MUTYH exon 7 and 13 mutations associated with colorectal cancer (MAP syndrome) are not commonly associated with sporadic pancreatic cancer.

BACKGROUND: Biallelic MUTYH exon 7 and 13 mutations are associated with a high frequency of somatic K-ras gene guanine to thymine transversion mutations at codon 12 position 1 in MUTYH-associated polyposis patients who have increased risk of colon cancer. The purpose of this study was to determine if a similar association exists between exon 7 and 13 MUTYH mutations and pancreatic cancer. METHODS: Genomic DNA samples from 140 patients with pancreatic cancer and 107 controls were sequenced and analyzed for mutations in each of MUTYH exons 7 and 13. RESULTS: Two patients with pancreatic cancer were identified as heterozygous for a MUTYH Y165C germline mutation. One pancreatic cancer patient was heterozygous for a G382D mutation and an additional patient was heterozygous for a novel missense mutation, L406M. No biallelic mutations were identified in pancreatic cancer or control subjects. CONCLUSION: Despite their association with somatic K-ras mutations and an increased risk of colorectal cancer in MUTYH-associated polyposis patients, MUTYH exon 7 and 13 mutations were not associated with pancreatic cancer in our cohort.

Psychological correlates of purging disorder as compared with other eating disorders: an exploratory investigation.

OBJECTIVE: Keel et al. introduced the diagnostic category of purging disorder (PD), an eating disorder characterized by recurring purging behaviors in the absence of objective binges. The current study sought to investigate psychological correlates among individuals with a lifetime diagnosis of PD as compared to those with other eating disorders, and those with no eating disorder. METHOD: The current sample included 294 ethnically diverse undergraduate women. Subjects diagnosed with different types of eating disorders [i.e., anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD)] were compared to one another, as well as to individuals with no eating disorder on a variety of indices. RESULTS: Women with PD displayed similar levels of drive for thinness as women with AN and BED. Individuals with BN and BED exhibited anxiety levels significantly higher than those with PD. Those with PD displayed levels of impulsivity that were significantly higher than those of individuals with AN or BED, but significantly lower than those of individuals with BN. They also displayed similar levels of bulimic symptoms as those with AN and BED; however, analysis of item 53 on the EDI revealed that those with PD had similar levels of purging ideation as those with BN. Women with any eating disorder diagnosis were more likely to have a comorbid Axis I disorder than women in the non-eating disorder group. CONCLUSION: Our data replicated and extended the findings of Keel et al. and gave further support to the validity and distinctiveness of PD.

Exercise caution: over-exercise is associated with suicidality among individuals with disordered eating.

We conducted four studies to examine the relationship between over-exercise and suicidality. Study 1 investigated whether over-exercise predicted suicidal behavior after controlling for other eating disorder behaviors in a patient sample of 204 women (144 with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) Bulimia Nervosa [BN]). Study 2 tested the prospective association between over-exercise and acquired capability for suicide (ACS) in a sample of 171 college students followed for 3-4 weeks. Study 3 investigated whether pain insensitivity accounted for the relationship between over-exercise and ACS in a new sample of 467 college students. Study 4 tested whether ACS accounted for the relationship between over-exercise and suicidal behavior in a sample of 512 college students. In Study 1, after controlling for key covariates, over-exercise was the only disordered eating variable that maintained a significant relationship with suicidal behavior. In Study 2, Time 1 over-exercise was the only disordered eating behavior that was associated with Time 2 ACS. In Study 3, pain insensitivity accounted for the relationship between over-exercise and ACS. In Study 4, ACS accounted for the relationship between over-exercise and suicidal behavior. Over-exercise appears to be associated with suicidal behavior, an association accounted for by pain insensitivity and the acquired capability for suicide; notably, this association was found across a series of four studies with different populations.

Do major depressive disorder and dysthymic disorder confer differential risk for suicide?

BACKGROUND: Although there has been a tremendous amount of research examining the risk conferred for suicide by depression in general, relatively little research examines the risk conferred by specific forms of depressive illness (e.g., dysthymic disorder, single episode versus recurrent major depressive disorder [MDD]). The purpose of the current study was to examine differences in suicidal ideation, clinician-rated suicide risk, suicide attempts, and family history of suicide in a sample of outpatients diagnosed with various forms of depressive illness. METHODS: To accomplish this aim, we conducted a cluster analysis using the aforementioned suicide-related variables in a sample of 494 outpatients seen between January 2001 and July 2007 at the Florida State University Psychology Clinic. Patients were diagnosed using DSM-IV criteria. RESULTS: Two distinct clusters emerged that were indicative of lower and higher risk for suicide. After controlling for the number of comorbid Axis I and Axis II diagnoses, the only depressive illness that significantly predicted cluster membership was recurrent MDD, which tripled an individual's likelihood of being assigned to the higher risk cluster. LIMITATIONS: The use of a cross-sectional design; the relatively low suicide risk in our sample; the relatively small number of individuals with double depression. CONCLUSIONS: Our results demonstrate the importance of both chronicity and severity of depression in terms of predicting increased suicide risk. Among the various forms of depressive illness examined, only recurrent MDD appeared to confer greater risk for suicide.

Serum immunoglobulin G fraction 4 levels in pancreatic cancer: elevations not associated with autoimmune pancreatitis.

CONTEXT: Autoimmune pancreatitis is an uncommon, inflammatory disease of the pancreas that presents with clinical features, such as painless jaundice and a pancreatic mass, similar to those caused by pancreatic cancer. Patients with autoimmune pancreatitis frequently have elevated serum immunoglobulin G fraction 4 (IgG4) levels, and their pancreatic tissue may show IgG4-positive plasma cell infiltration. It is imperative to differentiate autoimmune pancreatitis from pancreatic cancer because autoimmune pancreatitis typically responds to corticosteroid treatment. A previous Japanese study reported that serum IgG4 greater than 135 mg/dL was 97% specific and 95% sensitive in predicting autoimmune pancreatitis. OBJECTIVE: To prospectively measure serum IgG4 levels in pancreatic cancer patients to ascertain whether increased levels might be present in this North American population. DESIGN: We collected blood samples and phenotypic information on 71 consecutive pancreatic cancer patients and 103 healthy controls who visited our clinics between October 2004 and April 2006. IgG4 levels were determined using a single radial immunodiffusion assay. A serum IgG4 level greater than 135 mg/dL was considered elevated. RESULTS: Five cancer patients had IgG4 elevation, with a mean serum IgG4 level of 160.8 mg/dL. None of our cancer patients with plasma IgG4 elevation demonstrated evidence of autoimmune pancreatitis. One control subject demonstrated elevated serum IgG4 unrelated to identified etiology. CONCLUSIONS: As many as 7% of patients with pancreatic cancer have serum IgG4 levels above 135 mg/dL. In patients with pancreatic mass lesions and suspicion of cancer, an IgG4 level measuring between 135 and 200 mg/dL should be interpreted cautiously and not accepted as diagnostic of autoimmune pancreatitis without further evaluation.

Genetic counseling for nonsyndromic pancreatitis.

An appreciation for the background of disease, not to mention the medical management of individuals, may be significantly affected by testing for mutations and genetic variants associated with pancreatitis. Pretest and posttest counseling are essential for patients and families to benefit fully from genetic testing for a susceptibility to develop pancreatitis. The clinician, often working directly with a qualified genetic counselor, must ensure that patients and families appreciate the benefits and limitations of genetic tests, that results are interpreted accurately, and that patients understand implications of information for both their medical care and personal decisions. This article focuses on the approach to genetic counseling for pancreatitis and implications of recent advances.

The multifaceted role of distress tolerance in dysregulated eating behaviors.

OBJECTIVE: Few empirical studies have examined the potential role of affect in dysregulated eating. The authors hypothesized that distress tolerance would predict EDI-Bulimia, even when controlling for several covariates, including depressive and anxiety symptoms, and all four subscales of the UPPS Impulsive Behavior Scale. Additionally, the authors predicted low levels of distress tolerance would interact with high levels of urgency to predict EDI-Bulimia. Finally, the authors predicted that distress tolerance would mediate the previously reported relationship between anxiety sensitivity and EDI-Bulimia. METHOD: A sample of undergraduates (N = 200) filled out a series of questionnaires pertaining to the variables of interest, including the Eating Disorder Inventory, UPPS Impulsive Behavior Scale, Distress Tolerance Scale, and Anxiety Sensitivity Index. RESULTS: All three hypotheses were supported by the data. CONCLUSION: Authors suggest that deficits in distress tolerance might play a significant role in the etiology and maintenance of bulimic symptoms.

Taxometric analysis: introduction and overview.

OBJECTIVE: The purpose of this article is to provide an introduction to taxometric procedures, and a set of mathematical tools utilized to examine the latent structure of constructs as they occur in nature (i.e., categorical versus dimensional). METHOD: Taxometric procedures have the potential to inform the Diagnostic and Statistical Manual of Mental Disorders (DSM) conceptualization of eating disorders, and provide unique information about the construct validity of the current diagnostic scheme. Existing empirical studies which utilize taxometric procedures are reviewed, and the current DSM diagnostic categories are evaluated in terms of how well they square with empirical findings. CONCLUSION: Finally, the implications of the taxometrics literature for future DSM classification of eating disorders, as well as guidelines for future areas of research, are discussed.

Nuclear export of the oncoprotein v-ErbA is mediated by acquisition of a viral nuclear export sequence.

v-ErbA, an oncogenic derivative of the thyroid hormone receptor alpha (TRalpha) carried by the avian erythroblastosis virus, contains several alterations including fusion of a portion of avian erythroblastosis virus Gag to its N terminus, N- and C-terminal deletions, and 13 amino acid substitutions. Nuclear export of v-ErbA occurs through a CRM1-mediated pathway. In contrast, nuclear export of TRalpha and another isoform, TRbeta, is CRM1-independent. To determine which amino acid changes in v-ErbA confer CRM1-dependent nuclear export, we expressed a panel of green and yellow fluorescent protein-tagged mutant and chimeric proteins in mammalian cells. The sensitivity of subcellular trafficking of these mutants to leptomycin B (LMB), a specific inhibitor of CRM1, was assessed by fluorescence microscopy. Our data showed that a nuclear export sequence resides within a 70-amino acid domain in the C-terminal portion of the p10 region of Gag, and in vitro binding assays demonstrated that Gag interacts directly with CRM1. However, a panel of ligand-binding domain mutants of v-ErbA lacking the Gag sequence exhibited greater nuclear localization in the presence of LMB, suggesting that the various amino acid substitutions/deletions may cause a conformation shift, unmasking an additional CRM1-dependent nuclear export sequence. In contrast, the altered DNA-binding domain of the oncoprotein did not contribute to CRM1-dependent nuclear export. Heterokaryon experiments revealed that v-ErbA did not undergo nucleocytoplasmic shuttling when the CRM1 export pathway was blocked by LMB treatment, suggesting that the ability to follow the export pathway used by TRalpha has been lost by the oncoprotein during its evolution. Our findings thus point to the intriguing possibility that acquisition of altered nuclear export capabilities contributes to the oncogenic properties of v-ErbA.