286 research outputs found
101: High-dose chemotherapy with autologous stem cell transplantation in 61 patients with light chain amyloidosis A single centre experience
Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity
We initially performed a mutation screen of the coding region of the MC4R in 808 extremely obese children and adolescents and 327 underweight or normal-weight controls allowing for a case-control study. A total of 16 different missense, nonsense, and frameshift mutations were found in the obese study group; five of these have not been observed previously. In vitro assays revealed that nine [the haplotype (Y35X; D37V) was counted as one mutation] of the 16 mutations led to impaired cAMP responses, compared with wild-type receptor constructs. In contrast, only one novel missense mutation was detected in the controls, which did not alter receptor function. The association test based on functionally relevant mutations was positive (P = 0.006, Fisher's exact test, one-sided). We proceeded by screening a total of 1040 parents of 520 of the aforementioned obese young index patients to perform transmission disequilibrium tests. The 11 parental carriers of functionally relevant mutations transmitted the mutation in 81.8% (P = 0.033; exact one-sided McNemar test). These results support the hypothesis that these MC4R mutations represent major gene effects for obesity
Cosmic Evolution of Star Formation In SDSS Quasar Hosts Since z=1
We present Spitzer IRS observations of a complete sample of 57 SDSS type-1
quasars at z~1. Aromatic features at 6.2 and/or 7.7 um are detected in about
half of the sample and show profiles similar to those seen in normal galaxies
at both low- and high-redshift, indicating a star-formation origin for the
features. Based on the ratio of aromatic to star-formation IR (SFIR)
luminosities for normal star-forming galaxies at z~1, we have constructed the
SFIR luminosity function (LF) of z~1 quasars. As we found earlier for
low-redshift PG quasars, these z~1 quasars show a flatter SFIR LF than do z~1
field galaxies, implying the quasar host galaxy population has on average a
higher SFR than the field galaxies do. As measured from their SFIR LF,
individual quasar hosts have on average LIRG-level SFRs, which mainly arise in
the circumnuclear regions. By comparing with similar measurements of
low-redshift PG quasars, we find that the comoving SFIR luminosity density in
quasar hosts shows a much larger increase with redshift than that in field
galaxies. The behavior is consistent with pure density evolution since the
average SFR and the average SFR/BH-accretion-rate in quasar hosts show little
evolution with redshift. For individual quasars, we have found a correlation
between the aromatic-based SFR and the luminosity of the nuclear radiation,
consistent with predictions of some theoretical models. We propose that type 1
quasars reside in a distinct galaxy population that shows elliptical morphology
but that harbors a significant fraction of intermediate-age stars and is
experiencing intense circumnuclear star formation.Comment: Accepted for publication in ApJ, 20 pages, 11 figure
PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment
Kaposiâs sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis.Fil: Naipauer, Julian. Miami University; Estados Unidos. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Rosario, Santas. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Gupta, Sachin. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Premer, Courtney. Miami University; Estados UnidosFil: MĂ©ndez SolĂs, Omayra. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Schlesinger, Mariana. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Ponzinibbio, Maria Virginia. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Jain, Vaibhav. University of Florida; Estados UnidosFil: Gay, Lauren. University of Florida; Estados UnidosFil: Renne, Rolf. University of Florida; Estados UnidosFil: Chan, Ho Lam. Miami University; Estados UnidosFil: Morey, Lluis. Miami University; Estados UnidosFil: Salyakina, Daria. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Abba, MartĂn Carlos. Miami University; Estados Unidos. Universidad Nacional de La Plata. Facultad de Ciencias MĂ©dicas. Centro de Investigaciones InmunolĂłgicas BĂĄsicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Williams, Sion. Miami University; Estados UnidosFil: Hare, Joshua M.. Miami University; Estados UnidosFil: Goldschmidt Clermont, Pascal. Miami University; Estados UnidosFil: Mesri, Enrique Alfredo. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Miami University; Estados Unido
Familial Mediterranean fever, Inflammation and Nephrotic Syndrome: Fibrillary Glomerulopathy and the M680I Missense Mutation
BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by inflammatory serositis (fever, peritonitis, synovitis and pleuritis). The gene locus responsible for FMF was identified in 1992 and localized to the short arm of chromosome 16. In 1997, a specific FMF gene locus, MEFV, was discovered to encode for a protein, pyrin that mediates inflammation. To date, more than forty missense mutations are known to exist. The diversity of mutations identified has provided insight into the variability of clinical presentation and disease progression. CASE REPORT: We report an individual heterozygous for the M680I gene mutation with a clinical diagnosis of FMF using the Tel-Hashomer criteria. Subsequently, the patient developed nephrotic syndrome with biopsy-confirmed fibrillary glomerulonephritis (FGN). Further diagnostic studies were unremarkable with clinical workup negative for amyloidosis or other secondary causes of nephrotic syndrome. DISCUSSION: Individuals with FMF are at greater risk for developing nephrotic syndrome. The most serious etiology is amyloidosis (AA variant) with renal involvement, ultimately progressing to end-stage renal disease. Other known renal diseases in the FMF population include IgA nephropathy, IgM nephropathy, Henoch-Schönlein purpura as well as polyarteritis nodosa. CONCLUSION: To our knowledge, this is the first association between FMF and the M680I mutation later complicated by nephrotic syndrome and fibrillary glomerulonephritis
High-dose chemotherapy and autologous stem cell transplantation of patients with multiple myeloma in an outpatient setting
Background: High-dose (HD) chemotherapy with melphalan and autologous blood stem cell transplantation (ABSCT) for treatment of symptomatic multiple myeloma (MM) on an outpatient basis has been well established in the USA and Canada, whereas in Germany and Western Europe an inpatient setting is the current standard. We report on a German single-centre program to offer the procedure on an outpatient basis to selected patients. Methods: Major requirements included: patients had to have family and/or other caregivers, had to be able to reach the hospital within 45Â min and have an ECOG performance score of 0â1. Patients with severe co-morbidities were not included. Results: From September 2012 until April 2016, 21 patients with MM stage IIIA were enrolled. All engrafted within the expected time range (median 14Â days), and no severe adverse events occurred. 14 patients (67%) had an episode of neutropenic fever and blood cultures were positive in 4 patients (19%). Although rather liberal criteria for hospital admission were applied, 14 patients (67%) were treated entirely on an outpatient basis. Conclusions: HD chemotherapy and ABSCT on an outpatient basis is safe and feasible if it is conducted in an elaborate surveillance program. The feedback from patients was very positive, thus encouraging further expansion of the program
Optical variability properties of high luminosity AGN classes
We present the results of a comparative study of the intra-night optical
variability (INOV) characteristics of radio-loud and radio-quiet quasars, which
involves a systematic intra-night optical monitoring of seven sets of high
luminosity AGNs covering the redshift range {\it z} to {\it z}
. The sample, matched in the optical luminosity -- redshift (M
-- z) plane, consists of seven radio-quiet quasars (RQQs), eight radio
lobe-dominated quasars (LDQs), six radio core-dominated quasars (CDQs) and five
BL Lac objects (BLs). Systematic CCD observations, aided by a careful data
analysis procedure, have allowed us to detect INOV with amplitudes as low as
1%. Present observations cover a total of 113 nights (720 hours) with only a
single quasar monitored as continuously as possible on a night. Considering
cases of only unambiguous detections of INOV we have estimated duty cycles
(DCs) of 17%, 12%, 20% and 72% respectively for RQQs, LDQs, CDQs, and BLs. The
low amplitude and low DC of INOV shown by RQQs compared to BLs can be
understood in terms of their having optical synchrotron jets which are modestly
misdirected from us. From our fairly extensive dataset, no unambiguous general
trend of a correlation between the INOV amplitude and the apparent optical
brightness of the quasar is noticed.Comment: 36 pages, 14 Figures, due to large size Fig. 5,6,11 and 12 are not
included. Intersted people contact to [email protected]. Submitted to
Journal of Astrophysics and Astronom
Sensitivity of a tonne-scale NEXT detector for neutrinoless double beta decay searches
The Neutrino Experiment with a Xenon TPC (NEXT) searches for the neutrinoless
double-beta decay of Xe-136 using high-pressure xenon gas TPCs with
electroluminescent amplification. A scaled-up version of this technology with
about 1 tonne of enriched xenon could reach in less than 5 years of operation a
sensitivity to the half-life of neutrinoless double-beta decay decay better
than 1E27 years, improving the current limits by at least one order of
magnitude. This prediction is based on a well-understood background model
dominated by radiogenic sources. The detector concept presented here represents
a first step on a compelling path towards sensitivity to the parameter space
defined by the inverted ordering of neutrino masses, and beyond.Comment: 22 pages, 11 figure
a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma
Background Despite novel therapeutic agents, most multiple myeloma (MM)
patients eventually relapse. Two large phase III trials have shown
significantly improved response rates (RR) of lenalidomide/dexamethasone
compared with placebo/dexamethasone in relapsed MM (RMM) patients. These
results have led to the approval of lenalidomide for RMM patients and
lenalidomide/dexamethasone has since become a widely accepted second-line
treatment. Furthermore, in RMM patients consolidation with high-dose
chemotherapy plus autologous stem cell transplantation has been shown to
significantly increase progression free survival (PFS) as compared to
cyclophosphamide in a phase III trial. The randomized prospective ReLApsE
trial is designed to evaluate PFS after lenalidomide/dexamethasone induction,
high-dose chemotherapy consolidation plus autologous stem cell transplantation
and lenalidomide maintenance compared with the well-established
lenalidomide/dexamethasone regimen in RMM patients. Methods/Design ReLApsE is
a randomized, open, multicenter phase III trial in a planned study population
of 282 RMM patients. All patients receive three lenalidomide/dexamethasone
cycles and - in absence of available stem cells from earlier harvesting -
undergo peripheral blood stem cell mobilization and harvesting. Subsequently,
patients in arm A continue on consecutive lenalidomide/dexamethasone cycles,
patients in arm B undergo high dose chemotherapy plus autologous stem cell
transplantation followed by lenalidomide maintenance until discontinuation
criteria are met. Therapeutic response is evaluated after the 3rd (arm Aâ+âB)
and the 5th lenalidomide/dexamethasone cycle (arm A) or 2 months after
autologous stem cell transplantation (arm B) and every 3 months thereafter
(arm Aâ+âB). After finishing the study treatment, patients are followed up for
survival and subsequent myeloma therapies. The expected trial duration is 6.25
years from first patient in to last patient out. The primary endpoint is PFS,
secondary endpoints include overall survival (OS), RR, time to best response
and the influence of early versus late salvage high dose chemotherapy plus
autologous stem cell transplantation on OS. Discussion This phase III trial is
designed to evaluate whether high dose chemotherapy plus autologous stem cell
transplantation and lenalidomide maintenance after lenalidomide/dexamethasone
induction improves PFS compared with the well-established continued
lenalidomide/dexamethasone regimen in RMM patients. Trial registration:
ISRCTN16345835 (date of registration 2010-08-24)
High-dose chemotherapy and autologous stem cell transplantation of patients with multiple myeloma in an outpatient setting
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