemistry on the potency of a-methoxy-6-phenylpropanoic acids. Bioorg. Med. Chem. (1999) 7(5):821–830.
  • HENKE BR, BLANCHARD SG, BRACKEEN MF et al: N-(2-Benzoylpheny1)-L-tyrosine PPARy agonists. 1. Discovery of a novel series of potent antihypergly-cemic and antihyperlipidemic agents. J. Med. Chem. (1998) 41(25): 5020–5036.
  • BERGER J, LEIBOWITZ MD, DOEBBER TW et al: Novelperoxisome proliferator-activated receptor (PPAR) and PPARy ligands produce distinct biological effects. J. Biol. Chem. (1999) 274(106718–6725.
  • XU HE, LAMBERT MH, MONTANA VG et al: Molecularrecognition of fatty acids by peroxisome proliferator-activated receptors. Mol. Cell. (1999) 3(3):397–403.
  • HENRY RR. Type 2 diabetes care: the role of insulin-sensitizing agents and practical implications for cardiovascular disease prevention. Am. J. Med. (1998) 105(1M:205–265.
  • BROWN KK, HENKE BR, BLANCHARD SG et al. A novel-aryl tyrosine activator of peroxisome proliferator-activated receptor-gamma reverses the diabetic phenotype of the Zucker diabetic fatty rat. Diabetes (1999) 48(7):1415–1424.
  • WATKINS PB, WHITCOMB RW: Hepatic dysfunction associated with troglitazone. New Engl. J. Med. (1998) 338(13):916–917.
  • AMOWITZ LL, SOBEL BE: Cardiovascular consequences of polycystic ovary syndrome. Endocrinol. Metab. North Am. (1999) 28(2):439–458.
  • EHRMANN DA, SCHNEIDER DJ, SOBEL BE et al.: Troglita-zone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. (1997) 82 (7) :2108–2116.
  • DUNAIF A, SCOTT D, FINEGOOD D, QUINTANA B, WHITCOMB R: The insulin-sensitizing agent troglita-zone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J.. Metab. (1996) 81 (9):3299–3306.
  • •Clinical study on the effects of a thiazolidinedione on sex hormone abnormalities in a gynaecological endocrine disease.
  • ANDREWS RC, WALKER BR: Glucocorticoids and insulinresistance: old hormones, new targets. Clin. Sci. (Colch.). (1999) 96 (5) :513–523.
  • OKUMURA S, TAKEDA N, TAKAMI K et al: Effects oftroglitazone on dexamethasone-induced insulin resistance in rats. Metabolism (1998) 47(3) :351–354.
  • FONSECA VA, VALIQUETT TR, HUANG SM, GHAZZI MN, WHITCOMB RW: Troglitazone monotherapy improves glycemic control in patients with Type 2 diabetes mellitus: a randomized, controlled study. The Troglita-zone Study Group. J. Clin. Endocrinol. Metab. (1998) 83 (9):3169–3176.
  • ZHANG HY, REDDY SR, KOTCHEN TA: Antihypertensive effect of pioglitazone is not invariably associated with increased insulin sensitivity. Hypertension (1994) 24 (1):106–110.
  • ••Excellent paper demonstrating that the antihypertensiveeffect of pioglitazone is not necessarily related to insulin resistance.
  • OGIHARA T, RAKUGI H, IKEGAMI H, MASUO K: Enhance- of insulin sensitivity by troglitazone lowers blood pressure in diabetic hypertensives. Am. J. Hypertens. (1995) 8(3):316–320.
  • •First demonstration in humans of an antihypertensive effect of a thiazolidinedione.
  • SUNG BH, IZZO JL, JR, DANDONA P, WILSON MF: Vasodi-latory effects of troglitazone improve blood pressure at rest and during mental stress in Type 2 diabetes mellitus. Hypertension (1999) 34 (7) 83–88.
  • NAKAMURA Y, OHYA Y, ONAKA U, FUJII K, ABE I, FUJISHIMA M: Inhibitory action of insulin-sensitizing agents on calcium channels in smooth muscle cells from resistance arteries of guinea-pig. Br. J. Pharmacol (1998) 123:675–682.
  • ITOH H, DOI K, TANAKA T et al.: Hypertension and insulin resistance: role of peroxisome proliferator-activated receptor-y. Clin. Exp. Pharmacol. Physic)]. (1999) 26(7):558–560.
  • FUJISHIMA S, OHYA Y, NAKAMURA Y, ONAKA U, ABE I, M: Pioglitazone, an insulin sensitizer, increases forearm blood flow in humans. Am. J. Hypertens. (1998) 11(9):1134–1137.
  • •Evidence for a beneficial effect of a thiazolidinedione on endothelial function in man.
  • MURAKAMI T, MIZUNO S, OHSATO K et al.: Effects of on frequency of coronary vasospastic-induced angina pectoris in patients with diabetes mellitus. Am. J. Cardiol (1999) 84(0:92-94. A8.
  • •First demonstration of a therapeutic effect of a thiazolidine-dione on angina pectoris in humans.
  • TACK CJ, SMITS P, DEMACKER PN, STALENHOEF AF: Troglitazone decreases the proportion of small, dense LDL and increases the resistance of LDL to oxidation in obese subjects. Diabetes Care (1998) 21(5):796–799.
  • YAMASAKI Y, KAWAMORI R, WASADA T et al.: Pioglita-zone (AD-4833) ameliorates insulin resistance in patients with NIDDM. AD-4833 Glucose Clamp Study Group, Japan. Tohoku. J. Exp. Med. (1997) 183 (3):173–183.
  • ROSS R: Atherosclerosis-an inflammatory disease. New Engl. J. Med. (1999) 340(2):115–126.
  • MORIKANG E, BENSON SC, KURTZ TW, PERSHADSINGH HA: Effects of thiazolidinediones on growth and differ-entiation of human aorta and coronary myocytes. Am. Hypertens. (1997) 10(4 Pt 0:440–446.
  • RICOTE M, LI AC, WILLSON TM, KELLY CJ, GLASS CK: The peroxisome proliferator-activated receptor-y is a negative regulator of macrophage activation. Nature (1998) 391 (6662):79–82.
  • •First article to demonstrate inhibitory effect of PPARy agonists on MMP activity.
  • JIANG C, TING AT, SEED B: PPAR-y agonists inhibit of monocyte inflammatory cytokines. Nature. (1998) 391 (6662):82–86.
  • •Article on anti-inflammatory effects of PPARy agonists in macrophages.
  • PLUTZKY J: Atherosclerotic plaque rupture: emerging insights and opportunities. Am. J. Cardiol. (1999) 84 (1A) :15J–20J.
  • MARX N, SUKHOVA G, MURPHY C, LIBBY P, PLUTZKY J: Macrophages in human atheroma contain PPARy: differentiation-dependent peroxisomal proliferator-activated receptor-y(PPARy) expression and reduction of MMP-9 activity through PPARy activation in mononuclear phagocytes in vitro. Am. J. Pathol (1998) 153 (1):17–23.
  • •Comprehensive study on PPARy activation and inhibition of MMP-9 enzyme activity and gene expression.
  • FONSECA VA, REYNOLDS T, HEMPHILL D et al.: Effect of on flbrinolysis and activated coagulation in patients with non-insulin-dependent diabetes mellitus. J. Diabetes Complications (1998) 12(4):181–186.
  • CHINETTI G, GRIGLIO S, ANTONUCCI M et al.: Activation proliferator-activated receptors and induces apoptosis of human monocyte-derived macrophages. J. Biol. Chem. (1998) 2 73 (40):25573–25580.
  • ••Excellent article providing explanation for controversialpro-atherogenic role of PPARy activation in monocyte/macrophages.
  • MINAMIKAWA J, TANAKA S, YAMAUCHI M, INOUE D, H: Potent inhibitory effect of troglitazone on carotid arterial wall thickness in Type 2 diabetes. J. Clin. Endocrinol. Metab. (1998) 83(5):1818–1820.
  • ••First demonstration in humans that a thiazolidinedioneameliorates atherosclerosis.
  • IGARASHI M, TAKEDA Y, ISHIBASHI N: Pioglitazone reduces smooth muscle cell density of rat carotid arterial intima induced by balloon catheterization. Horm. Metab. Res. (1997) 29(9):444–449.
  • TAKAGI T, YOSHIDA K, AKASAKA T et al: Troglitazone reduces intimal hyperplasia after coronary stent implantation in patients with Type 2 diabetes mellitus: a serial intravascular ultrasound study. J. Am. Coll. Cardiol. (1999) 33:100A.
  • ••First demonstration in humans that a thiazolidinedioneprevents arterial restenosis after an invasive vascular procedure.
  • YOSHIMOTO T, NARUSE M, NISHIKAWA M et al.: Antihy- and vasculo- and renoprotective effects of pioglitazone in genetically obese diabetic rats. Am. J. Physiol. (1997) 272(6 Pt 1):E989–E996.
  • LYDAKIS C, LIP GY: Microalbuminuria and cardiovas-cular risk. QJM (1998) 91(6):381–391.
  • IMANO E, KANDA T, NAKATANI Y et al.: Effect of troglita-zone on microalbuminuria in patients with incipient diabetic nephropathy. Diabetes Care (1 9 9 8) 2 1 (12):2135–2139.
  • •First demonstration in humans that a thiazolidinedione reverses diabetic nephropathy.
  • MILLER JW: Vascular endothelial growth factor and ocular neovascularization. Am. J. Pathol. (1997) 151(0:13–23.
  • ISHIBASHI T, MURATA T, HANGAI M: Advanced glycation end products in age-related macular.Arch.Ophthalmol.(1 9 9 8)116(12)1629–1632.
  • MURATA T, NAGAI R, ISHIBASHI T, INOMUTA H, IKEDA K, HORIUCHI S: The relationship between accumula-tion of advanced glycation end products and expres-sion of vascular endothelial growth factor in human diabetic retinas. Diabetologia (1997) 40(7)764–769.
  • XIN X, YANG S, KOWALSKI J, GERRITSEN ME: Peroxi-some proliferator-activated receptory ligands are potent inhibitors of angiogenesis in vitro and in vivo. J. Biol. Chem. (1999) 274(13):9116–9121.
  • ••First demonstration of the anti-angiogenic potential ofPPARy activation.
  • MURATA T, HE S, HANGAI M, RYAN SJ, LAW RE, HINTON: Peroxisome proliferator-activated receptor (PPAR)-y ligands inhibit intraocularThe Proceedings of the Association for Research in Vision and Ophthalmology (ARVO), Fort Lauderdale, USA (1999):918.
  • ••First demonstration that thiazolidinedione PPARy agonistsmay be a treatment for neovascular retinopathy.
  • CURSIEFEN C, KUCHLE M, NAUMANN GO: Angiogenesis corneal diseases: histopathologic evaluation of 254 human corneal buttons with neovascularization. Cornea (1998) 17(6):611–613.
  • FINI ME, PARKS WC, RINEHART WB et al.: Role of matrix metalloproteinases in failure to re-epithelialize after corneal injury. Am. J. Pathol. (1996) 149(4):1287–1302.
  • SASAKI H, FUKUSHIMA M: Prostaglandins in the treatment of cancer. AntiCancer Drugs (1994) 5(2):131–138.
  • BISHOP-BAILEY D, HLA T: Endothelial cell apoptosis Induced by the peroxisome proliferator-activated receptory (PPARy) ligand 15-deoxy-12'14_prostaglandin J2. J. Biol. Chem. (1999) 274:17042–17048.
  • FUJIMURA S, SUZUMIYA J, NAKAMURA K, ONO J: Effects of troglitazone on the growth and differentiation of hematopoietic cell lines. Int. J. Oncol. (1998) 13(6):1263–1267.
  • TAKAHASHI N, OKUMURA T, MOTOMURA W, FUJIMOTO Y, KAWABATA I, KOHGO Y: Activation of PPARy inhibits cell growth and induces apoptosis in human gastric cancer cells. FEBS Lett. (1999) 455(1-2):135–139.
  • SYLVESTER AM, CHEN D, KRASINSKI K, ANDRES V: Role of c-fos and E2F in the induction of cyclin A transcrip-tion and vascular smooth muscle cell proliferation. J. Clin. Invest. (1998) 101(5)940–948.
  • ALTIOK S, XU M, SPIEGELMAN BM: PPARy induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes Dev. (1997) 11(15):1987–1998.
  • •Article on potential molecular mechanism of PPARy-induced growth arrest.
  • MUELLER E, SARRAF P, TONTONOZ P et al.: Terminal of human breast cancer through PPARy. Mol. Cell (1998) 1(3):465–470.
  • •Article on the antitumour effect of a thiazolidinedione and the differential expression of PPARy in both hormone-dependent and hormone-independent breast cancer cells.
  • KUBOTA T, KOSHIZUKA K, WILLIAMSON EA et al.: Ligand peroxisome proliferator-activated receptor-y (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo. Cancer Res. (1998) 58(15):3344–3352.
  • •Article on the antitumour effect of a thiazolidinedione in hormone-dependent and hormone-independent human prostate cancer cell lines, and the potential efficacy of PPARy ligands in the treatment of prostate cancer.
  • CAMP HS, TAFURI SR, LEFF T: c-Jun N-terminal kinase peroxisome proliferator-activated receptor-yl and negatively regulates its transcrip-tional activity. Endocrinology (1999) 140(1)392–397.
  • DEMETRI GD, FLETCHER CD, MUELLER E et al. Induction solid tumor differentiation by the peroxisome-activated receptor-y ligand troglitazone in patients with liposarcoma. Proc. Natl. Acad. Sci. USA (1999) 96(7):3951–3956.
  • ••First clinical demonstration of an anticancer effect of athiazolidinedione.
  • SARRAF P, MUELLER E, JONES D et al.: Differentiation and reversal of malignant changes in colon cancer through PPARy. Nature Med. (1998) 4 (9):1046–1052.
  • SU CG, WEN X, BAILEY ST et al.: A novel therapy for colitis utilizing PPAR-y ligands to inhibit the epithelial inflammatory response. J. Clin. Invest. (1999) 104(4)383-389. P, MUELLER E, SMITH WM et al.: Loss-of-function mutations in PPARy associated with human colon cancer. Mol. Cell. (1999) 3(6):799–804. article on differential effects of PPARy agonists depending on functional mutation in the PPARy receptor. E, TONTONOZ P, NELSON MC et al.: Activators of the nuclear receptor PPARy enhance colon polyp formation. Nature Med. (1998) 4 (9) :1058–106.
  • LEFEBVRE AM, CHEN I, DESREUMAUX P et al: Activation of the peroxisome proliferator-activated receptor-y promotes the development of colon tumors in C57BL/6J-APCMin/+ mice. Nature Med. (1998) 4(9):1053–1057.
  • GELMAN L, FRUCHART JC, AUWERX J: An update on the mechanisms of action of the peroxisome proliferator-activated receptors (PPARs) and their roles in inflam-mation and cancer. Cell. Mol. Life Sci. (1999) 55 (6-7):932–943.
  • •Most recent article on regulation of PPARy?transcriptional activity by their nuclear co-factors and the role of PPARs in inflammation and cancer.
  • HIMELSTEIN BP, CANETE-SOLER R, BERNHARD EJ, DILKS DW, MUSCHEL RJ: Metalloproteinases in tumor progression: the contribution of MMP-9. Invasion Metastasis (1994–95) 14 (1–6):246–258.
  • ITOH T, TANIOKA M, MATSUDA H et al.: Experimental metastasis is suppressed in MMP-9 deficient mice. Clin. Exp. Metastasis (1999) 17 (2) :177–181.
  • REDDY KB, KRUEGER JS, KONDAPAKA SB, DIGLIO CA: Mitogen-activated protein kinase (MAPK) regulates the expression of progelatinase B (MMP-9) in breast epithelial cells. Int. J. Cancer. (1999) 82(2):268–273.
  • KOIVUNEN E, ARAP W, VALTANEN H: Tumor targeting with a selective gelatinase inhibitor. Nature Biotechnol (1999) 17(8):768–774.
  • •Review on targeting metalloproteinase inhibition as an approach to preventing tumour metastasis.
  • VEIKKOLA T, ALITALO K: VEGFs, receptors and angiogenesis. Semin. Cancer Biol. (1999) 9 (3):211–220.
  • BALSARI A, MAIER JA, COLNAGHI MI, MENARD S: Correlation between tumor vascularity, vascular endothelial growth factor production by tumor cells, serum vascular endothelial growth factor levels, and serum angiogenic activity in patients with breast carcinoma. Lab. Invest. (1999) 79(7)897–902.
  • GREAVES MW, WEINSTEIN GD: Treatment of psoriasis. New Engl. J. Med. (1995) 332(9):581–588.
  • RIVIER M, SAFONOVA I, GRIFFITHS CEM, AILHAUD G, MICHER S: Differential expression of peroxisome proliferator activated receptor subtypes during the differentiation of human keratinocytes. J. Invest. Dermatol. (1998) 111:1116–1121.
  • VAN RUISSEN F, VAN DE KERKHOF PC, SCHALKWIJK J: Signal transduction pathways in epidermal prolifera-tion and cutaneous inflammation. Clin. Dermatol. (1995) 13(2):161–190.
  • BARKER JN: Psoriasis as a T cell-mediated autoimmune disease. Hosp. Med. (1998) 59(7):530–533.
  • MIZUTANI H, OHMOTO Y, MIZUTANI T, MURATA M, SHIMIZU M: Role of increased production of monocytes TNF-a, IL-1 and IL-6 in psoriasis: relation to focal infection, disease activity and responses to treatments. J. Dermatol Sci. (1997) 14(2):145–153.
  • GIORGINI AE, BEALES PE, MIRE-SLUIS A, SCOTT D, LIDDI R, POZZILLI P: Troglitazone exhibits immunomodula-tory activity on the cytokine production of activated human lymphocytes. Horm. Metab. Res. (1999) 31(1):1–4.
  • TANAKA T, ITOH H, DOI K et al: Down regulation of peroxisome proliferator-activated receptor expres-sion by inflammatory cytokines and its reversal by thiazolidinediones. Diabetologia (1999) 42(6)702–710.
  • ELLIS CN, KANG S, VINIK Al, GREKIN RC, CUNNINGHAM WJ, VOORHEES JJ: Glucose and insulin responses are improved in patients with psoriasis during therapy with etretinate. Arch. Dermatol. (1987) 123(4):471–475.
  • TALLMAN MS, ANDERSEN JW, SCHIFFER CA et al.: All-trans-retinoic acid in acute promyelocytic leukemia. N Engl. J. Med. (1997) 337(15):1021–1028.
  • ORFANOS CE, ZOUBOULIS CC, ALMOND-ROESLER B, GEILEN CC: Current use and future potential role of retinoids in dermatology. Drugs (1997) 53 (3):358–388.
  • LEHMANN JM, LENHARD JM, OLIVER BB, RINGOLD GM, KLIEWER SA: Peroxisome proliferator-activated receptors and are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J. Biol. Chem. (1997) 272(6):3406–3410.
  • NEURATH. MF, FUSS I, SCHURMANN G et al.: Cytokine gene transcription by NF-?B family members in patients with inflammatory bowel disease. Ann. NY Acad. Sci. (1998) 859:149–159.
  • DESREUMAUX P, ERNST 0, GEBOES K et al.: Inflamma-tory alterations in mesenteric adipose tissue in Crohn's disease. Gastroenterology (1999) 117(0:73–81.
  • •Evidence for PPARy activation as a rational approach to the treatment of Crohn's disease.
  • BAERT FJ, RUTGEERTS PR: Anti-TNF strategies in Crohn's disease: mechanisms, clinical effects, indica-tions. Int. J. Colorectal Dis. (1999) 14 (0 :47–51.
  • BRENNAN FM, MAINI RN, FELDMANN M: Cytokine expression in chronic inflammatory disease. Br. Med. Bull. (1995) 51(2):368–384.
  • FEARON U, REECE R, SMITH J, EMERY P, VEALE DJ: Synovial cytokine and growth factor regulation of MMPs/TIMPs: implications for erosions and angiogenesis in early rheumatoid and psoriatic arthritis patients. Ann. NY Acad. Sci. (1999) 878:619–821.
  • AMIN AR, ATTUR M, ABRAMSON SB: Nitric oxide synthase and cyclooxygenases: distribution, regula-tion, and intervention in arthritis. Curr. Opin. Rheumatol. (1999) 11(3):202–209.
  • OBERFIELD JL, COLLINS JL, HOLMES C: A peroxisome proliferator-activated receptor-y ligand inhibits adipocyte differentiation. Proc. Natl. Acad. Sci. USA (1999) 96(10:6102–6106.
  • ••First article to describe the synthesis, and cellular andmolecular properties of a PPARy antagonist.
  • REME CE, GRIMM C, HAFEZI F, MARTI A, WENZEL A: Apoptotic cell death in retinal degenerations. Prog. Retin. Eye Res. (1998) 17(4):443–464.
  • MICHEL PP, LAMBENG N, RUBERG M: Neuropharma-cologic aspects of apoptosis: significance for neurode-generative diseases. Clin. Neuropharmacol (1999) 22(3):137–150.
  • BENNETT J, ZENG Y, BAJWA R, KLATT L, LI Y, MAGUIRE AM: Adenovirus-mediated delivery of rhodopsin-promoted bc1-2 results in a delay in photoreceptor cell death in the rd/rd mouse. Gene Ther. (1998) 5 (9):1156–1164.
  • SAILLE C, MARIN P, MARTINOU JC, NICOLE A, LONDON J, CEBALLOS-PICOT I: Transgenic murine cortical neurons expressing human Bc1-2 exhibit increased resistance to amyloid 8-peptide neurotoxicity. Neuroscience (1999) 92 (4):1455–1463.
  • ISNER JM, LOSORDO DW: Therapeutic angiogenesis for heart failure. Nature Med. (1999) 5(5):491–492. A Pershadsingh Medical Center, 1830 Flower Street, Bakersfield, CA 93305,.: +1 661 326 2113; Fax: +1 661 326 2114;: [email protected]

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