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Results for “association testing”

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At least 253 records · Page 14Linked to original sources
PubMed2001

Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element-binding protein expression in nucleus accumbens.

Drugs of abuse regulate the transcription factor cAMP response element-binding protein (CREB) in striatal regions, including the nucleus accumbens (NAc). To explore how regulation of CREB in the NAc affects behavior, we used herpes simplex virus (HSV) vectors to elevate CREB expression in this region or to overexpress a dominant-negative mutant CREB (mCREB) that blocks CREB function. Rats treated with HSV-mCREB in place conditioning studies spent more time in environments associated with cocaine, indicating increased cocaine reward. Conversely, rats treated with HSV-CREB spent less time in cocaine-associated environments, indicating increased cocaine aversion. Studies in which drug-environment pairings were varied to coincide with either the early or late effects of cocaine suggest that CREB-associated place aversions reflect increased cocaine withdrawal. Because cocaine withdrawal can be accompanied by symptoms of depression, we examined how altered CREB function in the NAc affects behavior in the forced swim test (FST). Elevated CREB expression increased immobility in the FST, an effect that is opposite to that caused by standard antidepressants and is consistent with a link between CREB and dysphoria. Conversely, overexpression of mCREB decreased immobility, an effect similar to that caused by antidepressants. Moreover, the kappa opioid receptor antagonist nor-Binaltorphimine decreased immobility in HSV-CREB- and HSV-mCREB-treated rats, suggesting that CREB-mediated induction of dynorphin (an endogenous kappa receptor ligand) contributes to immobility behavior in the FST. Exposure to the FST itself dramatically increased CREB function in the NAc. These findings raise the possibility that CREB-mediated transcription within the NAc regulates dysphoric states.

Animals↗
PubMed2003

Positive response to ice water test associated with high-grade bladder outlet obstruction in patients with benign prostatic hyperplasia.

OBJECTIVES: To elucidate the clinical significance of detrusor overactivity (DO) that is probably due to C-fiber activation caused by bladder outlet obstruction (BOO), we examined the responses to the ice water test (IWT) in patients with benign prostatic hyperplasia (BPH) and assessed the results with reference to the clinical manifestations and urodynamic findings. METHODS: A total of 127 patients without neurologic disease, who were older than 50 years of age, with an International Prostate Symptom Score of 8 points or greater and a quality of life index of 2 or more points, were enrolled in this study. We tested the response to ice water instillation by monitoring the intravesical pressure in all cases and assessed the results with reference to the findings of International Prostate Symptom Score and quality of life index questionnaires, BOO indexes, 48-hour frequency volume charts, prostate volume, and data from free-flowmetry and pressure flow studies for detecting DO. Twenty patients with neurogenic bladder dysfunction underwent IWT as a control group. RESULTS: The responders to the IWT accounted for 14 (70%) of the 20 patients with neurogenic bladder dysfunction and 35 (27%) of the 127 patients without neurologic disease. All of these responders showed DO on the pressure flow studies. The patients without neurologic disease who responded to the IWT had higher BOO indexes than did the nonresponders and had a smaller volume at a maximal desire to void on the urodynamic studies. The largest single-voided volume recorded from the 48-hour frequency volume charts was also smaller for the responders than for the nonresponders. CONCLUSIONS: The patients with BPH clearly showed that DO was mainly due to active C-fibers stimulated by high-grade BOO and that DO was a cause of urgency and frequency-related symptoms with decreased bladder capacity. It will be necessary to assess the inhibitory effect of capsaicin on DO caused by activation of C-fibers and the reversibility of C-fiber activation after surgical treatment for BPH, so that the criteria for decision-making for the treatment of BPH may be clarified with the aid of the IWT.

Administration, Intravesical↗
PubMed1988

False-positive secretin-KABI provocation test associated with achlorhydria.

Two patients with chronic abdominal pain and fasting hypergastrinemia had increases in serum gastrin of 440 and 300 pg/ml after injection of 2 U/kg Secretin-KABI. Both subsequently proved to have pentagastrin-fast achlorhydria. Intragastric instillation of 0.1 N HCl suppressed serum gastrin concentration by greater than 60%. In both, the pancreas was normal by sonography or computed tomography (CT) scan and at laparotomy in one. Both are currently asymptomatic 12 and 18 months later. We conclude that achlorhydria may be associated after injection of Secretin-KABI with a false-positive rise in fasting serum gastrin concentration of greater than 200 pg/ml and that gastric analysis for hypochlorhydria should be performed before secretin provocation testing.

Achlorhydria↗
PubMed2004

A von Willebrand's factor genomic nucleotide variant and polymerase chain reaction diagnostic test associated with inheritable type-2 von Willebrand's disease in a line of german shorthaired pointer dogs.

Heritable, type-2 von Willebrand's disease (vWD) was studied in a line of German Shorthaired Pointers (GSPs) in which some members had a nucleotide variant in exon 28 of the von Willebrand factor (VWF) gene. A polymerase chain reaction (PCR) diagnostic test for the nucleotide variant was developed to establish the disorder's mode of inheritance and to eliminate it from the line. Thirty-six of the 49 GSPs in the line, 14 unrelated GSP controls, and 71 unrelated dogs of various breeds were tested for the presence of the variant nucleotide. All the dogs with a vWF antigen deficiency (<70% of normal) were either homozygous or heterozygous for the nucleotide variant. The variant was not located in any tested dog in the line or outside of the line with a vWF antigen value greater than 68%. Of the GSPs in the line tested, two were homozygous for the variant, 15 were heterozygous, and 19 were variant free. The collective evidence of this and other studies is consistent with the variant nucleotide being the cause of the type-2 vWD in this line of GSPs and German Wirehaired Pointers. The PCR diagnostic test for the variant nucleotide was successfully used to select and produce progeny that were variant free and vWD free. This test should be effective in the subsequent elimination of this same variant from other lines of dogs.

Amino Acid Sequence↗
PubMed1997

Autoimmune hemolytic anemia and positive Coombs test associated with ulcerative colitis.

OBJECTIVES: To estimate the frequency of autoimmune hemolytic anemia and Coombs positivity without overt hemolysis in ulcerative colitis, to determine possible subsets of patients with ulcerative colitis susceptible to this complication, and to assess the efficacy of the applied therapeutic modalities. METHODS: Three hundred and two patients with ulcerative colitis treated at the University Hospital of Heraklion, Crete, over a 6-yr period were included. Within this group, a subgroup of 152 patients were studied prospectively for the presence of a positive direct Coombs test. RESULTS: Autoimmune hemolytic anemia was diagnosed in five of 302 patients with ulcerative colitis (1.7%). One more patient developed Coombs-positive hemolytic anemia, attributed to sulfasalazine. A positive Coombs test without evidence of hemolysis was found in three of 152 patients (2%). The mean age of all Coombs-positive patients was 50.5 yr, and there was a definitive male preponderance (male: female, 2:1). Autoimmune hemolytic anemia occurred during active colitis in all cases. The mean time between the onset of colitis and the diagnosis of autoimmune hemolytic anemia was 17 months. Three of five patients with autoimmune hemolytic anemia (60%) and seven of nine of all Coombs-positive patients (77.7%) had total colitis. All patients with autoimmune hemolytic anemia were treated initially with large doses of corticosteroids. Three of five (60%) had good hematological responses. One patient responded to the addition of azathioprine, and one underwent splenectomy and proctocolectomy. CONCLUSIONS: In this study, the frequency with which autoimmune hemolytic anemia was associated with ulcerative colitis was higher than in previous reports. The complication occurred early in the course of colitis and was related to activity and extent of the disease. In contrast to others studies, we found a preponderance of males. Although corticosteroids and/or immunosuppressive therapy was successful in most of our cases, one patient required surgery.

Adolescent↗
PubMed2005

Association testing of the protein tyrosine phosphatase 1B gene (PTPN1) with type 2 diabetes in 7,883 people.

Protein tyrosine phosphatase (PTP)-1B, encoded by the PTPN1 gene, inactivates the insulin signal transduction cascade by dephosphorylating phosphotyrosine residues in insulin signaling molecules. Due to its chromosomal location under a chromosome 20 linkage peak and the metabolic effects of its absence in knockout mice, it is a candidate gene for type 2 diabetes. Recent studies have associated common sequence variants in PTPN1 with type 2 diabetes and diabetes-related phenotypes. We sought to replicate the association of common single nucleotide polymorphisms (SNPs) and haplotypes in PTPN1 with type 2 diabetes, fasting plasma glucose, and insulin sensitivity in a large collection of subjects. We assessed linkage disequilibrium, selected tag SNPs, and typed these markers in 3,347 cases of type 2 diabetes and 3,347 control subjects as well as 1,189 siblings discordant for type 2 diabetes. Despite power estimated at >95% to replicate the previously reported associations, no statistically significant evidence of association was observed between PTPN1 SNPs or common haplotypes with type 2 diabetes or with diabetic phenotypes.

Base Sequence↗
PubMed1999

False-positive pregnancy test associated with gonadoblastoma.

Gonadoblastomas are known to be hormonally active tumors that occur in streak or dysgenetic gonads of patients with intersex abnormalities. Several reports document their ability to produce beta-human chorionic gonadotropin (HCG), but none have documented an elevated peripheral serum beta-HCG. We report on the case of a patient with pure gonadal dysgenesis with XY karyotype who was found to have an elevated peripheral serum beta-HCG after a positive pregnancy test. Knowledge of gonadoblastoma's potential to elevate serum beta-HCG levels may prevent unnecessary searches for other causes.

Adolescent↗
PubMed2005

On the sample size requirement in genetic association tests when the proportion of false positives is controlled.

With respect to the multiple-tests problem, recently an increasing amount of attention has been paid to control the false discovery rate (FDR), the positive false discovery rate (pFDR), and the proportion of false positives (PFP). The new approaches are generally believed to be more powerful than the classical Bonferroni one. This article focuses on the PFP approach. It demonstrates via examples in genetic association studies that the Bonferroni procedure can be more powerful than the PFP-control one and also shows the intrinsic connection between controlling the PFP and controlling the overall type I error rate. Since controlling the PFP does not necessarily lead to a desired power level, this article addresses the design issue and recommends the sample sizes that can attain the desired power levels when the PFP is controlled. The results in this article also provide rough guidance for the sample sizes to achieve the desired power levels when the FDR and especially the pFDR are controlled.

Algorithms↗
PubMed2004

Quantitative association tests of immune responses to antigens of Mycobacterium tuberculosis: a study of twins in West Africa.

There is now considerable evidence that host genetic factors are important in determining the outcome of infection with Mycobacterium tuberculosis (MTB). The aim of this study was to assess the role of several candidate genes in the variation observed in the immune responses to MTB antigens. In-vitro assays of T-cell proliferation, an in-vivo intradermal delayed hypersensitivity response; cytokine and antibody secretions to several mycobacterial peptide antigens were assessed in healthy, but exposed, West African twins. Candidate gene polymorphisms were typed in the NRAMP1, Vitamin D receptor, IL10, IL4, IL4 receptor and CTLA-4 genes. Variants of the loci IL10 (-1082 G/A), CTLA-4 (49 A/G) and the IL4 receptor (128 A/G) showed significant associations with immune responses to several antigens. T-cell proliferative responses and antibody responses were reduced, TNF-alpha responses were increased for subjects with the CTLA-4 G allele. The T-cell proliferative responses of subjects with IL10 GA and GG genotypes differed significantly. IL4 receptor AG and GG genotypes also showed significant differences in their T-cell proliferative responses to MTB antigens. These results yield a greater understanding of the genetic mechanisms that underlie the immune responses in tuberculosis and have implications for the design of therapeutic interventions.

Adolescent↗
PubMed2006

Evaluating the thresholds of abnormal second trimester multiple marker screening tests associated with intra-uterine growth restriction.

Our objective was to evaluate the optimal thresholds for unexplained abnormal multiple marker screening (MMS) results that are associated with intrauterine growth restriction (IUGR). This was a case-control study from our perinatal database. MMS analyte levels (multiples of median [MoM]) of cases with IUGR (birthweight < 5th percentile for gestational age) were compared with a control group without IUGR. Pregnancies with fetal anomalies were excluded. Biochemical markers evaluated include alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3). Using receiver operating characteristic curves, the optimal thresholds of MMS (OTMs) associated with IUGR were determined. We identified 255 (12.3%) cases with IUGR and complete MMS records from the database. These were compared with 1785 controls without IUGR randomly selected from our perinatal database in a 1:7 ratio. The OTMs associated with IUGR were AFP > 2.0 MoM (odds ratio [OR] = 2.3; 95% confidence interval [CI], 1.4 to 3.7), hCG > 2.5 MoM (OR = 1.8; 95% CI, 1.1 to 3.2) and uE3 < 0.9 MoM (OR = 2.7; 95% CI, 2.0 to 3.7). The sensitivity, specificity, and positive and negative predictive values for predicting IUGR in the presence of at least one abnormal MMS were 46, 66, 11, and 90%, respectively. Elevated AFP > 2.0 MoM and hCG > 2.5 MoM were the most specific markers for MMS, with specificity of 94 and 95%, respectively. When all three analytes were abnormal, the specificity for predicting IUGR increased to 99%. Abnormal MMS results are associated with IUGR. As a screening tool for IUGR, the biochemical markers were associated with poor sensitivity. Elevated AFP and hCG, however, were highly specific in predicting IUGR. The provided thresholds could be useful in designing policies regarding women who would benefit most from sonographic screening for IUGR.

Adult↗