PubMed Health⌕ Search

Biomedical subjects

Jason Robarge

Publications and source records attributed to Jason Robarge.

6 recordsLinked to original sources
PubMed2007

Predicting asparaginase-associated pancreatitis.

BACKGROUND: Pancreatitis is a well-known, but little-understood complication of asparaginase. There is no predictor of who will develop asparaginase-associated pancreatitis (AAP). To better define this population, we present a retrospective analysis regarding AAP and provide a review of the relevant literature. METHODS: We systematically reviewed medical records of 254 asparaginase recipients during a 5-year period. Pancreatitis was defined and graded according to CTCAE v3.0. RESULTS: Pancreatitis was diagnosed in 48 (19%) patients. Thirty-three (13%) patients were identified as having AAP. Twelve cases occurred after Escherichia coli asparaginase and 20 followed PEG-asparaginase. Pancreatitis was independent of the individual or cumulative asparaginase dose. The interval to pancreatitis diagnosis was longer for PEG-asparaginase than E. coli asparaginase (P = 0.02). AAP was seen more frequently in patients receiving prednisone (P = 0.02) and daunomycin (P = 0.006) while less frequent with dexamethasone (P = 0.04). Other chemotherapy agents appeared to have no association with AAP. As observed by others, those with pancreatitis were older (P = 0.001), but the significance of this remains uncertain. CONCLUSIONS: This study emphasizes our inability to predict who will develop pancreatic toxicity from asparaginase and suggests that those at risk might have an unidentified genetic predisposition.

Antineoplastic Agents↗
PubMed2006

A mixture model-based discriminate analysis for identifying ordered transcription factor binding site pairs in gene promoters directly regulated by estrogen receptor-alpha.

MOTIVATION: To detect and select patterns of transcription factor binding sites (TFBSs) which distinguish genes directly regulated by estrogen receptor-alpha (ERalpha), we developed an innovative mixture model-based discriminate analysis for identifying ordered TFBS pairs. RESULTS: Biologically, our proposed new algorithm clearly suggests that TFBSs are not randomly distributed within ERalpha target promoters (P-value < 0.001). The up-regulated targets significantly (P-value < 0.01) possess TFBS pairs, (DBP, MYC), (DBP, MYC/MAX heterodimer), (DBP, USF2) and (DBP, MYOGENIN); and down-regulated ERalpha target genes significantly (P-value < 0.01) possess TFBS pairs, such as (DBP, c-ETS1-68), (DBP, USF2) and (DBP, MYOGENIN). Statistically, our proposed mixture model-based discriminate analysis can simultaneously perform TFBS pattern recognition, TFBS pattern selection, and target class prediction; such integrative power cannot be achieved by current methods. AVAILABILITY: The software is available on request from the authors. CONTACT: lali@iupui.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Algorithms↗
PubMed2006

HOXD10 M319K mutation in a family with isolated congenital vertical talus.

Congenital vertical talus (CVT) is a primary dislocation of the talonavicular joint that often occurs in neuromusculoskeletal syndromes, but may also be seen as an isolated abnormality. Six families with isolated CVT were ascertained. DNA was isolated from 21 affected individuals and 17 unaffected individuals from these families, as well as from five sporadic patients with CVT. Variable expressivity was noted in three families, manifesting as clubfoot in three individuals. Genome-wide linkage analysis generated a maximum two-point logarithm of odds score on chromosome 2q with D2S1353 (Zmax = 1.43 at theta(max) = 0.1), 17 Mb from the HOXD gene cluster. DNA from one affected individual of each family was subjected to mutational analysis of the HOXD10 gene. A single missense mutation was identified (M319K, 956T > A) in the homeodomain recognition helix of the HOXD10 gene that segregated with disease in one large British family. This mutation was recently described in a family of Italian descent with CVT and Charcot-Marie-Tooth deformity HOXD10 gene mutations were not identified in any of the other families or sporadic patients with CVT, suggesting that genetic heterogeneity underlies this disorder.

Chromosomes, Human, Pair 2↗
PubMed2005

Variable hand and foot abnormalities in family with congenital vertical talus and CDMP-1 gene mutation.

Isolated foot anomalies, including congenital vertical talus, were shown recently to occur in heterozygous carriers of CDMP-1 (cartilage-derived morphogenetic protein-1) gene mutations. Six families with isolated congenital vertical talus with apparent autosomal dominant inheritance were ascertained. DNA was isolated from 17 affected individuals and 24 unaffected individuals from these families and subjected to mutational analysis of the CDMP-1 gene. A missense mutation was identified (1312C>T) that results in an R438C substitution in the CDMP-1 active domain. This segregated with disease in one Northeren American family. Phenotypic variability in this family includes brachydactyly type C, clinodactyly, calcaneo valgus deformity, and congenital vertical talus. Metacarpophalangeal profiles (MCPPs) confirm incomplete penetrance in one family member. Hence, CDMP-1 mutations may be found in individuals with apparently isolated CVT, although careful examination of family members may reveal additional, subtle hand and foot abnormalities. However, mutations in CDMP-1 do not appear to be a frequent cause of isolated congenital vertical talus.

Bone Morphogenetic Proteins↗
PubMed2003

A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis.

Psoriasis (OMIM 177900) is a chronic inflammatory skin disorder of unknown pathogenesis affecting approximately 2% of the Western population. It occurs more frequently in individuals with human immunodeficiency virus, and 20-30% of individuals with psoriasis have psoriatic arthritis. Psoriasis is associated with HLA class I alleles, and previous linkage analysis by our group identified a second psoriasis locus at 17q24-q25 (PSORS2; ref. 7). Linkage to this locus was confirmed with independent family sets. Additional loci have also been proposed to be associated with psoriasis. Here we describe two peaks of strong association with psoriasis on chromosome 17q25 separated by 6 Mb. Associated single-nucleotide polymorphisms (SNPs) in the proximal peak lie in or near SLC9A3R1 (also called EBP50 and NHERF1) and NAT9, a new member of the N-acetyltransferase family. SLC9A3R1 is a PDZ domain-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family and is implicated in diverse aspects of epithelial membrane biology and immune synapse formation in T cells. The distal peak of association is in RAPTOR (p150 target of rapamycin (TOR)-scaffold protein containing WD-repeats). Expression of SLC9A3R1 is highest in the uppermost stratum Malpighi of psoriatic and normal skin and in inactive versus active T cells. A disease-associated SNP lying between SLC9A3R1 and NAT9 leads to loss of RUNX1 binding. This is the second example of loss of a RUNX1 binding site associated with susceptibility to an autoimmune disease. It also suggests defective regulation of SLC9A3R1 or NAT9 by RUNX1 as a susceptibility factor for psoriasis.

Arylamine N-Acetyltransferase↗