tbuckley/cabot-search huggingface dataset:
Development and characterization of hepatitis C virus genotype 1-7 cell culture systems: Role of CD81 and scavenger receptor class B type I and effect of antiviral drugs # †
Authors: Judith M. Gottwein, Troels K. H. Scheel, Tanja B. Jensen, Jacob B. Lademann, Jannick C. Prentoe, Maria L. Knudsen, Anne M. Hoegh, Jens Bukh
Journal: Hepatology (2008)

Abstract Six major hepatitis C virus (HCV) genotypes and numerous subtypes have been described, and recently a seventh major genotype was discovered. Genotypes show significant molecular and clinical differences, such as differential response to combination therapy with interferon-α and ribavirin. Recently, HCV research has been accelerated by cell culture systems based on the unique growth capacity of strain JFH1 (genotype 2a). By development of JFH1-based intergenotypic recombinants containing Core, envelope protein 1 and 2 (E1, E2), p7, and nonstructural protein 2 (NS2) of genotype 6a and 7a strains, as well as subtype 1b and 2b strains, we have completed a panel of culture systems for all major HCV genotypes. Efficient growth in Huh7.5 cells depended on adaptive mutations for HK6a/JFH1 (6a/2a, in E1 and E2) and J4/JFH1 (1b/2a, in NS2 and NS3); viability of J8/JFH1 (2b/2a) and QC69/JFH1 (7a/2a) did not require adaptation. To facilitate comparative studies, we generated virus stocks of genotype 1–7 recombinants with infectivity titers of 10 3.7 to 10 5.2 50% tissue culture infectious dose/mL and HCV RNA titers of 10 7.0 to 10 7.9 IU/mL. Huh7.5 cultures infected with genotype 1–6 viruses had similar spread kinetics, intracellular Core, NS5A, and lipid amounts, and colocalization of Core and NS5A with lipids. Treatment with interferon-α2b but not ribavirin or amantadine showed a significant antiviral effect. Infection with all genotypes could be blocked by specific antibodies against the putative coreceptors CD81 and scavenger receptor class B type I in a dose-dependent manner. Finally, neutralizing antibodies in selected chronic phase HCV sera had differential effects against genotype 1–7 viruses. Conclusion: We completed and characterized a panel of JFH1-based cell culture systems of all seven major HCV genotypes and important subtypes and used these viruses in comparative studies of antivirals, HCV receptor interaction, and neutralizing antibodies. (Hepatology 2009.)
Medical Oncology: Medical Aspects of Malignant Disease
Authors: Philip S. Schein
Journal: JAMA (1975)

This text represents the efforts of 24 contributors (predominantly British) to review comprehensively specific aspects of tumor biology, diagnostic procedures, and therapy pertinent to the field of medical oncology. The overall result is unbalanced with a wide variation in relative quality of individual chapters. The specific sections dealing with tumor immunology, cell kinetics, and trophoblastic disease are well written and informative. The treatment of the terminal patient, a subject conspicuously absent from current available oncologic texts, offers a concise and useful review of this very important and often difficult clinical problem. The clinical pharmacology of anticancer drugs is presented with extreme brevity, but the basic information is included. In several instances, however, the recommended dosages for specific agents do not conform with what is considered safe and accepted practice in this country. Many chapters, such as those describing the metabolic abnormalities and serum monitoring of tumors, present a wealth of
Anomalous origin of left coronary artery in young athletes with syncope
Authors: Matthias Kumpf, Ludger Sieverding, Matthias Gass, Renate Kaulitz, Gerhard Ziemer, Michael Hofbeck
Journal: BMJ (2006)

Possible causes of exercise induced syncope or sudden death in young athletes include undetected cardiomyopathies, myocarditis, arrhythmias (especially inherited arrhythmia syndromes—such as long QT syndrome, Brugada syndrome), coronary artery abnormalities and disease, and aortic rupture.1 2 3 Coronary artery anomalies are of special interest as they are potentially treatable lesions.4 5 The most frequent coronary artery anomaly is anomalous origin of the left coronary or the left anterior descending artery from the right coronary sinus of the aorta. According to a recent north Italian study, anomalous origin of left or right coronary artery from the opposite aortic sinus is the third most frequent cardiovascular cause of deaths associated with exercise among athletes aged 12-35 years.2



Fig 1 
Coronary artery anatomy in case 1 as shown by echocardiography from the parasternal short axis: both the right and left coronary arteries originate from the right aortic sinus. The main left coronary artery courses between the aorta and pulmonary artery and divides into left anterior descending artery and left circumflex branch



We report on two adolescents who presented with a history of recurrent exertional pain and syncope during exercise. The results of previous cardiological evaluation—including 12 lead electrocardiography, exercise testing, and echocardiography—had been normal. Both patients were admitted to our hospital after life threatening events of ventricular fibrillation. The diagnosis of the coronary artery anomaly was detected in both patients by transthoracic echocardiography. These two cases show that this potentially fatal anomaly cannot be excluded by a negative exercise test.1 4

### Case 1

This 15 year old boy was a talented, competitive soccer player with a history of recurrent syncope during soccer training at the age of 6, 7, and 11. Previous …
43 A multicenter, randomized, open-label study of peginterferon alpha-2b vs interferon alpha-2b for the treatment of chinese patients with HBeAg+VE chronic hepatitis B
Authors: H. Zhao, C.-W. Si, L. Wei, M.-B. Wan, Y.-K. Ying, J.-L. Hou, J.-Q. Niu, G.-Q. Wang, M. Masashi
Journal: Journal of Hepatology (2006)
Syntactic representations and the L2 acquisition device
Authors: William O'Grady
Journal: Behavioral and Brain Sciences (1996)

Abstract Epstein et al.'s theory of SLA is heavily dependent on assumptions about both the nature of the acquisition device and the grammar that it produces. This commentary briefly explores the consequences of an alternative set of assumptions, focusing on the possibility that the acquisition device does not include UG and that syntactic representations do not contain functional projections.
Metformin, hepatitis C, and insulin resistance: Sufficient evidence?
Authors: Yusuf Yilmaz, Oya Yonal, Nese Imeryuz
Journal: Hepatology (2009)

The prospective, multicentered, randomized, double-blinded, placebo-controlled trial by Romero-Gómez and coworkers1 demonstrating that adding metformin to peginterferon and ribavirin was safe and improved insulin sensitivity in treatment-naïve patients without diabetes who are chronically infected with genotype 1 hepatitis C virus (HCV) raises a number of issues. First, the cutoff used for insulin resistance in this study (i.e., HOMA [homeostasis model assessment] index > 2) was somewhat low, and the reasons behind this choice are not sufficiently explained by the authors. In clinical research, the decision on what cutoff points to use is crucial to give optimal enlightenment of individuals in need of pharmacological interventions because of increased insulin resistance. This choice must be made by considering the overall impact on health due to intervention (e.g., improvement of insulin resistance) and potential burden of overtreatment if a low cutoff point is employed. Second, the analysis by Romero-Gómez et al. is limited to patients with genotype 1 chronic hepatitis C. Because insulin resistance in patients with chronic hepatitis C does not differ among HCV genotypes,2 the reasons for this strict inclusion criteria is not sufficiently elucidated. Third, serum HCV RNA levels do not seem to predict insulin resistance in patients with chronic hepatitis C,2 and thus it is unclear whether the increased viral decline as seen in the metformin arm is the cause of improved HOMA values. Finally, the positive effects of metformin on sustained virological response and viral decline were confined to female patients. Notably, these findings were mainly derived from a sex-based subgroup analysis. Meaningful information from subgroup analyses within a randomized trial is restricted by low statistical power and the issue of multiple testing. In order to minimize the risk of accepting and publishing false positives, it has been proposed that the results of subgroup analysis be accepted merely as hypotheses.3 Given the risks of false positive findings when multiple subgroup analyses are done, it is not surprising that a subgroup-specific test may show a significant (P < 0.05) or suggestive (P = 0.05 to P = 0.10) effect of treatment, even when the trial failed to do so overall.3, 4 Of note, this is exactly the case of the study by Romero-Gómez et al.1 In order to support the validity of a claimed subgroup effect, there are some potential strategies, including the availability of a biological explanation (that is clearly missing in the published trial) or replication in another independent study.3 Taken together, the evidence published by Romero-Gómez et al. is likely insufficient to guide clinical care in patients with chronic hepatitis C who have insulin resistance. Yusuf Yilmaz*, Oya Yonal*, Nese Imeryuz*, * Department of Gastroenterology, Marmara University School of Medicine, Istanbul, Turkey.
Left anterior and left posterior hemiblock in tricuspid atresia and transposition of the great vessels: observations and electrocardiographic nomenclature and electrophysiologic mechanisms.
Authors: J Schatz, E Krongrad, J R Malm
Journal: Circulation (1976)

A patient with tricuspid atresia and characteristic electrocardiographic features of counterclockwise and superiorly oriented frontal plane QRS loop (left anterior hemiblock) is presented. Operative intervention resulted in a clockwise and inferior rotation of the frontal QRS loop (left posterior hemiblock) without the development of complete left bundle branch block. This observation suggests that the electrocardiographic pattern of left anterior hemiblock may result from other mechanisms in addition to block of the left bundle branch fibers oriented toward the anterior part of the left ventricle. The case further suggests that electrocardiographic patterns of apparent A-V conduction defects may not be at all associated with true block in the A-V conduction system. Further, it emphasizes the fact that various electrophysiologic mechanisms may account for identical electrocardiographic patterns.
THE RELATION OF THE WATER SUPPLY TO DISEASES OF THE ISTHMUS.
Authors: D. N. CARPENTER
Journal: JAMA (1905)

The attention of American sanitarians has recently been directed to the Isthmus of Panama, and it was therefore thought of interest to this Section to present the following observations relating to the water supply, also the diseases studied while I was on duty with the U. S. Marines at Obispo and Empire last year. During the days of the old French canal company the water supply of each section was obtained from the adjacent rivers or streams and pumped into tanks and relay stations to be distributed to the buildings occupied by the French employes. The native quarters were supplied by street hydrants. The official charts indicated the position of each pumping station, tank, and their connections with the liberal network of lead piping. All these had not been in use for years and were found in need of extensive repair. After the missing parts of pumps and pipes had
Recovery of Human Immunodeficiency Virus From Serum
Authors: Barbara A. Michaelis
Journal: JAMA (1987)

To the Editor.—  Our laboratory has reported the isolation of the human immunodeficiency virus (HIV) from peripheral mononuclear blood cells (PMCs) from over 300 individuals with the acquired immunodeficiency syndrome (AIDS) or AIDS-related conditions and from asymptomatic individuals from the risk groups.1,2We have also isolated the AIDS virus from a variety of body fluids, including serum, plasma, tears, urine, saliva, and genital secretions.3,4We now report the results of a survey of serum samples from 78 randomly selected, seropositive individuals, of whom about 30% were asymptomatic. Infectious virus was recovered from the serum of 20 (25.6%) of these individuals and was generally present in low titers. Only undiluted serum (not a tenfold dilution) yielded infectious virus as detected by assays on uninfected PMCs.2In one serum sample, 25000 infectious particles per milliliter were detected as measured by end dilution of the serum. This sample came from
Thrombotic microangiopathy (TMA) and stroke due to human herpesvirus‐6 (HHV‐6) reactivation in an adult receiving high‐dose melphalan with autologous peripheral stem cell transplantation
Authors: Amy Belford, Otha Myles, Alan Magill, James Wang, Rick C. Myhand, Jamie K. Waselenko
Journal: American Journal of Hematology (2004)

Abstract We report an adult autologous stem cell transplant (ASCT) patient who developed transplant‐associated thrombotic microangiopathy (TMA) due to human herpesvirus‐6 (HHV‐6) reactivation. A 58‐year‐old female with Stage IIIA IgGκ multiple myeloma received a melphalan (200 mg/m 2 ) ASCT with discharge home after resolution of ASCT‐related toxicities. She presented on D+20 with dyspnea, rash, and fever to 105°F, followed by worsening dyspnea, hypotension, and capillary leak. Mental status (MS) changes were noted on D+23, but head CT and EEG were unremarkable. On D+29, a generalized seizure occurred with decline in platelet count and haptoglobin. TMA was noted on peripheral blood smear and therapeutic plasma exchange (TPE) was initiated on D+31. Lumbar puncture (LP) revealed CSF protein 74 mg/dL and white blood count 7,000/mm 3 with 74% lymphocytosis. TPE was continued without improvement in her MS or thrombocytopenia despite improvement in microangiopathy. An MRI of the brain showed a left hippocampus abnormality, and an EEG was consistent with encephalopathy. Serum polymerase chain regimen (PCR) was negative for CMV, HSV1, and HSV2 but was strongly positive for HHV‐6. Repeat LP protein was 597 mg/dL. Foscarnet was initiated, and cerebrospinal fluid (CSF) PCR for HHV‐6 revealed 1,400 DNA copies/mL. Her MS greatly improved within 48 hr of antiviral therapy, serum HHV‐6 became negative, and TPE was tapered without recurrence of her TMA. TMA with HHV‐6 reactivation is likely an underdiagnosed entity. Given its fulminant course and favorable response to therapy, HHV‐6 reactivation should be considered a potential etiology in patients with TMA after ASCT. Am. J. Hematol. 76:156–162, 2004. © 2004 Wiley‐Liss, Inc.
Phase 1 results of a phase 1b/2, multicenter, open-label trial to evaluate safety and efficacy of talimogene laherparepvec (T-VEC) and ipilimumab (ipi) vs ipi alone in previously untreated, unresected stage IIIB-IV melanoma
Authors: Igor Puzanov, Mohammed Milhem, Robert Andtbacka, David Minor, Omid Hamid, Ai Li, Ari VanderWalde, Howard Kaufman
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts T-VEC is a herpes simplex virus type-1-derived oncolytic immunotherapy designed to produce GM-CSF and to selectively replicate in and lyse tumors to induce a systemic anti-tumor immune response. A phase 3 study of T-VEC in Stage IIIB-IV melanoma demonstrated a significant
Lung cancer teams pair up to review care processes and improve outcomes
Authors: S. Mayor
Journal: BMJ (2012)

Thirty lung cancer teams across England have observed how other services do things in a novel experiment to help them identify reasons for variations in lung cancer outcomes and to devise ways to improve the quality of care.

The Improving Lung Cancer Outcomes Project was set up to identify reasons for the variation in clinical outcomes and in patients’ experiences shown in the NHS’s national lung cancer audit.

Lung cancer teams in England have been submitting data to the national audit since 2005. Results have shown improvements in measures of processes and outcomes but also a large variation that is not wholly explained by differences in case mix ( BMJ 2011;342:d3211, doi:10.1136/bmj.d3211). Results from the latest audit, for 2010, showed that the proportion of lung cancer patients discussed at a multidisciplinary meeting ranged from 67% to 100% at different NHS trusts (www.ic.nhs.uk/services/national-clinical-audit-support-programme-ncasp/audit-reports/lung-cancer).

The Royal College of Physicians and eight partner organisations, including the national cancer action team and patients’ …
The junctional modifications of a T cell receptor gamma chain are determined at the level of thymic precursors.
Authors: K Ikuta, I L Weissman
Journal: The Journal of Experimental Medicine (1991)

T precursors from fetal liver and adult bone marrow were compared for their ability to give rise to V gamma 4+ T cell development. Fetal thymic lobes were repopulated with fetal liver or adult bone marrow cells, and the organ-cultured thymocytes were analyzed for their T cell receptor expression by the polymerase chain reaction (PCR). Both day 14 fetal liver and adult bone marrow cells gave rise to thymocytes with V gamma 4-J gamma 1 transcripts. However, the average size of the PCR products derived from adult precursors was slightly larger than that from fetal precursors. DNA sequence analysis of the V gamma 4-J gamma 1 transcripts showed that early fetal liver precursors predominantly gave rise to thymocytes with the V gamma 4-J gamma 1 transcripts without N nucleotide insertion, while late fetal liver and adult marrow precursors predominantly gave rise to thymocytes with modified V gamma 4-J gamma 1 junctions. These results suggest the possibility that the level of the N nucleotide insertion is programmed at the level of thymic precursors. This study also supported the model presented previously that the developmental potential of hematopoietic stem cells may change during ontogeny.
Role of ERK-BIM and STAT3-Survivin Signaling Pathways in ALK Inhibitor–Induced Apoptosis in EML4-ALK–Positive Lung Cancer
Authors: Ken Takezawa, Isamu Okamoto, Kazuto Nishio, Pasi A. Jänne, Kazuhiko Nakagawa
Journal: Clinical Cancer Research (2011)

EML4-ALK (echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase) was recently identified as a transforming fusion gene in non-small cell lung cancer. The purpose of the present study was to characterize the mechanism of malignant transformation by EML4-ALK.We established NIH 3T3 cells that stably express variant 1 or 3 of EML4-ALK and examined the signaling molecules that function downstream of EML4-ALK.Forced expression of EML4-ALK induced marked activation of extracellular signal-regulated kinase (ERK) and STAT3, but not that of AKT. Inhibition of ERK or STAT3 signaling resulted in substantial attenuation of the proliferation of cells expressing either variant of EML4-ALK, suggesting that these signaling pathways function downstream of EML4-ALK in lung cancer cells. The specific ALK inhibitor TAE684 induced apoptosis that was accompanied both by upregulation of BIM, a proapoptotic member of the Bcl-2 family, and by downregulation of survivin, a member of the inhibitor of apoptosis protein (IAP) family, in EML4-ALK-expressing NIH 3T3 cells as well as in H3122 human lung cancer cells harboring endogenous EML4-ALK. Depletion of BIM and overexpression of survivin each inhibited TAE684-induced apoptosis, suggesting that both upregulation of BIM and downregulation of survivin contribute to TAE684-induced apoptosis in EML4-ALK-positive lung cancer cells. Furthermore, BIM and survivin expression was found to be independently regulated by ERK and STAT3 signaling pathways, respectively.ALK inhibitor-induced apoptosis is mediated both by BIM upregulation resulting from inhibition of ERK signaling as well as by survivin downregulation resulting from inhibition of STAT3 signaling in EML4-ALK-positive lung cancer cells.
Distribution of Medical College Graduates.
Authors: Robert Luedeking
Journal: JAMA (1904)

St. Louis, Oct.18, 1904. <h3>To the Editor:</h3> —In your Educational Number, Aug. 13, 1904, is printed a "Table of State Board Examination Results" for the year 1903. The table is incomplete, as indicated by asterisks, as to the returns from Illinois, Kansas, Montana and Pennsylvania, and yet the statistical genius that got up this table proceeds to calculate "percentages of failures" from these faulty data. The Medical Department of Washington University is made a victim of this inaccuracy and misleading conclusion. We are quoted as having had 13 men up for examination, viz.: 4 in California, 1 in Indiana, 1 in Iowa, 1 in Michigan, 1 in New York, 1 in North Carolina, 3 in Oklahoma, and 1 in Washington. Three failures are recorded, viz.: 2 in California and 1 in Oklahoma. And so we are charged with a failure of 23 per cent. I have before
Endoscopic Ultrasonography - Technique, Orientation and Diagnostic Possibilities
Authors: G. Lux, N. Heyder, H. Lutz, L. Demling
Journal: Endoscopy (1982)

40 patients were examined by peroral endoscopic ultrasonography with two new prototypes (Prototype II and III, Olympus Optical Co., Tokyo, Japan). Indications were various intestinal diseases. Topographical orientation was facilitated by standard positions of the instrument. The organs identified included liver, gall bladder, common bile duct, pancreas, spleen and kidneys. Pathological lesions of the organs mentioned were characterized by the echo pattern known from external ultrasonography. At present endoscopic ultrasonography is not a routine method but may provide additional information to peroral endoscopy and external ultrasonography without replacing these methods.
A Glucose-6-Phosphate Dehydrogenase Isoenzyme Characteristic of Preneoplastic and Neoplastic Mouse Mammary Tissue 2
Authors: Russell Hilf, William Rector, S. Abraham
Journal: JNCI Journal of the National Cancer Institute (1973)

The mammary glands of virgin, pregnant, and lactating BALB/c mice, the preneoplastic hyperplastic alveolar-nodule outgrowths, and mammary adenocarcinomas from BALB/c mice were examined for glucose-6-phosphate dehydrogenase (G6PD) isoenzymes. Normal mammary gland contained 2 isoenzymes (G6PD-2, G6PD-3), whereas a third, more rapidly migrating isoenzyme (G6PD-1) was found in significant levels only in the preneoplastic and neoplastic mammary tissues. Thus expression of a specific G6PD isoenzyme seems related to neoplastic transformation.