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- Carling, Tobias, et al.
(författare)
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Parathyroid MEN 1 gene mutations in relation to clinical characteristics of non-familial primary hyperparathyroidism
- 1998
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 83:8, s. 2960-2963
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Tidskriftsartikel (refereegranskat)abstract
- Biochemical signs and severity of symptoms of primary hyperparathyroidism (pHPT) differ among patients, and little is known of any coupling of clinical characteristics of nonfamilial pHPT to genetic abnormalities in the parathyroid tumors. Mutations in the recently identified MEN1 gene at chromosome 11q13 have been found in parathyroid tumors of nonfamilial pHPT. Using microsatellite analysis for loss of heterozygosity (LOH) at 11q13 and DNA sequencing of coding exons, the MEN1 gene was studied in 49 parathyroid lesions of patients with divergent symptoms, operative findings, histopathological diagnosis, and biochemical signs of nonfamilial pHPT. Allelic loss at 11q13 was detected in 13 tumors, and 6 of them demonstrated previously unrecognized somatic missense and frameshift deletion mutations of the MEN1 gene. Many of the detected mutations would most likely result in a nonfunctional menin protein, consistent with a tumor suppressor mechanism. Clinical and biochemical characteristics of HPT were apparently unrelated to the presence or absence of LOH and the MEN1 gene mutations. However, the demonstration of LOH at 11q13 and MEN1 gene mutations in small parathyroid adenomas of patients with slight hypercalcemia and normal serum PTH levels suggest that altered MEN1 gene function may also be important for the development of mild sporadic pHPT.
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| 6. |
- Hessman, Ola, et al.
(författare)
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Mutation of the Multiple Endocrine Neoplasia Type 1 gene in nonfamilial, malignant tumors of the endocrine pancreas
- 1998
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 58:3, s. 377-379
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Tidskriftsartikel (refereegranskat)abstract
- Endocrine pancreatic tumors are rare neoplasms that occur sporadically or as part of a multiple endocrine neoplasia type 1 (MEN1) syndrome. Germ-line mutations of the MEN1 gene, located at 11q13, have been demonstrated in MEN1 kindreds, and loss of heterozygosity (LOH) on 11q13 together with somatic MEN1 mutations have been detected in 20% of nonfamilial parathyroid tumors. Here, we examine 11 non-MEN1 malignant tumors of the endocrine pancreas, 9 nonfunctioning tumors, and 2 glucagonomas. LOH of at least one informative locus on 11q13 was found in 70% of the tumors. Three tumors displayed somatic mutations of the MEN1 gene together with LOH on 11q13, whereas the corresponding germ-line DNA was normal. These findings support the hypothesis that MEN1 gene mutations contribute to the tumorigenesis of nonfamilial, malignant endocrine pancreatic tumors.
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- Westin, Jonas
(författare)
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Laninar-turbulent boundary layer transition influenced by free stream turbulence
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Laminar-turbulent transition in a flat plate boundary layerhas been considered, with a special emphasis on the influencefrom free stream turbulence (FST)First, experiments on linear stability ofTollmien-Schlichting (TS) waves in a Blasius boundary layer wasstudied. This is a well-known example from hydrodynamicstability theory, which has hitherto suffered from unresolveddiscrepancies between experiments and linear theory. Thepresent results showed good agreement with the theory, and itwas also shown that inappropriate leading edge conditions mayhave affected earlier experimental studies.In a series of experiments the interest has been focussed ontransition at moderate levels of free stream turbulence. Theresponse of a laminar boundary layer subjected to a free streamturbulence level of 1.5% formed the basis for the study, andthe general characteristics of FST-induced disturbances weredetermined. It was shown that the FST gives rise tonon-stationary streaky structures inside the laminar boundarylayer, which result in streamwise fluctuations with rms-valuesof the order of 10% before transition starts. Moreover, it wasshown that the introduction of TS-waves together with the largeamplitude streaks could lead to a considerable enhancement ofthe transition process.Since the random character of FST-induced boundary layerdisturbances can effectively obscure important details in theflow, a model experiment simulating the process through whichfree stream eddies transform into streaky structures inside theboundary layer was studied. This was done by means of alocalized free stream disturbance introduced upstream of theleading edge. The importance of streamwise vorticity in thereceptivity process was clearly indicated. It was also shownthat localized streaky structures, which decayed in amplitudeduring the downstream development, could exhibit a strongamplification if a TS-wave was generated simultaneously. It issuggested that similar non-linear interactions may occur in aboundary layer subjected to moderate levels of free streamturbulence.Besides the experimental work, a study related to transitionprediction at high levels of free stream turbulence is includedin the thesis. The possibility to use differential ReynoldsStress Transport Models for transition prediction isconsidered, and some aspects concerning the sensitivity to freestream boundary conditions are discussed.Keywords:Laminar-turbulent transition, hot-wiremeasurements, Tollmien-Schlichting waves, free streamturbulence, receptivity, localized disturbances, nonlinearinteraction, transition modelling
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