tbuckley/cabot-search huggingface dataset:
Identification of the advanced glycation end products Nvarepsilon-carboxymethyllysine in the synovial tissue of patients with rheumatoid arthritis
Authors: S Drinda
Journal: Annals of the Rheumatic Diseases (2002)

Generation of advanced glycation end products (AGEs) is an inevitable process in vivo and can be accelerated under pathological conditions such as oxidative stress. In serum and synovial fluid of patients with rheumatoid arthritis (RA) raised AGE levels have been found.To determine the presence of N(epsilon)-carboxymethyllysine (CML; marker of oxidative stress) in RA synovial tissue by immunohistology.Frozen synovial tissue samples from 10 patients with RA and eight controls (four patients without joint disease and four patients with osteoarthritis (OA)) were treated with rabbit-anti-CML-IgG and goat-antirabbit-IgG. Immunostaining was visualised by streptavidine-alkaline phosphatase (chromogen fuchsin). Cell differentiation was performed with antibodies against CD68, CD45RO, and CD20.CML was detected in the synovial lining, sublining, and endothelium in 10/10 RA and 4/4 OA synovial specimens. In RA some macrophages (CD68+) and T cells (CD45RO+) showed positive immunostaining for CML, whereas B cells were negative. Staining in OA synovial sublining was weak compared with RA.CML was detected for the first time in RA and OA synovial tissue. Different patterns of immunostaining in RA and OA and the presence of CML on macrophages and T cells, suggest a role for CML in the pathogenesis of RA. This might be due to presentation of new epitopes which can maintain or even trigger an autoimmune response.
Analysis on Frequency and Density of Microsatellites in Coding Sequences of Several Eukaryotic Genomes
Authors: Bin Li, Qingyou Xia, Cheng Lu, Zeyang Zhou, Zhonghuai Xiang
Journal: Genomics Proteomics & Bioinformatics (2004)

Abstract Microsatellites or simple sequence repeats (SSRs) have been found in most organisms during the last decade. Since large-scale sequences are being generated, especially those that can be used to search for microsatellites, the development of these markers is getting more convenient. Keeping SSRs in viewing the importance of the application, available CDS (coding sequences) or ESTs (expressed sequence tags) of some eukaryotic species were used to study the frequency and density of various types of microsatellites. On the basis of surveying CDS or EST sequences amounting to 66.6 Mb in silkworm, 37.2 Mb in fly, 20.8 Mb in mosquito, 60.0 Mb in mouse, 34.9 Mb in zebrafish and 33.5 Mb in Caenorhabditis elegans, the frequency of SSRs was 1/1.00 Kb in silkworm, 1/0.77 Kb in fly, 1/1.03 Kb in mosquito, 1/1.21 Kb in mouse, 1/1.25 Kb in zebrafish and 1/1.38 Kb in C. elegans. The overall average SSR frequency of these species is 1/1.07 Kb. Hexanucleotide repeats (64.5%–76.6%) are the most abundant class of SSR in the investigated species, followed by trimeric, dimeric, tetrameric, monomeric and pentameric repeats. Furthermore, the A-rich repeats are predominant in each type of SSRs, whereas G-rich repeats are rare in the coding regions.
Peritoneal seeding in intraductal papillary mucinous neoplasm of the pancreas patients who underwent endoscopic ultrasound-guided fine-needle aspiration: The PIPE Study
Authors: Won Yoon, Ebubekir S. Daglilar, Carlos Castillo, Mari Mino-Kenudson, Martha Pitman, William Brugge
Journal: Endoscopy (2014)

<b>Background and study aims:</b> There have been concerns about peritoneal seeding after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of mucinous pancreatic cystic lesions. The aims of this study were to determine the frequency of postoperative peritoneal seeding in patients with intraductal papillary mucinous neoplasm (IPMN) who had undergone pre-operative EUS-FNA and to compare it with that of patients with IPMN who had surgery with no pre-operative tissue sampling. <b>Patients and methods:</b> A total of 175 patients who had undergone resection of IPMNs with pre-operative EUS-FNA (EUS-FNA group) were analyzed and compared with 68 patients who had undergone resection with no pre-operative tissue sampling (No Sampling group). Patient characteristics, pathology, and frequency of peritoneal seeding after surgery were analyzed and compared. Peritoneal seeding was diagnosed based on pathology or image findings. <b>Results:</b> The two groups were comparable with respect to sex, age, follow-up duration, involvement of the pancreatic head, involvement of the main duct, grade of dysplasia, and size of histologically proven branch-duct IPMNs. Four patients (2.3 %) with invasive IPMN developed peritoneal seeding in the EUS-FNA group, whereas three (4.4 %, two with invasive IPMN and one with high-grade dysplasia) developed peritoneal seeding in the No Sampling group (<i>P </i> = 0.403). No peritoneal seeding was noted during surgery in these cases. Except for one patient in the EUS-FNA group, no spillage occurred during resection in these patients. <b>Conclusions:</b> In this cohort of patients undergoing resection of IPMN, the difference in the frequency of peritoneal seeding in the EUS-FNA group and the No Sampling group was not significant.
A conditioning platform based on fludarabine, busulfan, and 2 days of rabbit antithymocyte globulin results in promising results in patients undergoing allogeneic transplantation from both matched and mismatched unrelated donor
Authors: Raynier Devillier, Sabine Fürst, Roberto Crocchiolo, Jean El‐Cheikh, Luca Castagna, Samia Harbi, Angela Granata, Evelyne D'Incan, Diane Coso, Christian Chabannon, Christophe Picard, Anne Etienne, Boris Calmels, Jean-Marc Schiano, Claude Lemarie, Anne-Marie Stoppa, Reda Bouabdallah, Norbert Vey, Didier Blaise
Journal: American Journal of Hematology (2013)

Conditioning regimen including fludarabine, intravenous busulfan (Bx), and 5 mg/kg total dose of rabbit antithymocyte globulin (r-ATG) (FBx-ATG) results in low incidence of graft-versus-host disease (GVHD) and non-relapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) from HLA-matched related or unrelated donors (MUD). However, whether this platform produces similar results in the setting of one mismatch unrelated donor (MMUD) Allo-HSCT is not known. We retrospectively analyzed patients aged less than 65 years who were diagnosed with hematological malignancies and received FBx-ATG regimen prior to Allo-HSCT from MUD (N = 74) or MMUD (N = 40). We compared outcome of MUD versus MMUD patients. There was no difference in the cumulative incidence of grades II-IV acute GVHD (MUD: 34% vs. MMUD: 35%, P = 0.918), but MMUD patients developed more grade III-IV acute GVHD (MUD: 5% vs. MMUD: 15%, P = 0.016). The cumulative incidences of overall chronic GVHD (MUD: 33% vs. MMUD: 22%, P = 0.088) and extensive chronic GVHD (MUD: 20% vs. MMUD: 19%, P = 0.594) were comparable. One-year NRM was similar in both groups (MUD: 16% vs. MMUD: 14%, P = 0.292); similarly, progression-free survival (MUD: 59% vs. MMUD: 55%, P = 0.476) and overall survival (MUD: 63% vs. MMUD: 61%, P = 0.762) were not different between both groups. With a median follow up of 24 months, 35 of 74 MUD patients (47%) and 19 of 40 MMUD patients (48%) were free of both disease progression and immunosuppressive treatment. We conclude that the FBx-ATG regimen results in low incidences of NRM and GVHD in both MUD and the MMUD recipients.
Randomized Controlled Economic Evaluation of Asthma Self-Management in Primary Health Care
Authors: Tjard R. Schermer, Bart P. Thoonen, Guido van den Boom, Reinier P. Akkermans, Richard P. Grol, Hans T. Folgering, Chris van Weel, Constant P. van Schayck
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

In this randomized controlled economic evaluation we compared guided asthma self-management with usual asthma care according to guidelines for Dutch family physicians. Nineteen family practices were randomized, and 193 adults with stable asthma (98 self-management, 95 usual care) were included and monitored for 2 years. We hypothesized that introducing self-management would not compromise asthma control and cost would be equal to or lower than in usual care. Patient-specific cost data were collected, preference-based utilities were assessed, and incremental cost per quality-adjusted life year (QALY) and successfully treated week gained was calculated. Self-management patients gained 0.039 QALY (95% confidence interval [CI], 0.003 to 0.075) and experienced 81 (95% CI, 78 to 84) successfully treated weeks in 2 years' time; the corresponding figures for usual care were 0.024 (95% CI, -0.022 to 0.071) and 75 (95% CI, 72 to 78). Total costs were 1,084 euros(95% CI, 938 to 1,228) for self-management and 1,097 euros (95% CI, 933 to 1,260) for usual care. Self-management patients consumed 1,680 (95% CI, 1,538 to 1,822) puffs of budesonide, usual care patients 1,897 (95% CI, 1,679 to 2,115). Mean productivity cost due to limited activity days was 213 euros lower among self-management patients. When all costs were included, self-management was cost-effective on all outcomes. The probability that self-management was cost-effective relative to usual care in terms of QALYs was 52%. We conclude that guided self-management is a safe and efficient alternative approach compared with asthma treatment usually provided in Dutch primary care.
Gefitinib-Induced Killing of NSCLC Cell Lines Expressing Mutant EGFR Requires BIM and Can Be Enhanced by BH3 Mimetics
Authors: Mark S Cragg, Junya Kuroda, Hamsa Puthalakath, David C. S Huang, Andreas Strasser
Journal: PLoS Medicine (2007)

Background The epidermal growth factor receptor (EGFR) plays a critical role in the control of cellular proliferation, differentiation, and survival. Abnormalities in EGF-EGFR signaling, such as mutations that render the EGFR hyperactive or cause overexpression of the wild-type receptor, have been found in a broad range of cancers, including carcinomas of the lung, breast, and colon. EGFR inhibitors such as gefitinib have proven successful in the treatment of certain cancers, particularly non-small cell lung cancers (NSCLCs) harboring activating mutations within the EGFR gene, but the molecular mechanisms leading to tumor regression remain unknown. Therefore, we wished to delineate these mechanisms. Methods and Findings We performed biochemical and genetic studies to investigate the mechanisms by which inhibitors of EGFR tyrosine kinase activity, such as gefitinib, inhibit the growth of human NSCLCs. We found that gefitinib triggered intrinsic (also called "mitochondrial") apoptosis signaling, involving the activation of BAX and mitochondrial release of cytochrome c, ultimately unleashing the caspase cascade. Gefitinib caused a rapid increase in the level of the proapoptotic BH3-only protein BIM (also called BCL2-like 11) through both transcriptional and post-translational mechanisms. Experiments with pharmacological inhibitors indicated that blockade of MEK–ERK1/2 (mitogen-activated protein kinase kinase–extracellular signal-regulated protein kinase 1/2) signaling, but not blockade of PI3K (phosphatidylinositol 3-kinase), JNK (c-Jun N-terminal kinase or mitogen-activated protein kinase 8), or AKT (protein kinase B), was critical for BIM activation. Using RNA interference, we demonstrated that BIM is essential for gefitinib-induced killing of NSCLC cells. Moreover, we found that gefitinib-induced apoptosis is enhanced by addition of the BH3 mimetic ABT-737. Conclusions Inhibitors of the EGFR tyrosine kinase have proven useful in the therapy of certain cancers, in particular NSCLCs possessing activating mutations in the EGFR kinase domain, but the mechanisms of tumor cell killing are still unclear. In this paper, we demonstrate that activation of the proapoptotic BH3-only protein BIM is essential for tumor cell killing and that shutdown of the EGFR–MEK–ERK signaling cascade is critical for BIM activation. Moreover, we demonstrate that addition of a BH3 mimetic significantly enhances killing of NSCLC cells by the EGFR tyrosine kinase inhibitor gefitinib. It appears likely that this approach represents a paradigm shared by many, and perhaps all, oncogenic tyrosine kinases and suggests a powerful new strategy for cancer therapy.
Combination of Farnesyltransferase and Akt Inhibitors Is Synergistic in Breast Cancer Cells and Causes Significant Breast Tumor Regression in ErbB2 Transgenic Mice
Authors: Maria E. Balasis, Kara D. Forinash, Y. Ann Chen, William J. Fulp, Domenico Coppola, Andrew D. Hamilton, Jin Q. Cheng, Saïd M. Sebti
Journal: Clinical Cancer Research (2011)

Abstract The Akt activation inhibitor triciribine and the farnesyltransferase inhibitor tipifarnib have modest to little activity in clinical trials when used as single agents. In this article, preclinical data show that the combination is more effective than single agents both in cultured cells and in vivo. Combination index data analysis shows that this combination is highly synergistic at inhibiting anchorage-dependent growth of breast cancer cells. This synergistic interaction is also observed with structurally unrelated inhibitors of Akt (MK-2206) and farnesyltransferase (FTI-2153). The triciribine/tipifarnib synergistic effects are seen with several cancer cell lines including those from breast, leukemia, multiple myeloma and lung tumors with different genetic alterations such as K-Ras, B-Raf, PI3K (phosphoinositide 3-kinase), p53 and pRb mutations, PTEN, pRB and Ink4a deletions, and ErbB receptor overexpression. Furthermore, the combination is synergistic at inhibiting anchorage-independent growth and at inducing apoptosis in breast cancer cells. The combination is also more effective at inhibiting the Akt/mTOR/S6 kinase pathway. In an ErbB2-driven breast tumor transgenic mouse model, the combination, but not single agent, treatment with triciribine and tipifarnib induces significant breast tumor regression. Our findings warrant further investigation of the combination of farnesyltransferase and Akt inhibitors. Clin Cancer Res; 17(9); 2852–62. ©2011 AACR.
Integrin-Linked Kinase, a Hypoxia-Responsive Molecule, Controls Postnatal Vasculogenesis by Recruitment of Endothelial Progenitor Cells to Ischemic Tissue
Authors: Seung-Pyo Lee, Seock-Won Youn, Hyun-Jai Cho, Lian Li, Tae-Youn Kim, Hyung-Seon Yook, Jae-Woong Chung, Jin Hur, Chang-Hwan Yoon, Kyung-Woo Park, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Circulation (2006)

Recruitment and adhesion of endothelial progenitor cells (EPCs) to hypoxic endothelial cells (ECs) is essential for vasculogenesis in ischemic tissue; little is known, however, about the key signals or intracellular signaling pathways involved in orchestrating the expression of adhesion molecules by ECs in response to hypoxia and how this is related to the recruitment of EPCs to the ischemic tissue. Here, we report that endogenous integrin-linked kinase (ILK) is a novel molecule that responds to hypoxia in ECs that regulates the expression of stromal cell-derived factor-1 (SDF-1) and intercellular adhesion molecule-1 (ICAM-1) through nuclear factor-kappaB and hypoxia-inducible factor-1alpha and induces recruitment of EPCs to ischemic areas.Under hypoxia, both the endogenous amount and kinase activity of ILK were time-dependently upregulated in ECs, which was associated with increased ICAM-1 and SDF-1. This upregulation of ILK was mediated by stabilization of ILK by heat shock protein 90. ILK overexpression in normoxic ECs resulted in ICAM-1 and SDF-1 upregulation through dual control by nuclear factor-kappaB and hypoxia-inducible factor-1alpha. Blockade of ILK in hypoxic ECs significantly abrogated the expression of both molecules, which led to decreased EPC incorporation into ECs. A hindlimb ischemia model showed that ILK blockade significantly reduced EPC homing to ischemic limb and consequently led to poor neovascularization. Overexpression of ILK in the Matrigel plug significantly improved neovascularization in vivo, whereas the blockade of ILK resulted in the opposite effect.Endogenous ILK is a novel and physiological upstream responder of numerous intracellular molecules involved in hypoxic stress in ECs and may control the recruitment of EPCs to ischemic tissue.
F-18 FDG Positron Emission Tomographic Imaging in a Case of Ruptured Breast Implant: Inflammation or Recurrent Tumor?
Authors: Robert Hurwitz
Journal: Clinical Nuclear Medicine (2003)

F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has proved clinically useful for both malignant and inflammatory lesions. The author describes a 54-year-old woman with previously treated carcinoma of the breast. There was spontaneous rupture of a breast implant placed previously as part of a reconstruction. While being evaluated clinically, prominent axillary lymph nodes were palpated on the ipsilateral side of the recent implant rupture. An F-18 FDG PET scan demonstrated intense uptake in these nodes. Lymph node biopsy demonstrated benign inflammatory reaction and no recurrence of malignancy.
Tumour necrosis factor in refractory asthma: new insight
Authors: S A Nachman
Journal: Thorax (2006)

▴ Berry MA, Hargadon B, Shelley M, et al . Evidence of a role of tumour necrosis factor α in refractory asthma. N Engl J Med2006;354:697–708[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] The authors showed that monocytes from 10 patients with refractory asthma expressed significantly higher levels of TNF-α receptor 1, … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.aulast%253DBerry%26rft.auinit1%253DM.%2BA.%26rft.volume%253D354%26rft.issue%253D7%26rft.spage%253D697%26rft.epage%253D708%26rft.atitle%253DEvidence%2Bof%2Ba%2BRole%2Bof%2BTumor%2BNecrosis%2BFactor%2B%257Balpha%257D%2Bin%2BRefractory%2BAsthma%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa050580%26rft_id%253Dinfo%253Apmid%252F16481637%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa050580&link_type=DOI [3]: /lookup/external-ref?access_num=16481637&link_type=MED&atom=%2Fthoraxjnl%2F61%2F6%2F495.atom [4]: /lookup/external-ref?access_num=000235316100006&link_type=ISI
Effect of Atrial Fibrillation on Atrial Thrombogenesis in Humans: Impact of Rate and Rhythm
Authors: Han S. Lim, Scott R. Willoughby, Carlee Schultz, Cheryl Gan, Muayad Alasady, Dennis H. Lau, Darryl P. Leong, Anthony G. Brooks, Glenn D. Young, Peter M. Kistler, Jonathan M. Kalman, Matthew I. Worthley, Prashanthan Sanders
Journal: Journal of the American College of Cardiology (2013)
Helmet therapy in infants with positional skull deformation: randomised controlled trial
Authors: R. M. van Wijk, L. A. van Vlimmeren, C. G. M. Groothuis-Oudshoorn, C. P. B. Van der Ploeg, M. J. IJzerman, M. M. Boere-Boonekamp
Journal: BMJ (2014)

<b>Objective</b> To determine the effectiveness of helmet therapy for positional skull deformation compared with the natural course of the condition in infants aged 5-6 months. <b>Design</b> Pragmatic, single blinded, randomised controlled trial (HEADS, HElmet therapy Assessment in Deformed Skulls) nested in a prospective cohort study. <b>Setting</b> 29 paediatric physiotherapy practices; helmet therapy was administered at four specialised centres. <b>Participants</b> 84 infants aged 5 to 6 months with moderate to severe skull deformation, who were born after 36 weeks of gestation and had no muscular torticollis, craniosynostosis, or dysmorphic features. Participants were randomly assigned to helmet therapy (n=42) or to natural course of the condition (n=42) according to a randomisation plan with blocks of eight. <b>Interventions</b> Six months of helmet therapy compared with the natural course of skull deformation. In both trial arms parents were asked to avoid any (additional) treatment for the skull deformation. <b>Main outcome measures</b> The primary outcome was change in skull shape from baseline to 24 months of age assessed using plagiocephalometry (anthropometric measurement instrument). Change scores for plagiocephaly (oblique diameter difference index) and brachycephaly (cranioproportional index) were each included in an analysis of covariance, using baseline values as the covariate. Secondary outcomes were ear deviation, facial asymmetry, occipital lift, and motor development in the infant, quality of life (infant and parent measures), and parental satisfaction and anxiety. Baseline measurements were performed in infants aged between 5 and 6 months, with follow-up measurements at 8, 12, and 24 months. Primary outcome assessment at 24 months was blinded. <b>Results</b> The change score for both plagiocephaly and brachycephaly was equal between the helmet therapy and natural course groups, with a mean difference of −0.2 (95% confidence interval −1.6 to 1.2, P=0.80) and 0.2 (−1.7 to 2.2, P=0.81), respectively. Full recovery was achieved in 10 of 39 (26%) participants in the helmet therapy group and 9 of 40 (23%) participants in the natural course group (odds ratio 1.2, 95% confidence interval 0.4 to 3.3, P=0.74). All parents reported one or more side effects. <b>Conclusions</b> Based on the equal effectiveness of helmet therapy and skull deformation following its natural course, high prevalence of side effects, and high costs associated with helmet therapy, we discourage the use of a helmet as a standard treatment for healthy infants with moderate to severe skull deformation. <b>Trial registration</b> Current Controlled Trials ISRCTN18473161.
Angiogenesis Inhibitors Endostatin or TNP-470 Reduce Intimal Neovascularization and Plaque Growth in Apolipoprotein E–Deficient Mice
Authors: Karen S. Moulton, Eric Heller, Moritz A. Konerding, Evelyn Flynn, Wulf Palinski, Judah Folkman
Journal: Circulation (1999)

Background —Neovascularization within the intima of human atherosclerotic lesions is well described, but its role in the progression of atherosclerosis is unknown. In this report, we first demonstrate that intimal vessels occur in advanced lesions of apolipoprotein E–deficient (apoE −/−) mice. To test the hypothesis that intimal vessels promote atherosclerosis, we investigated the effect of angiogenesis inhibitors on plaque growth in apoE −/− mice. Methods and Results —ApoE −/− mice were fed a 0.15% cholesterol diet. At age 20 weeks, mice were divided into 3 groups and treated for 16 weeks as follows: group 1, recombinant mouse endostatin, 20 mg · kg −1 · d −1 ; group 2, fumagillin analogue TNP-470, 30 mg/kg every other day; and group 3, control animals that received a similar volume of buffer. Average cholesterol levels were similar in all groups. Plaque areas were quantified at the aortic origin. Median plaque area before treatment was 0.250 mm 2 (range, 0.170 to 0.348; n=10). Median plaque areas were 0.321 (0.238 to 0.412; n=10), 0.402 (0.248 to 0.533; n=15), and 0.751 mm 2 (0.503 to 0.838; n=12) for the endostatin, TNP-470, and control groups, respectively ( P ≤0.0001). Therefore, endostatin and TNP-470 inhibited plaque growth during the treatment period by 85% and 70%. Intimal smooth muscle cell contents of plaques from control and treated mice were similar. Conclusions —Prolonged treatment with either angiogenesis inhibitor reduced plaque growth and intimal neovascularization in apoE −/− mice. Although the mechanism of plaque inhibition induced by these agents is not established, these results suggest that intimal neovascularization may promote plaque development.
Depression and Insulin Resistance: Additional Support for the Novel Heuristic Model in Perimenopausal Depression
Authors: Pasi J. Eskola, Jari Jokelainen, Marjo-Riitta Järvelin, Sirkka Keinänen-Kiukaanniemi, Aimo Ruokonen, Katri Puukka, Markku Timonen, Juha P. Auvinen
Journal: American Journal of Psychiatry (2015)