Biomedical subjects

J S Verducci

Publications and source records attributed to J S Verducci.

5 recordsLinked to original sources

PubMed2002

Pharmacogenomic analysis: correlating molecular substructure classes with microarray gene expression data.

Genomic studies are producing large databases of molecular information on cancers and other cell and tissue types. Hence, we have the opportunity to link these accumulating data to the drug discovery processes. Our previous efforts at 'information-intensive' molecular pharmacology have focused on the relationship between patterns of gene expression and patterns of drug activity. In the present study, we take the process a step further-relating gene expression patterns, not just to the drugs as entities, but to approximately 27,000 substructures and other chemical features within the drugs. This coupling of genomic information with structure-based data mining can be used to identify classes of compounds for which detailed experimental structure-activity studies may be fruitful. Using a systematic substructure analysis coupled with statistical correlations of compound activity with differential gene expression, we have identified two subclasses of quinones whose patterns of activity in the National Cancer Institute's 60-cell line screening panel (NCI-60) correlate strongly with the expression patterns of particular genes: (i) The growth inhibitory patterns of an electron-withdrawing subclass of benzodithiophenedione-containing compounds over the NCI-60 are highly correlated with the expression patterns of Rab7 and other melanoma-specific genes; (ii) the inhibitory patterns of indolonaphthoquinone-containing compounds are highly correlated with the expression patterns of the hematopoietic lineage-specific gene HS1 and other leukemia genes. As illustrated by these proof-of-principle examples, we introduce here a set of conceptual tools and fluent computational methods for projecting directly from gene expression patterns to drug substructures and vice versa. The analysis is presented in terms of the NCI-60 cell lines and microarray-based gene expression patterns, but the concept and methods are broadly applicable to other large-scale pharmacogenomic database sets as well. The approach (SAT for Structure-Activity-Target) provides a systematic way to mine databases for the design of further structure-activity studies, particularly to aid in target and lead identification.

Algorithms↗

PubMed1998

Study IV: concurrent validity of the DSM-IV revised Children's Interview for Psychiatric Syndromes (ChIPS).

OBJECTIVE: To determine validity of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) (DSM-IV) revised Children's Interview for Psychiatric Syndromes (ChIPS) in inpatient children and adolescents. METHOD: Participants were 47 psychiatric inpatients 6-12 (n = 23) and 12 to 18 years of age (n = 24). ChIPS was administered to all participants. The Diagnostic Interview for Children and Adolescents-Revised-Child Version (DICA-R-C) was administered to 40 participants. Discharge diagnoses were recorded for all participants. Kappas, low base rate kappas, and percentage agreement were used to assess diagnostic agreement between sources for 18 disorders. RESULTS: ChIPS/DICA-R-C kappas could not be calculated for two disorders because of 100% agreement on their absence. Fourteen of 16 kappas were significant (p < 0.05). The remaining 2 of 16 disorders had 98% agreement (kappax = 0.494, p < 0.157). When ChIPS results were compared with discharge diagnoses, sensitivity for each disorder averaged 70%, whereas specificity averaged 84%. When disagreements occurred between all three sources, ChIPS was somewhat more likely than DICA-R-C to agree with discharge diagnoses (27% versus 22%). Analysis were repeated for children and adolescents, then for boys and girls. Boys and children had fewer significant ChIPS and DICA-R-C kappa coefficients compared with girls and adolescents; this appeared to be related to the fewer number of diagnoses they endorsed. ChIPS/clinician agreement was similar for boys and girls as well as for children and adolescents. Administration time was less for ChIPS than for DICA-R-C (p < 0.08). CONCLUSION: Psychometric properties of the DSM-IV revised ChIPS compare favorably with that of other structured interviews. ChIPS appears to work well for adolescents as well as children.

Adolescent↗

PubMed1998

Study V: Children's Interview for Psychiatric Syndromes (ChIPS): psychometrics in two community samples.

OBJECTIVE: To determine sensitivity and specificity of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) (DSM-IV) revised Children's Interview for Psychiatric Syndromes (ChIPS) in nonclinical samples. METHOD: Participants were 40 children 6 to 18 years of age from a community sample (n = 22) or a bereaved sample 1 to 2 years following the death of a parent (n = 18). ChIPS and the Diagnostic Interview for Children and Adolescents (DICA-R-C) were administered in a Latin Square design. A consensus conference (CC) of child psychopathology experts determined presence or absence of syndromes or symptoms after reviewing assessment materials not including ChIPS. RESULTS: Sensitivity is commensurate with epidemiologic base rates (17.5% of participants endorsed at least one syndrome). Low base rate kappas and percentage agreement were calculated to determine agreement on symptom or syndrome endorsement for 20 disorders. For syndrome analyses, over half the kappas could not be calculated due to 100% agreement on absence. For symptom analyses, 3 of 20 kappas could not be calculated (100% agreement on absence). Eleven of ChIPS/DICA-R-C symptom kappas were significant (p < 0.04), 2 of 17 had 95% agreement (kappas, p < 0.08), and 4 of 17 had 97.5% agreement (kappas, p < 0.16). Thirteen of 17 ChIPS/CC symptom kappas were significant (p < 0.04), and 4 of 17 had 97.5% agreement (kappas, p < 0.16). CONCLUSION: ChIPS' psychometrics in nonclinical samples compares favorably with that of other structured interviews.

Adolescent↗

PubMed1998

Changes in measured resting energy expenditure after Roux-en-Y gastric bypass for clinically severe obesity are not related to bypass limb-length.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) for clinically severe obesity (CSO) results in a 'paradoxical' response of the measured resting energy expenditure (MREE) in which the MREE remains within the predicted range based upon the Harris-Benedict (HB) equation, despite a significant decrease in caloric intake to 500-1000 kcal/day. The mechanism for this response is unknown. A study was undertaken to determine whether the changes in MREE after RYGB are related to limb-length of the gastric bypass. METHODS: A prospective clinical trial of varying limb-lengths based on body mass index (BMI) in patients having RYGB for CSO. The records of patients who underwent RYGB for CSO and had MREE measured at baseline, 6 months and 12 months postoperation were reviewed. MREE was performed using a Med Graphics CCM system after an overnight fast or at least 4 hours after a light meal, and a 30 minute rest in a supine position in a neutral environment, on the same day of the week between the hours of 10 a.m. and 4 p.m. Patients were selected for RYGB in accordance with NIH recommendations. RYGB was performed in a standardized fashion with the Roux limb-length varied as follows: (A) BMI < or = 51 kg/m2 - 75 cm limb (n = 20); (B) BMI < or = 51 kg/m2 - 150 cm limb (n = 16); (C) BMI > or = 51 kg/m2 - 150 cm limb (n = 18); or (D) BMI > or = 51 kg/m2 - 250 cm limb (n = 6). RESULTS: Data from 60 patients (nine male, 51 female; mean age 39 years; mean baseline BMI 51.5 +/- 10 kg/m2; mean baseline weight 145 +/- 32 kg) were analyzed. There were no significant differences in MREE or percentage HB-predicted energy expenditure between the groups. CONCLUSIONS: These data suggest that the observed changes in MREE following RYGB for CSO are not related to the limb-length of the bypass.

Adult↗

PubMed1995

A symmetric analysis of paired rankings with application to temporal patterns of hormonal concentration.

Mallows (1957, Biometrika 44, 114-130) introduced a simple model to describe the distribution of subjects' rankings of the items from some fixed set. Both Feigin (1992, in Probability Models and Statistical Analyses for Ranking Data, 75-91. New York: Springer-Verlag) and Critchlow and Verducci (1992, Journal of the Royal Statistical Society, Series C 41, 17-29) have considered an asymmetric extension of this model, designed to analyze the distribution of subjects' post-treatment rankings, conditional on their pretreatment rankings. Here a symmetric extension is introduced and is used to analyze the joint distribution of paired rankings associated with the patterns of prolactin hormonal response of wife-husband pairs during the course of a marital conflict. Locally most powerful tests are developed to check for independence of the wife and husband responses, and for differences in their divergence from a theoretical pattern of response. Additionally, conditional on the rankings of one group (e.g., the wives), the locally most powerful test of an affinity for the theoretical pattern in the other group (e.g., the husbands) turns out to be closely related to the test given by Critchlow and Verducci.

Adult↗