tbuckley/cabot-search huggingface dataset:
Hepatitis C genotype 1 virus with low viral load and rapid virologic response to peginterferon/ribavirin obviates a protease inhibitor
Authors: Brian L. Pearlman, Carole Ehleben
Journal: Hepatology (2013)

The new standard of care for treatment-naïve patients with hepatitis C virus (HCV) genotype 1 includes triple therapy with peginterferon, ribavirin, and a protease inhibitor. However, patients who achieve a rapid virologic response after 4 weeks of peginterferon and ribavirin therapy are likely to achieve a sustained virologic response (SVR), and we hypothesized that protease inhibitor therapy may be unnecessary in these patients. Treatment-naïve, noncirrhosis patients infected with genotype-1 HCV and a low viral load at baseline were considered for inclusion (n = 233). After 4 weeks of lead-in therapy with peginterferon α-2b and ribavirin, 101 patients (48%) had a rapid virologic response (defined as undetectable levels of hepatitis C virus RNA at 4 weeks) and were eligible to participate. Patients were randomized 1:1 to 20 weeks of additional therapy with peginterferon α-2b and ribavirin (double therapy) or to 24 weeks of peginterferon α-2b, ribavirin, and boceprevir (triple therapy). There was no significant difference in rates of SVR-12 in patients treated with double versus triple therapy. This similarity persisted regardless of viral subtype (genotype 1a or 1b), interleukin (IL)−28b genotype (CC or non-CC), or ethnicity (African American versus non-Hispanic white). Conclusion: Protease inhibitor therapy could be obviated in genotype 1-infected treatment-naïve patients with low viral load at baseline who achieve undetectable viremia after 4 weeks of peginterferon/ribavirin.(Hepatology 2014;58:71–77)
Addition of Weekly Oxaliplatin to Standard Preoperative Chemoradiation for Locally Advanced Rectal Cancer
Authors: Carlo Aschele, Sara Lonardi
Journal: Journal of Clinical Oncology (2007)

compared with 16% of patients experiencing grade 3-4 events. This might depend on differences in drug and RT scheduling. The interval between OXA administration and delivery of RT prescribed in CALGB 89901 might have resulted in more effective RT sensitization and, therefore, toxicity. However, the similar antitumor activity observed between the two studies argues against this explanation. Similarly, although the shortened duration of OXA infusion in the US study (1 hour) might theoretically affect toxicity, a selective effect on gastrointestinal toxicity is unlikely. Neurotoxicity rates were in fact slightly higher in our study (grade 1-2, 80% v66%). This difference may have other explanations. While patients in our study were accrued and treated at a single institution, patientsintheUSstudywererecruitedatseveralcenters.Different toxicity grading systems may have also been used. While in our study toxicity was scored according to the Nation Cancer Institute Common Toxicity Criteria version 2, the scoring system used in theUStrialwasnotspecified.Despitethehigherincidenceofgrade
Complement 1 Inhibitor Is a Regulator of the Alternative Complement Pathway
Authors: Haixiang Jiang, Eric Wagner, Huamei Zhang, Michael M. Frank
Journal: The Journal of Experimental Medicine (2001)

We studied complement 1 inhibitor (C1-INH) as an inhibitor of the alternative complement pathway. C1-INH prevented lysis, induced by the alternative complement pathway, of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes in human serum. It inhibited the binding of both factors B and C3 to PNH and rabbit erythrocytes and blocked the ability of factor B to restore alternative-pathway function in factor B–depleted serum. C1-INH did not bind to factors B or D but did bind to immobilized C3b and cobra venom factor (CVF), a C3b analogue. C1-INH prevented factor B from binding to CVF-coated beads and dissociated bound factor B from such beads. Factor B and C1-INH showed cross competition in binding to CVF-coated beads. Factor D cleaved factor B into Bb and Ba in the presence of C3b. Cleavage was markedly inhibited when C3b was preincubated with C1-INH. C1-INH inhibited the formation of CVFBb and decreased the C3 cleavage. Removal of C1-INH from serum, in the presence of Mg-EGTA with an anti–C1-INH immunoabsorbant, markedly increased alternative-pathway lysis. C1-INH interacts with C3b to inhibit binding of factor B to C3b. At physiologic concentrations, it is a downregulator of the alternative pathway convertase.
Mast Cells Are Essential for Early Onset and Severe Disease in a Murine Model of Multiple Sclerosis
Authors: Virginia H. Secor, W. Evan Secor, Claire-Anne Gutekunst, Melissa A. Brown
Journal: The Journal of Experimental Medicine (2000)

In addition to their well characterized role in allergic inflammation, recent data confirm that mast cells play a more extensive role in a variety of immune responses. However, their contribution to autoimmune and neurologic disease processes has not been investigated. Experimental allergic encephalomyelitis (EAE) and its human disease counterpart, multiple sclerosis, are considered to be CD4(+) T cell-mediated autoimmune diseases affecting the central nervous system. Several lines of indirect evidence suggest that mast cells could also play a role in the pathogenesis of both the human and murine disease. Using a myelin oligodendrocyte glycoprotein (MOG)-induced model of acute EAE, we show that mast cell-deficient W/W(v) mice exhibit significantly reduced disease incidence, delayed disease onset, and decreased mean clinical scores when compared with their wild-type congenic littermates. No differences were observed in MOG-specific T and B cell responses between the two groups, indicating that a global T or B cell defect is not present in W/W(v) animals. Reconstitution of the mast cell population in W/W(v) mice restores induction of early and severe disease to wild-type levels, suggesting that mast cells are critical for the full manifestation of disease. These data provide a new mechanism for immune destruction in EAE and indicate that mast cells play a broader role in neurologic inflammation.
Calcification in saphenous vein graft: clinical correlates and intravascular ultrasound findings
Authors: Marco T. Castegna, Gary S. Mintz, Neil J. Weissman, Akiko Maehara, Jun-ichi Kotani, Javed M. Ahmed, Martine Gilard, Daniel Canos, William O. Suddath, Lowell F. Satler, Ron Waksman, Kenneth M. Kent, Augusto D. Pichard
Journal: Journal of the American College of Cardiology (2002)
Angiographic variables predict increased riskfor adverse ischemic events after coronarystenting with glycoprotein IIb/IIIa inhibition
Authors: Mitchell J Ross, Howard C Herrmann, David J Moliterno, James C Blankenship, Laura Demopoulos, Peter M DiBattiste, Stephen G Ellis, Ziyad Ghazzal, Jack L Martin, Jennifer White, Eric J Topol
Journal: Journal of the American College of Cardiology (2003)
Centrosomal PKCβII and Pericentrin Are Critical for Human Prostate Cancer Growth and Angiogenesis
Authors: Jeewon Kim, Yoon-La Choi, Alice Vallentin, Ben S. Hunrichs, Marc K. Hellerstein, Donna M. Peehl, Daria Mochly-Rosen
Journal: Cancer Research (2008)

Abstract Angiogenesis is critical in the progression of prostate cancer. However, the interplay between the proliferation kinetics of tumor endothelial cells (angiogenesis) and tumor cells has not been investigated. Also, protein kinase C (PKC) regulates various aspects of tumor cell growth, but its role in prostate cancer has not been investigated in detail. Here, we found that the proliferation rates of endothelial and tumor cells oscillate asynchronously during the growth of human prostate cancer xenografts. Furthermore, our analyses suggest that PKCβII was activated during increased angiogenesis and that PKCβII plays a key role in the proliferation of endothelial cells and tumor cells in human prostate cancer; treatment with a PKCβII-selective inhibitor, βIIV5-3, reduced angiogenesis and tumor cell proliferation. We also find a unique effect of PKCβII inhibition on normalizing pericentrin (a protein regulating cytokinesis), especially in endothelial cells as well as in tumor cells. PKCβII inhibition reduced the level and mislocalization of pericentrin and normalized microtubule organization in the tumor endothelial cells. Although pericentrin has been known to be up-regulated in epithelial cells of prostate cancers, its level in tumor endothelium has not been studied in detail. We found that pericentrin is up-regulated in human tumor endothelium compared with endothelium adjacent to normal glands in tissues from prostate cancer patients. Our results suggest that a PKCβII inhibitor such as βIIV5-3 may be used to reduce prostate cancer growth by targeting both angiogenesis and tumor cell growth. [Cancer Res 2008;68(16):6831–9]
Electrocardiographic measures of left ventricular hypertrophy in children across the distribution of blood pressure: the Muscatine study.
Authors: R M Schieken, W R Clarke, R Prineas, V Klein, R M Lauer
Journal: Circulation (1982)

We sought to test the effectiveness of the ECG as a measure of increased left ventricular wall mass in children with high blood pressure. One hundred eighty-one children, ages 9-18 years, were selected from the lowest, middle and highest quintile of systolic blood pressure from the Muscatine Study, based upon two biennial school screenings. After correction for age, sex, height, weight and skinfold thickness, children with the highest blood pressure had increased echocardiographic left ventricular wall mass (p less than 0.02). Voltage measurements of maximum R and S waves in the standard and precordial leads were measured by computer. We correlated blood pressure and echocardiographic measurements of the interventricular septum, left ventricular posterior wall and left ventricular wall mass to electrocardiographic combinations used to predict left ventricular hypertrophy in both children and adults. The electrocardiographic correlations ranged from -0.01 to + 0.17. Poor correlations were found between electrocardiographic measures and blood pressure, left ventricular wall thickness or left ventricular wall mass. Skinfold thickness and weight had negative correlations, suggesting a damping effect upon measured voltage. We conclude that the echocardiogram is a more sensitive measurement of increased left ventricular mass than the ECG in children with elevated blood pressure.
A Sign of Carcinoma
Authors: A. D. Wright
Journal: BMJ (1948)

in hospital practice.The incidence of rheumatic fever was 'found by Coombs to be 5 girls to 4 boys ; yet the incideiice of mitral stenosis in females must be in the region of 5 to 1 male.This is due to the less active life led by girls, who are seldom permitted to be out of range of the maternal eye; they sit and knit and acquire obstructive stenosis and provide most examples of auricular fibrillation in the forties.Her brother with the same diseases escapes to the playground and, despite restrictive advice, ensures that the cusps of the mitral valve are kept well 'apart by the vigour of his exercise, thereby securing a greater volume in flow and growth of the left ventricle.At the same time he prolongs his life.Convalescent heart homes are not the nurseries for the cultivation of mitral stenosis tlhat they used to be ; nevertheless the introduction of the sedimentation rate has tended to in- crease bed rest in these cases, and mitral stenosis is actively encouraged once again.Because the sedimentation rate is increased, active endocarditis is presumed with often no justification ; it might well be tonsil, sinus, or other infection.Immobilization and fibrosis are inseparable bed-mates and are no companions for growing hearts.-Iam, etc., London, W.I.
The anabolic steroid stanozolol upregulates collagen synthesis through the action of transforming growth factor–β1
Authors: Anna F. Falabella
Journal: Journal of the American Academy of Dermatology (1998)

Stanozolol, an anabolic steroid first synthesized in 1959, is a synthetic derivative of testosterone. Like many other anabolic steroids, it was synthesized in an attempt to dissociate the anabolic and androgenic actions of testosterone. Stanozolol has one of the largest anabolic/androgenic ratios, considered to be up to 100:1. Stanozolol is presently approved for clinical use for treatment of angioedema. In recent years, however, there has been increasing interest in using anabolic steroids in conditions such as aging, wound healing, and wasting diseases. 1 Falanga V Kirsner RS Eaglstein WH et al. Stanozolol in treatment of leg ulcers due to cryofibrinogenemia. Lancet. 1991; 338: 347-348 Abstract PubMed Scopus (60) Google Scholar , 2 Helfman T Falanga V. Stanozolol as a novel therapeutic agent in dermatology. J Am Acad Dermatol. 1995; 32: 254-258 Abstract Full Text PDF Scopus (63) Google Scholar The exact mode of action of stanozolol is unknown. However, it is known that stanozolol has fibrinolytic actions 3 Gribbin HR Flavell Matts SG. Mode of action and use of anabolic steroids. Br J Clin Pract. 1976; 30: 3-9 PubMed Google Scholar and that it decreases the level of tissue plasminogen activator inhibitor, mean plasma fibrinogen levels, and extravascular fibrin deposits. It has been previously reported that anabolic steroids enhance tensile strength of wounds by increasing the amount of chondroitin sulfate, and it has been shown that stanozolol stimulates procollagenase production.
When is it sensible to use PET to study brain function?
Authors: Shane M. O'Mara
Journal: Behavioral and Brain Sciences (1995)

Abstract Posner &amp; Raichle's book is a superbly presented and wellwritten overview of a fast-developing and important field in contemporary neuroscience. It suffers from being an overview, however, because it does not go into sufficient detail or depth in many of the issues that it raises. It also neglects many other important areas of current research, for example, technical advances in other areas, learning and memory, and lesion analysis of brain function.
Expression of p95HER2, a Truncated Form of the HER2 Receptor, and Response to Anti-HER2 Therapies in Breast Cancer
Authors: M. Scaltriti, F. Rojo, A. Ocana, J. Anido, M. Guzman, J. Cortes, S. Di Cosimo, X. Matias-Guiu, S. Ramon y Cajal, J. Arribas, J. Baselga
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundWomen with HER2–overexpressing breast cancers have poor prognosis, and many are resistant to the HER2 monoclonal antibody trastuzumab. A subgroup of HER2–overexpressing tumors also express p95HER2, an amino terminally truncated receptor that has kinase activity. Because p95HER2 cannot bind to trastuzumab but should be responsive to the HER2 tyrosine kinase inhibitor lapatinib, we compared the sensitivity of tumors expressing p95HER2 and tumors expressing the full-length HER2 receptor to these agents.
The Glial Nature of Embryonic and Adult Neural Stem Cells
Authors: Arnold Kriegstein, Arturo Alvarez-Buylla
Journal: Annual Review of Neuroscience (2009)

Glial cells were long considered end products of neural differentiation, specialized supportive cells with an origin very different from that of neurons. New studies have shown that some glial cells—radial glia (RG) in development and specific subpopulations of astrocytes in adult mammals—function as primary progenitors or neural stem cells (NSCs). This is a fundamental departure from classical views separating neuronal and glial lineages early in development. Direct visualization of the behavior of NSCs and lineage-tracing studies reveal how neuronal lineages emerge. In development and in the adult brain, many neurons and glial cells are not the direct progeny of NSCs, but instead originate from transit amplifying, or intermediate, progenitor cells (IPCs). Within NSCs and IPCs, genetic programs unfold for generating the extraordinary diversity of cell types in the central nervous system. The timing in development and location of NSCs, a property tightly linked to their neuroepithelial origin, appear to be the key determinants of the types of neurons generated. Identification of NSCs and IPCs is critical to understand brain development and adult neurogenesis and to develop new strategies for brain repair.
Acute Psychological Stress Accelerates Reverse Cholesterol Transport via Corticosterone-Dependent Inhibition of Intestinal Cholesterol Absorption
Authors: Reija Silvennoinen, Joan Carles Escola-Gil, Josep Julve, Noemi Rotllan, Gemma Llaverias, Jari Metso, Annabel F. Valledor, Jianming He, Liqing Yu, Matti Jauhiainen, Francisco Blanco-Vaca, Petri T. Kovanen, Miriam Lee-Rueckert
Journal: Circulation Research (2012)

Psychological stress is associated with an increased risk of cardiovascular diseases. However, the connecting mechanisms of the stress-inducing activation of the hypothalamic-pituitary-adrenal axis with atherosclerosis are not well-understood.To study the effect of acute psychological stress on reverse cholesterol transport (RCT), which transfers peripheral cholesterol to the liver for its ultimate fecal excretion.C57Bl/6J mice were exposed to restraint stress for 3 hours to induce acute psychological stress. RCT in vivo was quantified by measuring the transfer of [(3)H]cholesterol from intraperitoneally injected mouse macrophages to the lumen of the small intestine within the stress period. Surprisingly, stress markedly increased the contents of macrophage-derived [(3)H]cholesterol in the intestinal lumen. In the stressed mice, intestinal absorption of [(14)C]cholesterol was significantly impaired, the intestinal mRNA expression level of peroxisome proliferator-activated receptor-α increased, and that of the sterol influx transporter Niemann-Pick C1-like 1 decreased. The stress-dependent effects on RCT rate and peroxisome proliferator-activated receptor-α gene expression were fully mimicked by administration of the stress hormone corticosterone (CORT) to nonstressed mice, and they were blocked by the inhibition of CORT synthesis in stressed mice. Moreover, the intestinal expression of Niemann-Pick C1-like 1 protein decreased when circulating levels of CORT increased. Of note, when either peroxisome proliferator-activated receptor α or liver X receptor α knockout mice were exposed to stress, the RCT rate remained unchanged, although plasma CORT increased. This indicates that activities of both transcription factors were required for the RCT-accelerating effect of stress.Acute psychological stress accelerated RCT by compromising intestinal cholesterol absorption. The present results uncover a novel functional connection between the hypothalamic-pituitary-adrenal axis and RCT that can be triggered by a stress-induced increase in circulating CORT.
Incidence and detection of occult hepatic metastases in colorectal carcinoma.
Authors: I G Finlay, D R Meek, H W Gray, J G Duncan, C S McArdle
Journal: BMJ (1982)

Isotope liver scan, ultrasonography, and computed tomography of the liver were performed during the postoperative period in 43 consecutive patients undergoing laparotomy for colorectal carcinoma. Obvious hepatic metastases were detected in six patients at the time of surgery. Eleven patients considered to have a disease-free liver at laparotomy developed hepatic metastases during the two-year follow-up period. These patients were considered to have had occult hepatic metastases at the time of surgery. Postoperative isotope liver scan, ultrasonography, and computed tomography detected the presence of overt metastases in four, five, and six patients respectively. Of the 11 patients with occult metastases, isotope liver scan, ultrasonography, and computed tomography detected one, three, and nine respectively. These observations suggest that 29% of patients undergoing apparently curative resection for colorectal carcinoma possess occult hepatic metastases and that computed tomography is superior to ultrasonography and isotope liver scan in detecting them.
The DC receptor DNGR-1 mediates cross-priming of CTLs during vaccinia virus infection in mice
Authors: Salvador Iborra, Helena M. Izquierdo, María Martínez-López, Noelia Blanco-Menéndez, Caetano Reis e Sousa, David Sancho
Journal: Journal of Clinical Investigation (2012)

In order to prime T cells, DCs integrate signals emanating directly from pathogens and from their noxious action on the host. DNGR-1 (CLEC9A) is a DC-restricted receptor that detects dead cells. Therefore, we investigated the possibility that DNGR-1 affects immunity to cytopathic viruses. DNGR-1 was essential for cross-presentation of dying vaccinia virus–infected (VACV-infected) cells to CD8+ T cells in vitro. Following injection of VACV or VACV-infected cells into mice, DNGR-1 detected the ligand in dying infected cells and mediated cross-priming of anti-VACV CD8+ T cells. Loss of DNGR-1 impaired the CD8+ cytotoxic response to VACV, especially against those virus strains that are most dependent on cross-presentation. The decrease in total anti-VACV CTL activity was associated with a profound increase in viral load and delayed resolution of the primary lesion. In addition, lack of DNGR-1 markedly diminished protection from infection induced by vaccination with the modified vaccinia Ankara (MVA) strain. DNGR-1 thus contributes to anti-VACV immunity, following both primary infection and vaccination. The non-redundant ability of DNGR-1 to regulate cross-presentation of viral antigens suggests that this form of regulation of antiviral immunity could be exploited for vaccination.
Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: A case report of sustained hematologic response following an abbreviated exposure
Authors: Fahd Quddus, Jessica Clima, Helen Seedham, Ghulam Sajjad, Naomi Galili, Azra Raza
Journal: Journal of Hematology & Oncology (2010)

Abstract Treatment options for patients with lower risk non-del(5q) myelodysplastic syndromes (MDS) who fail erythroid stimulating agents are restricted to one of the hypomethylating drugs with an expected response rate of ~50%. Ezatiostat HCl, an agent with the potential for producing multi-lineage responses in this population is currently in clinical investigation phase. This case report describes a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bone marrow showed the disappearance of the del(5q) but the appearance of a new clonal abnormality t(2;3). Given that the patient had a complete cytogenetic response to a truncated exposure to lenalidomide followed by a trilineage response to an even briefer course of ezatiostat HCl suggests a potential role for ezatiostat HCl in del(5q) patients who relapse following lenalidomide.