SHORT NOW STATURE - Nature

323

SHORT N O W STATURE - PSYCHOLOOICAL RESPONSE TO OROWTH HORMONE TREATMENT. L.D.Vose, J.Mulligan, E.S.Mc Caughey, P . R . B e t t s , Southampton U n i v e r s i t y H o s p i t a l s , Southampton, SO9 4XY, UK

INSULIN-LIm GKOW'I'It FACTOK BINDING PRO'I'I'INS (ICt7UPs) IN CONDITIONED MEDlUhl IY110MIIIJMAN NEUROBI.ASTOMA CELL LINES. K. Massoud*. M A ~ ~ ~ ~ ~ ~ c l ~ ~ x i e o ~ P e IC, ru~~elli***, S. Ilcrnxdi~u*. S. Ci.t~ll;lral~~**. Fcdcrlci* uld U Uohclsrini'* I)cp~nrncnts ol *Uiology. '*P,sdulrics, md ***ExperimenLI1 Mcdicinc, "Tur Vergata" U~llvcrsily,K U I I II-(X117J ~. Italy. A variety of cancer ccll lines Ildve k e n sla~wnto prcduce I(;FUPs, to dntc. I~owevcr. Ew data exlst on human ncurc~hla\lonra ccll lincs.Tls prcscncc ol ICFUPs was invcstigaled, in basal co~ld~liulrr and allcr add~t~on o l rctII1oIc acid (IIA), in conditioned nlcdlulll (CM) fmnl two llulllal~ neuruhlastu~n,~all lilro: SK-N-UE(2). a l i ~ ~l~igllly c wmWvc to RA thllcrentialing ;~cliuo,and UE(2)-M17. FHIIIY .xlbitive 10 RA. TIE cells wcre grown in MEM Eagle nldilied IIAMS-F12 (50/50 vlv), and PCS (12 %>), and allowed to reach 8093 co~rllucr~cy. RA (5 pM) was added lor 24, 72, 2nd 120 IIOII~S. During OK: 1 s t 24 hours uf inc~h~tlllll, llle cclla, alter two wasllillgs, wcre Il;i~lrlcrredillto relulllI . CM I ~ I I I I Urc last 24 liour, w;~s collccsd, dyali~ed.aid lree ~ I ~ U I I Serum-lrec concentrated 125 lirlrer by ultr.dillrauon and lyopl~ili~nli(~~l The ~ ~ l l l p l ewere h abrcssed Ib lutal protein content (UCA) and 3LXJ pg applied to SDS-PAGE, and alulyred by westerrl ligmd blotting (WLQ). Raholabelled ICFUPs were visualil.cd hy autoradiograplly and quantitated hy densitomcuy. SK-N-UE(2) CM was also incubntcd will1 IrunlaIl serum m d U~ens s c s x d by WLU fur tllc prewncc ufprotcolytic actibity :~gainrt%rum IGFUPs. Two llrajur hands with an approxil~v.ncM, ol about 37.5% a~ld25K were fuund ill hot11 cell linch. III SK-N-BE(2) tlle 37.5K balld deercased coosidelahly ;~ltcr72 Ilr exposure to RA (5L11h dccrese at deruttomclnc analyhis). Nu proteolylic acllvily aglinsl seruel ICFBPs w& h o d in the CM. Our results dc~llonslnti:tllc prcsctlcc ol lwu I'orllls ol ICFBPs in CM lrn~lltwo dilli.rcnt hurlran ocur~~blahtu~~la cell lines. T l e sccretioa ol 37 5K IGFBP In SKN-BE(?) sccnrs to he nl(ldulatcd by KA. suggesting a role ul'tl~cICF-ICFBP system in RA~ ~ s h ~ccll t c difterent~auon. d

We have r e c e n t l y shown t h e p s y c h o s o c i a l s t a t u s of s h o r t normal p r e - p u b e r t a l c h i l d r e n t o b e unimpaired p r o v i d e d s e l e c t r o n b i a s i s a v o i d e d . I n o r d e r t o e v a l u a t e t h e p s y c h o l o g i c a l e f f e c t s of t r e a t m e n t i n t h i s community based g r o u p , 15 s h o r t normal c h i l d r e n 2 500 Kg; n o signs of dysmorphic dlse a s e ; stature below the 3rd centtle for chronological a g e (CA), height veloclty below the 25th centile for bone a g e (BA); n o signs of puberty; growlh hormone res p o n s e to pharmacolog~calstimulation >10 nglml, no evidence of organlc d ~ s e a s e ; treatment with dally subcutaneous a d m ~ n ~ s t r a t ~ oofn sGH a t the d o s a g e of 12-16 Ul/m2/week MAIN OUTCOME MEASURES: Eight pre-treatment auxological vanables: HV Increase after six months o f therapy. fi HV increase >2.5 cmly w a s consldered a s a posit~veresponse RESULTS Thirty-tv.0 (58 2%) pallents were responslve uslng unlvar~ateanalysis, the v a r ~ a b l e sfound to have predictive value (pcO 001) were h e ~ g h tvelocity (SD for CA) and bone a g e (SD). T h e s e variables were employed In the mult~var~ate dlscrimlnant a n a l y s ~ s The equatlon obtained w a s . Score=l 09x1 - 0 83x2 + 0 19 (Xl=HV, X?=BA) Using this scorlng system we ~ t y91 0% in predicting responsiveo b t a ~ n e da sensitivity of 95.7% a n d a s p e c ~ f ~ c of n e s s to GH (xZ with Yates correction=36 78, p