A candidate precursor to serous carcinoma that originates in the distal fallopian tube

The tubal fimbria is a common site of origin for early (tubal intraepithelial carcinoma or TIC) serous carcinomas in women with familial BRCA1 or 2 mutations (BRCA+). Somatic p53 tumour suppressor gene mutations in these tumours suggest a pathogenesis involving DNA damage, p53 mutation, and progressive loss of cell cycle control. We recently identified foci of strong p53 immunostaining-termed 'p53 signatures'-in benign tubal mucosa from BRCA+ women. To examine the relationship between p53 signatures and TIC, we compared location (fimbria vs ampulla), cell type (ciliated vs secretory), evidence of DNA damage, and p53 mutation status between the two entities. p53 signatures were equally common in non-neoplastic tubes from BRCA+ women and controls, but more frequently present (53%) and multifocal (67%) in fallopian tubes also containing TIC. Like prior studies of TIC, p53 signatures predominated in the fimbriae (80-100%) and targeted secretory cells (HMFG2 + /p73-), with evidence of DNA damage by co-localization of gamma-H2AX. Laser-capture microdissected and polymerase chain reaction-amplified DNA revealed reproducible p53 mutations in eight of 14 fully-analysed p53 signatures and all of the 12 TICs; TICs and their associated ovarian carcinomas shared identical mutations. In one case, a contiguous p53 signature and TIC shared the same mutation. Morphological intermediates between the two, with p53 mutations and moderate proliferative activity, were also seen. This is the first report of an early and distinct alteration in non-neoplastic upper genital tract mucosa that fulfils many requirements for a precursor to pelvic serous cancer. The p53 signature and its malignant counterpart (TIC) underline the significance of the fimbria, both as a candidate site for serous carcinogenesis and as a target for future research on the early detection and prevention of this disease.     

Search for bipolar disorder susceptibility loci: The application of a modified genome scan concentrating on gene‐rich regions

Conducting genome wide screens for evidence of genetic linkage has become a well‐established method for identifying regions of the human genome harboring susceptibility loci for complex disorders. For bipolar disorder, a number of such studies have been performed, and several regions of the genome have potentially been implicated in the disorder. The classic design for a genome screen involves examining polymorphic genetic markers spaced at regular intervals throughout the genome, typically every 10 cM, for evidence of linkage. An alternative design, based on the observation that genes do not appear to be evenly distributed, was proposed, enabling the number of markers examined in a genome wide screen to be reduced. This article describes the application of such a modified screen to a collection of 48 Irish families with bipolar disorder, comprising a total of 82 affected sib‐pairs. From the results obtained a number of regions are highlighted for further study. One of these regions (17q11.1‐q12) coincides with the location of a candidate gene, the serotonin transporter, whereas others concur with the findings of published studies. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:728–732, 2000. © 2000 Wiley‐Liss, Inc.     

Coexistence of myasthenia gravis and serological markers of neurological autoimmunity in neuromyelitis optica

We systematically evaluated the frequency of neurological disorders and muscle and neural autoantibodies in 177 patients with neuromyelitis optica (NMO) and in 250 control subjects (173 healthy; 77 multiple sclerosis, MS, patients). An excess of myasthenia gravis (MG, 2%), and muscle‐type acetylcholine receptor antibody (11%) was detected among NMO patients. The presence of neural or muscle autoantibodies was more common in NMO patients (34%) than in MS patients or healthy controls (7%), P < 0.0001. The coexistence of NMO and MG should be considered in atypical or refractory presentations of either disorder. © 2008 Wiley Periodicals, Inc. Muscle Nerve 39: 87–90, 2009     

Investigating the construct validity of the SPAI-C: comparing the sensitivity and specificity of the SPAI-C and the SAS-A

Investigates the construct validity of the Social Phobia and Anxiety Inventory for Children (SPAI-C) by comparing its sensitivity and specificity with another self-report measure of social anxiety, the Social Anxiety Scale for Adolescents (SAS-A). Participants were 252 adolescents (124 males and 128 females) 13-17 years old. Adolescents completed the SPAI-C and the SAS-A and were interviewed using the Anxiety Disorders Interview Schedule for DSM-IV: Child Version (ADIS-IV:C). Parents were also interviewed and composite diagnoses were formed. Youth were classified as socially phobic or non-anxious based on these composite diagnoses. By comparing clinical cutoff scores with diagnostic group classification, the sensitivity and the specificity of the SPAI-C and SAS-A were compared. Results indicated that the SPAI-C was a more sensitive measure than the SAS-A (61.5% vs. 43.6%) providing evidence of the scale's construct validity. The two measures were similar with regard to specificity (82.7% for both). Implications of these results for assessment and research are discussed.