1,362 research outputs found
Studies on thyroidal protein biosynthesis in relation to thyroid hormone biosynthesis
1. The object of the study was the isolation from thyreoglobulin
of peptides containing iodothyronines or iodotyrosines, followed
by investigation of these peptides as the actual or potential sites
of thyroid hormone synthesis in thyreoglobulin.2. A cell free preparation capable of incorporating amino acids
into protein was isolated from rat thyroid. Some of the unusual
properties of this preparation were studied.3. Thyroglobulin containing Ā¹ā“C-amino acids was isolated from
whole rat thyroids after Incubation with Ā¹ā“C-amino acids. Under
similar conditions sheep thyroid slices rapidly incorporated Ā¹ā“C-
amino acids and Ā¹Ā³Ā¹Iā» yielding thyroglobulia highly labelled with
both isotopes.4. Thyroglobulin isolated from sheep thyroid slices was purified,
by fractionation with ammonium sulphate or by gel filtration on
Sephadex G-200. The purity of the preparation was determined by
a variety of methods including gel filtration, electrophoresis and
ultraoentrifugation. Suorose gradient centrifugation revealed
a highly iodinated lighter protein fraction.5. Labelled thyroglobulin was hydrolysed by Ī±-chymotrypsin and
the resulting hydrolysate subjected to electrophoresis followed by
chromatography at right angles (peptide mapping). Autoradiograms
of these peptide maps revealed the presence of a number of peptides
labelled with Ā¹Ā³Ā¹Iā and a larger number labelled with Ā¹ā“C-tyrosine.
None of the Ā¹Ā³Ā¹I-peptides was unequivocally labelled with Ā¹ā“C-
tyrosine.6. The most highly labelled Ā¹Ā³Ā¹ I-peptides were isolated, in some
cases purified by electrophoresis at pH 8.2, and their iodoamino
acid contents found after pronase hydrolysis and chromatography.
Each peptide contained only one iodotyrosine confirming the
specific nature of tyrosyl iodination indicated by the small number
of intensely labelled Ā¹Ā³Ā¹I-peptides compared with a larger number
of Ā¹ā“Cātyrosine peptides.7. The approximate sizes of the Ā¹Ā³Ā¹I-peptides were determined by
estimation Ā©i the bonds hydrolysed by Ī±C-chymotrypsin and by gel
filtration of the peptides on Sephadex 0-25.8. During the incorporation of Ā¹Ā³Ā¹Iā» into thyroid slices over a
period of 5 hr. the activity of each Ā¹Ā³Ā¹I-peptide, as a percentage
of the total Ā¹Ā³Ā¹Iā in thyroglobulin, did not alter although the
ratio of the Ā¹Ā³Ā¹I-activities of mono- to diiodotyrosine fell
throughout this period.9. Monoiodotyrosyl peptide Aā
was iodinated chemically with Ā¹Ā³Ā¹Iā.
The product was not identical with already isolated diiodotyrosyl
peptides of similar mobilities on peptide mapping.10. Peptide Aā
was associated with another peptide (separated by
electrophoresis at pH 8.2) whose products of iodination were
identical with those of Aā
and which, it is suggested, is the
unlodinated form of Aā
.11. This latter peptide taken together with Aā
, is present as
4 moles per mole of thyroglobulin as determined by iodination with
131Iā of known specifio aotivity. Two other peptides, Nā and
Nāā' are each present as 5 moles per mole of thyroglobulin. It ya
is suggested that this confirms the evidence that thyroglobulin
oomprises four identioal sub-units and that iodotyrosyl residues
can remain partially uniodinated as well as being mono- or diiodinated
Adjunctive strategies in the management of resistant, 'undilatable' coronary lesions after successfully crossing a CTO with a guidewire.
Successful revascularisation of chronic total occlusions (CTOs) remains one of the greatest challenges in the era of contemporary percutaneous coronary intervention (PCI). Such lesions are encountered with increasing frequency in current clinical practice. A predictable increase in the future burden of CTO management can be anticipated given the ageing population, increased rates of renal failure, graft failure and diabetes mellitus. Given recent advances and developments in CTO PCI management, successful recanalisation can be anticipated in the majority of procedures undertaken at high-volume centres when performed by expert operators. Despite advances in device technology, the management of resistant, calcific lesions remains one of the greatest challenges in successful CTO intervention. Established techniques to modify calcific lesions include the use of high-pressure non-compliant balloon dilation, cutting-balloons, anchor balloons and high speed rotational atherectomy (HSRA). Novel approaches have proven to be safe and technically feasible where standard approaches have failed. A step-wise progression of strategies is demonstrated, from well-recognised techniques to techniques that should only be considered when standard manoeuvres have proven unsuccessful. These methods will be described in the setting of clinical examples and include use of very high-pressure non-compliant balloon dilation, intentional balloon rupture with vessel dissection or balloon assisted micro-dissection (BAM), excimer coronary laser atherectomy (ECLA) and use of HSRA in various 'offlabel' settings
Discovery of a very X-ray luminous galaxy cluster at z=0.89 in the WARPS survey
We report the discovery of the galaxy cluster ClJ1226.9+3332 in the Wide
Angle ROSAT Pointed Survey (WARPS). At z=0.888 and L_X=1.1e45 erg/s (0.5-2.0
keV, h_0=0.5) ClJ1226.9+3332 is the most distant X-ray luminous cluster
currently known. The mere existence of this system represents a huge problem
for Omega_0=1 world models.
At the modest (off-axis) resolution of the ROSAT PSPC observation in which
the system was detected, ClJ1226.9+3332 appears relaxed; an off-axis HRI
observation confirms this impression and rules out significant contamination
from point sources. However, in moderately deep optical images (R and I band)
the cluster exhibits signs of substructure in its apparent galaxy distribution.
A first crude estimate of the velocity dispersion of the cluster galaxies based
on six redshifts yields a high value of 1650 km/s, indicative of a very massive
cluster and/or the presence of substructure along the line of sight. While a
more accurate assessment of the dynamical state of this system requires much
better data at both optical and X-ray wavelengths, the high mass of the cluster
has already been unambiguously confirmed by a very strong detection of the
Sunyaev-Zel'dovich effect in its direction (Joy et al. 2001).
Using ClJ1226.9+3332 and ClJ0152.7-1357 (z=0.835), the second-most distant
X-ray luminous cluster currently known and also a WARPS discovery, we obtain a
first estimate of the cluster X-ray luminosity function at 0.8<z<1.4 and
L_X>5e44 erg/s. Using the best currently available data, we find the comoving
space density of very distant, massive clusters to be in excellent agreement
with the value measured locally (z<0.3), and conclude that negative evolution
is not required at these luminosities out to z~1. (truncated)Comment: accepted for publication in ApJ Letters, 6 pages, 2 figures, uses
emulateapj.st
The WARPS survey - IV: The X-ray luminosity-temperature relation of high redshift galaxy clusters
We present a measurement of the cluster X-ray luminosity-temperature relation
out to high redshift (z~0.8). Combined ROSAT PSPC spectra of 91 galaxy clusters
detected in the Wide Angle ROSAT Pointed Survey (WARPS) are simultaneously fit
in redshift and luminosity bins. The resulting temperature and luminosity
measurements of these bins, which occupy a region of the high redshift L-T
relation not previously sampled, are compared to existing measurements at low
redshift in order to constrain the evolution of the L-T relation. We find a
best fit to low redshift (z1 keV, to be L proportional
to T^(3.15\pm0.06). Our data are consistent with no evolution in the
normalisation of the L-T relation up to z~0.8. Combining our results with ASCA
measurements taken from the literature, we find eta=0.19\pm0.38 (for Omega_0=1,
with 1 sigma errors) where L_Bol is proportional to (1 + z)^eta T^3.15, or
eta=0.60\pm0.38 for Omega_0=0.3. This lack of evolution is considered in terms
of the entropy-driven evolution of clusters. Further implications for
cosmological constraints are also discussed.Comment: 11 pages, 7 figures, accepted for publication in MNRA
The Butcher-Oemler Effect in High Redshift X-ray Selected Clusters
We are engaged in a wide-field, multi-colour imaging survey of X-ray selected
clusters at intermediate and high redshift. We present blue fractions for the
first 8 out of 29 clusters, covering almost a factor of 100 in X-ray
luminosity. We find no correlation of blue fraction with redshift or X-ray
luminosity. The lack of a correlation with L, places strong constraints
on the importance of ram-pressure stripping as a driver of the Butcher-Oemler
effect.Comment: 4 pages, 4 figures, to be puplished in the proceedings of the ''Sesto
2001-Tracing Cosmic Evolution with Galaxy Clusters'', Sesto 3-6 July 2001,
Italy, eds, Stefano Borgan
A randomized, blinded, controlled trial investigating the gastrointestinal health effects of drinking water quality.
A double-blinded, randomized, controlled trial was carried out in in Melbourne, Australia, to determine the contribution of drinking water to gastroenteritis. Melbourne is one of the few major cities in the world that draws drinking water from a protected forest catchment with minimal water treatment (chlorination only). Six hundred families were randomly allocated to receive either real or sham water treatment units (WTUs) installed in their kitchen. Real units were designed to remove viruses, bacteria, and protozoa. Study participants completed a weekly health diary reporting gastrointestinal symptoms during the 68-week observation period. There were 2,669 cases of highly credible gastroenteritis (HCG) during the study (0.80 cases/person/year). The ratio of HCG episode rates for the real WTU group compared to the sham WTU group was 0.99 (95% confidence interval, 0.85-1.15, p = 0.85). We collected 795 fecal specimens from participants with gastroenteritis, and pathogens were not more significantly common in the sham WTU group. We found no evidence of waterborne disease in Melbourne. The application of this methodology to other water supplies will provide a better understanding of the relationship between human health and water quality
The WARPS survey: III. The discovery of an X-ray luminous galaxy cluster at z=0.833 and the impact of X-ray substructure on cluster abundance measurements
The WARPS team reviews the properties and history of discovery of
ClJ0152.7-1357, an X-ray luminous, rich cluster of galaxies at z=0.833. At L_X
= 8 x 10^44 h^(-2) erg/s (0.5-2.0 keV) ClJ0152.7-1357 is the most X-ray
luminous cluster known at redshifts z>0.55. The high X-ray luminosity of the
system suggests that massive clusters may begin to form at redshifts
considerably greater than unity. This scenario is supported by the high degree
of optical and X-ray substructure in ClJ0152.7-1357, which is similarly complex
as that of other X-ray selected distant clusters and consistent with the
picture of cluster formation by mass infall along large-scale filaments. X-ray
emission from ClJ0152.7-1357 was detected already in 1980 with the EINSTEIN
IPC. However, because the complex morphology of the emission caused its
significance to be underestimated, the corresponding source was not included in
the EMSS cluster sample and hence not previously identified. Simulations of the
EMSS source detection and selection procedure suggest a general bias of the
EMSS against X-ray luminous clusters with pronounced substructure. If highly
unrelaxed, merging clusters are common at high redshift, they could create a
bias in some samples as the morphological complexity of mergers may cause them
to fall below the flux limit of surveys that assume a unimodal spatial source
geometry. Conversely, the enhanced X-ray luminosity of mergers might cause them
to, temporarily, rise above the flux limit. Either effect could lead to
erroneous conclusions about the evolution of the comoving cluster space
density. A high fraction of morphologically complex clusters at high redshift
would also call into question the validity of cosmological studies that assume
that the systems under investigation are virialized.Comment: 17 pages, 7 figures; revised to focus on possible detection biases
caused by substructure in clusters; accepted for publication in ApJ; uses
emulateapj.sty; eps files of figures 1 and 2 can be obtained from
ftp://hubble.ifa.hawaii.edu/pub/ebeling/warp
How close are we to standardised extended RAS gene mutation testing? The UK NEQAS evaluation
Aims: Since 2008, KRAS mutation status in exon 2 has been used to predict response to anti-EGFR therapies. Recent evidence has demonstrated that NRAS status is also predictive of response. Several retrospective āextended RASā analyses have been performed on clinical trial material. Despite this, are we really moving towards such extended screening practice in reality? Methods: Data were analysed from four consecutive UK National External Quality Assessment Service for Molecular Genetics Colorectal cancer External Quality Assessment schemes (during the period 2014ā2016), with up to 110 laboratories (worldwide) participating in each scheme. Testing of four or five tumour samples is required per scheme. Laboratories provided information on which codons were routinely screened, and provided genotyping and interpretation results for each sample. Results: At least 85% of laboratories routinely tested KRAS codons 12, 13 and 61. Over the four schemes, an increasing number of laboratories routinely tested KRAS codons 59, 117 and 146. Furthermore, more laboratories were introducing next generation sequencing technologies. The pattern of āextended testingā was reassuringly similar for NRAS, although fewer laboratories currently test for mutations in this gene. Alarmingly, still only 36.1% and 24.1% of participating laboratories met the ACP Molecular Pathology and Diagnostics Group and American Society of Clinical Oncology guidelines, respectively, for extended RAS testing in the latest assessment. Conclusions: Despite recommendations in the UK and USA on extended RAS testing, there has clearly been, based on these results, a delay in implementation. Inadequate testing results in patients being subjected to harmful treatment regimens, which would not be the case, were routine practice altered, in line with evidence-based guidelines
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