Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation.

Background: MEN1 mutations can inactivate or disrupt menin function and are leading to multiple endocrine neoplasia type 1, a rare heritable tumor syndrome.

Case Presentation: We report on a MEN1 family with a novel heterozygous germline mutation, c.674delG; p.

Effect of Isothermal Conditions on the Charge Trapping/Detrapping Parameters in e-Beam Irradiated Thermally Aged XLPE Insulation in SEM.

The effect of isothermal conditions on the trapping/detrapping process of charges in e-beam irradiated thermally aged XLPE insulation in scanning electron microscopy (SEM) has been investigated. Different isothermal conditions ranging from room temperature to 120 °C are applied on both unaged and aged XLPE samples (2 mm thick) by a suitable arrangement associated with SEM. For each applied test temperature, leakage, and influence currents have been measured simultaneously during and after e-beam irradiation.

Study of temperature effects on the electrical behavior of polypropylene-clay nanocomposites submitted to electron beam irradiation in a SEM.

Charge transport and electron emission properties in polypropylene and its nanocomposites filled with nanoclay particles submitted to an electron irradiation, in a Scanning Electron Microscope (SEM), are investigated using induced displacement and leakage currents. The measurements have been performed at various temperatures ranging from 20°C to 75°C at a primary beam energy of 20keV and a primary beam current of 1nA with the aim to highlight the effect of temperature and nanoclay content on these properties. The results show, at a given temperature, that the incorporation of clay in polypropylene (PP) matrix paradoxically leads to a concomitant increase in the electrical conductivity and the charge accumulated.

Multiple endocrine neoplasia type 1 associated with a new germline Men1 mutation in a family with atypical tumor phenotype.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant hereditary disorder associated with the development of endocrine tumors due to reduced expression of the tumor suppressor protein menin. Recent studies indicate a general role of menin in carcinogenesis, affecting the prevalence and clinical course of common non-endocrine tumors such as breast cancer, hepatocellular carcinoma and melanoma. Here we report a new germline missense mutation of Men1 in a German family with atypical tumor phenotype over three generations.

Prevalence and clinical spectrum of nonsecretory medullary thyroid carcinoma in a series of 839 patients with sporadic medullary thyroid carcinoma.

Background: Medullary thyroid carcinoma (MTC) is characterized by the synthesis and secretion of calcitonin (Ct). MTC without Ct secretion has been reported on rare occasions. The aim of this study was to analyze the prevalence and clinical spectrum of nonsecretory MTC in two tertiary centers that cared for 839 patients with sporadic MTC.

Clinical relevance of RET variants G691S, L769L, S836S and S904S to sporadic medullary thyroid cancer.

Background: Based on reports of higher frequencies among patients with sporadic medullary thyroid cancer (MTC) relative to external controls, the RET (REarranged during Transfection) variants G691S, L767L, S836S and S904S have been considered disease modifiers, suggesting greater lifetime risks of MTC. Other studies, employing different external controls, failed to confirm this association. Using a complementary approach, this study aimed at exploring differences in clinico-pathological characteristics among patients with sporadic MTC carrying no (wildtype), one (heterozygotes) or both (homozygotes) homologue RET variants in the germline, with wildtype cases acting as internal controls.

[Hereditary variants of primary hyperparathyroidism--MEN1, MEN2, HPT-JT, FHH, FIHPT].

Objective: The challenge in diagnosing primary hyperparathyroidism (HPT) is to detect hereditary cases before first surgery. About 5% of cases are hereditary and integral component of multiple endocrine neoplasia type 1 and 2 (MEN1/MEN2), hyperparathyroidism-jaw tumor syndrome (HPT-JT), familial hypocalciuric hypercalcemia (FHH), and familial isolated hyperparathyroidism (FIHPT). Aim of this study was to evaluate similarities and differences in hereditary varieties of HPT.

Molecular genetics and phenomics of RET mutations: Impact on prognosis of MTC.

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant hereditary cancer syndrome caused by missense gain-of-function mutations of the RET proto-oncogene. Three distinct clinical subtypes of MEN 2 have been characterized: MEN 2A, MEN 2B, and familial medullary thyroid carcinoma (FMTC). The specific RET mutation may suggest a predilection toward a particular phenotype and clinical course, with strong genotype-phenotype correlations.

New mutations in the RET protooncogene-L881V - associated with medullary thyroid carcinoma and -R770Q - in a patient with mixed medullar/follicular thyroid tumour.

Unlabelled: Clinical studies are needed to classify rare and novel RET mutations associated with hereditary medullary thyroid carcinoma (MTC) into one of the clinical risk groups. Here we describe two new RET mutations/variants, R770Q and L881V, in patients with MTC and analyzed genotype-phenotype correlations associated with these RET mutations in the gene carriers. FAMILY 1: Calcitonin screening in a 42-year-old female patient with multinodular goiter showed elevated levels.

Characterization of the RET protooncogene transmembrane domain mutation S649L associated with nonaggressive medullary thyroid carcinoma.

Context: For rare and novel RET mutations associated with hereditary medullary thyroid carcinoma (MTC), clinical and functional studies are needed to classify the RET mutation into one of the three clinical risk groups.

Objective: We analyzed proliferative properties and clinical implications associated with the RET protooncogene transmembrane domain mutation S649L.

Design: The transforming potential and mitogenic properties of S649L mutation were investigated clinically and by evaluating kinase activity, cell proliferation, and colony formation.

Change in the spectrum of RET mutations diagnosed between 1994 and 2006.

Medullary thyroid carcinoma (MTC) is a rare calcitonin producing tumor. About 70-75% of patients with MTC have sporadic disease while the others suffer from hereditary MTC. Hereditary MTC is divided into three clinical subtypes: multiple endocrine neoplasia (MEN) type 2A is characterized by MTC, pheochromocytoma and primary hyperparathyroidism.

Long-term outcome in 46 gene carriers of hereditary medullary thyroid carcinoma after prophylactic thyroidectomy: impact of individual RET genotype.

Objective: In children with RET proto-oncogene mutation, curative treatment of medullary thyroid carcinoma (MTC) is possible by prophylactic thyroidectomy. Recommendations on the timing and extent of thyroidectomy are based upon a model that utilises genotype-phenotype correlations to stratify mutations into three risk groups.

Design: We evaluated the long-term outcome (mean follow-up 6.

Primary hyperparathyroidism as the leading symptom in a patient with a Y791F RET mutation.

Primary hyperparathyroidism (PHP; serum calcium 2.75 mmol/L, PTH 226 pg/ml) had been the first clinical manifestation of MEN-2A in a female patient (aged 55 years) with a mutation (Y791F, TAT-->TTT) in exon 13 of the RET proto-oncogene. The patient has a pentagastrin-induced rise in serum calcitonin (up to 57 pg/ml) considered normal for noncarriers but abnormal in family members of MEN-2 patients.

Coincidence of multiple endocrine neoplasia types 1 and 2: mutations in the RET protooncogene and MEN1 tumor suppressor gene in a family presenting with recurrent primary hyperparathyroidism.

Context: Primary hyperparathyroidism (HPT) presents as a part of inherited syndromes such as multiple endocrine neoplasia (MEN) types 1 and 2. In patients with MEN1, parathyroid hyperplasia or multiple adenomas occur in approximately 90-95%. MEN2A-related HPT is characterized by a mild hypercalcemia, which is mostly asymptomatic.

Charge implantation measurement on electron-irradiated insulating materials by means of an SEM technique.

The goal of this article is first to review the charging effects occurring when an insulating material is subjected to electron irradiation in a scanning electron microscope (SEM) and next their consequences from both scanning electron microscopy and electron probe microanalysis (EPMA) points of view. When bare insulators are observed, the so-called pseudo mirror effect leads to an anomalous contrast and also to an erroneous surface potential, V(S), measurement when a Duane-Hunt limit (DHL) method is used. An alternative possibility is to use an electron toroidal spectrometer (ETS), specially adapted to a SEM, which directly gives the V(S) value.

[Hereditary medullary thyroid carcinoma--genotype-phenotype characterization].

Background And Objective: Hereditary medullary thyroid carcinoma (MTC) is caused by germline mutations of the RET proto-oncogene. A genotype - phenotype correlation has been established, showing clustering of mutations in exons 10 and 11 in classical MEN 2 A syndrome, in exon 16 codon 918 in MEN 2 B syndrome and in exons 13-15 in familial MTC. A line of evidence suggested that the development and the aggressiveness of MTC in the different cancer syndromes is variable.

Mutational spectrum of the steroid 21-hydroxylase gene in Austria: identification of a novel missense mutation.

This study attempted an analysis of the mutational spectrum of 21-hydroxylase deficiency in 79 unrelated Austrian patients with classical and nonclassical forms of congenital adrenal hyperplasia and their respective 112 family members. Apparent large gene deletions/conversions were present in 31% of the 158 unrelated congenital adrenal hyperplasia alleles, whereas the most frequent point mutations were intron 2 splice (22.8%), I172N (15.

A helper phage to improve single-chain antibody presentation in phage display.

We show here that the number of single-chain antibody fragments (scFv) presented on filamentous phage particles generated with antibody display phagemids can be increased by more than two orders of magnitude by using a newly developed helper phage (hyperphage). Hyperphage have a wild-type pIII phenotype and are therefore able to infect F(+) Escherichia coli cells with high efficiency; however, their lack of a functional pIII gene means that the phagemid-encoded pIII-antibody fusion is the sole source of pIII in phage assembly. This results in an considerable increase in the fraction of phage particles carrying an antibody fragment on their surface.

Epitopes fused to F-pilin are incorporated into functional recombinant pili.

In order to develop a system which allows infection by an epitope-specific phage-antibody via an F-pilus expressing that epitope, a study on the expression of foreign sequences on F-pilin was undertaken. Initially, a plasmid library was constructed with random sequences encoding one to five amino acid residues fused to the C terminus of F-pilin (traA) which was used to complement an F-plasmid with an amber mutation in traA. Functional F-pilin fusions were detected using the filamentous phage, fUSE2, which transduces tetracycline resistance, as well as immunoblots using a monoclonal antiserum specific for the acetylated N terminus of pilin.

Following ion diffusion in solution.

An x-ray projection microscope equipped with a charge-coupled device camera allows direct observation of zinc (Zn(2+)) ions diffusing in aqueous hydrochloric acid solution during the corrosion of zinc foil and pellets. Time series of microradiographic images with a lateral resolution on the order of 10 micrometers allow observation of the time and spatial evolution of the colorless Zn(2+) ions in solution without any previous treatment. The concentration distribution of the ions can be quantified from these images.