tbuckley/cabot-search huggingface dataset:
Effectiveness and Safety of Sirolimus-Eluting Stents in the Treatment of Restenosis After Coronary Stent Placement
Authors: Franz-Josef Neumann, Walter Desmet, Eberhard Grube, Johannes Brachmann, Patrizia Presbitero, Paolo Rubartelli, Andreas Mügge, Francesco Di Pede, Diana Füllgraf, Wim Aengevaeren, Leonardo Spedicato, Jeffrey J. Popma
Journal: Circulation (2005)

Background— In-stent restenosis is notoriously difficult to treat by repeat catheter intervention because of its propensity for aggressive recurrent neointimal formation. This study sought to assess the effectiveness and safety of the sirolimus-eluting stent in the treatment of in-stent restenosis. Methods and Results— The study was designed as a prospective multicenter registry. We included 162 patients with in-stent restenosis of a native coronary artery who had a clinical indication for repeat intervention. Patients were scheduled for follow-up angiography at 6 months. The primary end point was in-lesion late loss. Follow-up angiography was performed in 155 patients. We obtained an in-lesion late loss of 0.08±0.49 mm and a binary restenosis rate of 9.7% (15/155), which prompted reintervention in 7.4% (12/162) at 9 months. The 9-month rate of death was 1.2% (2/162) and that of nonfatal myocardial infarction was 1.2% (2/162). Conclusions— Sirolimus-eluting stents were highly efficacious and safe in the treatment of in-stent restenosis. Our study provides rationale for the use of sirolimus-eluting stents in the treatment of in-stent restenosis.
Multivariate analysis of prognostic factors in metastatic breast cancer.
Authors: G N Hortobagyi, T L Smith, S S Legha, K D Swenerton, E A Gehan, H Y Yap, A U Buzdar, G R Blumenschein
Journal: Journal of Clinical Oncology (1983)

Univariate and multivariate analyses were conducted on data collected from the records of 619 patients with metastatic breast cancer in whom an Adriamycin-containing chemotherapeutic regimen was used. Using a forward, stepwise logistic regression procedure, several models or equations in which a small number of pretreatment factors were incorporated were generated and the probability of response to therapy was accurately predicted. The predictive ability of these models was tested retrospectively in 546 of the 619 patients from whom the data were derived and prospectively in a new population of 200 patients with metastatic breast cancer also treated with a therapeutically equivalent Adriamycin combination. Using similar univariate techniques, pretreatment factors were correlated with the length of survival after therapy. The proportional hazard model of Cox was used to develop a regression model relating survival to pretreatment characteristics in much the same manner as that of the response model. The total population of the initial group of patients was divided according to four levels of hazard ratio, and survival distributions were compared. This model also was tested progressively and its predictive capability was confirmed. The prediction of individual outcome is a valuable capability in the comparison of clinical trials and the continuing evaluation of biologic changes in patients with metastatic carcinoma; such a method is described in this paper.
Increase in laminin expression in allergic airway remodelling and decrease by dexamethasone
Authors: P.E. Christie, M. Jonas, C-H. Tsai, E.Y. Chi, W.R. Henderson
Journal: European Respiratory Journal (2004)

Lung expression of the extracellular matrix protein, laminin, and its receptor, laminin‐1 receptor, were examined in a mouse model of asthma with airway remodelling. Ovalbumin (OVA) was administered to BALB/c mice, intraperitoneally on days 0 and 14, and intranasally periodically between days 14 and 75. The mice developed airway eosinophil and mononuclear inflammatory cell infiltration and fibrosis. On day 76, a marked increase in total laminin was seen in the airways of OVA‐treated mice compared to controls by Western blot analysis. The increased laminin expression was detected immunocytochemically in the thickened subepithelial basement membrane and around airways and blood vessels. The OVA‐treated mice showed increased expression of the α1, β1, and γ1 chains of the laminin‐1 isoform in monocytes, macrophages and eosinophils infiltrating the airways. Laminin‐1 receptor expression was increased in inflammatory and endothelial cells in the lungs of OVA‐treated mice compared to controls. Treatment of OVA‐sensitised/challenged mice with dexamethasone reduced airway expression of laminin and laminin‐1 receptor in OVA‐treated mice but not airway hyperresponsiveness to methacholine. Laminin deposition may be an important component of the airway remodelling observed in chronic allergic lung inflammation and is a process modulated by corticosteroids.
Studies on the Coronary Circulation during Rejection of the Heterotopically Transplanted Dog Heart
Authors: HENRY J. PAOLONI, DAVID E. L. Wilcken, ATHOL W. J. Lykke
Journal: Circulation Research (1973)

Coronary blood flow and vascular reactivity were studied at intervals after donor dog hearts were transplanted into the necks of recipient dogs. Coronary blood flow was measured with an electromagnetic flow transducer on the carotid artery of the recipient dog, and coronary vascular reactivity was assessed from the response of the coronary vessels to the vasodilator drugs, dipyridamole and adenosine. During the first 4 days after the transplant, resting coronary blood flow and vascular resistance did not change. Responses to dipyridamole and adenosine were unchanged during the first 2 days but were reduced on the third and fourth days. Increased vascular permeability to circulating Evans blue dye and deposition of colloidal carbon in venules occurred in association with small increases in left ventricular myocardial water content 3 and 4 days after the transplant. These changes indicate that an inflammatory response accompanies the onset of histological evidence of rejection at 3 and 4 days. The reduced vascular reactivity of the transplanted heart at 3 and 4 days may be related to morphological changes in arterioles rather than to gross edema formation during rejection.
Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity
Authors: Hitoshi Suzuki, Run Fan, Zhixin Zhang, Rhubell Brown, Stacy Hall, Bruce A. Julian, W. Winn Chatham, Yusuke Suzuki, Robert J. Wyatt, Zina Moldoveanu, Jeannette Y. Lee, James Robinson, Milan Tomana, Yasuhiko Tomino, Jiri Mestecky, Jan Novak
Journal: Journal of Clinical Investigation (2009)

IgA nephropathy (IgAN) is characterized by circulating immune complexes composed of galactose-deficient IgA1 and a glycan-specific IgG antibody. These immune complexes deposit in the glomerular mesangium and induce the mesangioproliferative glomerulonephritis characteristic of IgAN. To define the precise specificities and molecular properties of the IgG antibodies, we generated EBV-immortalized IgG-secreting lymphocytes from patients with IgAN and found that the secreted IgG formed complexes with galactose-deficient IgA1 in a glycan-dependent manner. We cloned and sequenced the heavy- and light-chain antigen-binding domains of IgG specific for galactose-deficient IgA1 and identified an A to S substitution in the complementarity-determining region 3 of the variable region of the gene encoding the IgG heavy chain in IgAN patients. Furthermore, site-directed mutagenesis that reverted the residue to alanine reduced the binding of recombinant IgG to galactose-deficient IgA1. Finally, we developed a dot-blot assay for the glycan-specific IgG antibody that differentiated patients with IgAN from healthy and disease controls with 88% specificity and 95% sensitivity and found that elevated levels of this antibody in the sera of patients with IgAN correlated with proteinuria. Collectively, these findings indicate that glycan-specific antibodies are associated with the development of IgAN and may represent a disease-specific marker and potential therapeutic target.
Interleukin-1β and Tumor Necrosis Factor-α Decrease Collagen Synthesis and Increase Matrix Metalloproteinase Activity in Cardiac Fibroblasts In Vitro
Authors: Deborah A. Siwik, Donny L.-F. Chang, Wilson S. Colucci
Journal: Circulation Research (2000)

Abstract —We tested the hypothesis that the inflammatory cytokines can regulate fibroblast extracellular matrix metabolism. Neonatal and adult rat cardiac fibroblasts cultures in vitro were exposed to interleukin (IL)–1β (4 ng/mL), tumor necrosis factor-α (TNF-α; 100 ng/mL), IL-6 (10 ng/mL), or interferon-γ (IFN-γ; 500 U/mL) for 24 hours. IL-1β, and to a lesser extent TNF-α, decreased collagen synthesis, which was measured as collagenase-sensitive [ 3 H]proline incorporation, but had no effect on cell number or total protein synthesis. IL-1β decreased the expression of procollagen α 1 (I), α 2 (I), and α1(III) mRNA, but increased the expression of procollagen α 1 (IV), α 2 (IV), and fibronectin mRNA, indicating a selective transcriptional downregulation of fibrillar collagen synthesis. IL-1β and TNF-α each increased total matrix metalloproteinase (MMP) activity as measured by in-gel zymography, causing specific increases in the bands corresponding to MMP-13, MMP-2, and MMP-9. IL-1β increased the expression of proMMP-2 and proMMP-3 mRNA, suggesting that increased metalloproteinase activity is due, at least in part, to increased transcription. The effects of IL-1β were not dependent on NO production. Thus, IL-1β and TNF-α decrease collagen synthesis and activate MMPs that degrade collagen. These observations suggest that IL-1β and TNF-α may contribute to ventricular dilation and myocardial failure by promoting the remodeling of interstitial collagen.
Expansion of a Regional ST-Segment–Elevation Myocardial Infarction System to an Entire State
Authors: James G. Jollis, Hussein R. Al-Khalidi, Lisa Monk, Mayme L. Roettig, J. Lee Garvey, Akinyele O. Aluko, B. Hadley Wilson, Robert J. Applegate, Greg Mears, Claire C. Corbett, Christopher B. Granger
Journal: Circulation (2012)

Despite national guidelines calling for timely coronary artery reperfusion, treatment is often delayed, particularly for patients requiring interhospital transfer.One hundred nineteen North Carolina hospitals developed coordinated plans to rapidly treat patients with ST-segment-elevation myocardial infarction according to presentation: walk-in, ambulance, or hospital transfer. A total of 6841 patients with ST-segment-elevation myocardial infarction (3907 directly presenting to 21 percutaneous coronary intervention hospitals, 2933 transferred from 98 non-percutaneous coronary intervention hospitals) were treated between July 2008 and December 2009 (age, 59 years; 30% women; 19% uninsured; chest pain duration, 91 minutes; shock, 9.2%). The rate of patients not receiving reperfusion fell from 5.4% to 4.0% (P=0.04). Treatment times for hospital transfer patients substantially improved. First-hospital-door-to-device time for hospitals that adopted a "transfer for percutaneous coronary intervention" reperfusion strategy fell from 117 to 103 minutes (P=0.0008), whereas times at hospitals with a mixed strategy of transfer or fibrinolysis fell from 195 to 138 minutes (P=0.002). Median door-to-device times for patients presenting directly to PCI hospitals fell from 64 to 59 minutes (P<0.001). Emergency medical services-transported patients were most likely to reach door-to-device goals, with 91% treated within 90 minutes and 52% being treated with 60 minutes. Patients treated within guideline goals had a mortality of 2.2% compared with 5.7% for those exceeding guideline recommendations (P<0.001).Through extension of regional coordination to an entire state, rapid diagnosis and treatment of ST-segment-elevation myocardial infarction has become an established standard of care independently of healthcare setting or geographic location.
Role of Quantitative Bone Scanning in the Assessment of Bone Turnover in Patients With Charcot Foot
Authors: Robert Bem, Alexandra Jirkovská, Michal Dubský, Vladimira Fejfarová, Marie Buncová, Jelena Skibová, Edward B. Jude
Journal: Diabetes Care (2009)

To assess the new quantitative bone scan parameters as markers of Charcot neuroosteoarthropathy (CNO) activity.Forty-two patients with acute (n = 21) and nonacute (n = 21) CNO underwent quantitative bone scanning. Patients with acute CNO were followed for 3-12 months and bone scans were repeated after treatment. New quantitative parameters were assessed and compared with markers of bone turnover and with skin temperature difference (STD).Significant correlations between quantitative bone scan parameters and bone turnover markers were observed (all P < 0.05). These parameters decreased after treatment of CNO, and its reduction to the baseline value correlated with differences of bone turnover markers and STD (all P < 0.05).Our study suggests that bone scanning can be used not only for diagnosis of CNO but also for monitoring disease activity by quantitative bone scan parameters.
Diarrhoea and massive duodenal round cell infiltration in a 27-year-old HIV positive female
Authors: C. Neufert, A. Agaimy, J. Wacker, H. Neumann, M. F. Neurath, M. Raithel
Journal: Gut (2011)

A 27-year-old black female with recently diagnosed HIV infection (CD4+ T cells 9/μl; viral load >106 copies/ml) was admitted to the hospital with diarrhoea, malaise, weight loss and ‘heavy legs’. On clinical examination, the emaciated patient (body mass index 15.8) was in a compromised clinical condition with bilateral ankle oedema. Laboratory tests revealed several pathological values including low albumen 15 g/l (reference level: 34–48) and severe pancytopenia (haemoglobin 4.5 g/dl, reference 12–16; white blood cell count (WBC) 3.6/nl, reference 4–10, platelet count (PLT, 61/nl, reference 140–400). Mean corpuscular volume (MCV, 80.2 fl) was at the lower limit of the reference level (80–99).

Upper gastrointestinal endoscopy showed a striking picture …
Genetic Determinants of Response to Warfarin during Initial Anticoagulation
Authors: Ute I. Schwarz, Marylyn D. Ritchie, Yuki Bradford, Chun Li, Scott M. Dudek, Amy Frye-Anderson, Richard B. Kim, Dan M. Roden, C. Michael Stein
Journal: New England Journal of Medicine (2008)

Genetic variants of the enzyme that metabolizes warfarin, cytochrome P-450 2C9 (CYP2C9), and of a key pharmacologic target of warfarin, vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to various warfarin doses, but the role of these variants during initial anticoagulation is not clear.In 297 patients starting warfarin therapy, we assessed CYP2C9 genotypes (CYP2C9 *1, *2, and *3), VKORC1 haplotypes (designated A and non-A), clinical characteristics, response to therapy (as determined by the international normalized ratio [INR]), and bleeding events. The study outcomes were the time to the first INR within the therapeutic range, the time to the first INR of more than 4, the time above the therapeutic INR range, the INR response over time, and the warfarin dose requirement.As compared with patients with the non-A/non-A haplotype, patients with the A/A haplotype of VKORC1 had a decreased time to the first INR within the therapeutic range (P=0.02) and to the first INR of more than 4 (P=0.003). In contrast, the CYP2C9 genotype was not a significant predictor of the time to the first INR within the therapeutic range (P=0.57) but was a significant predictor of the time to the first INR of more than 4 (P=0.03). Both the CYP2C9 genotype and VKORC1 haplotype had a significant influence on the required warfarin dose after the first 2 weeks of therapy.Initial variability in the INR response to warfarin was more strongly associated with genetic variability in the pharmacologic target of warfarin, VKORC1, than with CYP2C9.
Effects of Energy-Restricted Diets Containing Increased Protein on Weight Loss, Resting Energy Expenditure, and the Thermic Effect of Feeding in Type 2 Diabetes
Authors: N.D. Luscombe, P.M. Clifton, M. Noakes, B. Parker, G. Wittert
Journal: Diabetes Care (2002)

OBJECTIVE—To determine the effect of a high-protein (HP) diet compared with a low-protein (LP) diet on weight loss, resting energy expenditure (REE), and the thermic effect of food (TEF) in subjects with type 2 diabetes during moderate energy restriction. RESEARCH DESIGN AND METHODS—In this study, 26 obese subjects with type 2 diabetes consumed a HP (28% protein, 42% carbohydrate) or LP diet (16% protein, 55% carbohydrate) during 8 weeks of energy restriction (1,600 kcal/day) and 4 weeks of energy balance. Body weight and composition and REE were measured, and the TEF in response to a HP or LP meal was determined for 2 h, at weeks 0 and 12. RESULTS—The mean weight loss was 4.6 ± 0.4 kg (P &amp;lt; 0.001), of which 4.5 ± 0.4 kg was fat (P &amp;lt; 0.001), with no effect of diet (P = 0.6). At both weeks 0 and 12, TEF was greater after the HP than after the LP meal (0.064 vs. 0.050 kcal · kcal−1 energy consumed · 2 h−1, respectively; overall diet effect, P = 0.003). REE and TEF were reduced similarly with each of the diets (time effects, P = 0.02 and P &amp;lt; 0.001, respectively). CONCLUSIONS—In patients with type 2 diabetes, a low-fat diet with an increased protein-to-carbohydrate ratio does not significantly increase weight loss or blunt the fall in REE.
Cells Derived from Young Bone Marrow Alleviate Renal Aging
Authors: Hai-Chun Yang, Michele Rossini, Li-Jun Ma, Yiqin Zuo, Ji Ma, Agnes B. Fogo
Journal: Journal of the American Society of Nephrology (2011)

Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less β-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show β-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor β. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney.
Alzheimer's researchers face trial for scientific fraud and defrauding US government
Authors: J. H. Tanne
Journal: BMJ (2012)

A leading US researcher in Alzheimer’s disease and two Harvard teaching hospitals face trial later this year, charged with using fraudulent scientific data to obtain a grant from the National Institutes of Health. The suit relies on the False Claims Act of 1863, which penalises contractors who defraud the government.

The case is thought to be the first such involving alleged scientific fraud to go to trial in the United States—most previous cases have dealt with contractors defrauding the government by providing faulty supplies.

More lawsuits brought under the False Claims Act on the basis of scientific data manipulation may be expected, said Michael Kohn, of the Kohn, Kohn & Colapinto law firm in Washington, DC, who represents the whistleblower who exposed the fraud. “This is a major breakthrough holding universities accountable for the integrity of reported research results,” he said.

Those charged are Marilyn Albert, a former professor of psychiatry at Harvard Medical …
From pathogen genomes to host plant processes: the power of plant parasitic oomycetes
Authors: Marina Pais, Joe Win, Kentaro Yoshida, Graham J Etherington, Liliana M Cano, Sylvain Raffaele, Mark J Banfield, Alex Jones, Sophien Kamoun, Diane GO Saunders
Journal: Genome biology (2013)

Recent pathogenomic research on plant parasitic oomycete effector function and plant host responses has resulted in major conceptual advances in plant pathology, which has been possible thanks to the availability of genome sequences.
PTEN Acetylation Modulates Its Interaction with PDZ Domain
Authors: Tsuneo Ikenoue, Ken Inoki, Bin Zhao, Kun-Liang Guan
Journal: Cancer Research (2008)

Abstract The PTEN tumor suppressor gene is frequently inactivated in human cancer. As a major tumor suppressor, PTEN function must be tightly regulated. Both phosphorylation and membrane association have been reported to regulate PTEN activity. In addition, the COOH terminus of PTEN has a typical PDZ domain-binding motif that interacts with several PDZ domain-containing proteins. In this report, we show that PTEN is acetylated on Lys402, which is in the COOH-terminal PDZ domain-binding motif. We show that CBP plays a major role in PTEN acetylation, whereas the SIRT1 deacetylase is mainly responsible for PTEN deacetylation. Interestingly, Lys402 acetylation modulates PTEN interaction with PDZ domain-containing proteins, indicating a potential role of acetylation in regulating PTEN function. [Cancer Res 2008;68(17):6908–12]
Experimental myocardial ischemia: dynamic alterations in ventricular contractility and relaxation with dissociation of speed and force in the isovolumic dog heart.
Authors: J R Serur, J R Galyean, C W Urschel, E H Sonnenblick
Journal: Circulation Research (1976)

Although the time course of changes in myocardial function during ischemia has been demonstrated for the papillary muscle, this time course in the intact heart is less well understood. Accordingly, in 24 isolated, isovolumic, perfused dog hearts, coronary perfusion pressure (PP) was lowered to various fixed levels. Left ventricular developed pressure (LVP) rapidly fell and reached 63 +/- 3% of control at 1 minute of ischemia 50 +/- 5% at 6 minutes; this was due primarily to an abbreviation of time to peak tension (TPP). dP/dt was 70 +/- 3% of control at 1 minute and 56 +/- 5% at 6 minutes. The rate of relaxation as reflected by negative dP/dt declined as well to 49 +/- 4% of control at 1 minute of ischemia and to 41 +/- 4% control at 6 minutes. These changes were directly correlated with the decrease in PP. When PP was restored to normal, an overshoot of LVP and dP/dt was noted, peaking at 1 minute, returning to control by 5 minutes, and then gradually declining to 90 +/- 2% of control following 25 minutes of recovery. Depression of the rate of relaxation was reduced, but persisted throughout recovery. Diminution of force development early in ishcemia is due primarily to decreased duration of contraction accompanied by a decrease in relaxation rate. Later, the rate of force development also falls, but some preservation of force development may result from the return toward normal of the duration of contraction.