The subcellular localization of the epidermal growth factor receptor (EGFR) in polarized epithelial cells profoundly affects the activity of the intracellular signaling pathways activated after EGF ligand binding. Therefore, changes in EGFR localization and signaling are implicated in various human diseases, including different types of cancer. We have performed the first in vivo EGFR localization screen in an animal model by observing the expression of the EGFR ortholog LET-23 in the vulval epithelium of live C. elegans larvae. After systematically testing all genes known to produce an aberrant vulval phenotype, we have identified 81 genes regulating various aspects of EGFR localization and expression. In particular, we have found that ERM-1, the sole C. elegans Ezrin/Radixin/Moesin homolog, regulates EGFR localization and signaling in the vulval cells. ERM-1 interacts with the EGFR at the basolateral plasma membrane in a complex distinct from the previously identified LIN-2/LIN-7/LIN-10 receptor localization complex. We propose that ERM-1 binds to and sequesters basolateral LET-23 EGFR in an actin-rich inactive membrane compartment to restrict receptor mobility and signaling. In this manner, ERM-1 prevents the immediate activation of the entire pool of LET-23 EGFR and permits the generation of a long-lasting inductive signal. The regulation of receptor localization thus serves to fine-tune the temporal activation of intracellular signaling pathways.
The aim of this study was to investigate the effect of bleaching treatment with 10% carbamide peroxide in white spot lesionsaffected teeth treated with caries infiltration technique. Cylindrical enamel-dentin specimens were prepared from bovine incisors. Baseline color measurement was performed by a spectrophotometer using the CIE L*a*b* system and specimens were divided in two groups: Sound (S) and demineralized (D) enamel. The group S was divided into two subgroups (n = 20): Nonbleached (SNB) and bleached (SB). The group D was divided in four subgroups (n = 20): Nonbleached (DNB), bleached (DB), resin infiltrated/nonbleached (DRNB) and resin infiltrated/ bleached (DRB). Artificial white spot lesions were produced in all groups D, simulating the presence of active lesions in labial tooth surface, and after demineralization, caries infiltration with low viscosity resin was performed in the resin infiltrated groups. In the bleached groups, 10% carbamide peroxide gel was applied (2 hours/day for 14 days). New color measurements were performed after bleaching and color alteration was calculated using E parameter. Data were submitted to oneway ANOVA and Tukey test (5%). There were significant differences among groups when E was evaluated (p = 0.001). Means (± standard deviation) and results of Tukey test were: SNB (2.53 ± 0.48)a; DRNB (2.88 ± 1.03)ab; DNB (3.15 ± 0.65) ab; DRB (2.88 ± 1.03)bc; SB (4.33 ± 0.93)cd; DB (5.27 ± 1.33)d. The bleaching treatment with 10% carbamide peroxide produced no significant color alteration in demineralized enamel treated with resin infiltration technique.
Sincc 1971, 7 children with AL ( 5 ALL, 2 ANL) have been transplanted a t the University Children's Hospital. 2 of the donors wcre i d e n t i c a l twins, 4 wcre s i b l i n g s , 1 the HLA-identical father. Thc ALL children were transplanted a f t e r 2 to 4 relapses, the ANL e a r l i c r . 3 were i n C R , 2 in PR and 2 i n relapse. A l l got i n t r n s i v e chemotherapy, and 5 t o t a l body i r r a d i a t i o n (TBI).3 died of early complications, a l l others showed a take. 1 boy ( W / O TBI) relapsed a f t e r 2 months, 1 with an AML had a t e s t i c u l a r relapse a f t e r 4 months, but i s i n CR again since 10+ months under chcmothcrapy. The most recent p a t i e n t shovs a normal bone marrow, and no acute G v H , a f t e r 1 month. 1 boy s t a y s i n CR since 40+ mo.Our r e s u l t s suggest, and those from S e a t t l e show t h a t bone marrow transplantation in AL i s f e a s i b l e . As i n t e r s t i t i a l pneumonia and relapse a r e the most important obstacles t o success, the children should be in remission ( t o s t a r t with a lower tumor load) and gct an intensive c y t o s t a t i c pretreatment, but -to avoid pneumonitis -should not get more than 750 r t o the lungs. The enzyme 5-formyl t e t r a h y d r o f o l a t e cyclodehydrase c o n v e r t s 5-formyl t e t r a h y d r o f o l a t e t o 5,lO-methenyl t e t r ahydrofo1ate.A method has been devised f o r t h e cytochemical demonstration of t h i s enzyme u s i n g 5-formyl t e t r a h y d r o f o l at e a s substrate.The a c t i v i t y of t h e enzyme has been s t u d i e d i n l e u k o c y t e s of c h i l d r e n with a c u t e 1eukaemia.Comparison of enzymatic a c t i v i t y i n t h e same t y p e s of c e l l s showed no s i g n i f i c a n t v a r i a t i o n between normal c o n t r o l s and t h e p a t i e n t s w i t h a c u t e 1eukaemia.The enzyme a c t i v i t y was found t o i n c r e a s e w i t h c e l l m a t u r a t i o n and was s t r o n g l y p o s i t i v e i n polymorphonuclear l e u k o c y t e s and eosinophils.The b l a s t c e l l s of p a t i e n t s w i t h a c u t e leukaemia were weakly p o s i t i v e o r negative. T h i s f i n d i n g i s of i n t e r e s t s i n c e t h e b l a s t c e l l s a r e c a p a b l e of division.Two p o p u l a t i o n s of lymphocyt e s were observedrone p o s i t i v e w i t h a few g r a n u l e s and one negative.Methotrexote decreased enzyme a c t i v i t y i n some p a t i e n t s ; t h e enzyme may be a t a r g e t f o r t h e a c t i o n of f o l i c a c i d a n t a g o n i s t s . T h e a b s olute number a n d t l~e p r o p o r t i o n of I & a n d I g I I -s u r f ace-bcarin;: 1 1 -c e l l s a n d t l~e " n u l l " -c e l l s w e r e e l e v at e d . I n c l~i l d r c n r r i t l~o u t i n c r e a s e d i n f e c t i o n s t i l e p r o p o r t i o n o f T -c e l l s o n l y was d c c r c a s e d . K i t h r e -{:art1 t o c l u r ; i t i o n , s c v c r i t : -o r d i s e a s e , s o r t of a n t i -::en, s e r u~.~ I c -: : -l c v c l s , c o s ...
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