Metastatic parathyroid carcinoma in the MEN2A syndrome

We report a patient with a metastatic parathyroid carcinoma and medullary carcinoma of the thyroid. This patient represents a variation of the multiple endocrine neoplasia syndrome (MEN) type 2A. There was no evidence of a phaeochromocytoma. The case illustrates the difficulties that may be encountered in localising the source of PTH secretion; the patient underwent four unsuccessful exploratory operations of the neck and mediastinum before further investigations revealed a single metastatic deposit of parathyroid carcinoma involving the first thoracic vertebra. PCR amplification and sequencing of the RET oncogene from the metastatic parathyroid carcinoma and genomic DNA revealed a heterozygous mutation (Cys634Tyr) in exon 11, as has previously been described to occur in MEN 2A. In addition, loss of tumour heterozygosity was demonstrated at loci from chromosomes 1, 2, 3p, 13q and 16p. This represents the first report of a parathyroid carcinoma in a MEN2A patient, in which the multiple allelic deletions are consistent with the generalised losses observed in aggressive tumours.     

Experimental and computational analysis on guide vane losses of impulse turbine for wave energy conversion

This paper deals with the detailed flow analysis of impulse turbine with experimental and computed results for wave energy power conversion. Initially, several turbulence models have been used in two-dimensional (2-D) computational fluid dynamic (CFD) analysis to find a suitable model for this kind of slow speed unconventional turbine. Experiments have been conducted to validate the CFD results and also to analyze the aerodynamics at various stations of the turbine. The three-dimensional (3-D) CFD model with tip clearance has been generated to predict the internal flow and to understand the effect of tip clearance leakage flow on behavior of the turbine in design and off-design conditions. As a result, it is found from the 2-D results that the comparison between computed and experimental data is good, qualitatively and the turbulence model, standard k–ε can predict the experimental values reasonably well, especially the efficiency of the turbine. Experimental results reveal that the downstream guide vanes are more responsible for low efficiency of the turbine and it is measured that 21% average pressure is lost due to downstream guide vanes. It is proved from the 3-D CFD model with tip clearance that it can predict the experimental values quantitatively and qualitatively. Furthermore, it is estimated from the computed results that the efficiency of the turbine has been reduced about 4%, due to tip clearance leakage flow at higher flow coefficients.     

Utilising semantic technologies for intelligent indexing and retrieval of digital images

The proliferation of digital media has led to a huge interest in classifying and indexing media objects for generic search and usage. In particular, we are witnessing a colossal growth in digital image repositories that are difficult to navigate using free-text search mechanisms, which often return inaccurate matches as they in principle rely on statistical analysis of query keyword recurrence in the image annotation or surrounding text. In this paper we present a semantically-enabled image annotation and retrieval engine that is designed to satisfy the requirements of the commercial image collections market in terms of both accuracy and efficiency of the retrieval process. Our search engine relies on methodically structured ontologies for image annotation, thus allowing for more intelligent reasoning about the image content and subsequently obtaining a more accurate set of results and a richer set of alternatives matchmaking the original query. We also show how our well-analysed and designed domain ontology contributes to the implicit expansion of user queries as well as the exploitation of lexical databases for explicit semantic-based query expansion.     

A comparison of two meshing schemes for CFD analysis of the impulse turbine for wave energy applications

This paper presents the comparison of a three-dimensional Computational Fluid Dynamics (CFD) analysis with empirical performance data of a 0.6 m Impulse Turbine with Fixed Guide Vanes used for wave energy power conversion. Pro-Engineer, Gambit and Fluent 6 were used to create a 3-D model of the turbine. A hybrid meshing scheme was used with hexahedral cells in the near blade region and tetrahedral and pyramid cells in the rest of the domain. The turbine has a hub-to-tip ratio of 0.6 and results were obtained over a wide range of flow coefficients. Satisfactory agreement was obtained with experimental results. The model yielded a maximum efficiency of approximately 54% as compared to a maximum efficiency of around 49% from experiment. A degree of insight into flow behaviour, not possible with experiment, was obtained. Sizeable areas of separation on the pressure side of the rotor blade were identified toward the tip. The aim of the work is to benchmark the CFD results with experimental data and to investigate the performance of the turbine using CFD and to with a view to integrating CFD into the design process.     

Intra-renal and subcellular distribution of the human chloride channel, CLC-5, reveals a pathophysiological basis for Dent's disease

Dent's disease, which is a renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, is associated with inactivating mutations of the X-linked chloride channel, CLC-5. However, the manner in which a functional loss of CLC-5 leads to such diverse renal abnormalities remains to be defined. In order to elucidate this, we performed studies to determine the segmental expression of CLC-5 in the human kidney and to define its intracellular distribution. We raised and characterized antisera against human CLC-5, and identified by immunoblotting an 83 kDa band corresponding to CLC-5 in human kidney cortex and medulla. Immunohistochemistry revealed CLC-5 expression in the epithelial cells lining the proximal tubules and the thick ascending limbs of Henle's loop, and in intercalated cells of the collecting ducts. Studies of subcellular human kidney fractions established that CLC-5 distribution was associated best with that of Rab4, which is a marker of recycling early endosomes. In addition, confocal microscopy studies using the proximal tubular cell model of opossum kidney cells, which endogenously expressed CLC-5, revealed that CLC-5 co-localized with the albumin-containing endocytic vesicles that form part of the receptor-mediated endocytic pathway. Thus, CLC-5 is expressed at multiple sites in the human nephron and is likely to have a role in the receptor-mediated endocytic pathway. Furthermore, the functional loss of CLC-5 in the proximal tubules and the thick ascending limbs provides an explanation for the occurrences of low molecular weight proteinuria and hypercalciuria, respectively. These results help to elucidate further the patho-physiological basis of the renal tubular defects of Dent's disease.     

Computational Fluid Dynamics Benchmark of an Impulse Turbine with Fixed Guide Vanes

This paper presents the comparison of a three dimensional Computational Fluid Dynamics (CFD) analysis with empirical performance data of a 0.6 m impulse turbine with fixed guide vanes used for wave energy power conversion. Pro-Engineer, Gambit and Fluent 6 were used to create a 3-D model of the turbine. A hybrid meshing scheme was used with hexahedral cells in the near blade region and tetrahedral and pyramid cells in the rest of the domain. The turbine has a hub-to-tip ratio of 0.6 and results were obtained over a wide range of flow coefficients. The model yielded a maximum efficiency of approximately 54% as compared to a maximum efficiency of around 49% from experiment. A degree of insight into flow behaviour, not possible with experiment, was obtained.     

Mutations of CLCN5 in Japanese children with idiopathic low molecular weight proteinuria, hypercalciuria and nephrocalcinosis

We designed the present study to examine the cross-sectional relation between age-related lens opacities and vitamin C supplement use over a 10-12-y period before assessment of lens status in women without diagnosed cataract or diabetes. This design avoids biased measurement of nutrient intake that results when knowledge of lens opacities influences nutrition-related behavior or its reporting. The participants were 247 Boston-area women aged 56-71 y selected from the Nurses' Health Study cohort with oversampling of women with high or low vitamin C intakes. Lens opacities were graded with the Lens Opacification Classification System II. Use of vitamin C supplements for > or = 10 y (n = 26) was associated with a 77% lower prevalence of early lens opacities (odds ratio: 0.23; 95% CI: 0.09, 0.60) at any lens site and a 83% lower prevalence of moderate lens opacities (odds ratio: 0.17; 95% CI: 0.03, 0.85) at any lens site compared with women who did not use vitamin C supplements (n = 141) after adjustment for age and other potentially confounding variables. Women who consumed vitamin C supplements for < 10 y showed no evidence of a reduced prevalence of early opacities. These data, together with data from earlier experimental and epidemiologic studies, suggest that long-term consumption of vitamin C supplements may substantially reduce the development of age-related lens opacities.     

Molecular genetic studies of sporadic pituitary tumors

Tumor formation may result from the activation of dominant oncogenes or by inactivation of recessive, tumor suppressor genes. The role of such mutations in the development of pituitary tumors has been studied. Tumors from 88 patients, representing the 4 major classes of adenoma, were investigated. In DNA extracted from matched leukocyte and tumor samples, allelic deletions were sought with 15 probes identifying restriction fragment length polymorphisms on chromosomes 1, 5, 10, 11, 13, 17, 20, and 22. Evidence of amplification or rearrangement of 10 recognized cellular oncogenes (N-ras, mycL1, mycN, myc, H-ras, bcl1, H-stf1, sea, kraS2, and fos) was sought in tumor DNA. Activating dominant mutations of Gs alpha were detected using the polymerase chain reaction to amplify exons 7-10 and hybridizing the product to normal and mutant allele-specific oligonucleotides. Allelic deletions on chromosome 11 were identified in 16 tumors (18%) representing all 4 major subtypes. Deletions on other autosomes were observed in less than 6% of tumors. Three adenomas had deletions on multiple autosomes, 2 of these were aggressive and recurrent. Mutations of Gs alpha were confirmed to be specific to somatotrophinomas, being identified in 36% of such tumors in this series. No evidence of amplification or rearrangement of other recognized cellular oncogenes was found. Inactivation of a recessive oncogene on chromosome 11 is an important and possibly early event in the development of the four major types of pituitary adenoma, whereas activating mutations of Gs alpha are confirmed to be specific to somatotropinomas. Two aggressive tumors were found to have multiple autosomal losses, suggesting a multistep progression in the development of tumors of this phenotype.     

Disorders of the calcium-sensing receptor

From 1990 to 1995, 12 patients with cavo-atrial renal cell carcinoma underwent resection of the tumor. Circulatory arrest was employed in 11/12 cases. The neoplasm extended to the inferior vena cava in two patients and to the intrahepatic veins or right atrium in five cases. Two severely cardiac compromised patients died perioperatively. Of five patients who showed preoperative suspicion of isolated metastases, 3 patients died postoperatively because of relapsing disease after a mean period of 10.8 months. Five patients are alive and doing well after a mean follow-up of 14.8 months. In our experience myocardial dysfunction determined poor immediate survival. Mid-term survival was influenced by preoperative metastases and lymph-node involvement, but not by intracaval extension. Circulatory arrest appears to be a relatively safe technique to remove renal carcinoma with cavo-atrial extension and should be indicated whenever there are no metastases.     

Non-penetrance and late appearance of polyps in families with familial adenomatous polyposis

One case of non-penetrance of the familial adenomatous polyposis (FAP) gene at 59 years of age and late onset of polyps on endoscopy and biopsy in this and two other families is described. Screening protocols should include dental screening as well as indirect ophthalmoscopy and endoscopy to detect minimal manifestations of the gene. In the absence of a specific DNA predictive test, bowel screening should continue well beyond 30 years of age.