426 research outputs found
Cellular radiosensitivity of primary and metastatic human uveal melanoma cell lines
PURPOSE: To investigate the radiosensitivity of uveal melanoma cell lines
by a clonogenic survival assay, to improve the efficiency of the radiation
regimen. METHODS: Four primary and four metastatic human uveal melanoma
cell lines were cultured in the presence of conditioned medium. After
single-dose irradiation (0-12 Gy), colonies were allowed to form for 6 to
14 days. Two cutaneous melanomas cell lines were also tested for
comparison. The survival curves were analyzed by the linear quadratic (LQ)
model, and the surviving fraction at a dose of 2 Gy (SF(2)), the SF at 10
Gy (SF(10)), the ratio of initial irreparably damaged DNA
(alpha-coefficient) to the capacity to repair sublethally damaged DNA
(beta-coefficient), and the plating efficiency were calculated. RESULTS:
The melanomas displayed a wide range of initial irreparable DNA damage
(alpha-component), as well as a capacity for repair of sublethal DNA
damage (beta-component), which ultimately resulted in a wide range of
alpha/beta ratios. These findings were similar in both primary and
metastatic melanomas and were comparable with data obtained from two
cutaneous melanomas. CONCLUSIONS: Cell lines obtained from primary and
metastatic human uveal melanomas displayed a wide range of
radiosensitivity, similar to that published for cutaneous melanomas.
Translating these data to the clinical setting indicates that a
fractionated dose of 8 to 10 Gy administered in three to four fractions,
as currently delivered in many centers, should be sufficient to eradicate
tumors of approximately 1 cm(3)
Books
Human neurology The Human Central Nervous System: A Synopsis and Atlas. 3rd revised ed. Ed. by R. Nieuwenhuys, J. Voogd, C. H. R. van Huijzen. Pp. xii + 437. Illustrated. DM 85. Berlin: SpringerVerlag. 1988.Paediatric respiratory disorders Kendig's Disorders of the Respiratory Tract in Children. 5th ed. Ed. by Victor Chernick. Consulting ed. Edwin L. Kendig, jun. Pp. xxi + 1055. Philadelphia: WB Saunders. 1990.Maxillofacial imaging Maxillofacial Imaging. Ed. by A. M. Delbalso. pp. Vlll + 799. Illustrated. Kent: Harcourt Brace Jovanovich. 1990.Introduction to philosophy of medicine Philosophy of Medicine: An Introduction. Ed. by H. R. Wulff, S. A. Pedersen and R. Rosenberg. pp. xv + 222. £14,95. Oxford: Blackwell. 1990.Cataract management Management of Cataract in Primary Health Care Services. Pp. vi + 43. Illustrated. SFr. 15. Geneva: WHO. 1990.Family practice-management Family Practice Management. Ed. by G. J. and C. M. 1. Pistorius. Pp. 587. Illustrated. R99,50. Parow: Haurn/De Jager. J99O.Obstetrics and gynaecology Essential Obstetrics and Gynaecology. By E. Malcolm Symonds. pp. vi + 266. Illustrated. Edinburgh: Maskew Miller Longman.Surgical memoirs Surgical Roots and Branches. Ed. by R. Murley. Pp. x + 341. Illustrated. £18,50. Hamilton: Libriger Book Distribution. 1990.Survival in a hostile environment Staying Alive. Ed. by Ron Reid-Daly. Pp. ix + 259. Illustrated. R49,95. Rivonia: Ashami. 1990.Urolithiasis Urolithiasis: Medical and Surgical Reference. Ed. by M. 1. Resnick and C. Y. C. Pak. Pp. x + 375. Illustrated. R53,50. Kent: Harcoun Brace Jovanovich. 1990.Mental health in primary health care The Introduction of a Mental Health Component into Primary Health Care. pp. 1-59. SFr. 11,50. Geneva: WHO. 1990Tuberculosis in South Africa White Plague, Black Labor: Tuberculosis and the Political Economy of Health and Disease in South Africa. Ed. by Randall M. Packard. pp. xxii + 389. Illustrated. 15,95 (paperback). California: University of California Press. 1989.Medical research Research in Medicine:"A Guide to Writing a Thesis in the Medical Sciences. Ed. by G. Murrell, C. Huang and H. Ellis. PP: xii + 105. Illustrated. £19,50 (hIb) £7,50 (Plb). Cambridge: Cambridge University Press. 1990
Detection of genetic prognostic markers in uveal melanoma biopsies using fluorescence in situ hybridization
PURPOSE: In uveal melanoma, specific chromosomal abnormalities are known
to correlate with the risk of metastases; changes in chromosomes 3 and 8q
correlate strongly with a decreased survival of the patient, whereas
chromosome 6 abnormalities are associated with a better prognosis.
Usual
Metastatic disease in polyploid uveal melanoma patients is associated with BAP1 mutations
PURPOSE. Most of the uvea melanoma (UM) display a near-diploid (normal, ~2N) karyotype with only a few chromosomal changes. In contrast to these simple aberrations 18% of the UM samples show a polyploid character (>2N) and this was associated with an unfavorable prognosis. This study attempts to gain insight in the prognostic value of polyploidy in UM. METHODS. In 202 patients the ploidy status of the UM was determined using cytogenetic analysis, fluorescence-in-situ-hybridization (FISH), multiplex ligation dependent probe amplification (MLPA), and/or single nucleotide polymorphism (SNP) array analysis. Immunohistochemistry was used to determine the BAP1 expression and mutation analyses of BAP1 (coding regions) and the mutation hotspots for the SF3B1, EIF1AX, GNAQ, and GNA11 genes was carried out using Sanger sequencing or whole-exome sequencing. RESULTS. Twenty-three patients had a polyploid UM karyotype (11.4%). Patients with a polyploid tumor had larger tumors (15.61 vs. 13.13 mm, P = 0.004), and more often loss of heterozygosity of chromosome 3 (P ¼ 0.003). No difference in occurrence of mutations between polyploid and diploid tumors was observed for BAP1, SF3B1, EIF1AX, GNAQ, and GNA11. Polyploidy did not affect survival (P = 0.143). BAP1 deficiency was the only significant independent prognostic predictor for patients with polyploid tumors, with a 16- fold increased hazard ratio (HR 15.90, P = 0.009). CONCLUSIONS. The prevalence of mutations in the UM related genes is not different in polyploid UM compared with diploid UM. Moreover, similar to patients with diploid UM, BAP1 mutation is the most significant prognostic predictor of metastasis in patients with polyploid UM
Master Sculptor at Work: Enteropathogenic Escherichia coli Infection Uniquely Modifies Mitochondrial Proteolysis during Its Control of Human Cell Death
Enteropathogenic Escherichia coli (EPEC) causes severe diarrheal disease
and is present globally. EPEC virulence requires a bacterial type III secretion system
to inject 20 effector proteins into human intestinal cells. Three effectors travel to
mitochondria and modulate apoptosis; however, the mechanisms by which effectors
control apoptosis from within mitochondria are unknown. To identify and quantify
global changes in mitochondrial proteolysis during infection, we applied the mitochondrial terminal proteomics technique mitochondrial stable isotope labeling by
amino acids in cell culture-terminal amine isotopic labeling of substrates (MS-TAILS).
MS-TAILS identified 1,695 amino N-terminal peptides from 1,060 unique proteins
and 390 N-terminal peptides from 215 mitochondrial proteins at a false discovery
rate of 0.01. Infection modified 230 cellular and 40 mitochondrial proteins, generating 27 cleaved mitochondrial neo-N termini, demonstrating altered proteolytic processing within mitochondria. To distinguish proteolytic events specific to EPEC from
those of canonical apoptosis, we compared mitochondrial changes during infection
with those reported from chemically induced apoptosis. During infection, fewer than
half of all mitochondrial cleavages were previously described for canonical apoptosis, and we identified nine mitochondrial proteolytic sites not previously reported,
including several in proteins with an annotated role in apoptosis, although none occurred at canonical Asp-Glu-Val-Asp (DEVD) sites associated with caspase cleavage.
The identification and quantification of novel neo-N termini evidences the involvement of noncaspase human or EPEC protease(s) resulting from mitochondrialtargeting effectors that modulate cell death upon infection. All proteomics data are
available via ProteomeXchange with identifier PXD016994.
IMPORTANCE To our knowledge, this is the first study of the mitochondrial proteome or N-terminome during bacterial infection. Identified cleavage sites that had
not been previously reported in the mitochondrial N-terminome and that were not
generated in canonical apoptosis revealed a pathogen-specific strategy to control
human cell apoptosis. These data inform new mechanisms of virulence factors targeting mitochondria and apoptosis during infection and highlight how enteropathogenic Escherichia coli (EPEC) manipulates human cell death pathways during infection, including candidate substrates of an EPEC protease within mitochondria. This
understanding informs the development of new antivirulence strategies against the
many human pathogens that targe
Spliceosome mutations in uveal melanoma
Uveal melanoma (UM) is the most common primary intraocular malignancy of the eye. It has a high metastatic potential and mainly spreads to the liver. Genetics play a vital role in tumor classification and prognostication of UM metastatic disease. One of the driver genes mutated in metastasized UM is subunit 1 of splicing factor 3b (SF3B1), a component of the spliceosome complex. Recurrent mutations in components of the spliceosome complex are observed in UM and other malignancies, suggesting an important role in tumorigenesis. SF3B1 is the most common mutated spliceosome gene and in UM it is associated with late-onset metastasis. This review summarizes the genetic and epigenetic insights of spliceosome mutations in UM. They form a distinct subgroup of UM and have similarities with other spliceosome mutated malignancies
Genetics of ocular melanoma: Insights into genetics, inheritance and testing
Ocular melanoma consists of posterior uveal melanoma, iris melanoma and conjunctival melanoma. T
Search for charginos in e+e- interactions at sqrt(s) = 189 GeV
An update of the searches for charginos and gravitinos is presented, based on
a data sample corresponding to the 158 pb^{-1} recorded by the DELPHI detector
in 1998, at a centre-of-mass energy of 189 GeV. No evidence for a signal was
found. The lower mass limits are 4-5 GeV/c^2 higher than those obtained at a
centre-of-mass energy of 183 GeV. The (\mu,M_2) MSSM domain excluded by
combining the chargino searches with neutralino searches at the Z resonance
implies a limit on the mass of the lightest neutralino which, for a heavy
sneutrino, is constrained to be above 31.0 GeV/c^2 for tan(beta) \geq 1.Comment: 22 pages, 8 figure
Hadronization properties of b quarks compared to light quarks in e+e- -> q qbar from 183 to 200 GeV
The DELPHI detector at LEP has collected 54 pb^{-1} of data at a
centre-of-mass energy around 183 GeV during 1997, 158 pb^{-1} around 189 GeV
during 1998, and 187 pb^{-1} between 192 and 200 GeV during 1999. These data
were used to measure the average charged particle multiplicity in e+e- -> b
bbar events, _{bb}, and the difference delta_{bl} between _{bb} and the
multiplicity, _{ll}, in generic light quark (u,d,s) events: delta_{bl}(183
GeV) = 4.55 +/- 1.31 (stat) +/- 0.73 (syst) delta_{bl}(189 GeV) = 4.43 +/- 0.85
(stat) +/- 0.61 (syst) delta_{bl}(200 GeV) = 3.39 +/- 0.89 (stat) +/- 1.01
(syst). This result is consistent with QCD predictions, while it is
inconsistent with calculations assuming that the multiplicity accompanying the
decay of a heavy quark is independent of the mass of the quark itself.Comment: 13 pages, 2 figure
Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector
A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
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