Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders

Innes AM, Boycott KM, Puffenberger EG, Redl D, MacDonald IM, Chudley AE, Beaulieu C, Perrier R, Gillan T, Wade A, Parboosingh JS. A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders. Bardet‐Biedl syndrome (BBS) is a multisystem genetically heterogeneous disorder, the clinical features of which are largely the consequence of ciliary dysfunction. BBS is typically inherited in an autosomal recessive fashion, and mutations in at least 14 genes have been identified. Here, we report the identification of a founder mutation in the BBS2 gene as the cause for the increased incidence of this developmental disorder in the Hutterite population. To ascertain the Hutterite BBS locus, we performed a genome‐wide single nucleotide polymorphism (SNP) analysis on a single patient and his three unaffected siblings from a Hutterite family. The analysis identified two large SNP blocks that were homozygous in the patient but not in his unaffected siblings, one of these regions contained the BBS2 gene. Sequence analysis and subsequent RNA studies identified and confirmed a novel splice site mutation, c.472‐2A>G, in BBS2. This mutation was also found in homozygous form in three subsequently studied Hutterite BBS patients from two different leuts, confirming that this is a founder mutation in the Hutterite population. Further studies are required to determine the frequency of this mutation and its role, if any, in the expression of other ciliopathies in this population.     

Chromosome imbalances in thyroid follicular neoplasms: a comparison between follicular adenomas and carcinomas

The underlying genetic events associated with follicular thyroid tumorigenesis are still ill defined. In this study, we performed a screening for chromosome imbalances by comparative genomic hybridization (CGH) in a group of 12 follicular adenomas (FAs) and 20 follicular carcinomas (FTCs) previously characterized by conventional cytogenetics and flow cytometry analysis. In general, a great similarity was observed between the CGH profiles of the FAs and FTCs. In both benign and malignant tumors, a combination of gains affecting 5, 7, 12, 17, 19, and 20 was observed. Chromosome 7 was the most frequently affected chromosome, with three regions of consensus gains: 7p11-12, 7q11.3-q21, and 7q31. Recurrent gains of chromosomes 5 and 12 involved 5p11, 5p15, 5q13-q22, 5q21-q23, 12p11, and 12q11-q12. DNA sequence losses were also observed in both tumor groups. Chromosomal arms deleted in at least five of the neoplasms were (in order of frequency): in adenomas, 15q, 2p/2q, 3q, 6p/6q, 11q, and 22q; and in FTCs, 3p, 2p, 8q, 1p, 2q, 3q, 6q, 8p, 9p, 11q, 13q, 6p, and 18q. The statistical evaluation of the CGH data demonstrated that 15q loss was significantly associated with FA. Two regions of minimal common loss were defined by CGH at 15: 15q11-q21 and 15q26-qter. The identification of these regions provides a basis for further molecular studies.     

Specific primers for rapid detection of Microsporum audouinii by PCR in clinical samples

This report describes application of PCR fingerprinting to identify common species of dermatophytes using the microsatellite primers M13, (GACA)4, and (GTG)5. The initial PCR analysis rendered a specific DNA fragment for Microsporum audouinii, which was cloned and sequenced. Based on the sequencing data of this fragment, forward (MA_1F) and reverse (MA_1R) primers were designed and verified by PCR to establish their reliability in the diagnosis of M. audouinii. These primers produced a singular PCR band of 431 bp specific only to strains and isolates of M. audouinii, based on a global test of 182 strains/isolates belonging to 11 species of dermatophytes. These findings indicate these primers are reliable for diagnostic purposes, and we recommend their use in laboratory analysis.     

The biography of Mary E. O'Sullivan: an early American headache specialist

The aim of this study was to review the life of Mary E. O'Sullivan and to summarize her important contributions to the study of migraine. Mary E. O'Sullivan underwent extensive training to become a neurologist at a time when only 5% of women in America were physicians. She published five papers on migraine. In a 1936 Journal of the American Medical Association article, she described a patient with ergotamine overuse headache and recommended that daily doses of oral ergotamine should be avoided. Three years later she described migraine as a 'complex' syndrome with multiple causes and multiple cures. Mary E. O'Sullivan, an ambitious female headache specialist of the 1930s, was an early advocate of the use of ergotamine to treat migraine, yet she was one of the first to report ergotamine overuse headache. Although her life was short, her research, knowledge and ambition at a time when women had limited opportunities in medicine have left a mark.     

Benign salivary gland tumors: A cytogenetic study of 21 cases

Cytogenetic findings of 21 benign salivary gland tumors, including 14 pleomorphic adenomas, 5 Warthin's tumors, 1 myoepithelioma, and 1 cystadenoma, are reported. The present study confirms that pleomorphic adenomas characteristically have highly specific rearrangements involving only a few chromosome regions (3p21, 8q12 and 12q13–15) which suggests their specific role in the mixed tumors genesis. Warthin's tumors also show nonrandom numerical and structural alterations that were concurrent in one of the cases studied. To our knowledge no cytogenetic data are available in myoepitheliomas and cystadenomas. The former reveals a normal karyotype and the latter shows only clonal numerical alterations (gain of chromosomes 2 and 18). © 1995 Wiley-Liss, Inc.     

Diagnosis of intrapericardial tumor in an infant by two-dimensional echocardiography

Summary Two-dimensional echocardiography is a useful noninvasive tool for diagnosing intrapericardial tumors as a cause of respiratory distress or abnormal cardiomediastinal shadow on chest x-ray. Early recognition of these tumors within the pericardium is important since surgical removal is often curative. Cardiac cineangiography is unnecessary to delineate further the tumor and should be reserved for those in which associated intracardiac defects are suspected.     

Quality assessment of the public water supply in Nova Iguaçu, Rio de Janeiro

This study proposes to develop methodologies for public water supply quality control by implementing evaluation and control mechanisms and enhancing environmental health surveillance decision-making. These objectives were based on data for waterborne diseases recorded at the Rio de Janeiro State Health Department. We selected the following neighborhoods: Posse (1st Township) and Caioaba (5th Township), with dissimilar situations, allowing us to produce a model of water supply coverage in the Municipality of Nova Igua?u, Rio de Janeiro State. The study underscored the poor quality of the water supply in the two townships, since 61% of the samples were positive on bacteriological examination, showing the undesirable effects of differential sanitation, especially in developing countries.