bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of MEN1 and HRPT2 somatic mutations in paraffin‐embedded (sporadic) parathyroid carcinomas
Authors: Haven C. J. , Van Puijenbroek M. , Tan M. H. , Teh B. T. , Fleuren G. J. , Van Wezel T. , Morreau H. 
Published: June 2007

SummaryObjective  Parathyroid carcinoma remains difficult to diagnose. Recently, it has been shown that mutations in the HRPT2 gene (encoding parafibromin) are associated with the development of parathyroid carcinoma. Although MEN1 is not typically thought to be involved in carcinoma formation, parathyroid carcinoma may be an extremely rare feature of the multiple endocrine neoplasia type 1 (MEN1) syndrome. We recently concluded that loss of heterozygosity (LOH) of the MEN1 gene is present in a relatively large number of parathyroid carcinomas, often in combination with LOH at the HRPT2 locus. The aim of this study was to evaluate the role of MEN1 and HRPT2 mutations in sporadic parathyroid tumours fulfilling histological criteria for malignancy.Patients and design  Formalin‐fixed, paraffin‐embedded (FFPE) parathyroid carcinoma tissue from 28 cases identified in the period 1985–2000 in the Netherlands was studied. HRPT2 (27/28 cases) and MEN1 (23/28 cases) were analysed by direct sequencing.Results  Somatic MEN1 mutations were found in three of 23 (13%) sporadic parathyroid carcinoma cases; these consisted of one missense and two frameshift mutations. One of the latter two cases displayed lymph‐node and lung metastases during follow‐up. Six HRPT2 mutations were found in 4/27 cases (15%): five were truncating mutations and one was a missense mutation. Consistent with previously published reports, we found double mutations (2×) and germline mutations (2×) in apparently sporadic parathyroid carcinomas.Conclusions  These results suggest that not only HRPT2 but also MEN1 mutations may play a role in sporadic parathyroid cancer formation.
Novel MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1
Authors: Toledo Rodrigo A. , Lourenco Delmar M. , Coutinho Flavia L. , Quedas Elisangela , Mackowiack Ivone , Machado Marcel C. C. , Montenegro Fabio , Cunha‐Neto Malebranche B. C. , Liberman Bernardo , Pereira Maria A. A. , Correa Pedro H. S. , Toledo Sergio P. A. 
Published: June 2007

SummaryObjective  To characterize clinical features and identify MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1 (MEN1).Settings  Non‐profit academic centre.Patients  Fourteen Brazilian families with MEN1 and 141 at‐risk relatives.Results  We identified 12 different MEN1 disease‐causing mutations, seven of them previously unreported: 308delC; 375del21; 549A>T (I147F); 1243delA; 1348T>G (L413R); 1351T>C (L414P) and 1523G>T (W471C). Families with the recurrent mutations 360delTCTA and L413R were shown to be unrelated by mitochondrial‐DNA and Y‐chromosome haplotype analyses. Most of the MEN1 single point mutations involved evolutionarily conserved residues, whereas most of the deletion/frameshift changes occurred in GC‐rich repetitive regions. Genetic screening of 141 at‐risk family members identified 38 MEN1 mutation carriers, 37 (97·4%) of whom had at least one major MEN1‐related tumour upon clinical investigation.Conclusions  High frequencies of MEN1 gene mutations were detected in Brazilian families with MEN1, including seven new genetic mutations that are predicted to cause inactivation of the MEN1 tumour suppressor gene. Our data underscore the need to implement a systematic MEN1 screening programme in Brazil.
Clinical relevance of highly sensitive Tg assay in monitoring patients treated for differentiated thyroid cancer
Authors: Iervasi A. , Iervasi G. , Ferdeghini M. , Solimeo C. , Bottoni A. , Rossi L. , Colato C. , Zucchelli G. C. 
Published: June 2007

SummaryObjective  Serum thyroglobulin (Tg) represents a highly specific biomarker for detecting residual thyroid tissue/recurrence/metastases after treatment for differentiated thyroid cancer (DTC). We evaluated the clinical impact of a highly sensitive Tg assay during routine follow‐up of DTC patients.Design  Tg values were measured by a highly sensitive Tg assay during L‐T4 suppressive therapy and after recombinant human thyrotropin (rh‐TSH) stimulation and were compared with those obtained by using a routinely employed Tg assay.Patients  One hundred and sixty consecutive DTC‐treated patients (papillary carcinoma n = 124, follicular carcinoma n = 36) were studied.Measurements  Measured variables included neck ultrasonography, 131I whole body scanning, and Tg assayed by Immulite (Diagnostic Products Corporation, Los Angeles, CA) and by the highly sensitive Access assay (Beckman Coulter, Brea, CA).Results  During L‐T4 therapy, measurable Tg was found in only two patients (1% of total) by Immulite and in 23 patients (14% of total) by Access assay. Using the institutional cut‐off of 2 µg/l after rh‐TSH, a negative response was associated with undetectable Immulite Tg during L‐T4 therapy in all patients (negative predictive value, NPV, 100%) and in 137 out of 152 patients with Access assay (NPV 90%). Measurable Tg during L‐T4 therapy was found in 17% of positive patients with Immulite and in 100% of patients with Access, respectively.Conclusions  The use of a highly sensitive Tg assay may represent a useful diagnostic tool for improving the interpretation of Tg results during monitoring of DTC‐treated patients for the early detection of recurrence and for optimizing the use of the more expensive rh‐TSH test.
A technique for the orientation of endoscopically resected laryngeal lesions
Authors: Murray C.E. , Cooper L. , Handa K.K. , MacLeod T. , MacKenzie K. 
Published: June 2007

Keypoints• Endoscopic resection is a widely accepted method of treating early laryngeal malignancies.• Accurate histological assessment of resected laryngeal specimens can be difficult due to their small size and potential damage and distortion caused by standard orientation and processing techniques.• A new technique is described which employs dehydrated cucumber to mount laryngeal specimens for orientation and processing• This technique is quick, easy, cheap and reliable, allowing accurate histological assessment of potentially malignant lesions.• Better orientating and processing of laryngeal specimens can optimise treatment decisions based on histological results.
Silver nitrate cauterisation, does concentration matter?
Authors: M. Amin , F. Glynn , S. Phelan , P. Sheahan , P. Crotty , D. McShane 
Published: June 2007

Keypoints• Epistaxis from the anterior septum is frequently treated with a topical application of silver nitrate. There are two concentrations commercially available and in use by otolaryngologists, these are 75% and 95% silver nitrate. The purpose of the present study was to investigate the histological effect of the two different silver nitrate concentrations on mucosal tissue at a fixed contact time of 5 s.• Twelve children undergoing routine tonsillectomy were included in this study. Prominent blood vessels on the mucosal surface of the tonsils were identified and a single vessel on each tonsil was selected for application of either 75% or 95% concentration of silver nitrate for 5 s.• Depth of penetration across the tonsil tissue was measured following application of the two different silver nitrate concentrations.• This study demonstrated a significant difference in depth of tissue penetration with the 95% averaging a twofold increase in penetration depth.• It is likely that the increased depth of penetration with 95% silver nitrate may increase the risk of complication of nasal cautery such as septal perforation, particularly in patients undergoing repeated or bilateral nasal cautery.
Primary hyperparathyroidism: do perioperative biochemical variables correlate with parathyroid adenoma weight or volume?
Authors: Randhawa P.S. , Mace A.D. , Nouraei S.A.R. , Stearns M.P. 
Published: June 2007

Objectives:  To investigate the relationship between clinical variables and biochemical markers of calcium homeostasis and parathyroid adenoma size, in patients undergoing surgery for primary hyperparathyroidism. To determine the potential clinical utility of the findings in preoperative planning and prediction of postoperative hypocalcaemia.Design:  Retrospective data analysis.Participants:  Ninety‐two patients treated surgically for primary hyperparathyroidism caused by a solitary parathyroid adenoma between 1996 and 2006.Main outcome measures:  Complete data was obtained for 77 participants including patient demographics, perioperative calcium, parathyroid hormone and phosphate levels, adenoma weight and histological dimensions. Multiple and binary logistic regression analyses were used to investigate the relationship between clinical and biochemical variables and adenoma weight and volume. Similar analysis was used to identify predictors of postoperative hypocalcaemia.Setting:  University Teaching Hospital Otolaryngology Department.Results:  The mean age at presentation was 59 years. The mean preoperative calcium and PTH levels were 2.86 ± 0.2 mmol/L and 17.2 ± 12.3 ng/L, respectively, falling to 2.3 ± 0.01 and 4.1 ± 2.7 postoperatively. The mean adenoma weight was 1.71 ± 1.41 g. No correlation existed between clinical variables and preoperative biochemical markers of calcium homeostasis and adenoma weight or volume. There was a weak correlation between the preoperative to postoperative change in calcium and PTH levels {[δCa2+] vs. [δPTH]} (r = 0.24; P < 0.05) but no predictors of postoperative hypocalcaemia could be identified.Conclusions:  Biochemical parameters will not accurately predict the size of a parathyroid adenoma. The size of a parathyroid adenoma does not correlate with postoperative calcium levels and is therefore not useful as a predictor of postoperative hypocalcaemia.
Foraging tactics in alternative heterochronic salamander morphs: trophic quality of ponds matters more than water permanency
Authors: DENOEL MATHIEU , WHITEMAN HOWARD H , WISSINGER SCOTT A. 
Published: June 2007

Summary1. In lentic freshwater habitats, the composition of animal assemblages shifts along a gradient from temporary to permanent basins. When habitats with different degrees of permanence are at the scale of the home range of species, they constitute alternatives in terms of energy acquisition through feeding.2. In this context, previous studies showed an advantage of metamorphic over paedomorphic tiger salamanders (Ambystoma tigrinum) in temporary ponds which are only available to metamorphs. The aim of this study was to establish whether salamanders obtain similar benefits in ponds that do not differ in water permanence and whether salamanders shifted from detrimental to advantageous ponds. To this end, we determined the feeding habits, body condition and movement patterns of the two morphs in a complex of four permanent and four temporary ponds.3. Consistent with previous studies, metamorphs consumed higher‐quality diets than paedomorphs in term of energy intake. However, these differences occurred because metamorphs consumed fairy shrimp in a single temporary pond. Individual movement patterns confirmed that most of the metamorphs used different aquatic habitats both within and between years and that most of them moved from permanent ponds for breeding towards the most profitable temporary pond in terms of foraging.4. These results indicate that habitat selection by salamanders is optimal in term of energy intake in metamorphs that use high quality ponds independently of hydroperiod. It seems that both spatial and temporal variation can influence the relative foraging success of each morph.
A subgroup of intrahepatic cholangiocarcinoma with an infiltrating replacement growth pattern and a resemblance to reactive proliferating bile ductules: ‘bile ductular carcinoma’
Authors: Kozaka K , Sasaki M , Fujii T , Harada K , Zen Y , Sato Y , Sawada S , Minato H , Matsui O , Nakanuma Y 
Published: June 2007

Aims:  The histogenesis and biological behaviour of peripheral intrahepatic cholangiocarcinoma (peripheral CC) remain unclarified. The aim of this study was to examine the growth pattern of peripheral CC (24 cases) in comparison with hepatocellular carcinoma (HCC, 27 cases) and metastatic colorectal adenocarcinoma (MCA, 24 cases).Methods and results:  Tumour/surrounding liver borders were classified as: (i) fibrous encapsulation, (ii) compressive growth, and (iii) infiltrating replacement. Nineteen of 24 peripheral CCs showed (iii), whereas 23 of 27 HCCs showed (i) and 17 of 24 MCAs showed (ii). In (iii), carcinoma cells infiltrated the surrounding liver without compression, and hepatic supporting vascular structures such as portal tracts were secondarily incorporated into the tumour. In (i) and (ii), the surrounding liver was compressed and no or few portal tracts were incorporated within the tumour. Fifteen of 24 peripheral CCs were composed of carcinoma cells resembling reactive bile ductules and these cells were positive for neural cell adhesion molecule (NCAM), a marker of proliferating bile ductules. The remaining nine peripheral CCs were composed of ordinary adenocarcinoma and negative for NCAM.Conclusions:  A subgroup of peripheral CCs with an infiltrating replacement growth pattern resembles reactive bile ductules and expresses NCAM. ‘Bile ductular carcinoma’ may be a better term for this subgroup.
Not all free‐living microorganisms have cosmopolitan distributions – the case ofNebela (Apodera) vasCertes (Protozoa: Amoebozoa: Arcellinida)
Authors: Smith Humphrey G. , Wilkinson David M. 
Published: June 2007

AbstractAim To review and critically assess the evidence that the testate amoeba speciesNebela vasdoes not have a cosmopolitan distribution, in contradiction to the paradigm of microbial distribution that ‘everything is everywhere’.Location Terrestrial and wetland habitats world‐wide.Methods Relevant data were assembled on the morphology, ecology and global geographical distribution ofN. vasfrom a comprehensive literature review of published original records. The data were collated, analysed and summarized. The roles of long‐term and short‐term agents of dispersal are discussed.Results A clear and repeated pattern has been elucidated of a microbial species, with a distinctive and unmistakeable morphology, that inhabits acid, damp terrestrial and wetland habitats in the southern cool‐temperate and sub‐Antarctic zones – including similar high‐altitude habitats in the Tropics. It is almost entirely confined to the Gondwanaland continents and Southern Hemisphere islands. It is definitively absent from Holarctic regions. It is proposed that the continental distribution ofN. vasis a consequence of continental drift following its original speciation in the Mesozoic or earlier, whereas its distribution on sub‐Antarctic islands (glaciated in the Pleistocene) has been effected by dispersal from South America by wind around the Southern Ocean.Main conclusion Nebela vasis a proven instance of a microbial species that does not have a cosmopolitan distribution.
Structure, castability and mechanical properties of commercially pure and alloyed titanium cast in graphite mould
Authors: CHENG W. W. , JU C. P. , LIN J. H. CHERN 
Published: June 2007

summary  This report is a study of structure, castability, mechanical properties as well as corrosion behaviour of titanium doped with up to 5 weight percentage (wt%) of a series of alloy elements, including Ta, Mo, Nb, Hf, Zr, Sn, Bi and Ag. The results indicate that, with addition of 1 wt% alloy element, Bi and Mo were most effective in enhancing the castability of titanium. With more alloy elements added, the castability values of most alloys more or less decreased. Except Ti–Mo system, all Ti alloys with a fine acicular morphology had the same crystal structure (hcp) as that of c.p. Ti with a typical lath type morphology. When 3 wt% or more Mo was added, a finer orthorhombic α’’ phase was formed. The microhardness and bending strength values of Ti alloys were all higher than those of c.p. Ti. Among all alloys, Ti–Mo system exhibited the highest hardness and strength level. For a certain alloy, the bending strength did not necessarily increase with its alloy content. Except Ti‐5Zr and Ti–Mo alloys, the bending moduli of most alloy systems were not much different from that of c.p. Ti. All alloys showed an excellent resistance to corrosion in Hanks’ solution at 37 °C.
Type VI secretion is a major virulence determinant in Burkholderia mallei
Authors: Schell Mark A. , Ulrich Ricky L. , Ribot Wilson J. , Brueggemann Ernst E. , Hines Harry B. , Chen Dan , Lipscomb Lyla , Kim H. Stanley , Mrázek Jan , Nierman William C. , DeShazer David 
Published: June 2007

SummaryBurkholderia mallei is a host‐adapted pathogen and a category B biothreat agent. Although the B. mallei VirAG two‐component regulatory system is required for virulence in hamsters, the virulence genes it regulates are unknown. Here we show with expression profiling that overexpression of virAG resulted in transcriptional activation of ∼60 genes, including some involved in capsule production, actin‐based intracellular motility, and type VI secretion (T6S). The 15 genes encoding the major sugar component of the homopolymeric capsule were up‐expressed > 2.5‐fold, but capsule was still produced in the absence of virAG. Actin tail formation required virAG as well as bimB, bimC and bimE, three previously uncharacterized genes that were activated four‐ to 15‐fold when VirAG was overproduced. Surprisingly, actin polymerization was found to be dispensable for virulence in hamsters. In contrast, genes encoding a T6S system were up‐expressed as much as 30‐fold and mutations in this T6S gene cluster resulted in strains that were avirulent in hamsters. SDS‐PAGE and mass spectrometry demonstrated that BMAA0742 was secreted by the T6S system when virAG was overexpressed. Purified His‐tagged BMAA0742 was recognized by glanders antiserum from a horse, a human and mice, indicating that this Hcp‐family protein is produced in vivo during infection.
Expression switching in the stevor and Pfmc‐2TM superfamilies in Plasmodium falciparum
Authors: Lavazec Catherine , Sanyal Sohini , Templeton Thomas J. 
Published: June 2007

SummaryPlasmodium falciparum possesses two multigenic families, var and rif, the products of which are expressed on the surface of infected erythrocytes, where via antigenic variation they contribute to malaria pathogenesis and evasion of antibody‐mediated host immunity. The products of two smaller gene families, stevor and Pfmc‐2TM, also localize to the erythrocyte membrane, although it is not known if they undergo antigenic switching. Herein we use gene‐specific quantitative reverse transcription polymerase chain reaction (RT‐PCR) to investigate the transcription pattern of the stevor and Pfmc‐2TM gene families, in both primary and second generation clonal lines of the P. falciparum isolate, NF54. We show that: (i) the expression of stevor and Pfmc‐2TM families is clonally variant, (ii) the expression of stevor and Pfmc‐2TM families undergoes switching, and (iii) switching rates vary among different variants and different isogenic clones at rates higher than 2% per generation. In addition, we show that chromosomal telomeric deletions are common in clonal lines and result in a spectrum of deletion genotypes. These findings provide evidence that the stevor and Pfmc‐2TM gene families play a role in P. falciparum antigenic variation.
Methods for improving the visualization and deconvolution of isotopic signals
Authors: TCHERKEZ GUILLAUME , GHASHGHAIE JALEH , GRIFFITHS HOWARD 
Published: June 2007

ABSTRACTStable isotopes and their associated mechanistic frameworks have provided the means to model biological transformations from inorganic sources to organic sinks, and their impact on long‐term terrestrial carbon reservoirs. However, stable isotopes have also the potential to diagnose the mechanisms by which biological systems operate, when using ‘multidimensional’ analyses of the isotopic outputs. For this purpose, we suggest that isotopic signals may be treated as mathematical vectors to reveal their interrelationships. These visualizations may be achieved, thanks to multidimensional representations (the ‘isotopology’ method), or by appreciating the colinearity of isotopic vectors to develop a clustering analysis (the ‘isotopomic’ method) similar to that used in molecular biology. Both methods converge to the same mathematical form, i.e. both lead to a covariation approach. Using simple practical examples, we argue that such procedures allow the deconvolution of plant biological systems by revealing the hierarchy of contributory physiological processes.
Intravascular large cell lymphoma
Authors: Reyes‐Castro Magdalena , Vega‐Memije Elisa 
Published: June 2007

A 19‐year‐old female presented at our hospital with a 1‐year history of a 5‐cm indurated nontender lesion on the left shoulder. Two months later, a similar lesion appeared in the left mammary region, accompanied by necrosis and fever.At admission to our department, she presented disseminated lesions in the left submandibular region, the sternal area and the posterior part of the upper and lower extremities.The lesions were indurated erythematous‐violaceous plaques affecting the adipose tissue, some with ulcerations and necrotic crusting (Fig. 1). The first histopathological report was thrombosis of the capillary vessels and focal vasculitis (Fig. 2).Ulceration and necrotic crusting lesion in the left mammary regionimageHistopathology showing dilation of thrombosed vessels with fibrin deposits (hematoxylin and eosin, magnification ×244)imageA biopsy from a lesion on the left thigh showed dilated vessels with large atypical intravascular cells with hyperchromatic nuclei and numerous atypical mytoses in the dermis and subcutaneous tissue. Some of these cells were immersed in fibrin thrombi or in the perivascular connective tissue (Fig. 3). An immunohistochemical study was positive for the common leukocytic antigen and for the B‐cell phenotype. The diagnosis was large B‐cell lymphoma. The patient persisted with a high fever, dry cough, pericardial effusion complicated by an abscess and left pleural effusion. She died before systemic workings for lymphoma could be carried out, and before chemotherapy could be attempted.Histopathology showing atypical intravascular lymphocytes (hematoxylin and eosin, magnification ×366)image
“Unknown Risks” of non‐steroid topical medications for atopic dermatitis
Authors: McNeill Anne Marie , Koo John Y. M. 
Published: June 2007

AbstractIntroduction  Tacrolimus ointment is a nonsteroid treatment for atopic dermatitis which is both effective and has a minimal side‐effect profile. However, some clinicians may be reluctant to use tacrolimus ointment due to the “unknown risks”, meaning those that have not been uncovered in human studies conducted thus far. Therefore, the available animal data regarding the “unknown risks” of topical tacrolimus therapy are reviewed, and a discussion of the interpretation of this available but limited data is presented.Animal studies  Some of the fear on the part of clinicians regarding the use of topical tacrolimus may come from the results of animal studies which showed an increase in lymphoma and UV‐induced skin cancer after treatment with topical tacrolimus in animal models of carcinogenesis. However, rigorous assessment of these studies suggest that it is somewhat likely that these represent a species‐specific response to tacrolimus in an animal already predisposed to tumor formation, and therefore may not be relevant in assessing the possibility of an increased human health risk.Conclusions  Animal and human studies suggest that topical tacrolimus is a safe alternative to topical steroids, with the major known adverse effect being a transient burning sensation, compared with the known adverse effects of topical steroids, including long‐lasting ones. Therefore, in the opinion of the authors, currently available data, including animal studies, does not suggest that “unknown risks” of topical tacrolimus need be any more concerning than the known side‐effects of the topical steroids.