tbuckley/cabot-search huggingface dataset:
Correlating 3D morphology with molecular pathology: fibrotic remodelling in human lung biopsies
Authors: Manuela Kellner, Judith Wehling, Gregor Warnecke, Marko Heidrich, Nicole Izykowski, Jens Vogel-Claussen, Raoul-Amadeus Lorbeer, Georgios Antonopoulos, Sabina Janciauskiene, Roman Grothausmann, Lars Knudsen, Tammo Ripken, Heiko Meyer, Hans Kreipe, Matthias Ochs, Danny Jonigk, Mark Philipp Kühnel
Journal: Thorax (2015)

Assessing alterations of the parenchymal architecture is essential in understanding fibrosing interstitial lung diseases. Here, we present a novel method to visualise fibrotic remodelling in human lungs and correlate morphological three-dimensional (3D) data with gene and protein expression in the very same sample. The key to our approach is a novel embedding resin that clears samples to full optical transparency and simultaneously allows 3D laser tomography and preparation of sections for histology, immunohistochemistry and RNA isolation. Correlating 3D laser tomography with molecular diagnostic techniques enables new insights into lung diseases. This approach has great potential to become an essential tool in pulmonary research.
The evaluation of risk of obstructive sleep apnea syndrome in individuals with dysglycaemia
Authors: Otilia Nita, Lidia Iuliana Graur, Dana Stefana Popescu, Alina Delia Popa, Daniela Boisteanu, Mariana Graur
Journal: European Respiratory Journal (2012)

Introduction . The prevalence of obstructive sleep apnea syndrome (OSAS) is known to be higher in individuals with prediabetes and diabetes mellitus.   Aims and objectives.  This study aims to evaluate the risk of OSAS in individuals with dysglycaemia, comparative with those with normal glucose tolerance, in a rural population, and to find out whether those with prediabetes or diabetes have a higher risk of OSAS.   Methods.  We conducted a cross-sectional study in a sample of 254 men and women, aged >18 years, from a rural population. Dysglycaemia was evaluated by fasting plasma glucose-FPG and performing an oral glucose tolerance test-OGTT in all individuals without diabetes and by determining glycated haemoglobin-HbA1c. WHO (1999) criteria for diagnosing diabetes and prediabetes and American Diabetes Association recommendations for HbA1c diagnostic values were used. The risk of OSAS was assessed using Berlin Questionnaire.   Results.  We found that a statistically higher percentage of those with diabetes and prediabetes, diagnosed by HbA1c (66,7% and 32,8% respectively) and by OGTT (57,1% and 30,3% respectively) had a high risk of OSAS (p=0,001 and p=0,022, respectively) as compared to those with normal glucose tolerance (27,5% and 31,3% respectively). When assessing dysglycaemia by FPG, our results showed no statistically significant differences in what concerns the risk of OSAS between the two categories, normoglycaemia and dysglycaemia (p=0,051).   Conclusions.  The evaluation of risk of OSAS should be performed in individuals with prediabetes and diabetes, thus allowing the identification of individuals who should be referred to a sleep center.
Abstract 3832: Characterizing breast cancer CTCs for brain metastasis competence
Authors: Dario Marchetti
Journal: Cancer Research (2014)

Abstract Mechanisms causing fatal breast cancer brain metastasis (BCBM) remain largely unknown as well as functionalities of brain-colonizing circulating tumor cells (CTCs) in BCBM disease.We have characterized CTCs isolated from peripheral blood mononuclear cells of patients with breast cancer by multi-parametric flow cytometry. In epithelial cell adhesion molecule (EpCAM)-negative CTCs, we identified a “brain metastasis selected marker” (BMSM) profile or HER2+/EGFR+, HPSE+ and Notch1+ CTCs. These CTCs, which are not captured by the CellSearchTM (Veridex, LLC)platform because of their EpCAM negativity, were analyzed for cell invasiveness and metastatic competency in vivo. CTCs expressing the BMSM profile were highly invasive and capable of generating metastases when xenografted in nude mice. Notably, increased brain metastatic capabilities, frequency and quantitation were detected in EpCAM− CTCs overexpressing the BMSM profile. The presence of proteins of this profile was also verified in the metastatic lesions of animals. Further, investigations of viable BMSM CTCs were carried out using the DEPArrayTM, a dielectrophoresis-based platform able to detect and sort pure CTCs which were investigated by whole genome amplification and proteomic content. CTC subsets were derived possessing combinatorial levels of the BMSM profile and distinct abilities to generate BCBM.Collectively, we provide evidence of isolation, culture and characterization of human breast cancer CTCs leading to the description of a BMSM protein profile that is considered necessary for CTC metastatic competency to brain. Studies are presently undergoing to capture multiple CTC subsets and validate the presence of the BMSM profile in longitudinal studies of populations of breast cancer patients with the objective to not only better understand BCBM onset but also to predict disease course for improved and informed clinical treatment. Citation Format: Dario Marchetti. Characterizing breast cancer CTCs for brain metastasis competence. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3832. doi:10.1158/1538-7445.AM2014-3832
The Association of Pediatric Low- and High-Density Lipoprotein Cholesterol Dyslipidemia Classifications and Change in Dyslipidemia Status With Carotid Intima-Media Thickness in Adulthood
Authors: Costan G. Magnussen, Alison Venn, Russell Thomson, Markus Juonala, Sathanur R. Srinivasan, Jorma S.A. Viikari, Gerald S. Berenson, Terence Dwyer, Olli T. Raitakari
Journal: Journal of the American College of Cardiology (2009)
Distribution of tracer doses of methionine tagged with radiosulfur in normal and neoplastic tissue.
Authors: Arnold J. Kremen, Samuel W. Hunter, George E. Moore, Claude R. Hitchcock
Journal: Cancer Research (1949)

Summary  1.The distribution of tracer doses of d-l-methionine tagged with radiosulfur has been studied in mice with spontaneous and transplanted neoplasms.  2.These studies indicate a high initial concentration of radiomethionine results in liver, tumor, kidney and intestinal wall.  3.Any therapeutic possibilities relating to introducing radioactive sulfur into tumor cells must await animal trial.
Canadian multicenter randomized trial comparing sequential and alternating administration of two non-cross-resistant chemotherapy combinations in patients with limited small-cell carcinoma of the lung.
Authors: R Feld, W K Evans, P Coy, I Hodson, A S MacDonald, D Osoba, D Payne, W Shelley, J L Pater
Journal: Journal of Clinical Oncology (1987)

In order to assess the effect of scheduling of chemotherapy on the outcome of patients with limited small-cell lung cancer (SCLC), the Clinical Trials Group of the National Cancer Institute of Canada carried out a randomized trial comparing the alternation of cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, OH; doxorubicin) and vincristine (CAV) with etoposide (VP-16) and cisplatin for six cycles to the administration of these two combinations in a sequential fashion (three cycles of CAV followed by three of VP-16/cisplatin). Three hundred eligible patients were enrolled on the trial from September 1981 to October 1984. All responding patients were also treated after completion of chemotherapy with thoracic irradiation in randomly allocated doses of 2,000 and 3,750 cGy. The complete response (CR) rate to chemotherapy was slightly, but not significantly, higher on the alternating arm (52% v 44%, P = .20). However, there was no difference in disease-free or overall survival on the alternating and sequential arms, respectively (47.3 weeks v 45.1 weeks, P = .26; 61.7 weeks v 59.5 weeks, P = .56). Data on the effect of radiotherapy dose on survival are not yet mature, but it does not appear the results of this portion of the trial will alter the interpretation of the chemotherapy comparison. Patient characteristics favorably influencing survival were female sex, good performance status, younger age, and absence of supraclavicular node involvement. Two interpretations of these and other results in SCLC are suggested: (1) the difference between the schedules used is too small for the predictions of the Goldie-Coldman model to be realized in a trial of this size, or (2) VP-16/cisplatin is actually a superior regimen and any schedule that exposes patients to these drugs early in treatment will produce improved results.
Human scalp skin and hair follicles express neurotrophin-3 and its high-affinity receptor tyrosine kinase C, and show hair cycle-dependent alterations in expression
Authors: M.A. Adly, H.A. Assaf, E.A. Nada, M. Soliman, M. Hussein
Journal: British Journal of Dermatology (2005)

Background Neurotrophin (NT)‐3 and its high‐affinity receptor tyrosine kinase C (Trk C) are essential for nervous system development. These members of the NT family are also involved in murine hair morphogenesis and cycling. However, their role in human hair follicle (HF) biology remains to be elucidated. Objectives To explore the role of NTs in human skin and HF biology. Methods The immunoreactivity (IR) of NT‐3 and Trk C was studied in human scalp skin and HFs by immunofluorescent and light microscopic immunohistology. Skin biopsies were obtained from normal human scalp containing mainly anagen VI HFs from women (age 53–57 years) undergoing elective plastic surgery. Results Both NT‐3 and Trk C showed prominent, yet distinct, IR patterns in human scalp anagen HFs (anagen VI), whereas they were weakly expressed in catagen and increased again in telogen HFs. Within HF compartments, NT‐3 IR was prominent in the outer root sheath, inner root sheath, dermal papilla and connective tissue sheath. Trk C IR was prominent in all HF epithelial and mesenchymal compartments. Outside the HF, both NT‐3 and Trk C showed prominent IR in the epidermis, sebaceous glands and sweat glands. Conclusions These observations provide the first indication that NT‐3 and Trk C are expressed in human scalp skin and HFs, and suggest that Trk C‐mediated signalling is involved not only in murine but also in human HF biology. They may be useful in determining therapeutic strategies for the treatment of hair cycle and skin‐related disorders.
Multi-drug resistant and extensively-drug resistant tuberculosis in the region of Seixal: A 6 years revision
Authors: Marta Fradinho, Clara Barroso, Cristina Cristovao, Fernando Nogueira
Journal: European Respiratory Journal (2011)

Introduction: Portugal is the european country with larger incidence of tuberculosis (TB). Multi-drug resistant tuberculosis (MDR-TB) corresponds to 1,9% of the new cases in Portugal among 2002-2006, of wich 22% were extensively resistant to the anti-TB therapy. MDR-TB is resistant either to, at least, isoniazid (H) and rifampicin (R) and extensively-drug resistant (XDR-TB) if there is resistance to HR, a Fluoroquinolones and at least 1 second line injectable therapy.

Objective and methods: Retrospective study with identification, characterization and evaluation of patients with TB, followed in the Pneumology Diagnosis Center (CDP) of Seixal CDP from 2002 to 2008 with diagnosis of MDR-TB and XDR-TB.

Results: There were notified 439 cases of TB in the area of the CDP of Seixal from January 2002 to December 2008. There were identified 9 cases of MDR-TB and no patient with XDR-TB. Concerning the 9 cases of MDR-TB, 4 showed resistance to all first anti-TB therapy. Sixty seven percent were male. The average of ages was of 38±17 years (21-79 years). Seven patients were diagnosed in hospital admittance. Forty four percent of the patients presented prior history of TB treatment. Five patients had alcoholic and/or drug habits, being 2 positive fo Human Immunodeficiency Virus (HIV) serology. Six patients presented lung TB. Six patients had good therapy adherence.

Conclusion: The number of new cases of MDR-TB in the studied population is smaller than in the general national population. The diagnosis of TB and its adequate treatment are crucial to avoid the emergence of MDR an XDR-TB, as leads to restrictions on the therapeutic options.
Functionalized nanocarrier combined seizure-specific vector with P-glycoprotein modulation property for antiepileptic drug delivery
Authors: Jiansheng Liu, Yajing He, Jun Zhang, Jiajia Li, Xiangrong Yu, Zhonglian Cao, Fanmin Meng, Yuwu Zhao, Xunyi Wu, Teng Shen, Zhen Hong
Journal: Biomaterials (2015)
Dissection of events mediating leukemogenisis or differentiation in response to activated mutants of the beta c subunit of GM-CSF/IL3/IL5 receptors
Authors: R. DAndrea, B. Reynolds, C. Wilkinson, M. Peters, G. Goodall, A. Tyskin, A. Holloway, P. Solomon, T. Gonda, A. Brown
Journal: Blood (2003)
An animal model for granulomatosis with polyangiitis
Authors: Lisa Hinkofer, Dieter Jenne
Journal: European Respiratory Journal (2014)

Proteinase 3 (PR3) is a serine protease of neutrophil granules and a major target of autoantibodies in Granulomatosis with PolyAngiitis (GPA). The disease starts in the respiratory tract and progresses to a generalized life-threatening vasculitis of small blood vessels in multiple essential organs. Anti-neutrophil cytoplasmic antibodies (ANCA) against PR3 are a laboratory biomarker for the diagnosis of GPA and are believed to be involved in disease progression.  Due to the lack of interaction of hPR3 antibodies with murine PR3, wild type animals cannot be used for ANCA transfers in mice. Thus a human PR3 knock-in mouse line expressing the human autoantigen in peripheral blood neutrophils was developed enabling both the transfer of ANCA and mouse monoclonal antibodies (mAb) to human PR3.  To confirm the expression and functionality of hPR3 in the knock-in mice, neutrophils were isolated from bone marrow and analyzed by ELISA, activity assays and flow cytometry.  Comparison of the expression of hPR3 in knock-in mice with murine PR3 in wild type mice revealed that the expression levels were similar in both lines. Furthermore we found that the hPR3 expressed from the endogenous mouse PR3 promoter was active. Upon activation of freshly isolated neutrophils, surface expression of hPR3 could be confirmed.  The newly generated hPR3 knock-in mouse line is able to store functional hPR3 in neutrophils. Upon activation hPR3 is expressed on the surface of these cells, making the hPR3 accessible to antibodies. Thus antibody binding to the neutrophil surface could lead to neutrophil activation and inflammatory burst. To investigate the pathogenicity of autoantibodies in GPA, transfer of mAb will give us first insights into the pathogenicity these.
Abstract 220: Detection of Cysteine Sulfenic Acid Formation: Role in Reactive Oxygen Species-dependent VEGF signaling Linked to Endothelial Migration
Authors: Yoshimasa Nakamura, Nihal Kaplan, Leslie B Poole, Tohru Fukai, Masuko Ushio-Fukai
Journal: Circulation (2008)

NADPH oxidase Nox2-derived reactive oxygen species (ROS) have been implicated in VEGF receptor type2 (VEGFR2)-mediated signaling linked to endothelial cell (EC) migration. ROS-mediated protein modification involves oxidation of reactive cysteine residues to form a cysteine sulfenic acid (Cys-SOH) and subsequent oxidation products. However, the role of Cys-SOH formation in VEGF signaling and EC migration remains unknown. Using a newly-developed Cys-SOH trapping reagent, here we show that VEGF stimulation significantly increases the total Cys-SOH formation of proteins in HUVECs. VEGFR2 immunoprecipitates show significant increase in Cys-SOH within 5 min (90.3%), which remained elevated at least for 30 min (30.1%). This VEGF-induced Cys-SOH formation of VEGFR2 is prevented by pretreatment with a thiol donor antioxidant, N-acetylcysteine, which is associated with inhibition of VEGFR2 autophosphorylation (80.2%). The trapping of endogenous Cys-SOH by dimedone blocks VEGFR2 autophosphorylation (50.3%), its downstream phosphorylation of PLCgamma (70.4%) and ERK1/2 (90.1%) as well as EC migration (80.3%) without affecting p38MAPK phosphorylation. Wound scratch assay and immunofluorescence analysis reveal that Cys-SOH modified proteins are accumulated at the leading edge where they colocalize with Nox2, phospho-VEGFR2, F-actin and IQGAP1, a novel VEGFR2- and actin-binding scaffold protein, in actively migrating ECs. A significant increase in Cys-SOH is also seen in IQGAP1 coprecipitates (~250 kDa) following VEGF stimulation with peak at 2 min (50.1% increase). Knockdown of IQGAP1 using siRNA, or trapping of Cys-SOH block wound-induced Cys-SOH formation at the leading edge as well as EC migration toward the injured site. In summary, these results suggest that VEGFR2 and IQGAP1-associated proteins are targets for Cys-SOH formation at the leading edge in actively migrating ECs. The present study provides a novel mechanism of redox regulation in VEGF signaling linked to EC migration, and a rationale for the importance of identification of novel proteins that form Cys-SOH during repair process after injury and angiogenesis in vivo. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Minimally Invasive Surgery for Esophageal Cancer
Authors: Alfredo A. Santillan, Jeffrey M. Farma, Kenneth L. Meredith, Nilay R. Shah, Scott T. Kelley
Journal: Journal of the National Comprehensive Cancer Network (2008)

Esophageal cancer represents a major public health problem worldwide. Several minimally invasive esophagectomy (MIE) techniques have been described and represent a safe alternative for the surgical management of esophageal cancer in selected centers with high volume and expertise in them. This article reviews the most recent and largest series evaluating MIE techniques. Recent larger series have shown MIE to be equivalent in postoperative morbidity and mortality rates to conventional surgery. MIE has been associated with less blood loss, less postoperative pain, and decreased intensive care unit and hospital length of stay compared with conventional surgery. Despite limited data, conventional surgery and MIE have shown no significant difference in survival, stage for stage. The myriad of MIE techniques complicates the debate of defining the optimal surgical approach for treating esophageal cancer. Randomized controlled trials comparing MIE with conventional open esophagectomy are needed to clarify the ideal procedure with the lowest postoperative morbidity, best quality of life after surgery, and long-term survival.
Spinal Locomotor Circuits Develop Using Hierarchical Rules Based on Motorneuron Position and Identity
Authors: Christopher A. Hinckley, William A. Alaynick, Benjamin W. Gallarda, Marito Hayashi, Kathryn L. Hilde, Shawn P. Driscoll, Joseph D. Dekker, Haley O. Tucker, Tatyana O. Sharpee, Samuel L. Pfaff
Journal: Neuron (2015)
Use of pulmonary hydrogen (H2) measurements to quantitate carbohydrate absorption
Authors: John H. Bond, Michael D. Levitt
Journal: Journal of Clinical Investigation (1972)

A technique was developed to quantitate the absorption of ingested carbohydrate by means of continuous measurements of pulmonary H(2) excretion. This technique is based on the observation that H(2) is produced in the colon when carbohydrate is fermented by colonic bacteria, and this H(2) is then excreted by the lungs. The quantitative relationship of pulmonary H(2) excretion to unabsorbed carbohydrate was studied in nine subjects. After ingestion of 6.5, 13, and 26 g of lactulose (a nonabsorbable disaccharide), H(2) excretion increased linearly, averaging (+/-1 SEM) 13+/-3.5, 23+/-7.2, and 49+/-7 ml per 2 hr. Because of consistent individual differences in H(2) excretion per gram of lactulose, the variability of this linear response was less in a given subject, with the H(2) excretion after 6.5 g and 26 g lactulose dosages averaging 55+/-4.2% and 214+/-16% of that observed after the 13 g dose. It was further demonstrated with fecal homogenates, as well as in rats after direct intracecal instillation of carbohydrate, that there was no significant difference in the rate of H(2) formation from lactulose as compared with the normally ingested sugars. Thus, a subject's H(2) excretion after a 13 g dose of lactulose can be used as a standard to convert H(2) excretion after ingestion of other carbohydrates into grams of carbohydrate not absorbed. Application of this technique to seven partially gastrectomized patients indicated all subjects malabsorbed a portion of a 100 g dose of glucose whereas six of seven completely absorbed a 25 g dose. Malabsorption of physiologic quantities of various carbohydrates was clearly demonstrated in one subject. This technique appears to provide quantitative information on carbohydrate malabsorption not readily obtained by presently available techniques.
Abstract 11185: Expression of Slow Skeletal TnI Confers Metabolic Protection to Ischemia via Increased Glycolysis
Authors: Kayla M Pound, Grace M Arteaga, Matthew Fasano, Chad M Warren, Tanganyika Wilder, Brandon J Biesiadecki, R. J Solaro, E D Lewandowski
Journal: Circulation (2010)

Changes in metabolic profiles coincide with modifications of contractile proteins in developing and stressed hearts. However, reciprocal adaptations between contractile and metabolic phenotypes are...
Risk of depression is higher in elderly patients with lowest serum cholesterol values
Authors: R. Rozzini, B. Bertozzi, P. Barbisoni, M. Trabucchi
Journal: BMJ (1996)

EDITOR,—We read with interest Paul H A Steegmans and colleagues' short report on serum cholesterol concentration and serotonin metabolism.1 We would like to add support to the hypothesis of an association between low serum cholesterol concentration and depression with data obtained in our geriatric evaluation and rehabilitation unit.

Data in this study were taken from 476 elderly patients consecutively admitted to our unit over 12 months (mean age 78.8 (SD 7.4); 70% women). …
Use of Cartilage Derived From Murine Induced Pluripotent Stem Cells for Osteoarthritis Drug Screening
Authors: Vincent P. Willard, Brian O. Diekman, Johannah Sanchez‐Adams, Nicolas Christoforou, Kam W. Leong, Farshid Guilak
Journal: Arthritis & Rheumatology (2014)

Objective The discovery of novel disease‐modifying drugs for osteoarthritis (OA) is limited by the lack of adequate genetically defined cartilage tissues for application in high‐throughput screening systems. We addressed this need by synthesizing cartilage from induced pluripotent stem cells (iPSCs) to establish and validate an in vitro model of OA. Methods Native or iPSC‐derived mouse cartilage samples were treated with the cytokine interleukin‐1α (IL‐1α) for 3 days to model the inflammatory environment of OA. The biochemical content, mechanical properties, and gene expression of the resulting tissues were assayed. In addition, the inflammatory and catabolic environment of the media was assessed. To establish high‐throughput capability, we used a 96‐well plate format and conducted a screen of previously identified candidate OA drugs. Glycosaminoglycan (GAG) release into the medium was used as the primary output for screening. Results Treatment of iPSC‐derived or native cartilage with IL‐1α induced characteristic features of OA in a rapid and dose‐dependent manner. In addition to the loss of GAGs and tissue mechanical properties, IL‐1α treatment induced the expression of matrix metalloproteinases and increased the production of the inflammatory mediators nitric oxide and prostaglandin E 2 . In the high‐throughput screen validation, all candidate OA therapeutic agents provided some benefit, but only the NF‐κB inhibitor SC514 effectively reduced cartilage loss in response to IL‐1α. Conclusion This work demonstrates the utility of iPSCs for studying cartilage pathology and provides a platform for identifying novel, patient‐specific therapeutic agents that prevent cartilage degradation and modify the course of OA development.