tbuckley/cabot-search huggingface dataset:
Complement Lysis of Human Erythrocytes
Authors: Charles H. Packman, Stephen I. Rosenfeld, David E. Jenkins, Patricia A. Thiem, John P. Leddy
Journal: Journal of Clinical Investigation (1979)

Although enhanced sensitivity of erythrocytes to complement-mediated lysis is a hallmark of paroxysmal nocturnal hemoglobinuria (PNH), subpopulations of erythrocytes in such patients vary significantly in this respect. One PNH erythrocyte subpopulation (termed type III) comprises exquisitely sensitive cells, whereas type II PNH erythrocytes are intermediate in complement sensitivity between PNH type III and normal human erythrocytes. Differences in the action of the terminal complement components that would account for the differing lytic behavior of types II and III PNH erythrocytes have been proposed but not directly demonstrated. The present studies, making use of carefully selected cases with pure populations of type II or type III erythrocytes, confirm a prior observation that antibody-coated PNH erythrocytes of both types II and III display comparably supranormal C3 binding in whole human serum. However, when lysis was induced by the isolated C5b-9 membrane attack mechanism, bypassing the requirement for C3 binding, only type III PNH cells exhibited greater than normal lysis. This finding suggests that type III PNH erythrocytes have an additional membrane abnormality not present in type II cells. Thus, the differing lytic behavior of these two cell types in whole serum may reflect the additive effects on type III cells of both exaggerated C3 binding and enhanced sensitivity to C5b-9, whereas the more moderate lysis of type II PNH cells may be determined mainly or entirely by the earlier-acting mechanism producing augmented C3 binding. The failure of guinea pig C8 and C9, as opposed to human C8 and C9, to reveal the true lytic sensitivity of PNH-III E in our earlier study is illustrated, and its implications briefly discussed.
Cytomegalovirus: Biology and Infection.
Authors: Monto Ho
Journal: Annals of Internal Medicine (1983)

1. History of Cytomegalovirus.- 2. Molecular Biology of Cytomegalovirus Replication.- 3. Gene Products of Cytomegalovirus and Their Immunologic Significance.- 4. Characteristics of Cytomegalovirus.- 5. Virological Diagnosis and Infections in Cells and Tissues.- 6. Serologic Tests for Cytomegalovirus Infections.- 7. Cell-Mediated Immunity to Cytomegalovirus Infection.- 8. Variants of Human Cytomegalovirus.- 9. Epidemiology of Cytomegalovirus Infection in Man.- 10. Pathology of Cytomegalovirus Infection.- 11. Congenital and Perinatal Human Cytomegalovirus Infections.- 12. Acquired Cytomegalovirus Infection in Immunocompetent Patients.- 13. Human Cytomegalovirus Infections in Immunosuppressed Patients.- 14. Treatment and Prevention of Cytomegalovirus Infections.- 15. Nonhuman Cytomegaloviruses.- 16. Murine Cytomegalovirus.- References.- Author Index.
Results of Extracorporeal Shock Wave Lithotripsy in the Pediatric Age Group
Authors: Oktay Nazl&inodot;, &Ccedil;a&gcaron; &Ccedil;al, Ceyhun &Ouml;zyurt, G&uuml;rhan G&uuml;nayd&inodot;n, &Idot;brahim C&uuml;reklibat&inodot;r, Vedat Avc&inodot;eri, &Ouml;zcan Erhan
Journal: European Urology (1998)
Harrison's Principles of Internal Medicine.
Authors: edotir's Eugene Braunwald...
Journal: Annals of Internal Medicine (1988)

Introduction To Clinical Medicine Cardinal Manifestations Of Disease Genetics And Disease Clinical Pharmacology Nutrition Infectious Disease Disorders Of The Cardiovascular System Disorders Of The Kidney And Urinary Tract Disorders Of The Gastrointestinal System Disorders Of The Immune System, Connective Tissue And Joints Hematology And Oncology Endocrinology And Metabolism Neurologic Disorders Environmental And Occupational Hazards.
Health-Related Quality of Life After Carotid Stenting Versus Carotid Endarterectomy
Authors: David J. Cohen, Joshua M. Stolker, Kaijun Wang, Elizabeth A. Magnuson, Wayne M. Clark, Bart M. Demaerschalk, Albert D. Sam, James R. Elmore, Fred A. Weaver, Herbert D. Aronow, Larry B. Goldstein, Gary S. Roubin, George Howard, Thomas G. Brott
Journal: Journal of the American College of Cardiology (2011)
Calculating infarct size.
Authors: M J Tansey
Journal: Circulation (1977)

To the Editor:Two publications in Circulation"' and one in Progress in Car- diovascular Diseases' concerning the enzymatic estimation of in- farct size erroneously report the proportionality constant, K, for calculating infarct size based on MB creatine phosphokinase (CPK), to be 4.1 X 10'-, a figure similar to that used in calculating infarct size based on total CPK, namely 5.9 X 10-'.By the method of enzymatic estimation, infarct size is the product of K, body weight and CPK release'' and, in the absence of extra- cardiac CPK, total CPK release is approximately ten times greater than MB CPK release.'If the value for K is similar in both instances the calculated infarct size based on MB CPK will be ap- proximately ten times smaller than that based on total CPK.The correct K value for determining infarct size using MB CPK' is 4.1 not 4.1 X 10. 1, and can be calculated using the relevant equa- tion and constants already published.
Long-term results of noncontact neodymium:yttrium–aluminum–garnet cyclophotocoagulation in neovascular glaucoma11The authors have no proprietary interest in any of the equipment or materials mentioned in this article.
Authors: Maria F Delgado, Christopher J Dickens, Andrew G Iwach, Gary D Novack, Diana S Nychka, Patricia C Wong, Ngoc Nguyen
Journal: Ophthalmology (2003)
Abstract #LB-13: TGF-\#946; receptor III is downregulated by \#916;Np63 and methylation and contributes to altered TGF-\#946; and NF-\#954;B signaling and the malignant phenotype in head and neck squamous cell cancer
Authors: Frederick Wang, Xinping Yang, Jeffrey Burnett, Jay Friedman, Hai Lu, Jonah Cohen, Zhong Chen, Carter Van Waes
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Alterations in the function of the TGF-\#946; signaling pathway have been implicated in the development and progression of many cancers, including head and neck squamous cell carcinoma (HNSCC). Microarray analysis of a panel of HNSCC cell lines revealed a distinct pattern of TGF-\#946; receptor expression that segregated based on p53 mutation status. HNSCC cell lines deficient in wild-type p53 expression had decreased while those with mutant p53 expression had increased TGF-\#946; receptor III (T\#946;R3) mRNA transcripts and protein relative to human epidermal keratinocytes (HEKA), leading us to investigate the role of T\#946;R3 in tumorigenesis. No mutations affecting amino acid sequence were observed. The cellular response to TGF-\#946;1 and TGF-\#946;2 was attenuated in HNSCC cell lines as assayed by cell proliferation, suggesting that the altered expression of T\#946;R3, which has a high affinity to TGF-\#946;2, may contribute to the malignant phenotype. TGF-\#946;1 and TGF-\#946;2 also differentially modulated the classical downstream genes of TGF\#946; pathway, such as PAI-1, MMP2, and MYC. \#916;Np63, a TP53 family member with oncogenic activity, suppressed T\#946;R3 gene expression and the downstream gene SMAD7. Treatment with 5-azacytidine also increased T\#946;R3 mRNA levels, suggesting that methylation may play a role in decreased T\#946;R3 levels. Overexpression of T\#946;R3 altered NF-\#954;B and PAI-1 reporter activity, demonstrating that T\#946;R3 is involved in signaling through both NF-\#954;B and TGF-\#946; pathways. The expression levels of several downstream targets of both signaling pathways were also affected, including ZEB2, a transcriptional repressor of E-cadherin important in regulating epithelial-mesenchymal transition (EMT). In summary, this is the first study to our knowledge to demonstrate that altered T\#946;R3 expression in subsets of HNSCC may contribute to aberrations in the signaling of both TGF-\#946; and NF-\#954;B pathways, leading to loss of negative control and aggressive malignancy. This work was supported by NIDCD Z01-DC-00016

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-13.
Glanzmann Thrombasthenia Caused by an 11.2-kb Deletion in the Glycoprotein IIIa (β3 ) Is a Second Mutation in Iraqi Jews That Stemmed From a Distinct Founder
Authors: Nurit Rosenberg, Rivka Yatuv, Yael Orion, Ariella Zivelin, Rima Dardik, Hava Peretz, Uri Seligsohn
Journal: Blood (1997)
Nodular lesions arising in a large congenital melanocytic naevus in a newborn with eruptive disseminated Spitz naevi
Authors: M. Feito-Rodríguez, R. de Lucas-Laguna, B.C. Bastian, P. LeBoit, M.J. González-Beato, J.C. López-Gutiérrez, L. Requena, A. Pizarro
Journal: British Journal of Dermatology (2011)

Congenital malignant melanoma within a pre-existing large congenital melanocytic naevus (CMN) is exceedingly rare. Its incidence is difficult to determine due to the small number of reported cases and because of problems associated with diagnosis. Some benign nodular proliferations (called proliferative nodules) arising in CMN, while rare, are significantly more common and can mimic malignant melanoma clinically or histologically. There are no reported cases of congenital melanoma or benign proliferative nodules in CMN in patients who also had eruptive disseminated Spitz naevi. We describe a girl who was noted to have a dark-brown plaque with several large erythematous nodules affecting the scalp at delivery, in addition to multiple erythematous dome-shaped papules that developed in a disseminated manner over several months, beginning at 10 days of age. It was difficult, not only clinically but also histologically, to determine the benign or malignant nature of all of these lesions. As primary cutaneous melanoma, atypical proliferative nodules in CMN, bland CMN or CMN with foci of increased cellularity and Spitz naevi show clear differences in the genetic aberration patterns, comparative genomic hybridization (CGH) could be a diagnostic help in ambiguous cases such as this. CGH performed on this patient showed multiple DNA copy number changes in the most atypical nodule, but such alterations could not be found in the remainder of the lesions. CGH showed differences between the nodular lesions that occurred in the CMN and helped us in supporting the diagnosis of this unique case of benign proliferative nodules and a possible congenital melanoma arising in a large CMN, associated with multiple widespread eruptive Spitz naevi.
Development of a companion diagnostic test for inhibitors of V600E BRAF
Authors: Rachel Langland, Thad Sharp, James Tsai, Mickey Williams, Lin Wu
Journal: Clinical Cancer Research (2006)

A13   Mutations of the human  BRAF  gene are detected in approximately 8% of cancer samples, primarily in cutaneous melanomas (70%). The most common mutation (90%) is a valine-to-glutamic acid mutation at residue 600 (V600E), which mimics the phosphorylation of the kinase domain activation segment that is thought to destabilize a hydrophobic interaction of V600 in the inactive state. PLX4032 is a novel small molecule selected for its specific inhibitory activity to the mutant B-Raf protein. This compound showed strong specificity for and potency against melanoma and colorectal cell lines bearing the V600E mutation. In addition, it demonstrated robust efficacy in xenograft models using a once-daily low oral dose, with evidence of tumor shrinkage and prolonged delay of tumor growth for a significant post-dosing period. The development of PLX4032 as a cancer therapy will be expedited by a companion diagnostic test to detect the  BRAF V600E   mutation as a biomarker for patient selection. For this important biomarker, we have initiated development of a real-time PCR assay on the Roche Molecular Diagnostics COBAS® TaqMan® 48. The assay, which can be used with fresh frozen or paraffin-embedded tissue, is based on the amplification of a short DNA fragment. We evaluated the sensitivity and specificity of the test with cell line DNA samples containing the V600E mutation, showing that it can detect the V600E mutation when it is present in only 10% of the mixture with the wild-type  BRAF  gene. We also validated the analytical performance of this test with clinical samples of melanomas. The development of our assay as a companion diagnostic test to select patients with the  BRAF V600E   mutation for treatment with PLX4032 is a compelling example of personalized medicine in cancer management.
Detection of tumor-derived DNA with EGFR mutations in different biological samples from cancer patients: feasibility and optimization of the method
Authors: Alexander S. Belokhvostov, Viktor M. Feniksov, Konstantin K. Vdovichenko, Andrew R. Zaretsky
Journal: Clinical Cancer Research (2006)

B19   The aim of the present study is to develop an assay for quick and reliable detection of tumor-derived point mutations in EGFR gene in different biological samples from cancer patients.Epidermal growth factor receptor is one of the most attractive targets for molecular therapy of cancer. Among different types of EGFR modulators that have already been successfully introduced into clinic there are synthetic small molecules designed to inhibit the intracellular tyrosine kinase domain of EGFR. Reliable markers that can be used to predict the effectiveness of these drugs would be of great value. The whole spectrum of predictive markers for such drugs as gefitinib and erlotinib is not yet known; nevertheless, some point mutations in the tyrosine kinase domain of EGFR are known to be connected with extreme responsiveness to these drugs and other point mutations in the same domain strongly predict tumor resistance to both Iressa and Tarceva.Several assays for detection of mutant EGFR in biopsy specimens or surgically removed tumor tissue have been developed. However, the early detection of newly-established resistance to EGFR inhibitors during the course of treatment with such drugs is also of crucial importance since it gives an opportunity to circumvent this resistance by means of polychemotherapy. We tried to establish an assay which can be used not only for initial determination of EGFR status, but also for its monitoring in dynamic.43 samples from 14 patients with different solid tumors were analyzed. DNA from tumor tissue, saliva, blood cells, blood plasma and urine cell sediment was extracted using the three-stage protocol (proteinase K treatment, phenol deproteinization and ethanol precipitation) with appropriate modifications. Exons 18 to 21 of EGFR gene were amplified by PCR and amplicons were analyzed by SSCP electrophoresis. All major bands were also analyzed by direct sequencing. Results of the sequencing were interpreted with the help of main genetic databases and literature search.All four techniques were found feasible when applied to every type of samples. Results of repeated SSCP experiments appeared to be reproducible. 5 germline heterozygous mutations in exon 20 and one somatic mutation in exon 19 were detected. All of them appeared to be silent.PCR-SSCP analysis of exons 18-21 of EGFR gene combined with direct sequencing of non-wild-type bands seems to be a reliable tool for establishing EGFR status in different biological samples and may be used in clinical trials of small-molecule EGFR inhibitors.
Bone: Bone as a Structural Material (Adv. Healthcare Mater. 9/2015)
Authors: Elizabeth A. Zimmermann, Robert O. Ritchie
Journal: Advanced Healthcare Materials (2015)

On page 1287, E. A. Zimmermann and R. O. Ritchie discuss how human cortical bone's hierarchical structure resists deformation and crack growth through physics-based mechanisms at small and large length-scales, which are essential to resist fracture. Using synchrotron micro-computed tomography, the three-dimensional structure of human cortical bone, with its vascular canals at the center of each osteon (in green), can be observed resisting the propagation of a crack (in yellow) through crack-tip shielding mechanisms, such as uncracked ligament bridging.
Retention of Pollen Grains in Human Lung
Authors: Mireille Solkr, Leon Le Bouffani, Jacquks Charpin
Journal: Allergy (1982)

The possibility of the penetration of pollen grains into the tracheobronchial tree is still a controversial question. To investigate this phenomenon further two different approaches were conducted: 1) Acetolysis (acidic degradation of organic constituents) of mucosal samples from different levels of the pig respiratory tract showed that specific (plane tree) inhaled pollens were not found beyond the main bronchi. 2) In contrast, a noticeable number of pollens were present in acetolyzed residues of lung surgical samples; this was shown to be due to contamination. In the first approach this problem was avoided; however, the analysis of surgical samples could be a valuable technique if suitable controls were included.
Abstract 17415: Similar Improvements in Outcomes Following 36 Sessions of Cardiac Rehabilitation Irrespective of Duration
Authors: Pallavi Gomadam, Matthew Sacrinty, Christopher Douglas, Dominic Johnson, Theresa Addison, Beverly Martin, Connie Paladenech, Natalie Austin, Killian Robinson
Journal: Circulation (2014)

Background: Cardiac Rehabilitation (CR) improves functional capacity in patients with CAD. The standard program requires completion of 36 sessions most often in 12 weeks. For various reasons, many patients are unable to complete a CR program in this time. Data comparing outcomes from standard 12-week programs to those of a greater duration are sparse. Hypothesis: We predicted that patients completing 36 sessions of CR in our standard 12-week program would achieve similar improvements in exercise capacity and risk factors as those taking longer than 12 weeks. Methods: Between 2004 and 2013, 836 patients (mean age 63.3 ± 11.0 years, 222 females and 614 males) completed 36 sessions of CR in 12-15 weeks (n=507), 15-19 weeks (n=234), or 19-67 weeks (n=95). Exercise capacity in metabolic equivalents (METs) and risk factors were measured before and after CR. Analysis of variance was used to compare groups. Results: All patients showed similar improvements in exercise capacity, weight, BMI, LDL, and HDL cholesterol (see table and figure). Systolic pressures decreased, though not significantly, but diastolic pressures remained unchanged. Conclusion: Although standard of care for CR is usually to complete 36 sessions in 12 weeks, a longer program incorporating the same number of sessions may achieve similar outcomes in relation to exercise capacity and risk factors, with the exception of blood pressure. Such programs may be suitable for patients who are unable to complete a CR program within the standard time frame due to social, occupational, or medical constraints.
Abstract 3640: IL-9 is involved in the establishment of a tolerogenic milieu that prevents anti-tumor immunity
Authors: Dominique B. Hoelzinger, Ana Lucia Dominguez, Peter A. Cohen, Sandra J. Gendker
Journal: Cancer Research (2014)

Abstract IL-9 is a Th2 cytokine associated with T regulatory cell function, parasite expulsion and allergic airway inflammation. In many tumors IL-9 contributes to the establishment of a tolerogenic / immunosuppressive environment or acts directly to drive tumor growth, whereas in melanomas it inhibits tumor growth. Little is known about the effect of IL-9 in breast cancer biology. Here we show that IL-9 is a key factor in establishing a permissive growth environment for two murine breast cancer cells lines: TUBO cells that express Her2/neu and 4T1 cells that resemble aggressive, triple-negative breast cancers. We observed that TUBO cells were rejected by 78%, and 4T1 cells by 68% of IL-9 -/- (IL-9ko) mice, and that in the remaining mice the tumors developed later and grew slower than in WT mice. Tumor rejection is CD8+ T cell dependent and is capable of producing a memory response against tumor rechallenge. Delayed depletion of CD8+ T cells in mice that had rejected 4T1 cells showed no tumor growth in 63 % of the mice, suggesting that in these mice the tumor had been completely eradicated and was not held in stasis by immune surveillance. Furthermore we found a 3.7 fold increase (p=0.007) in the number of activated CD8+ T cells derived from IL-9ko mice rejecting tumors as compared to CD8+ T cells from tumor bearing WT mice. More importantly, the transfer of activated splenocytes from IL-9ko mice led to tumor rejection in WT mice (p&amp;lt;0.001). Moreover, WT mice treated with neutralizing anti-IL-9 evidenced slower 4T1 tumor growth compared to untreated and isotype control antibody treated mice. These data suggest that IL-9 neutralization should be examined as an adjuvant to immunotherapeutic or chemotherapeutic approaches. Supported by the NCI : CA155295 Citation Format: Dominique B. Hoelzinger, Ana Lucia Dominguez, Peter A. Cohen, Sandra J. Gendker. IL-9 is involved in the establishment of a tolerogenic milieu that prevents anti-tumor immunity. [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 3640. doi:10.1158/1538-7445.AM2014-3640
Interpretation of Pulmonary Function Tests: A Practical Guide.
Authors: Robert E. Hyatt, Paul D. Scanlon, Masao Nakamura
Journal: Thorax (1998)

Preface: vii Acknowledgments: viii List of Abbreviations: ix 1. Introduction 2. Spirometry: Dynamic Lung Volumes 3. Static (Absolute) Lung Volumes 4. Diffusing Capacity of the Lungs 5. Bronchodilators and Bronchial Challenge Testing 6. Arterial Blood Gases 7. Other Tests of Lung Mechanics: Resistance and Compliance 8. Distribution of Ventilation 9. Maximal Respiratory Pressures 10. Preoperative Pulmonary Function Testing 11. Simple Tests of Exercise Capacity 12. Patterns in Various Diseases 13. When to Test and What to Order 14. An Approach to Interpreting Pulmonary Function Tests 15. Illustrative Cases Appendix Subject Inde
530. Spinal Interleukin-10 (IL-10) Gene Therapy Using Viral and Non-Viral Vectors Controls Inflammatory- and Chronic Constriction Injury-Induced Pain States in Rats
Authors: Erin D. Milligan, Raymond A. Chavez, Stephen J. Langer, Evan M. Sloane, Maru Chacur, Julie L. Wieseler-Frank, Matthew G. Frank, Terrence R. Flotte, Pedro Cruz, Leslie Leinwand, Jennifer A. Shumilla, John R. Forsayeth, Steven F. Maier, Linda R. Watkins
Journal: Molecular Therapy (2004)

Spinal cord glia, via proinflammatory cytokines (interleukin-1, tumor necrosis factor, & interleukin-6), critically mediate the creation/maintenance of pathological pain such as sciatic inflammatory neuropathy (SIN) & chronic constriction injury (CCI). The anti-inflammatory cytokine, IL-10, suppresses proinflammatory cytokine production & function. We have used a variety of gene therapy approaches to examine the efficacy of IL-10 in rat models of neuropathic pain. Behavior was assessed before & after induction of various pain models. Adenoviral vectors expressing the IL-10 gene block &/or reverse exaggerated pain (mechanical allodynia [von Frey test] & thermal hyperalgesia [Hargreaves test]) produced by intrathecal (IT) lumbosacral spinal (LS) delivery of gp120, SIN, & CCI. IT LS delivery of AAV2 encoding IL-10 (AAV2-IL-10) was able to block SIN allodynia [amp] reverse CCI allodynia [amp] thermal hyperalgesia. However, the effects of viral IL-10 delivery systems resulted in reversals in the pain state of short duration. An IL-10-encoding non-viral plasmid vector (NVV) was also introduced IT in the CCI model. In contrast to the viral vectors, this approach resulted in long-lasting reversals of the pain state. Ongoing experiments will assess additional effects of NVV-driven IL-10 protein expression, including the identification of transfected tissue(s). These results suggest that NVV-based IL-10 gene therapy may be a potent addition to the treatments available to neuropathic pain patients.