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13.296 -9.75 Td
[(permeability factor/vascular endothelial growth factor)-64.75 (,)]TJ
0.116 -10 Td
(microvascular hyperpermeability, and angiogenesis. Am J Pathol)Tj
0.091 -10 Td
(1995;146:1029-39.)Tj
-13.641 -9.75 Td
(6.)Tj
0.2 Tw 13 0 Td
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1 Tc 0 Tw 124 0 Td
(,W)Tj
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(ile M, Hatcher VB,)Tj
0.2 Tw -134.861 -10 Td
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0.125 Tw 0.088 -9.75 Td
(mitogen from a rat glioma-derived cell line. Proc Natl Acad Sci)Tj
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(USA1990;87:1323-7.)Tj
0 Tc -13.387 -10 Td
(7.)Tj
0.14999 Tw 13 0 Td
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0 Tw -0.13 -10 Td
(J Biol Chem 1995;270:31189-95.)Tj
-13.537 -9.75 Td
[(8.)-875 (Li J, Perrella MA, )-99.5 (T)]TJ
0.2 Tw 78.175 0 Td
(sai JC, et al. Induction of vascular endothelial)Tj
-64.698 -10 Td
(growth factor gene expression by interleukin-1 beta in rat aortic)Tj
0.199 -10 Td
(smooth muscle cells. J Biol Chem 1995;270:308-12.)Tj
0 Tw -13.558 -10 Td
(9.)Tj
0.2 Tw 13 0 Td
[(Jackson JR, Minton JA, Ho ML, )30.75 (W)]TJ
0 Tw 114.005 0 Td
[(ei N, )-18.625 (W)31.375 (inkler JD. Expression of)]TJ
0.2 Tw -113.632 -10 Td
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0.127 -10 Td
(by hypoxia and interleukin 1 beta. J Rheumatol 1997;24:1253-9.)Tj
0 Tw -17.517 -10 Td
(10.)Tj
0.2 Tw 17 0 Td
[(Freeman MR, Schneck FX, Gagnon ML, et al. Peripheral blood )33 (T)]TJ
0.375 -10 Td
(lymphocytes and lymphocytes infiltrating human cancers express)Tj
0.227 -10 Td
[(vascular endothelial growth factor: a potential role for )34.875 (T)]TJ
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(cells in)Tj
-183.167 -10 Td
(angiogenesis. Cancer Res 1995;55:4140-5.)Tj
-17.314 -10 Td
[(1)31.25 (1.)-875 (Ferrara N, Davis-Smyth )-74.75 (T.)-187.375 (The biology of vascular endothelial)]TJ
17.373 -10 Td
(growth factor. Endocr Rev 1997;18:4-25.)Tj
-17.536 -10 Td
[(12.)-875 (Cohen )-24.875 (T)93.875 (, Nahari D, Cerem L)-36.75 (W)]TJ
0.2 Tw 117.079 0 Td
(, Neufeld G, Levi BZ. Interleukin 6)Tj
0.144 Tw -99.526 -10 Td
(induces the expression of vascular endothelial growth factor. J Biol)Tj
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(Chem 1996;271:736-41.)Tj
-17.581 -10 Td
[(13.)-875 (Pertovaara L, Kaipainen A, Mustonen )-61.25 (T)93.875 (, et al. )-74.375 (V)124.875 (ascular endothelial)]TJ
0.2 Tw 17.448 -10 Td
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(1994;269:6271-4.)Tj
-17.641 -10 Td
(14.)Tj
0.10899 Tw 17 0 Td
(Cho CS, Cho ML, Min SY, et al. CD40 engagement on synovial)Tj
0.2 Tw 0.638 -10 Td
(fibroblast up-regulates production of vascular endothelial growth)Tj
0 Tw 0.083 -10 Td
(factor. J Immunol 2000;164:5055-61.)Tj
-17.693 -10 Td
(15.)Tj
0.14999 Tw 17 0 Td
(Blann AD, Belgore FM, McCollum CN, Silverman S, Lip PL, Lip)Tj
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(GY)Tj
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(.V)Tj
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(ascular endothelial growth factor and its receptor, Flt-1, in the)Tj
0.2 Tw -19.321 -10 Td
(plasma of patients with coronary or peripheral atherosclerosis, or)Tj
0.002 -10 Td
[(T)62.625 (ype II diabetes. Clin Sci 2002;102:187-94.)]TJ
0 Tw -17.41 -10 Td
(16.)Tj
0.2 Tw 17 0 Td
(Kikuchi K, Kubo M, Kadono )Tj
0.41701 Tc 0 Tw 96.52 0 Td
(T,Y)Tj
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[(azawa N, Ihn H, )-99.875 (T)62.625 (amaki K.)]TJ
0.2 Tw -109.09 -10 Td
(Serum concentrations of vascular endothelial growth factor in)Tj
-0.166 -10 Td
(collagen diseases. Br J Dermatol 1998;139:1049-51.)Tj
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(17.)Tj
0.2 Tw 17 0 Td
(Preliminary criteria for the classification of systemic sclerosis )Tj
0.538 -10 Td
(\(scleroderma\). Subcommittee for Scleroderma Criteria of the)Tj
0 Tw -0.042 -10 Td
(American Rheumatism Association Diagnostic and Therapeutic)Tj
0.164 -10 Td
(Criteria Committee. Arthritis Rheum 1980;23:581-90.)Tj
-17.637 -10 Td
(18.)Tj
0.2 Tw 17 0 Td
(LeRoy EC, Black C, Fleischmajer R, et al. Scleroderma \(systemic)Tj
0.581 -10 Td
(sclerosis\): classification, subsets and pathogenesis. J Rheumatol)Tj
0 Tw 0.052 -10 Td
(1988;15:202-5.)Tj
-17.641 -10 Td
(19.)Tj
0.117 Tw 17 0 Td
(Clements PJ, Lachenbruch PA, Seibold JR, et al. Skin thickness)Tj
0.2 Tw 0.449 -10 Td
(score in systemic sclerosis: an assessment of interobserver )Tj
0.19 -10 Td
(variability in 3 independent studies. J Rheumatol 1993;20:1892-6.)Tj
0 Tw -17.6 -10 Td
(20.)Tj
0.2 Tw 17 0 Td
(Lovy M, MacCarter D, Steigerwald JC. Relationship between )Tj
0.164 Tw 0.584 -10 Td
(nailfold capillary abnormalities and organ involvement in systemic)Tj
0 Tw 0.037 -10 Td
(sclerosis. Arthritis Rheum 1985;28:496-501.)Tj
-17.521 -10 Td
[(21.)-875 (Marth )6.375 (T)62.625 (, Strober )-18.625 (W)]TJ
0.2 Tw 79.39 0 Td
(, Kelsall BL. High dose oral tolerance in )Tj
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(ovalbumin TCR-transgenic mice: systemic neutralization of IL-12)Tj
-0.109 -10 Td
[(augments TGF-beta secretion and )-36 (T)-281.125 (cell apoptosis. J Immunol)]TJ
-0.06 -10 Td
(1996;157:2348-57.)Tj
-17.391 -10 Td
(22.)Tj
0.2 Tw 17 0 Td
(Kaminski MJ, Majewski S, Jablonska S, Pawinska M. Lowered)Tj
0.393 -10 Td
(angiogenic capability of peripheral blood lymphocytes in )Tj
-0.041 -10 Td
(progressive systemic sclerosis \(scleroderma\). J Invest Dermatol)Tj
0 Tw 0.169 -10 Td
(1984;82:239-43.)Tj
-17.641 -10 Td
(23.)Tj
0.144 Tw 17 0 Td
(Koch AE, Litvak MA, Burrows JC, Polverini PJ. Decreased )Tj
0.2 Tw 0.523 -10 Td
(monocyte-mediated angiogenesis in scleroderma. Clin Immunol)Tj
0 Tw 0.031 -10 Td
(Immunopathol 1992;64:153-60.)Tj
246.415 628.75 Td
(24.)Tj
0.2 Tw 17 0 Td
(Majewski S, Skopinska-Rozewska E, Jablonska S, et al.)Tj
0.16901 Tw 0.713 -10 Td
(Modulatory effect of sera from scleroderma patients on )Tj
0 Tw -0.107 -10 Td
(lymphocyte-induced angiogenesis. Arthritis Rheum 1985;)Tj
0.073 -10 Td
(28:1133-9.)Tj
-17.613 -10 Td
(25.)Tj
0.2 Tw 17 0 Td
(Marczak M, Majewski S, Skopinska-Rozewska E, Polakowski I,)Tj
0.509 -10 Td
(Jablonska S. Enhanced angiogenic capability of monocyte-enriched)Tj
0.044 -10 Td
(mononuclear cell suspensions from patients with systemic )Tj
0 Tw 0.088 -10 Td
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-17.626 -10 Td
[(26.)-875 (Needleman BW. Increased expression of intercellular adhesion)]TJ
17.618 -10 Td
(molecule 1 on the fibroblasts of scleroderma patients. Arthritis)Tj
-0.037 -10 Td
(Rheum 1990;33:1847-51.)Tj
-17.581 -10 Td
(27.)Tj
0.2 Tw 17 0 Td
[(Gruschwitz M, Sepp N, Kofler H, )-0.25 (W)62.625 (ick G. Expression of class )]TJ
0.493 -10 Td
(II-MHC antigens in the dermis of patients with progressive)Tj
0 Tw 0.147 -10 Td
(systemic sclerosis. Immunobiology 1991;182:234-55.)Tj
-17.689 -10 Td
[(28.)-875 (Jimenez SA, Hitraya E, )-99.125 (V)124.875 (arga J. Pathogenesis of scleroderma.)]TJ
17.596 -10 Td
(Collagen. Rheum Dis Clin North Am 1996;22:647-74.)Tj
-17.39 -10 Td
(29.)Tj
0.125 Tw 17 0 Td
(Feghali CA, Bost KL, Boulware DW, Levy LS. Control of IL-6)Tj
0.2 Tw 0.473 -10 Td
(expression and response in fibroblasts from patients with systemic)Tj
0 Tw 0.006 -10 Td
(sclerosis. Autoimmunity 1994;17:309-18.)Tj
-17.577 -10 Td
(30.)Tj
0.117 Tw 17 0 Td
(Feghali CA, Bost KL, Boulware DW, Levy LS. Mechanisms of)Tj
0.2 Tw 0.55 -10 Td
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0.172 Tw -0.126 -10 Td
(fibroblasts cultured from affected skin sites of patients with )Tj
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-17.732 -10 Td
(31.)Tj
0.155 Tw 17 0 Td
(Galindo M, Santiago B, Rivero M, Rullas J, Alcami J, Pablos JL.)Tj
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0.052 -10 Td
(regulation of monocyte chemoattractant protein 1 expression.)Tj
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(Arthritis Rheum 2001;44:1382-6.)Tj
-17.522 -10 Td
(32.)Tj
0.2 Tw 17 0 Td
(Steinbrech DS, Mehrara BJ, Chau D, et al. Hypoxia upregulates)Tj
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[(VEGF production in keloid fibroblasts. Ann Plast Sur)-80.25 (g)]TJ
-0.108 -10 Td
(1999;42:514-9.)Tj
-17.391 -10 Td
[(33.)-875 (Bollinger A, Jager K, Siegenthaler )-29.875 (W)93.875 (. Microangiopathy of )]TJ
0.2 Tw 17.55 -10 Td
(progressive systemic sclerosis: Evaluation by dynamic fluorescence)Tj
0 Tw -0.03 -10 Td
[(videomicroscopy)63.25 (.)-218.75 (Arch Intern Med 1986;146:1541-5.)]TJ
-17.435 -10 Td
[(34.)-875 (Faller DV. Endothelial cell responses to hypoxic stress. Clin Exp)]TJ
17.488 -10 Td
(Pharmacol Physiol 1999;26:74-84.)Tj
-17.522 -10 Td
[(35.)-875 (Stevens CR, Blake DR, Merry P, Revell PA, Levick JR. )1.125 (A)]TJ
0.2 Tw 17.57 -10 Td
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0 Tw -0.186 -10 Td
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0.095 -10 Td
(34:1508-13.)Tj
-17.613 -10 Td
[(36.)-875 (Ceponis A, Konttinen YT, Mackevicius Z, et al. Aberrant )]TJ
17.699 -10 Td
[(vascularity and von )-42.75 (W)62.625 (illebrand factor distribution in inflamed)]TJ
-0.018 -10 Td
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-17.501 -10 Td
[(37.)-875 (Naughton D, Whelan M, Smith EC, )-86.5 (W)31.375 (illiams R, Blake DR,)]TJ
0.144 Tw 17.394 -10 Td
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0.2 Tw 0.034 -10 Td
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0 Tw -0.126 -10 Td
(proton nuclear magnetic resonance spectroscopy. FEBS Lett)Tj
0.196 -10 Td
(1993;317:135-8.)Tj
-17.641 -10 Td
(38.)Tj
0.117 Tw 17 0 Td
(Choy JC, Granville DJ, Hunt DW, McManus BM. Endothelial cell)Tj
0.2 Tw 0.581 -10 Td
(apoptosis: biochemical characteristics and potential implications for)Tj
-0.089 -10 Td
(atherosclerosis. J Mol Cell Cardiol 2001;33:1673-90.)Tj
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[(39.)-875 (Dimmeler S, Rippmann )-42.625 (V,W)-62.5 (eiland U, Haendeler J, Zeiher AM.)]TJ
0.2 Tw 17.463 -10 Td
(Angiotensin II induces apoptosis of human endothelial cells.)Tj
0.164 Tw -0.112 -10 Td
(Protective effect of nitric oxide. Circ Res 1997;81:970-6.)Tj
0 Tw -17.51 -10 Td
(40.)Tj
0.2 Tw 17 0 Td
(Lindner H, Holler E, Ertl B, et al. Peripheral blood mononuclear)Tj
0.664 -10 Td
(cells induce programmed cell death in human endothelial cells and)Tj
-0.219 -10 Td
(may prevent repair: role of cytokines. Blood 1997;89:1931-8.)Tj
0 Tw -17.284 -10 Td
[(41.)-875 (Hebbar M, Peyrat JP, Hornez L, Hatron PY, Hachulla E, Devulder)]TJ
0.2 Tw 17.305 -10 Td
(B. Increased concentrations of the circulating angiogenesis inhibitor)Tj
0 Tw 0.052 -10 Td
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0.127 -10 Td
(2000;43:889-93.)Tj
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0.812 Tw 53.286 243 Td
(growth factor, basic fibroblast growth factor, endothelin-1,)Tj
1.737 Tw 0.078 -12 Td
(and VEGF)Tj
/TT0 6.25 Tf
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(34)Tj
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(.)Tj
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2.118 Tw -58.394 -12 Td
(versible structural remodeling of the vasculature and the)Tj
0.147 Tw 0.022 -12 Td
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-0.21899 Tw 0.022 -12 Td
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0.429 Tw 0.198 -12 Td
[(production in several cell types. )27 (W)100.2 (e found a positive corre)-23.9 (-)]TJ
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(serum )Tj
0.179 Tc 32.688 0 Td
(levels )Tj
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[(of )-500 (VEGF )-525.3 (and )]TJ
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(T G F - \247 .)Tj
3.595 Tw -209.278 -12 Td
(Collectively, it appears that VEGF can be induced in)Tj
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[(response )-450 (to )-374.8 (chronic )-449.5 (hypoxia )-449.7 (caused )-424.7 (by )-375 (microvascular)]TJ
0.068 -12 Td
(damage and by TGF stimulation.)Tj
1.45799 Tw 11.924 -12 Td
(On the other hand, new capillaries are rarely seen and)Tj
2.172 Tw -11.978 -12 Td
(broad avascular areas are common in SSc, even at high)Tj
-0.229 Tw 0.02 -12 Td
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0.397 Tw 264.006 408 Td
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3.41901 Tw -0.05 -12 Td
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-0.22501 Tw 0.02 -12 Td
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(metabolism)Tj
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1.04 0 0 1.04 364.235 438.25 Tm
(35-37)Tj
/TT0 10 Tf
0.592 Tw 1 0 0 1 379.066 435 Tm
(. Microvascular toxicity by oxidative stress,)Tj
1.30099 Tw -61.801 -12 Td
[(tumor necrosis factor)25.9 (-)]TJ
/TT1 10 Tf
90.903 0 Td
(a)Tj
/TT0 10 Tf
[0.1 (, and angiotensin II)]TJ
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0 Tw 1.04 0 0 1.04 495.332 426.25 Tm
(38-40)Tj
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(, which are)Tj
1.295 Tw -193.252 -12 Td
[(increased in SSc, might contribute to the defective angio)3.3 (-)]TJ
1.71201 Tw 0.017 -12 Td
[(genesis of SSc. In addition, Hebbar)51 (,)]TJ
/TT2 10 Tf
156.17 0 Td
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/TT0 6.25 Tf
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(41)Tj
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(demonstrated)Tj
1.21899 Tw -186.128 -12 Td
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1.851 Tw 0.02 -12 Td
(endostatin were observed in patients with SSc, and were)Tj
0.321 Tw 0.027 -12 Td
(associated with digital gangrene. These results indicate that)Tj
0 Tw -0.052 -12 Td
[(the )-374.7 (imbalance )-423.9 (between )-374.5 (angiogenic )-424.2 (and )-374.8 (anti-angiogenic)]TJ
1.091 Tw -0.122 -12 Td
(factors also explains the capillary loss in SSc, even in the)Tj
0.25 Tw 0.024 -12 Td
(presence of high VEGF levels.)Tj
0 Tw 12.023 -12 Td
(In conclusion, serum VEGF levels in SSc were enhanced)Tj
1.955 Tw -12.043 -12 Td
(and correlated well with the extent of skin sclerosis and)Tj
2.651 Tw 0.025 -12 Td
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1.942 Tw 0.043 -12 Td
(inversely associated with capillary density in SSc. These)Tj
0.909 Tw -0.047 -12 Td
(findings suggest that skin sclerosis might contribute to the)Tj
0.60699 Tw 0.024 -12 Td
(elevation of serum VEGF, and that serum VEGF may be a)Tj
0.69501 Tw -0.069 -12 Td
[(surrogate indicator of capillary damage in SSc. The under)2.71 (-)]TJ
2.431 Tw 0.203 -12 Td
(lying mechanism of impaired angiogenesis even at high)Tj
0.25 Tw 0.012 -12 Td
(VEGF concentrations remains to be determined.)Tj
/TT3 10 Tf
0 Tw -0.224 -24 Td
(REFERENCES)Tj
/TT0 10 Tf
67.236 0 Td
(.)Tj
/TT0 8 Tf
-60.25 -10 Td
(1.)Tj
0.2 Tw 13 0 Td
(LeRoy EC. Increased collagen synthesis by scleroderma skin)Tj
0.65 -10 Td
(fibroblasts in vitro: a possible defect in the regulation or activation)Tj
0.027 -10 Td
(of the scleroderma fibroblast. J Clin Invest 1974;54:880-9.)Tj
0 Tw -13.608 -10 Td
(2.)Tj
0.172 Tw 13 0 Td
(Kahaleh MB. The role of vascular endothelium in the pathogenesis)Tj
0 Tw 0.656 -10 Td
(of connective tissue disease: endothelial injury, activation, )Tj
0.2 Tw -0.045 -10 Td
(participation and response. Clin Exp Rheumatol 1990;8:595-601.)Tj
0 Tw -13.444 -10 Td
(3.)Tj
0.2 Tw 13 0 Td
(Maricq HR, LeRoy EC. Patterns of finger capillary abnormalities in)Tj
0.3 -10 Td
[(connective tissue disease by \322wide-field\323 microscopy)65.25 (.)]TJ
0 Tw 175.524 0 Td
(Arthritis)Tj
-175.391 -10 Td
(Rheum 1973;16:619-28.)Tj
-13.581 -10 Td
(4.)Tj
0.2 Tw 13 0 Td
[(Maricq HR, LeRoy EC, D\325Angelo )31.875 (W)]TJ
0 Tw 119.754 0 Td
(A, et al. Diagnostic potential)Tj
0.2 Tw -119.223 -10 Td
(of in vivo capillary microscopy in scleroderma and related )Tj
0 Tw 0.093 -9.75 Td
(disorders. Arthritis Rheum 1980;23:183-9.)Tj
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(Figure 2.)Tj
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(Correlations between serum VEGF levels and modified Rodnan skin score \(\
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(factor-\247 \(TGF-\247\) levels \(B\) in patients with SSc.)Tj
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48.25 298.75 249.5 188 re
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249.5 0 0 190 48.25 298.75 cm
/Im2 Do
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BT
/TT2 8 Tf
0 Tw 54.364 292.25 Td
(Figure 3. )Tj
/TT0 8 Tf
31.386 0 Td
(Inverse correlations of serum VEGF levels with capillary density)Tj
-31.415 -10 Td
(\(total )Tj
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(capillary )Tj
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[(loops/3 )-562.375 (mm\) )-468.375 (as )]TJ
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(determined )Tj
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(by )Tj
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[(nailfold )-436.7375 (capillary)]TJ
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[(microscopy)63 (.)]TJ
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(Personal, non-commercial use only. The Journal of Rheumatology Copyrig\
ht \251 2003. All rights reserved.)Tj
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( )Tj
0 0.48627 0.77255 rg
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(www.jrheum.org)Tj
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(Downloaded on March 28, 2024 from )Tj
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