172 research outputs found
Uniform semiclassical wave function for coherent 2D electron flow
We find a uniform semiclassical (SC) wave function describing coherent
branched flow through a two-dimensional electron gas (2DEG), a phenomenon
recently discovered by direct imaging of the current using scanned probed
microscopy. The formation of branches has been explained by classical
arguments, but the SC simulations necessary to account for the coherence are
made difficult by the proliferation of catastrophes in the phase space. In this
paper, expansion in terms of "replacement manifolds" is used to find a uniform
SC wave function for a cusp singularity. The method is then generalized and
applied to calculate uniform wave functions for a quantum-map model of coherent
flow through a 2DEG. Finally, the quantum-map approximation is dropped and the
method is shown to work for a continuous-time model as well.Comment: 9 pages, 7 figure
Dynamic Compaction of Biomaterial Powders
Dynamic compaction which requires no external heating for consolidation was used to compact hydroxyapatite. Static precompaction of 3 MPa and dynamic compaction using a projectile velocity of 50 m/s resulted in compacts having a compaction degree of 65% and a tensile strength of 12.4 ± 2.7 MPa This strength was very close to that obtained with sintered compacts one and seemed to indicate that some interparticle boundaries had been created during dynamic compaction
Rapid sulfation of 3,3',5'-triiodothyronine in native Xenopus laevis oocytes
Sulfation is an important metabolic pathway facilitating the degradation
of thyroid hormone by the type I iodothyronine deiodinase. Different human
and rat tissues contain cytoplasmic sulfotransferases that show a
substrate preference for 3,3'-diiodothyronine (3,3'-T2) > T3 > rT3 > T4.
During investigation of the expression of plasma membrane transporters for
thyroid hormone by injection of rat liver RNA in Xenopus laevis oocytes,
we found uptake and metabolism of iodothyronines by native oocytes. Groups
of 10 oocytes were incubated for 20 h at 18 C in 0.1 ml medium containing
500,000 cpm (1-5 nM) [125I]T4, [125I]T3, [125I]rT3, or [125I]3,3'-T2. In
addition, cytosol prepared from oocytes was tested for iodothyronine
sulfotransferase activity by incubation of 1 mg cytosolic protein/ml for
30 min at 21 C with 1 microM [125I]T4, [125I]T3, [125I]rT3, or
[125I]3,3'-T2 and 50 microM 3'-phosphoadenosine-5'-phosphosulfate.
Incubation media, oocyte extracts, and assay mixtures were analyzed by
Sephadex LH-20 chromatography for production of conjugates and iodide.
After 20-h incubation, the percentage of added radioactivity present as
conjugates in the media and oocytes amounted to 0.9 +/- 0.2 and 1.0 +/-
0.1 for T4, less than 0.1 and less than 0.1 for T3, 32.5 +/- 0.4 and 29.3
+/- 0.2 for rT3, and 3.8 +/- 0.3 and 2.3 +/- 0.2 for 3,3'-T2, respectively
(mean +/- SEM; n = 3). The conjugate produced from rT3 was identified as
rT3 sulfate, as it was hydrolyzed by acid treatment. After injection of
oocytes with copy RNA coding for rat type I iodothyronine deiodinase, we
found an increase in iodide production from rT3 from 2.3% (water-injected
oocytes) to 46.2% accompanied by a reciprocal decrease in rT3 sulfate
accumulation from 53.7% to 7.1%. After 30-min incubation with cytosol and
3'-phosphoadenosine-5'-phosphosulfate, sulfate formation amounted to 1.8%
for T4, less than 0.1% for T3, 77.9% for rT3, and 2.9% for 3,3'-T2. These
results show that rT3 is rapidly metabolized in native oocytes by
sulfation. The substrate preference of the sulfotransferase activity in
oocytes is rT3 >> 3,3'-T2 > T4 > T3. The physiological significance of the
high activity for rT3 sulfation in X. laevis oocytes remains to be
established
Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability
Although it was originally believed that thyroid hormones enter target
cells by passive diffusion, it is now clear that cellular uptake is
effected by carrier-mediated processes. Two stereospecific binding sites
for each T4 and T3 have been detected in c
Thyroid hormone transport by the heterodimeric human system L amino acid transporter
Transport of thyroid hormone across the cell membrane is required for
thyroid hormone action and metabolism. We have investigated the possible
transport of iodothyronines by the human system L amino acid transporter,
a protein consisting of the human 4F2 heavy chain and the human LAT1 light
chain. Xenopus oocytes were injected with the cRNAs coding for human 4F2
heavy chain and/or human LAT1 light chain, and after 2 d were incubated at
25 C with 0.01-10 microM [(125)I]T(4), [(125)I]T(3), [(125)I]rT(3), or
[(125)I]3,3'-diiodothyronine or with 10-100 microM [(3)H]arginine,
[(3)H]leucine, [(3)H]phenylalanine, [(3)H]tyrosine, or [(3)H]tryptophan.
Injection of human 4F2 heavy chain cRNA alone stimulated the uptake of
leucine and arginine due to dimerization of human 4F2 heavy chain with an
endogenous Xenopus light chain, but did not affect the uptake of other
ligands. Injection of human LAT1 light chain cRNA alone did not stimulate
the uptake of any ligand. Coinjection of cRNAs for human 4F2 heavy chain
and human LAT1 light chain stimulated the uptake of phenylalanine >
tyrosine > leucine > tryptophan (100 microM) and of 3,3'-diiodothyronine >
rT(3) approximately T(3) > T(4) (10 nM), which in all cases was Na(+)
independent. Saturation analysis provided apparent Michaelis constant
(K(m)) values of 7.9 microM for T(4), 0.8 microM for T(3), 12.5 microM for
rT(3), 7.9 microM for 3,3'-diiodothyronine, 46 microM for leucine, and 19
microM for tryptophan. Uptake of leucine, tyrosine, and tryptophan (10
microM) was inhibited by the different iodothyronines (10 microM), in
particular T(3). Vice versa, uptake of 0.1 microM T(3) was almost
completely blocked by coincubation with 100 microM leucine, tryptophan,
tyrosine, or phenylalanine. Our results demonstrate stereospecific
Na(+)-independent transport of iodothyronines by the human heterodimeric
system L amino acid transporter
Expression of rat liver cell membrane transporters for thyroid hormone in Xenopus laevis oocytes
The present study was conducted to explore the possible use of Xenopus
laevis oocytes for the expression cloning of cell membrane transporters
for iodothyronines. Injection of stage V-VI X. laevis oocytes with 23 ng
Wistar rat liver polyadenylated RNA (mRNA) resulted after 3-4 days in a
highly significant increase in [125I]T3 (5 nM) uptake from 6.4 +/- 0.8
fmol/oocyte x h in water-injected oocytes to 9.2 +/- 0.65 fmol/oocyte x h
(mean +/- SEM; n = 19). In contrast, [125I]T4 (4 nM) uptake was not
significantly stimulated by injection of total liver mRNA. T3 uptake
induced by liver mRNA was significantly inhibited by replacement of Na+ in
the incubation medium by choline+ or by simultaneous incubation with 1
microM unlabeled T3. In contrast, T3 uptake by water-injected oocytes was
not Na+ dependent. Fractionation of liver mRNA on a 6-20% sucrose gradient
showed that maximal stimulation of T3 uptake was obtained with mRNA of
0.8-2.1 kilobases (kb). In contrast to unfractionated mRNA, the 0.7- to
2.1-kb fraction also significantly stimulated transport of T4, and it was
found to induce uptake of T3 sulfate (T3S). Because T3S is a good
substrate for type I deiodinase (D1), 2.3 ng rat D1 complementary RNA
(cRNA) were injected either alone or together with 23 ng of the 0.8- to
2.1-kb fraction of rat liver mRNA. Compared with water-injected oocytes,
injection of D1 cRNA alone did not stimulate uptake of [125I]T3S (1.25
nM). T3S uptake in liver mRNA and D1 cRNA-injected oocytes was similar to
that in oocytes injected with mRNA alone, showing that transport of T3S is
independent of the metabolic capacity of the oocyte. Furthermore,
coinjection of liver mRNA and D1 cRNA strongly increased the production of
125I-, showing that the T3S taken up by the oocyte is indeed transported
to the cell interior. In conclusion, injection of rat liver mRNA into X.
laevis oocytes resulted in a stimulation of saturable, Na+-dependent T4,
T3 and T3S transport, indicating that rat liver contains mRNA(s) coding
for plasma membrane transporters for these iodothyronine derivatives
Iodine-131 labelled octreotide: Not an option for somatostatin receptor therapy
Gamma-emitting radiopeptides are useful for scintigraphy of tumours on the basis of receptor binding. Likewise, β-emitting radiopeptides may be used in radionuclide therapy of such tumours. As iodine-131 suggested to be suitable for this purpose, experiments were performed using three somatostatin analogues, in which the effects of coupling of a therapeutic dose of 131I to such peptides were investigated. This study deals with the radioiodination of very small amounts of peptide on a therapeutic scale, the required purification procedures after radioiodination, and the influence of high beta fluxes from 131I. On a peptide during radioiodination and purification. Based on the regularly used therapeutic doses of 131I in cancer treatment and our previous experience with [111In-DTPA-D-Phe1]-octreotide, it was assumed that a minimal effective therapeutic dose of 3.7 GBq 131I has to be coupled to a maximum of ≃ 100 μg peptide, representing only a slight excess of peptide over 131I. This contrasts with non-peptide radiopharmaceuticals in which high compound to radionuclide ratios are usually used. Labelling at low peptide to radionuclide ratios (low labelling yields) results in the formation of di-iodinated compounds, whereas at high peptide to radionuclide ratios (high labelling yields) mono-iodinated products of low specific activity are formed. Thus, after radioiodination the desired mono-iodinated peptide has to be separated from unreacted iodide, and from di-iodinated and unreacted peptide, as both compounds compete for the receptors. Possible radiolysis of the peptide during labelling and separation steps were investigated by irradiating 30 μg unlabelled peptide with 370 MBq 131I in a small volume. The peptide composition of the incubation mixtures was investigated by high-performance liquid chromatography after irradiation for 30 min to 24 h. The results showed that the peptide was degraded with a half-life of less than 1 h. During the preparation of a real therapeutic dose (at much higher β-flux) the peptide will be degraded even faster during the various steps required. In conclusion, intact mono-iodinated 131I-labelled somatostatin analogues for peptide receptor therapy will be difficult to obtain
Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner
Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth restriction. We studied the association of hCG concentrations with fetal growth and birth weight. In addition, we investigated effect modification by gestational age of hCG measurement and fetal sex. Total serum hCG (median 14.4 weeks, 95 % range 10.1–26.2), estimated fetal weight (measured by ultrasound during 18–25th weeks and >25th weeks) and birth weight were measured in 7987 mother–child pairs from the Generation R cohort and used to establish fetal growth. Small for gestational age (SGA) was defined as a standardized birth weight lower than the 10th percentile of the study population. There was a non-linear association of hCG with birth weight (P = 0.009). However, only low hCG concentrations me
Uptake of triiodothyronine sulfate and suppression of thyrotropin secretion in cultured anterior pituitary cells
To investigate the uptake of triiodothyronine sulfate (T3S) and its effect on thyrotropin-releasing hormone (TRH)-induced thyrotropin (TSH) secretion, anterior pituitary cells were isolated from euthyroid rats and cultured for 3 days in medium containing 10% fetal calf serum. Incubation was performed at 37°C in medium containing 0.5% bovine serum albumin (BSA). Exposure of the pituitary cells to TRH (0.1 μmol/L) for 2 hours stimulated TSH secretion by 176%. This effect was reduced by approximately 45% after a 2-hour preincubation with T3 (0.001 to 1 μmol/L). A significant inhibitory effect of T3S on TRH-induced TSH release was only observed at a concentration of 1 μmol/L. The uptake of [125I]T3 after 1 hour of incubation was reduced by 40% ± 4% (P < .001) by simultaneous addition of 10 nmol/L unlabeled T3, whereas 1 μmol/L T3S was required to obtain a reduction of the [125I]T3 uptake by 34% ± 2% (P < .001). The amount of T3 present in the unlabeled T3S preparation was 0.25% as determined by radioimmunoassay. When pituitary cells were incubated for 1 hour with [125I]T3S or [125I]T3 both 50,000 cpm/0.25 mL), the uptake of [125I]T3zS expressed as a percentage of the dose was 0.04% ± 0.02% (mean ± SE, n = 4), whereas that of [125I]T3 amounted to 3.0% ± 0.4% (n = 4). In contrast, when hepatocytes were incubated for 1 hour with [125I]T3S, the uptake amounted to 5.1% ± 0.8% (n = 9), whereas that of [125I]T3 was 22.1% ± 1.7% (n = 9). Furthermore, [125I]T3S was as rapidly deiodinated (iodide production, 14.9% ± 2.6%; n = 9) as [125I]T3 (12.1% ± 0.8%, n = 9) by hepatocytes. It is concluded that (1) T3S is poorly taken up by pituitary cells, and (2) the suppressive effect of high concentrations of T3S on TRH-induced TSH secretion and on [125I]T3 uptake can be explained by slight contamination with T3. Thus, it appears that T3S has only a minor biological effect, if any, on the pituitary
Thyroid Function and Premature Delivery in TPO Antibody-Negative Women: The Added Value of hCG
Conclusion: In TPOAb-negative women with high-normal TSH concentrations, only women with high hCG concentrations had a higher risk of premature delivery or pPROM. These results suggest a lower thyroidal response to hCG stimulation is also associated with premature delivery in TPOAb-negative women and that an additional measurement of hCG may improve thyroid-related risk assessments during pregnancy.Context: Human chorionic gonadotropin (hCG) stimulates thyroid function during pregnancy. We recently showed that thyroid autoimmunity severely attenuated the thyroidal response to hCG stimulation and that this may underlie the higher risk of premature delivery in thyroperoxidase antibody (TPOAb)-positive women. We hypothesized that a lower thyroidal response to hCG stimulation in TPOAb-negative women is also associated with a higher risk of premature delivery and preterm premature rupture of membranes (pPROM).Design, Setting, and Participants: Thyrotropin (TSH), free thyroxine (FT4), and hCG concentrations were available in 5644 TPOAb-negative women from a prospective cohort. We tested for interaction between TSH or FT4 and hCG in linear regression models for duration of pregnancy and logistic regression models for premature delivery/pPROM. Accordingly, analyses were stratified per TSH percentile (TSH ≥ 85th percentile) and hCG per 10,000 IU/L.Results: Women with high TSH and low hCG concentrations did not have a higher risk of premature delivery or pPROM, with protective effect estimates. In contrast, women with a high TSH concentration despite a high hCG concentration had twofold to 10-fold higher risk of premature delivery (Pdifference = 0.022) and an up to fourfold higher risk of pPROM (Pdifference = 0.079). hCG concentrations were not associated with premature delivery or pPROM
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