Genome-wide scan identifies novel modifier loci of acromegalic phenotypes for isolated familial somatotropinoma.

Isolated familial somatotropinoma (IFS) accounts for 18% of familial isolated pituitary adenoma (FIPA) cases. Recently, germline mutations of the aryl hydrocarbon receptor-interacting protein gene (AIP) have been found in families with pituitary adenoma predisposition, FIPA, and IFS. In this study, we investigate the AIP mutation status and perform a genome-wide scan to search for the modifier regions of acromegalic phenotypes in an IFS family of 31 aborigines from Borneo. Complete endocrine diagnosis and data could not be collected due to logistical and cultural reasons. AIP mutation screening was carried out by direct sequencing and the genome-wide scan was performed using 400 microsatellites. Non-parametric linkage analysis was performed to obtain the logarithm of odds (LOD) scores. A novel AIP frameshift mutation in exon 4 (c.500delC) (p.P167HfsX3) was identified in all members with acromegalic features, as well as in 15 members without acromegalic features, revealing incomplete penetrance of AIP. The data showed that patients with the same mutation may express acromegalic features of differing severity, suggesting the existence of modifier genes. The highest LOD score of 2.2 was obtained near D19S571 (19q13.41). We also found weak linkages on chromosomes 3q28, 8q12.1, and 21q22.13, with LOD scores of 1.1, 1.8, and 1.4 respectively. Our results show the first genome-wide scan that identifies novel modifier loci for acromegalic phenotypes in an IFS family. Identification of modifier loci may provide further insight into the disease mechanism and explain the clinical variability observed in its patients.

Novel application of depleted fullerene soot (DFS) as support of catalysts for low-temperature reduction of NO with CO.

Depleted fullerene soot (DFS) with fullerene residue content of about 2.2-3.2% are investigated in order to elucidate the possibility for their use as support of catalysts in low-temperature reduction of NO with CO. Bimetalic copper-cobalt and copper-manganese oxides supported on DFS are prepared. All samples are characterized by chemical analysis, XRD, SEM, IR spectroscopy, XPS, nitrogen adsorption measurements. The two DFS supported bimetallic catalysts manifest a high activity towards the reduction of NO with CO at temperatures below 150 degrees C, the CuCo/DFS being the more active one. The peculiarity of the support DFS predetermines the porous texture of the catalysts. The occurrence of a specific metal-support interaction favors the formation of the mixed oxide spinels CuCo2O4 and Cu1.5 Mn1.5 O4 that are responsible for the enhanced activity.

Beta zeolite colloidal nanocrystals supported on mesoporous MCM-41.

Zeolite-based composite materials prepared by the embedding of the beta zeolite nanophase from aqueous colloidal solution into matrices of preformed Si(Al)MCM-41 mesoporous molecular sieves have been characterized by different methods (XRD, SEM, FTIR, N2 adsorption, and TPD of NH3). Their potential as catalysts for toluene disproportionation has been compared to mechanical mixtures of freeze-dried nanobeta crystallites with Si(Al)MCM-41 mesoporous materials. It is found that the zeolite catalyst efficiency is not substantially changed by the presence of mesopores belonging to the matrix. It is suggested that formation of intergrown aggregates from the colloidal nanobeta particles provides own highly developed textural mesoporosity that makes the contribution of the diffusional alleviation of the support negligible.

Comparative study on removal efficiency of impregnated carbons for hydrogen cyanide vapors in air depending on their phase composition and porous textures.

Activated carbons impregnated with Cu and Zn have been prepared. They are characterized and investigated with respect to their efficiency in the removal of HCN vapors in air. The effect of negligible amounts of Cr and pyridine present in the Cu-Zn impregnants has also been tested. The removal efficiency against HCN vapors in air of the samples obtained is proved to be comparable with that of standard ASC Whetlerite carbon. Carbons impregnated with Cu and Zn and containing additional components in their active phases appear to be advantageous as an alternative of the ASC Whetlerite carbons.

Copper oxide supported on carbon modified alumina as catalyst for reduction of NO with CO.

Carbon-modified alumina-supported copper oxide catalysts have been investigated. The samples have been prepared by modified incipient techniques. The gamma-Al(2)O(3)-supported carbon phase permits sufficient modification of the chemical nature of the support surface in the region of low carbon contents without changing the specific surface area and the mesoporous character of the samples as compared to those of initial gamma-Al(2)O(3). In addition, the surface oxygen groups of the carbon phase, similar to the hydroxyl groups of the alumina surface, affect the formation and type of copper oxide phase. It has been established that the catalysts investigated have high activity in the reduction of NO with CO, the highest activity belonging to the Cu17AC/AL catalyst, which contains the largest amount of carbon. This sample is also active with respect to the direct decomposition of NO.

Clinical and genetic studies of Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant cancer syndrome characterised by benign skin tumours, renal tumours, and spontaneous pneumothorax. The gene has been mapped to chromosome 17p11.2 and recently identified, expressing a novel protein called folliculin. We report the clinical and genetic studies of four sporadic BHD cases and four families with a total of 23 affected subjects. Haplotype analysis of these families using BHD linked markers showed they did not share the same affected alleles, excluding common ancestry. Mutation analysis of the BHD gene identified two germline mutations on exon 11 (c.1733insC and c.1733delC) in three of four families as well as two of four sporadic cases. A novel somatic mutation, c.1732delTCinsAC, was detected in a BHD related chromophobe renal carcinoma. Our results confirmed the (C)8 tract in exon 11 as a mutational hot spot in BHD and should always be considered for future genetic testing. Our observation also indicated that the second hit (of Knudson's two hit theory) in some BHD related tumours is in the form of somatic mutation rather than LOH. In a large French family in which eight affected subjects carry the c.1733delC mutation, a phenocopy who has multiple episodes of spontaneous pneumothorax was identified. A total of five mutation carriers (aged between 37 to 66) did not have any evidence of BHD features, suggesting either reduced penetrance or late age of onset of the disease. In addition, six out of eight affected subjects who have positive germline mutation have confirmed neoplastic colonic polyps, indicating that colorectal neoplasia is an associated feature of BHD in some families. Our studies have observed several interesting genetic features in BHD: (1) the poly (C) tract in exon 11 as a mutational hot spot; (2) the existence of phenocopy; (3) reduced penetrance or late age of onset of disease; (4) association with colorectal neoplasia in some families; and (5) somatic mutation instead of LOH as the second hit in BHD tumours.