tbuckley/cabot-search huggingface dataset:
Increased serum concentrations of soluble HLA-class I antigens in hepatitis C virus related mixed cryoglobulinaemia
Authors: Sergio Migliaresi, Alessandro Bresciani, Lucia Ambrosone, Marcantonio Spera, Deborah Barbarulo, Vincenza Lombari, Giuseppe Pirozzi, Guglielmo Borgia, Maria Luisa Lombardi, Giuseppe Tirri, Ciro Manzo
Journal: Annals of the Rheumatic Diseases (2000)

To investigate whether quantitative alterations of both beta(2)microglobulin (beta(2)micro) associated HLA class I heavy chains (sHLA-I) and beta(2) micro free class I heavy chains (sHLA-FHC) in sera of patients with hepatitis C virus (HCV) infection occur and whether they distinguish patients with mixed cryoglobulinaemia (MC).83 HCV infected patients were studied and divided into three groups: (A) without cryoglobulinaemia (n=21), (B) with polyclonal MC (n=20), (C) with monoclonal MC (n=42). Serum sHLA-I and sHLA-FHC were measured by double determinant radioimmunoassay using monoclonal antibodies: TP25.99 as catching antibody, and NAMB-1 and HC-10 as revealing antibodies. Western blot identified HLA-I isoforms.The serum concentrations of sHLA-I and of sHLA-FHC in HCV infected patients versus controls were respectively 1.3(0.5) microg/ml (mean (SD)) versus 0.8 (0.3) (p<0. 001) and 13.9 (7.1) ng/ml versus 9.2 (5) (p<0.001). sHLA-I were 1.01 (0.4) microg/ml in group A, 1.04 (0.4) microg/ml in group B, and 1. 47 (0.4) microg/ml in group C (p=0.001). Statistical analysis showed a significant difference versus controls for groups B (p<0.02) and C (p<0.001). sHLA-FHC were 12.8 (8.3) ng/ml in group A, 17.2 (7.1) ng/ml in group B, and 12.9 (6.2) ng/ml in group C (p<0.02). A significant difference versus controls for each group was found (p<0. 02, p<0.001, and p<0.02, respectively). Different patterns of sHLA-I isoforms were observed.Increased serum concentrations of sHLA-I and sHLA-FHC characterise HCV infected patients. The highest sHLA-I concentrations seem to distinguish patients with monoclonal MC. In this last condition sHLA could play a part in the HCV escape and in B cell proliferation. The significance of sHLA-FHC is still undefined.
Four-year experience with Palmaz-Schatz stenting in coronary angioplasty complicated by dissection with threatened or present vessel closure.
Authors: A Schömig, A Kastrati, H Mudra, R Blasini, H Schühlen, V Klauss, G Richardt, F J Neumann
Journal: Circulation (1994)

Abrupt vessel closure after percutaneous transluminal coronary angioplasty (PTCA) is associated with major adverse events. Different surgical and nonsurgical approaches have been advocated to treat or prevent this complication. This study summarizes our 4-year experience with Palmaz-Schatz stenting for the management of 339 patients with present or threatened occlusion after PTCA.Stent implantation was attempted in a total of 339 and 4959 patients with PTCA during the study period and was successful in 327 (96.5%). During the follow-up, events like death, myocardial infarction, need for revascularization (bypass surgery and repeat in-stent angioplasty), and major vascular complications were recorded. Angiographic follow-up at 6 months was performed in 89.3% of the eligible patients. As part of an initial policy, stenting was intended as a bridge to nonemergency bypass surgery in 26 patients. In 301 patients for whom stenting was intended as permanent treatment, early clinical course (first 4 weeks) was characterized by a 1.3% cardiac mortality and a 4.0% nonfatal myocardial infarction rate; bypass surgery was necessary in 1%, and 6.3% required early repeat PTCA. Surgical repair for peripheral vascular complications was required in 5.6%, and major bleeding events were encountered in 9%. The incidence of subacute stent closure was 6.9%, with subsequent recanalization successful in 86%; subacute stent closure was predicted by presence of vessel occlusion before stenting and localization of the stent in a vessel other than the right coronary artery. Survival rate at 2 years was 95.4%, survival without myocardial infarction was 91.1%, and event-free survival was 70.7%. Survival at 2 years was lower for patients with stents in bypass vein grafts and with myocardial infarction after stenting. Six-month control angiography revealed a restenosis rate of 29.6%.Patients with present or threatened occlusion after PTCA may benefit from Palmaz-Schatz stenting. It is associated with a low mortality and myocardial infarction rate and with a long-term event-free rate comparable to that of uncomplicated PTCA.
Hsp70 Duplication in the Drosophila melanogaster Species Group: How and When Did Two Become Five?
Authors: Brian R. Bettencourt, Martin E. Feder
Journal: Molecular Biology and Evolution (2001)

To determine how the modern copy number (5) of hsp70 genes in Drosophila melanogaster evolved, we localized the duplication events that created the genes in the phylogeny of the melanogaster group, examined D. melanogaster genomic sequence to investigate the mechanisms of duplication, and analyzed the hsp70 gene sequences of Drosophila orena and Drosophila mauritiana. The initial two-to-four hsp70 duplication occurred 10–15 MYA, according to fixed in situ hybridization to polytene chromosomes, before the origin and divergence of the melanogaster and five other species subgroups of the melanogaster group. Analysis of more than 30 kb of flanking sequence surrounding the hsp70 gene clusters suggested that this duplication was likely a retrotransposition. For the melanogaster subgroup, Southern hybridization and an hsp70 restriction map confirmed the conserved number (4) and arrangement of hsp70 genes in the seven species other than D. melanogaster. Drosophila melanogaster is unique; tandem duplication and gene conversion at the derived cluster yielded a fifth hsp70 gene. The four D. orena hsp70 genes are highly similar and concertedly evolving. In contrast, the D. mauritiana hsp70 genes are divergent, and many alleles are nonfunctional. The proliferation, concerted evolution, and maintenance of functionality in the D. melanogaster hsp70 genes is consistent with the action of natural selection in this species.
Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial
Authors: David R Holmes, Vivek Y Reddy, Zoltan G Turi, Shephal K Doshi, Horst Sievert, Maurice Buchbinder, Christopher M Mullin, Peter Sick
Journal: The Lancet (2009)
Two factor XI mutations in a Chinese family with factor XI deficiency
Authors: W.Y. Au, J.W. Cheung, C.C.K. Lam, Y.L. Kwong
Journal: American Journal of Hematology (2003)

Abstract We describe a Chinese family with factor XI deficiency, the first reported to date. The proband had factor XI activity of 1% and was heterozygous for two nonsense mutations, an exon‐8 C713→T mutation resulting in Gln263→Term, and an exon‐10 C979→A mutation resulting in Tyr351→Term. Two daughters were heterozygous for the Gln263→Term mutation and two for the Try351→Term mutation. All showed a reduction of factor XI activity to about 50%. The Gln263→Term mutation has been described in two Japanese families, and it remains to be determined whether a common founder exists between the three kindreds. The Try351→Term mutation is novel. Am. J. Hematol. 74:136–138, 2003. © 2003 Wiley‐Liss Inc.
Painful shoulder: comparison of physical examination and ultrasonographic findings
Authors: E Naredo
Journal: Annals of the Rheumatic Diseases (2002)

Background: High frequency ultrasonography is an accurate non-invasive imaging technique for evaluating patients with painful shoulder. Objective: To compare the clinical diagnosis established by a physical examination with high frequency ultrasonographic findings in patients with painful shoulder. Methods: Thirty one consecutive patients with a first flare of shoulder pain were prospectively included in the study. All had a physical examination performed by two blinded rheumatologists. Ultrasonographic examination was carried out within one week of the physical examination by a third rheumatologist experienced in this technique who had no knowledge of the clinical findings. Ultrasonography was considered the optimal diagnostic technique. Results: Clinical assessment showed low accuracy in the diagnosis of periarticular shoulder lesions. Conclusion: Ultrasonography should be used wherever possible to improve diagnosis and treatment of painful shoulder.
Coronary Flow Velocity Reserve After Percutaneous Interventions Is Predictive of Periprocedural Outcome
Authors: M. Albertal, M. Voskuil, J.J. Piek, B. de Bruyne, G. Van Langenhove, P.I. Kay, M.A. Costa, E. Boersma, T. Beijsterveldt, J.E. Sousa, J.A. Belardi, P.W. Serruys
Journal: Circulation (2002)

Because heterogeneous results have been reported, we assessed coronary flow velocity changes in individuals who underwent percutaneous transluminal coronary angioplasty (PTCA) and examined their impact on clinical outcome.As part of the Doppler Endpoints Balloon Angioplasty Trial Europe (DEBATE) II study, 379 patients underwent Doppler flow-guided angioplasty. All patients were evaluated according to their coronary flow velocity reserve (CFVR) results (> or =2.5 or < 2.5) at the end of the procedure. A CFVR < 2.5 after angioplasty was associated with an elevated baseline blood flow velocity in both the target artery and reference artery. CFVR before PTCA and CFVR in the reference artery were independent predictors of an optimal CFVR after balloon angioplasty (CFVR before PTCA: odds ratio [OR], 2.26; 95% confidence interval [CI], 1.57 to 3.24; CFVR in reference artery: OR, 1.90; 95% CI, 1.21 to 2.98; both P<0.001) and stent implantation (before PTCA: OR, 2.54; 95% CI, 1.47 to 4.36; reference artery: OR, 1.97; 95% CI, 1.07 to 3.87; both P<0.05). A low CFVR at the end of the procedure was an independent predictor of major adverse cardiac events (MACE) at 30 days (OR, 4.71; 95% CI, 1.14 to 25.92; P=0.034) and at 1 year (OR, 2.06; 95% CI, 1.16 to 3.66; P=0.014). After excluding MACE at 30 days, no difference in MACE at 1 year was observed between the patients with and without a CFVR < 2.5 at the end of the procedure.A low postprocedural CFVR was associated with a worse periprocedural outcome (which was related to microcirculatory disturbances), but there was no significant difference at late follow-up.
Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance
Authors: Sungsoon Fang, Jae Myoung Suh, Shannon M Reilly, Elizabeth Yu, Olivia Osborn, Denise Lackey, Eiji Yoshihara, Alessia Perino, Sandra Jacinto, Yelizaveta Lukasheva, Annette R Atkins, Alexander Khvat, Bernd Schnabl, Ruth T Yu, David A Brenner, Sally Coulter, Christopher Liddle, Kristina Schoonjans, Jerrold M Olefsky, Alan R Saltiel, Michael Downes, Ronald M Evans
Journal: Nature Medicine (2015)
Molecular Population Genetics of the Insulin/TOR Signal Transduction Pathway: A Network-Level Analysis in Drosophila melanogaster
Authors: D. Alvarez-Ponce, S. Guirao-Rico, D. J. Orengo, C. Segarra, J. Rozas, M. Aguade
Journal: Molecular Biology and Evolution (2011)

The IT—insulin/target of rapamycin (TOR)—signal transduction pathway is a relatively well-characterized pathway that plays a central role in fundamental biological processes. Network-level analyses of DNA divergence in Drosophila and vertebrates have revealed a clear gradient in the levels of purifying selection along this pathway, with the downstream genes being the most constrained. Remarkably, this feature does not result from factors known to affect selective constraint such as gene expression, codon bias, protein length, and connectivity. The present work aims to establish whether the selective constraint gradient detected along the IT pathway at the between-species level can also be observed at a shorter time scale. With this purpose, we have surveyed DNA polymorphism in Drosophila melanogaster and divergence from D. simulans along the IT pathway. Our network-level analysis shows that DNA polymorphism exhibits the same polarity in the strength of purifying selection as previously detected at the divergence level. This equivalent feature detected both within species and between closely and distantly related species points to the action of a general mechanism, whose action is neither organism specific nor evolutionary time dependent. The detected polarity would be, therefore, intrinsic to the IT pathway architecture and function.
Recovery of cognitive function and mood after severe hypoglycemia in adults with insulin-treated diabetes.
Authors: M W Strachan, I J Deary, F M Ewing, B M Frier
Journal: Diabetes Care (2000)

OBJECTIVE: Acute hypoglycemia in humans impairs cognitive functions and alters mood states. The time required for cognitive functions and moods to return to normal after an acute episode of severe hypoglycemia is unknown. RESEARCH DESIGN AND METHODS: Cognitive functions and moods were studied prospectively in 20 subjects with insulin-treated diabetes who had recently experienced a spontaneous episode of severe hypoglycemia ("hypo" subjects) and 20 matched control subjects with insulin-treated diabetes who had not experienced severe hypoglycemia during the preceding year. The hypo subjects had a history of a greater number of episodes of severe hypoglycemia (P = 0.000). Cognitive function tests and mood scales were administered at 1.5, 9, and 30 days after the severe hypoglycemia and at similar intervals for the control subjects. RESULTS: For most of the cognitive tests, no evidence of a "hangover" effect of the acute hypoglycemia on cognitive function was observed (P &amp;gt; 0.05). A trend was noted for levels of hedonic tone (P = 0.082) and energetic arousal (P = 0.053) to improve with time in the hypo subjects but not in the control subjects. However, the hypo subjects had chronically elevated levels of depression (P = 0.011) and anxiety (P = 0.049) and persistently performed more poorly in several cognitive tests, such as the Digit Symbol Test (P = 0.009) and the Stroop Task (P = 0.007). CONCLUSIONS: These results suggest that, in general, recovery from any acute cognitive decrement after severe hypoglycemia was complete by 1.5 days. The cognitive decrements and altered mood states noted in the hypo subjects may be persistent and may be a consequence of previous exposure to recurrent episodes of severe hypoglycemia.
A NEW METHOD FOR MEASURING AIRWAY RESISTANCE IN MAN USING A BODY PLETHYSMOGRAPH: VALUES IN NORMAL SUBJECTS AND IN PATIENTS WITH RESPIRATORY DISEASE 1
Authors: Arthur B. DuBois, Stella Y. Botelho, Julius H. Comroe
Journal: Journal of Clinical Investigation (1956)

Satisfactory methods, utilizing measurements of transthoracic or transpulmonary pressure and airflow, are now available for determining "nonelastic" pulmonary resistance.However, the nonelastic pulmonary resistance has two components, tissue resistance and airway resistance, and no valid direct method is available for measuring either of these components separately in man.Since airway resistance is the ratio of alveolar pressure during flow to airflow, airway resistance alone could be measured if there were a method for determining alveolar pressure during flow.This report presents a new method for accomplishing this measurement, and gives data for airway re- sistance obtained in normal subjects and in patients with respiratory disease.Of previous attempts to measure airway re- sistance, one of the earliest was the painstaking study by Rohrer (1) who made anatomical measurements on the tracheobronchial tree of a human lung post mortem and calculated the cumulative resistance to airflow of the entire system using Poiseuille's law and turbulence theory.The first important experimental study of pulmonary resistance in the living animal was made by von Neergaard and Wirz who, in 1927 (2), analyzed intrapleural pressure into two major components, "dynamic" (which is essentially resistive) and "static" (which is predominantly elastic in nature).This approach made it possible to obtain values for total pulmonary resistance, though not for airway resistance alone.Bayliss and Robertson (3), reasoning that airway resistance, but not tissue resistance, would vary with the viscosity of the gases breathed, ventilated isolated animal lungs with gases of different density and viscosity;
Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis
Authors: H. B. Hammer, S. Odegard, M. K Fagerhol, R. Landewe, D. v. d. Heijde, T. Uhlig, P. Mowinckel, T. K Kvien
Journal: Annals of the Rheumatic Diseases (2007)

Calprotectin is a major leucocyte protein, shown to correlate well with laboratory and clinical assessments in several inflammatory rheumatic diseases, and large concentrations of calprotectin have been found in synovial fluid from patients with rheumatoid arthritis (RA). The objective of the present study was to examine correlations between calprotectin and joint damage.145 patients with RA were analysed cross sectionally with laboratory (calprotectin, C reactive protein (CRP), and erythrocyte sedimentation rate (ESR)), clinical (28 joint counts (tender, swollen), physician global VAS, DAS28 and RA Articular Damage score (RAAD)), and radiographic (plain hand radiographs; modified Sharp's method) measurements, on the same day.Calprotectin showed a highly significant correlation with measures of joint damage; modified Sharp score r = 0.43 (p<0.001) and RAAD r = 0.40 (p<0.001). The association with modified Sharp score and RAAD score was maintained after adjustment for CRP, ESR, rheumatoid factor, DAS28, sex, and age in a multiple regression analysis (p = 0.018 and p = 0.04, respectively), while neither CRP nor ESR showed any independent associations. Highly significant correlations (p<0.001) were also found between calprotectin and both laboratory and clinical markers of inflammation.Calprotectin was found to significantly and independently explain the variation in the radiological and clinical assessments of joint damage. Longitudinal studies are required to examine whether calprotectin may predict the progression of joint damage in RA.
Reduction of otherwise remarkably stable virus-specific cytotoxic T lymphocyte memory by heterologous viral infections.
Authors: L K Selin, K Vergilis, R M Welsh, S R Nahill
Journal: The Journal of Experimental Medicine (1996)

Experimental analyses of the acute cytotoxic T lymphocyte (CTL) response to viruses have focused on studying these infections in immunologically naive hosts. In the natural environment, however, viral CTL responses occur in hosts that are already immune to other infectious agents. To address which factors contribute to the maintenance and waning of immunological memory, the following study examined the frequencies of virus-specific CTL precursor cells (pCTL) not only using the usual experimental paradigm where mice undergo acute infections with a single virus, and in mice immune to a single virus, but also in immune mice after challenge with various heterologous viruses. As determined by limiting dilution assays, the pCTL frequency (p/f) per CD8+ T cell specific for lymphocytic choriomeningitis virus (LCMV), Pichinde virus (PV), or vaccinia virus (VV) increased during the acute infections, peaking at days 7-8 with frequencies as high as 1/27-1/74. Acute viral infections such as these elicit major expansions in the CD8+ T cell number, which has been reported to undergo apoptosis and decline after most of the viral antigen has been cleared. Although the decline in the total number of virus-specific pCTL after their peak in the acute infection was substantial, for all three viruses the virus-specific p/f per CD8+ T cell decreased only two- to fourfold and remained at these high levels with little fluctuation for well over a year. The ratios of the three immunodominant peptide-specific to total LCMV-specific clones remained unchanged between days 7 and 8 of acute infection and long-term memory, suggesting that the apoptotic events did not discriminate on the basis of T cell receptor specificity, but instead nonspecifically eliminated a large proportion of the activated T cells. However, when one to five heterologous viruses (LCMV, PV, VV, murine cytomegalovirus, and vesicular stomatitis virus) were sequentially introduced into this otherwise stable memory pool, the stability of the memory pool was disrupted. With each successive infection, after the immune system had returned to homeostasis, the memory p/f specific to viruses from earlier infections declined. Reductions in memory p/f were observed in all tested immunological compartments (spleen, peripheral blood, lymph nodes, and peritoneal cavity), and on average in the spleen revealed a 3 +/- 0.4-fold decrease in p/f after one additional viral infection and an 8.4 +/- 3-fold decrease after two additional viral infections. Thus, subsequent challenges with heterologous antigens, which themselves induce memory CTL, may contribute to the waning of CTL memory pool to earlier viruses as the immune system accommodates ever-increasing numbers of new memory cells within a limited lymphoid population. This demonstrates that virus infections do not occur in immunological isolation, and that CD8+ T cell responses are continually being modulated by other infectious agents.
High Levels of Nucleolar Expression of Nucleolin Are Associated with Better Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma
Authors: Lan Peng, John Liang, Hua Wang, Xianzhou Song, Asif Rashid, Henry F. Gomez, Lynda J. Corley, James L. Abbruzzese, Jason B. Fleming, Douglas B. Evans, Huamin Wang
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Nucleolin is a major nucleolar protein that has been shown to be overexpressed in rapidly dividing cells and plays an essential role in cell proliferation and survival. However, the expression and significance of nucleolin in pancreatic ductal adenocarcinoma (PDA) have not been studied. Experimental Design: We used a tissue microarray consisting of 1.0-mm cores of tumor and paired nonneoplastic pancreatic tissue from 69 pancreaticoduodenectomy specimens with stage II PDA. Nucleolin expression was evaluated by immunohistochemistry and scored quantitatively by image analysis. Nucleolin expression was classified as nucleolin-high or nucleolin-low using the median nucleolin labeling index of 3.5% as cutoff. Staining results were correlated with clinicopathologic features and survival. Results: Both PDAs and PDA cell lines showed nucleolar staining for nucleolin. Nucleolin expression was higher in PDAs and PDA cell lines than in nonneoplastic ductal epithelial cells. Among the 69 stage II PDAs, 34 (49%) were nucleolin-high. The median overall survival was 65.2 ± 16.3 months for patients who had nucleolin-high PDAs compared with 19.5 ± 3.3 months for patients whose tumors were nucleolin-low (P = 0.03, log-rank method). No significant correlation between nucleolin expression and other clinicopathologic parameters was found. In multivariate analysis, nucleolin expression was a prognostic factor for overall survival in patients with stage II PDA independent of patient's age, gender, tumor size, differentiation, and lymph node status. Conclusions: Nucleolin was overexpressed in PDAs and PDA cell lines. A high level of nucleolar expression of nucleolin was an independent prognostic marker for better survival for patients with stage II PDAs. Clin Cancer Res; 16(14); 3734–42. ©2010 AACR.