Biomedical subjects

W Ju

Publications and source records attributed to W Ju.

39 records · Page 3Linked to original sources

PubMedDate not supplied

Scrapie strain infection in vitro induces changes in neuronal cells.

PC12 cells, in the presence of nerve growth factor (NGF), support replication of the mouse-derived scrapie strains 139A and ME7, with the former yielding 100-1000-fold higher levels of infectivity. Infectivity remained cell-associated and cells did not show any gross morphological alterations, although changes were observed by electron microscopy in the form of an increased number of lipid droplets in 139A-infected cultures. Analysis of phospholipid metabolism in 139A infected cells indicated that scrapie replication did not change the inositol phosphate levels, but did stimulate phosphoinositide synthesis. Replication was not detected in PC12 cells infected with either the hamster-derived 263K or rat-derived 139R scrapie strains. Since scrapie-infected cultures did not exhibit cell death or any gross changes, any scrapie-induced effects would probably be manifested in nonvital cellular functions. When compared to controls, infection with the 139A scrapie strain resulted in decreased activity of the cholinergic pathway-related enzymes, as well as the GABA synthetic pathway; however, the adrenergic pathway was unaffected by scrapie infection. The effects of the 139A scrapie strain on the cholinergic system appeared to be dose-dependent and were first detected prior to the detection of scrapie agent replication in these cells. No neurotransmitter-related enzymatic changes were detected in 263K- or 139R-infected PC12 cells. The enzymatic changes observed in ME7-infected PC12 cells and in Chandler agent-infected mouse neuroblastoma cells suggest that the significant changes in neurotransmitter levels in cultures exhibiting low infectivity titers must involve factors other than, but not excluding, replication of the agent. The role of additional factors is also suggested in studies of protein kinase C activity in 139A- and 139R-infected PC12 cells. These studies emphasize the value of the PC12 cell model system in examining the scrapie strain-host cell interaction and, in addition, support the concept of variation among scrapie strains.

Acetylcholinesterase↗

PubMedDate not supplied

Heterogeneity of late-infantile neuronal ceroid lipofuscinosis.

PURPOSE: Late-infantile neuronal ceroid lipofuscinosis (LINCL), an autosomal recessively inherited lysosomal storage disorder characterized by autofluorescent inclusions and rapid progression of neurodegeneration, is due to CLN2 gene mutations. However, CLN2 mutation analysis has failed to identify some clinically diagnosed "late-infantile" NCL cases. This study was conducted to further characterize genetic heterogeneity in families affected by LINCL. METHODS: DNA mutations in the CLN1, CLN2, and CLN3 genes that underlie INCL (infantile NCL), LINCL, and JNCL (juvenile NCL), respectively, were studied with molecular analyses. RESULTS: A total of 252 families affected by childhood NCL were studied. Of 109 families clinically diagnosed as having LINCL, 3 were determined to have either INCL or JNCL by identification of mutation(s) in CLN1 or CLN3. Six families diagnosed initially as having JNCL were found to have LINCL based on the finding of mutations in the CLN2 gene. In addition, several novel mutations were identified. CONCLUSIONS: Clinical and genetic heterogeneity of LINCL was demonstrated in nine LINCL families studied.

Aminopeptidases↗

PubMedDate not supplied

CAG repeat length in exon 1 of the androgen receptor gene is related to age of diagnosis but not germ line BRCA1 mutation status in ovarian cancer.

It has been postulated that androgens, through their interaction with androgen receptors (AR), may play an important role in the development of ovarian cancer. Exon 1 of the AR gene contains three highly polymorphic trinucleotide repeats. The length of the (CAG)n repeat segment 1 is inversely correlated with the transactivation function of the AR. Recent studies have shown that BRCA1 may function as an AR coregulator or coactivator and play positive roles in androgen-induced cell death in cancer cells as well as other androgen/AR target organs. We hypothesize that the AR gene, involved in endocrine signaling, may modify BRCA1-associated ovarian cancer risk. To test this hypothesis, potential associations between the (CAG)n repeat length, germ line BRCA1 mutation status, and age of diagnosis for ovarian cancer were investigated. One hundred and eleven ovarian cancer patients (27 hereditary and 84 sporadic) were included. All the cases were allelotyped for CAG repeat length and genotyped for mutations in the BRCA1 gene by direct sequencing. No association between CAG repeat length and BRCA1 mutation status was identified. Furthermore, there were no differences between hereditary and sporadic ovarian cancer in the number of (CAG)n repeats of the short allele (P= 0.336), long allele (P= 0.875), or average allele length (P= 0.550). However, ovarian cancer patients from both groups (hereditary and sporadic) who carried any AR allele of (CAG)n < or = 22 repeats were diagnosed on average 8.17 years (95% confidence interval [1.3, 15.0]) earlier than the patients whose shortest AR allele (CAG)n was >22 (P= 0.020). In conclusion, it is suggested that the CAG repeat length in AR exon 1 may affect the age of diagnosis of ovarian cancer but does so independent of germ line BRCA1 carrier status.

Adult↗