299 research outputs found
Different Mechanisms of Calcitonin, Calcitonin Gene-Related Peptide, and Somatostatin Regulation by Glucocorticoids in a Cell Culture of Human Medullary Thyroid Carcinoma
We have employed the TT cell line, a model for the human medullary thyroid carcinoma cell, lo study the regulation of peptide hormone production by glucocorticoids. Complementary DNA probes were used to measure the calcitonin (CT), CT gene-related peptide (CGRP), and somatostatin (SRIF) mRNA levels. Dose-response experiments in serum-free medium showed that dexamethasone (six-day treatment) lowered somatostatin (to 1% of basal) and CGRP mRNA (to 50% of basal) and stimulated CT mRNA (threefold to thirteenfold) with a half-maximal effective concentration of 10−8 M. Time course studies for cells continuously exposed to 10−6 M dexamethasone showed a rapid (within hours) lowering of SRIF mRNA, whereas the effects on CT and CGRP mRNA required six to eight days. These results demonstrate the presence of two mechanisms, transcriptional (somatostatin) and posttranscriptional (the RNA splice decision to make CT or CGRP mRNA). that can be hormonally regulated
Transcriptional Regulation of the Human Calcitonin Gene: A Progress Report
We have applied DNA transfer techniques lo study the transcriptional regulation of the calcitonin (CT) gene in a C-cell line (TT) derived from a human medullary thyroid carcinoma. TT cells were transfected with a fusion gene containing the CT gene promoter and 5\u27 -flanking DNA attached to the promoter-less growth hormone gene (reporter). We quantitated the reporter gene product to monitor transcriptional activation by the CT promoter and deletion mutants of the 5\u27 -flanking DNA. We found that the proximal CT promoter which includes the DNA sequence from +1 to -129 bp upstream from the CT transcription start site did not induce transcription in C-cells or in NIH 3T3 cells. The attachment of additional 5\u27-flanking DNA, extending up to -1460 bp enhanced transcription up to twelvefold in TT cells but had no effect on transcription in 3T3 cells. Deletion of a sequence located at -1290 to -820 bp on the CT 5\u27 -flanking DNA abolished the transcription of the reporter gene. Attachment of the DNA sequence located between -1333 to -731 to the fusion gene, containing the CT promoter (+1 to -129) and the reporter gene, restored transcription of the reporter gene in TT cells. We conclude that an enhancer of CT transcription, which is active in C-cells but not in 3T3 cells, is located between -1290 and -820 of the CT 5\u27-flanking DNA
Impact of Prospective Screening for Multiple Endocrine Neoplasia Type 2
Prospective annual screening for hereditary medullary thyroid carcinoma (MTC) in the J-kindred, currently a 117-member family with multiple endocrine neoplasia type 2A, began in 1969. During the initial screening, 12 patients were found to have MTC. Subsequent screening has detected C-cell abnormalities (C-cell hyperplasia or microscopic MTC) in 22 of 23 addilional family members thyroidectomized for abnormal calcium- or pentagastrin-provocative calcitonin (CT) test results. Seven of the initial 12 patients thyroidectomized in 1970 to 1971 and 19 of 23 individuals thyroidectomized since 1971 remain disease-free by all criteria; three patients thyroidectomized since 1971 have had clearly abnormal serum CT measurements on one or more provocative tests. The significance of these abnormal test results is unclear because normal values were obtained when the samples were measured in another CT radioimmunoassay. Urine catecholamine abnormalities have been detected in 19 family members since 1969, resulting in ten bilateral and eight unilateral adrenalectomies. Four of the patients with initial unilateral adrenalectomy required reoperation for a pheochromocytoma in the contralateral gland nine to 13 years later. Hyperparathyroidism has not been observed in any of the family members with early C-cell disease. We conclude that prospective screening for hereditary MTC predicts histologic C-cell abnormalities in affected individuals, and follow-up of these patients provides support for the conclusion that early thyroidectomy is curative in most patients
Quantum transport and momentum conserving dephasing
We study numerically the influence of momentum-conserving dephasing on the
transport in a disordered chain of scatterers. Loss of phase memory is caused
by coupling the transport channels to dephasing reservoirs. In contrast to
previously used models, the dephasing reservoirs are linked to the transport
channels between the scatterers, and momentum conserving dephasing can be
investigated. Our setup provides a model for nanosystems exhibiting conductance
quantization at higher temperatures in spite of the presence of phononic
interaction. We are able to confirm numerically some theoretical predictions.Comment: 7 pages, 4 figure
Real space finite difference method for conductance calculations
We present a general method for calculating coherent electronic transport in
quantum wires and tunnel junctions. It is based upon a real space high order
finite difference representation of the single particle Hamiltonian and wave
functions. Landauer's formula is used to express the conductance as a
scattering problem. Dividing space into a scattering region and left and right
ideal electrode regions, this problem is solved by wave function matching (WFM)
in the boundary zones connecting these regions. The method is tested on a model
tunnel junction and applied to sodium atomic wires. In particular, we show that
using a high order finite difference approximation of the kinetic energy
operator leads to a high accuracy at moderate computational costs.Comment: 13 pages, 10 figure
Magnetization and Level Statistics at Quantum Hall Liquid-Insulator Transition in the Lattice Model
Statistics of level spacing and magnetization are studied for the phase
diagram of the integer quantum Hall effect in a 2D finite lattice model with
Anderson disorder.Comment: 4 pages, 6 figure
Effect of incoherent scattering on shot noise correlations in the quantum Hall regime
We investigate the effect of incoherent scattering in a Hanbury Brown and
Twiss situation with electrons in edge states of a three-terminal conductor
submitted to a strong perpendicular magnetic field. The modelization of
incoherent scattering is performed by introducing an additional voltage probe
through which the current is kept equal to zero which causes voltage
fluctuations at this probe. It is shown that inelastic scattering can lead in
this framework to positive correlations, whereas correlations remain always
negative for quasi-elastic scattering.Comment: 5 pages latex, 5 eps figure
FDG uptake, a surrogate of tumour hypoxia?
Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-D-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging.
Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant.
Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting
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