tbuckley/cabot-search huggingface dataset:
Antigen-Specific T Helper Cell Function
Authors: Joanne Fanelli Panus, Louise J. McHeyzer-Williams, Michael G. McHeyzer-Williams
Journal: The Journal of Experimental Medicine (2000)

Distinguishing between the development of functional potential in antigen-specific T helper (Th) cells and the delivery of these specialized functions in vivo has been difficult to resolve. Here, we quantify the frequency of cytokine-producing cells within the primary and memory B10.BR Th cell response to pigeon cytochrome c (PCC). In vitro analysis of acquired functional potential indicated no Th1/Th2 cytokine polarity at the peak of the primary response with surprisingly little evidence for the selective preservation of interleukin (IL)-2, tumor necrosis factor (TNF)-α, IL-4, and interferon (IFN)-γ potentials into the memory compartment. However, the expression of these functional potentials appears tightly regulated in vivo. The staggered appearance of primary response cytokines directly ex vivo contrasts markedly with their rapid coordinate expression in the memory response. Frequencies of IL-2–, TNF-α–, IFN-γ–, and IL-10–expressing memory responders increased over their primary response counterparts, but were still markedly lower than revealed in vitro. IL-4–, IFN-γ–, and IL-10–expressing Th cells remained at low but stable frequencies over the first 6 d of the memory response. Analysis of T cell receptor β chain sequences of IL-4– and TNF-α–expressing PCC-specific Th cells provides evidence for early functional commitment among clonal progeny. These data indicate that the development of functional potential is a consequence of initial antigen experience, but delivery of specialized functions is differentially regulated in primary and memory immune responses.
P515 NON-INVASIVE PREDICTION OF CLINICALLY SIGNIFICANT PORTAL HYPERTENSION USING TRANSIENT ELASTOGRAPHY AND SPLEEN DIAMETER/PLATELET COUNT RATIO IN B-VIRAL AND ALCOHOL CIRRHOSIS: EXTERNAL VALIDATION STUDY
Authors: S.K. Baik, Y.Z. Cho, M.Y. Kim, M.Y. Cho, H.W. Hwang, S.O. Kwon, D.J. Kim, K.T. Suk, G.J. Cheon, Y.D. Kim, D.H. Choi
Journal: Journal of Hepatology (2014)
Short Screening Scale for DSM-IV Posttraumatic Stress Disorder
Authors: Naomi Breslau, Edward L. Peterson, Ronald C. Kessler, Lonni R. Schultz
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The authors’ goal was to construct a short screening scale for DSM-IV posttraumatic stress disorder (PTSD). METHOD: They used data from the Detroit Area Survey of Trauma, which is a representative population sample of 2,181 subjects 18–45 years of age. Random digit dialing was used to select the sample, and a computer-assisted telephone interview was used to collect data on traumatic experiences and PTSD. Presence or absence of PTSD was assessed with a telephone-administered structured interview that closely followed the National Institute of Mental Health Diagnostic Interview Schedule for DSM-IV and the World Health Organization Composite International Diagnostic Interview, version 2.1. Best-subset regression analysis and receiver operating characteristic analysis were used to select a subset of items from the structured interview that most efficiently predicted PTSD as diagnosed in the full-length interview. RESULTS: A seven-symptom screening scale for PTSD was selected; five of the symptoms were from the avoidance and numbing group, and two were from the hyperarousal group. A score of 4 or greater on this scale defined positive cases of PTSD with a sensitivity of 80%, specificity of 97%, positive predictive value of 71%, and negative predictive value of 98%. CONCLUSIONS: The short screening scale is an efficient method to screen for PTSD in epidemiologic and clinical studies, given limitations on resources and burden on respondents.
Phase II Trial of Lomustine Plus Temozolomide Chemotherapy in Addition to Radiotherapy in Newly Diagnosed Glioblastoma: UKT-03
Authors: Ulrich Herrlinger, Johannes Rieger, Dorothee Koch, Simon Loeser, Britta Blaschke, Rolf-Dieter Kortmann, Joachim P. Steinbach, Thomas Hundsberger, Wolfgang Wick, Richard Meyermann, Ta-Chih Tan, Clemens Sommer, Michael Bamberg, Guido Reifenberger, Michael Weller
Journal: Journal of Clinical Oncology (2006)

To evaluate toxicity and efficacy of the combination of lomustine, temozolomide (TMZ) and involved-field radiotherapy in patients with newly diagnosed glioblastoma (GBM).Thirty-one adult patients (median Karnofsky performance score 90; median age, 51 years) accrued in two centers received involved-field radiotherapy (60 Gy in 2-Gy fractions) and chemotherapy with lomustine 100 mg/m2 (day 1) and TMZ 100 mg/m2/d (days 2 to 6) with individual dose adjustments according to hematologic toxicity.A median of five courses (range, one to six courses) were delivered. WHO grade 4 hematotoxicity was observed in five patients (16%) and one of these patients died as a result of septicemia. Nonhematologic toxicity included one patient with WHO grade 4 drug-induced hepatitis (leading to discontinuation of lomustine and TMZ) and one patient with WHO grade 2 lung fibrosis (leading to discontinuation of lomustine). The progression-free survival (PFS) rate at 6 months was 61.3%. The median PFS was 9 months (95% CI, 5.3 to 11.7 months), the median overall survival time (MST) was 22.6 months (95% CI, 12.5 to not assessable), the 2-year survival rate was 44.7%. O6-methylguanine-DNA methyltransferase (MGMT) gene-promoter methylation in the tumor tissue was associated with longer PFS (P = .014, log-rank test) and MST (P = .037).The combination of lomustine, TMZ, and radiotherapy had acceptable toxicity and yielded promising survival data in patients with newly diagnosed GBM. MGMT gene-promoter methylation was a strong predictor of survival.
Local `Shwartzman equivalent' reaction in active chronic hepatitis
Authors: M. J. Whelton
Journal: Gut (1972)

The development of a purpura-fulminans-like disorder which is a human equivalent of a local Shwartzman reaction in a woman with active chronic hepatitis is described. The cyclical appearance of blue-black, well circumscribed, haemorrhagic, acutely painful lesions in the buttocks, over the lateral aspects of the thighs, and on the arms suggested the diagnosis. Evidence of increased intravascular coagulation was obtained although interpretation of clotting factor deficiencies in the presence of parenchymal liver disease was difficult. Treatment with heparin arrested the disorder on three separate occasions. The reasons for the development of the syndrome are not clear and even more surprising was the occurrence of such a disorder in the presence of increased fibrinolysis. While disseminated intravascular coagulation has been described in association with liver disease, the development of features of purpura fulminans in such patients does not appear to have been noted.
Effects of exercise training in patients with idiopathic pulmonary arterial hypertension
Authors: F. S. de Man, M. L. Handoko, H. Groepenhoff, A. J. van 't Hul, J. Abbink, R. J. H. Koppers, H. P. Grotjohan, J. W. R. Twisk, H-J. Bogaard, A. Boonstra, P. E. Postmus, N. Westerhof, W. J. van der Laarse, A. Vonk-Noordegraaf
Journal: European Respiratory Journal (2009)

We determined the physiological effects of exercise training on exercise capacity and quadriceps muscle function in patients with idiopathic pulmonary arterial hypertension (iPAH). In total, 19 clinically stable iPAH patients (New York Heart Association II-III) underwent a supervised exercise training programme for the duration of 12 weeks. Maximal capacity, endurance capacity and quadriceps function were assessed at baseline and after 12 weeks. In 12 patients, serial quadriceps muscle biopsies were obtained. 6-min walk distance and peak exercise capacity did not change after training. However, endurance capacity improved significantly after training, demonstrated by a shift of the anaerobic threshold to a higher workload (from 32±5 to 46±6 W; p = 0.003) together with an increase in exercise endurance time (p&lt;0.001). Moreover, exercise training increased quadriceps strength by 13% (p = 0.005) and quadriceps endurance by 34% (p = 0.001). Training enhanced aerobic capacity of the quadriceps, by increasing capillarisation (1.36±0.10 to 1.78±0.13 capillaries per muscle fibre; p&lt;0.001) and oxidative enzyme activity, especially of the type-I (slow) muscle fibres. No changes were found in cross-sectional area and fibre type distribution. Exercise training in iPAH improves exercise endurance and quadriceps muscle function, which is also reflected by structural changes of the quadriceps.
Individual perception of recovery is related to subsequent sprint performance
Authors: Christian J Cook, Chris Martyn Beaven
Journal: British Journal of Sports Medicine (2013)

Training recovery is vital for adaptation and performance, and to avoid cumulative fatigue and symptoms associated with overtraining. The use of cold-water immersion (CWI) as a recovery strategy is common; however, the physiological and biochemical rationale behind its use remains unclear. This study aimed to assess the relationship between body temperature responses to water immersion and individual perception of recovery, with subsequent exercise performance.Twelve male rugby players participated in a 3-week cross-over trial where an intense 60 min conditioning session was followed immediately by 15 min of either 14°C CWI, 30°C warm-water immersion (WWI) or passive control (CON) recovery intervention. Postexercise body temperatures and subjective ratings of the recovery intervention were recorded and subsequently related to performance in a 5×40 m repeated sprint protocol undertaken 24 h later.CWI induced large reductions in core body temperature postimmersion (effect size (ES) range 1.05-3.21) and improved subsequent sprint performance compared to WWI (ES 1.04±0.84) and CON (ES 1.44±0.84). Both the degree of temperature decrease at 60 min postimmersion (r=0.6948; p=0.0121) and the subjective rating of the recovery intervention (r=0.5886; p=0.0441) were related to subsequent sprint performance. A very strong linear correlation was observed when these two factors were integrated (r=0.7743; p=0.0031).A combination of physiological and psychological indices provides an improved indication of subsequent performance and suggests an important role of individual perception in enhancing training recovery.
Molecular evolution of chloroplast DNA sequences.
Authors: S E Curtis, M T Clegg
Journal: Molecular Biology and Evolution (1984)

Comparative data on the evolution of chloroplast genes are reviewed. The chloroplast genome has maintained a similar structural organization over most plant taxa so far examined. Comparisons of nucleotide sequence divergence among chloroplast genes reveals marked similarity across the plant kingdom and beyond to the cyanobacteria (blue-green algae). Estimates of rates of nucleotide substitution indicate a synonymous rate of 1.1 x 10(-9) substitutions per site per year. Noncoding regions also appear to be constrained in their evolution, although addition/deletion events are common. There have also been evolutionary changes in the distribution of introns in chloroplast encoded genes. Relative to mammalian mitochondrial DNA, the chloroplast genome evolves at a conservative rate.
Combined Inhibition of c-Src and Epidermal Growth Factor Receptor Abrogates Growth and Invasion of Head and Neck Squamous Cell Carcinoma
Authors: Priya Koppikar, Seung-Ho Choi, Ann Marie Egloff, Quan Cai, Shinsuke Suzuki, Maria Freilino, Hiroshi Nozawa, Sufi M. Thomas, William E. Gooding, Jill M. Siegfried, Jennifer R. Grandis
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Increased expression and/or activation of epidermal growth factor receptor (EGFR) is associated with tumor progression and poor prognosis in many cancers, including head and neck squamous cell carcinoma (HNSCC). Src family kinases, including c-Src, mediate a variety of intracellular or extracellular signals that contribute to tumor formation and progression. This study was undertaken to elucidate the role of c-Src in the growth and invasion of HNSCC and to determine the effects of combined targeting of EGFR and Src kinases in HNSCC cell lines. Experimental Design: HNSCC cells were engineered to stably express a dominant-active form of c-Src and investigated in cell growth and invasion assays. The biochemical effects of combined treatment with the Src inhibitor AZD0530, a potent, orally active Src inhibitor with Bcr/Abl activity, and the EGFR kinase inhibitor gefitinib were examined, as well as the consequences of dual Src/EGFR targeting on the growth and invasion of a panel of HNSCC cell lines. Results: HNSCC cells expressing dominant-active c-Src showed increased growth and invasion compared with vector-transfected controls. Combined treatment with AZD0530 and gefitinib resulted in greater inhibition of HNSCC cell growth and invasion compared with either agent alone. Conclusions: These results suggest that increased expression and activation of c-Src promotes HNSCC progression where combined targeting of EGFR and c-Src may be an efficacious treatment approach.
ACUTE RHEUMATISM AND ITS RESULTS
Authors: K. D. Wilkinson
Journal: BMJ (1935)

Acute rheumatism is one of the most important diseases of this country-because it is common, because it causes serious cardiac damage and produces reduced efficiency, ill-health, or chronic invalidism in a considerable pro- portion of its victims, and because it shortens many lives.Its history is comparatively brief: Shakespeare makes no use of the word rheumatism in its modern sense, and it was only in the year of his death that acute arthritis was first called rheumatism by a Frenchman, Gwilliam de Baillou.Sydenham's DescriptionsThe first accurate clinical description was written by Sydenham at the end of the seventeenth century.He said: " The disease comes on at any time, but especially in the autumn, and chiefly seizes those that are in the flower of their age . . . it begins with shivering and shaking and presently heat, -restlessness and thirst, and other symptoms which accompany a fever.After a day or two, and sometimes sooner, the patient is troubled with a violent pain sometimes in this, sometimes in that joint, in the wrists and shoulders, but most commonly in the knees.It now and then changes places and seizes elsewhere, leaving some redness and swelling in the part last possessed."He described chorea too, but does not appear to have associated the two conditions.The picture of chorea is very good: " This disease is a kind of convulsion which seizes children of both sexes from the tenth to the four- teenth year.It manifests itself by a halting or un-
Phylodynamics of HIV-1 from a Phase-III AIDS Vaccine Trial in North America
Authors: M. Perez-Losada, D. V. Jobes, F. Sinangil, K. A. Crandall, D. Posada, P. W. Berman
Journal: Molecular Biology and Evolution (2009)

In 2003, a phase III placebo-controlled trial (VAX004) of a candidate HIV-1 vaccine (AIDSVAX B/B) was completed in 5,403 volunteers at high risk for HIV-1 infection from North America and the Netherlands. A total of 368 individuals became infected with HIV-1 during the trial. The envelope glycoprotein gene (gp120) from the HIV-1 subtype B viruses infecting 349 patients was sequenced from clinical samples taken as close as possible to the time of diagnosis, rendering a final data set of 1,047 sequences (1,032 from North America and 15 from the Netherlands). Here, we used these data in combination with other sequences available in public databases to assess HIV-1 variation as a function of vaccination treatment, geographic region, race, risk behavior, and viral load. Viral samples did not show any phylogenetic structure for any of these factors, but individuals with different viral loads showed significant differences (P = 0.009) in genetic diversity. The estimated time of emergence of HIV-1 subtype B was 1966–1970. Despite the fact that the number of AIDS cases has decreased in North America since the early 90s, HIV-1 genetic diversity seems to have remained almost constant over time. This study represents one of the largest molecular epidemiologic surveys of viruses responsible for new HIV-1 infections in North America and could help the selection of epidemiologically representative vaccine antigens to include in the next generation of candidate HIV-1 vaccines.
Induction of Telomere Dysfunction Mediated by the Telomerase Substrate Precursor 6-Thio-2′-Deoxyguanosine
Authors: Ilgen Mender, Sergei Gryaznov, Z. Gunnur Dikmen, Woodring E. Wright, Jerry W. Shay
Journal: Cancer Discovery (2014)

Abstract The relationships between telomerase and telomeres represent attractive targets for new anticancer agents. Here, we report that the nucleoside analogue 6-thio-2′-deoxyguanosine (6-thio-dG) is recognized by telomerase and is incorporated into de novo–synthesized telomeres. This results in modified telomeres, leading to telomere dysfunction, but only in cells expressing telomerase. 6-Thio-dG, but not 6-thioguanine, induced telomere dysfunction in telomerase-positive human cancer cells and hTERT-expressing human fibroblasts, but not in telomerase-negative cells. Treatment with 6-thio-dG resulted in rapid cell death for the vast majority of the cancer cell lines tested, whereas normal human fibroblasts and human colonic epithelial cells were largely unaffected. In A549 lung cancer cell–based mouse xenograft studies, 6-thio-dG caused a decrease in the tumor growth rate superior to that observed with 6-thioguanine treatment. In addition, 6-thio-dG increased telomere dysfunction in tumor cells in vivo. These results indicate that 6-thio-dG may provide a new telomere-addressed telomerase-dependent anticancer approach. Significance: Telomerase is an almost universal oncology target, yet there are few telomerase-directed therapies in human clinical trials. In the present study, we demonstrate a small-molecule telomerase substrate approach that induces telomerase-mediated targeted “telomere uncapping,” but only in telomerase-positive cancer cells, with minimal effects in normal telomerase-negative cells. Cancer Discov; 5(1); 82–95. ©2014 AACR. See related commentary by Wellinger, p. 19. This article is highlighted in the In This Issue feature, p. 1
Usefulness of ultrasonography in the diagnosis of gout: a meta-analysis
Authors: S Mathieu, B Pereira, M Couderc, M Soubrier
Journal: Annals of the Rheumatic Diseases (2013)

In an article published in Annals of the Rheumatic Diseases , Chowalloor et al 1 suggested, based on a literature review, that ultrasonography (US) is a promising tool that could be used in the diagnosis and management of gout. In this letter, we wish to add further data to Chowalloor et al's conclusion. We have performed a meta-analysis (up to July 2012) to investigate the frequency of ultrasonographic signs, that is, joint effusion, synovitis, bone erosion, tophi and double contour (DC), in gout and asymptomatic hyperuricaemia compared with controls (figure 1).



Figure 1 
Prevalence of double contour signs in …
Genome-Wide Allelotypes of Familial Pancreatic Adenocarcinomas and Familial and Sporadic Intraductal Papillary Mucinous Neoplasms
Authors: Tadayoshi Abe, Noriyoshi Fukushima, Kieran Brune, Corinne Boehm, Norihiro Sato, Hiroyuki Matsubayashi, Marcia Canto, Gloria M. Petersen, Ralph H. Hruban, Michael Goggins
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Most familial cancer susceptibility genes are tumor suppressor genes that are biallelically inactivated in familial neoplasms through somatic deletion of the wild-type allele. Identifying the genomic losses that occur in pancreatic neoplasms, particularly those that occur in familial and precursor neoplasms, may help localize the genes responsible for pancreatic cancer susceptibility. Experimental Design: Normal and neoplastic tissue DNA was isolated from fresh-frozen surgically resected tissues from 20 patients with primary familial pancreatic adenocarcinoma (defined as having at least one first-degree relative with pancreatic cancer), 31 with sporadic intraductal papillary mucinous neoplasms (IPMN), and 7 with familial IPMNs using laser capture microdissection. Microdissected DNA was whole genome amplified using multiple strand displacement. Genome-wide allelotypes were determined using 391 microsatellite markers. The accuracy of microdissection and fidelity of the whole genome amplification were determined by comparing the genotypes of microdissected primary pancreatic cancers to the genotypes of xenografts derived from these cancers and by comparing the results of amplified to nonamplified specimens. Results: The concordance of genotypes between LCM whole genome amplified primary pancreatic cancers and their corresponding pancreatic cancer xenograft DNAs was 98%. Among the 20 primary familial pancreatic adenocarcinomas, we found a high prevalence of loss of heterozygosity (LOH) with an average fractional allelic loss (FAL) of 49.9% of an aggregate of 2,378 informative markers. The level of FAL in the IPMNs (10%) was significantly lower than in the pancreatic adenocarcinomas. The most common locus of LOH in the IPMNs was at 19p (LOH at 24% of markers). The regions of frequent allelic loss observed in the familial pancreatic cancers were similar to those found in sporadic pancreatic cancers. Conclusions: The allelic loss patterns of familial and sporadic pancreatic cancers and IPMNs provide clues as to the genomic locations of tumor suppressor genes inactivated in these neoplasms.
Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: Results from the hepatitis C antiviral long-term treatment against cirrhosis trial
Authors: Gregory T. Everson, Mitchell L. Shiffman, John C. Hoefs, Timothy R. Morgan, Richard K. Sterling, David A. Wagner, Shannon Lauriski, Teresa M. Curto, Anne Stoddard, Elizabeth C. Wright
Journal: Hepatology (2011)

Abstract Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C virus (HCV). We measured disease severity by quantitative liver function tests (QLFTs) to determine cutoffs for QLFTs that identified patients who were at low and high risk for a clinical outcome. Two hundred and twenty-seven participants in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial underwent baseline QLFTs and were followed for a median of 5.5 years for clinical outcomes. QLFTs were repeated in 196 patients at month 24 and in 165 patients at month 48. Caffeine elimination rate (k elim ), antipyrine (AP) clearance (Cl), MEGX concentration, methionine breath test (MBT), galactose elimination capacity (GEC), dual cholate (CA) clearances and shunt, perfused hepatic mass (PHM), and liver and spleen volumes (by single-photon emission computed tomography) were measured. Baseline QLFTs were significantly worse ( P = 0.0017 to P &lt; 0.0001) and spleen volumes were larger ( P &lt; 0.0001) in the 54 patients who subsequently experienced clinical outcomes. QLFT cutoffs that characterized patients as “low” and “high risk” for clinical outcome yielded hazard ratios ranging from 2.21 (95% confidence interval [CI]: 1.29–3.78) for GEC to 6.52 (95% CI: 3.63–11.71) for CA clearance after oral administration (Cl oral ). QLFTs independently predicted outcome in models with Ishak fibrosis score, platelet count, and standard laboratory tests. In serial studies, patients with high-risk results for CA Cl oral or PHM had a nearly 15-fold increase in risk for clinical outcome. Less than 5% of patients with “low risk” QLFTs experienced a clinical outcome. Conclusion : QLFTs independently predict risk for future clinical outcomes. By improving risk assessment, QLFTs could enhance the noninvasive monitoring, counseling, and management of patients with chronic HCV. (Hepatology 2012)