tbuckley/cabot-search huggingface dataset:
Acute LRT infections among patients with shingles
Authors: Lidija Zabaznoska, Vesna Semenakova, Sunchica Bogoeva
Journal: European Respiratory Journal (2011)

Herpes Zoster is reactivation of VZV infection, triggered by stress, surgical intervention or lack of the immunocompetency. This intraganglionar latent viral RNA reactivation precede the viral migration trough the neural axons up to the associated dermatome cosing ballonic cell degeneration, multinuclear cell expression with intranuclear inclusions, sumultaneous inflammatory local reaction, finally expressed with characteristic shingles vesicles.  Material and methods: In a six year long period (2004-2010), 52 patients with shingles were hospitalized, 19 (36%) were immunocompromised due to immunosuppressive therapy, lymph reticular malignant illness, HIV infection; 23 (44.4%) patients with shingles had LRT inflammation sings.  Results: Based on the clinical symptoms and standard blood, biochemical, radiological, bacteriological, serological testing9s parallel bacterial LRT inflammation was proven among 20 of 23patients (86.9%), or 38.46% of 53 patients. This group of 20 with LRT bacterial inflammation includes 9 immunocompromised (45%) and 11 immunocompetent (55%) patients. Severe pulmonary inflammation had 6 (66.6%) of 9 immunocompromised (one of them nosocomial, transferred from the haematology clinic) and 5 (45.4%) of 11 immunocompetent, or 6 (30%) of 20 and 5 of 20 (25%).  Conclusions: The severity of the dermal expression as well as LRT inflammation was evident among immunocompromised patients. Their hospital treatment was prolonged, from 17days up to 7 weeks (average 23 days) compared to immunocompetent patients with shingles and LRT inflammation (11-27 days-average 14 days). Antimicrobial (antibiotic/antiviral) therapy bas empirically installed from the very beginning of hospital treatment, additionally improved where needed.
THE SEDIMENTATION RATE OF THE BIOLOGICAL ACTIVITIES OF INFLUENZA A VIRUS
Authors: Max A. Lauffer, Gail Lorenz Miller
Journal: The Journal of Experimental Medicine (1944)

The sedimentation rates of the mouse infectivity principles of the PR8 and the F12 strains of influenza A virus were shown by studies in the separation cell to have values which are not significantly different from sedimentation rates of the principal components of purified preparations. It was shown further that the bulk of the chicken red blood cell agglutinating activity and of the chick embryo infectivity of PR8 influenza virus preparations sediments at the same rate as that of the 100 mµ. component. Some activity was shown to be associated with aggregates. These results lend strong support to the assumption that the three biological activities are associated with the particles characterized as spheres with a diameter of about 100 mµ.
Familial Risk of Hepatocellular Carcinoma Among Chronic Hepatitis B Carriers and Their Relatives
Authors: M.-W. Yu
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Familial predisposition as a risk factor for hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) carriers has not been thoroughly explored. Methods: The HCC risk associated with having parents and/or siblings with HCC was evaluated by use of a cohort study of 4808 male HBV carriers. A case–control family study was also conducted on data from first-degree relatives of 553 HBV carriers who had newly diagnosed HCC (case subjects) and 4684 HBV carriers without HCC (control subjects). Results: In the cohort study, HBV carriers with a family history of HCC had a multivariate-adjusted rate ratio for HCC of 2.41 (95% confidence interval [CI] = 1.47–3.95) compared with HBV carriers without a family history of HCC. For carriers with two or more affected relatives, the ratio increased to 5.55 (95% CI = 2.02–15.26). Cumulative HCC risk by age 70 years was 235.6 per 1000 (95% CI = 95.3–375.9 per 1000) for HBV carriers with family history compared with 88.9 per 1000 (95% CI = 67.9–109.9 per 1000) for those without. In the case–control family study, first-degree relatives of case subjects were more likely to have HCC (age–sex-adjusted odds ratio [OR] = 2.57; 95% CI = 2.03–3.25) than first-degree relatives of control subjects. The excess risk of HCC among relatives was particularly evident in siblings (sisters—age-adjusted OR = 4.55 [95% CI = 2.22–9.31]; brothers—age-adjusted OR = 3.73 [95% CI = 2.64–5.27]), but it was also observed in parents. The cumulative risk of HCC to age 80 years was 83.0 per 1000 among relatives of case subjects and 42.0 per 1000 among relatives of control subjects. Among relatives of case subjects, the cumulative risk of HCC was greater if the case subjects were diagnosed before age 50 years (two-sided P = .047). Liver cirrhosis was 2.29 (95% CI = 1.68–3.11) times more frequent in relatives of case subjects than in relatives of control subjects. Conclusions: First-degree relatives of patients with HBV-related HCC appear to be at increased risk of HCC and should be considered in the formulation of HCC-screening programs.
Age-related EBV-associated lymphoproliferative disorders in the Western population: a spectrum of reactive lymphoid hyperplasia and lymphoma
Authors: Stefan D. Dojcinov, Girish Venkataraman, Stefania Pittaluga, Iwona Wlodarska, Jeffrey A. Schrager, Mark Raffeld, Robert K. Hills, Elaine S. Jaffe
Journal: Blood (2011)
Anaemia in lung transplant patient caused by parvovirus B19
Authors: H H Kariyawasam
Journal: Thorax (2000)

The case history is presented of a lung transplant patient who developed prolonged parvovirus B19 infection with severe transfusion dependent anaemia. The patient was treated with intravenous immunoglobulin after which the haemoglobin rose, together with a reticulocytosis. The patient then remained transfusion free and the virus cleared more than three months after the initial immunoglobulin treatment. The clinical and social implications for this group of patients are discussed.
Targeted therapy of liver fibrosis/cirrhosis and its complications
Authors: Klaas Poelstra, Detlef Schuppan
Journal: Journal of Hepatology (2011)

Do we need targeting to specific liver cells? Uptake of drugs in the liver is usually high. While most existing drugs are not cell-specific at all, they are effective. However, uptake by fibrogenic cells in the fibrotic liver is usually low and off-target effects can be high, e.g., due to compromised hepatic metabolism and excretion. Therefore, most experimental drugs are not effective at the preclinical level when they are administered in animals with advanced and established fibrosis (i.e. a situation similar to the clinical practice).
Effect of Surgical Lung Volume Reduction on Breathing Patterns in Severe Pulmonary Emphysema
Authors: KONRAD E. BLOCH, YIMING LI, JINNONG ZHANG, ROLAND BINGISSER, VLADIMIR KAPLAN, WALTER WEDER, ERICH W. RUSSI
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Surgical lung volume reduction may improve pulmonary function and dyspnea in advanced pulmonary emphysema. To investigate mechanisms of these beneficial effects we studied breathing patterns before and after surgery. Nineteen patients with diffuse pulmonary emphysema (FEV1 < 35% of predicted, total lung capacity > 130% predicted) were studied within 1 mo before, and 1.5 to 7 mo after thoracoscopic volume reduction. Changes of rib cage and abdominal volumes were monitored with calibrated respiratory inductive plethysmography for 20 to 60 min during natural breathing at rest. Pulmonary function and dyspnea were also assessed. Postoperative tidal volumes, respiratory cycle times, and minute ventilation were not significantly different from preoperative values. The contribution of abdominal volume changes to tidal volumes increased from a mean ± SD of 43 ± 17% preoperatively to 58 ± 14% postoperatively (p = 0.03). The fraction of inspiratory time with abdominal paradoxical motion decreased from 12.3 ± 8.3% preoperatively to 5.1 ± 5.1% postoperatively (p = 0.02). The phase shift between rib cage and abdominal motion was reduced postoperatively. Hyperinflation, airway obstruction, and subjective ratings of dyspnea were significantly improved. The better synchronization of rib cage–abdominal motion and the greater contribution of abdominal volume changes to tidal volumes are consistent with a reduction of inspiratory loading and a greater force-generating capacity of the diaphragm after surgery.
Seamless Phase I-II Trial Design for Assessing Toxicity and Efficacy for Targeted Agents
Authors: Antje Hoering, Mike LeBlanc, John Crowley
Journal: Clinical Cancer Research (2010)

The premise for phase I trials for cytostatic agents is different from that of cytotoxic agents. For cytostatic agents, toxicity and efficacy do not necessarily increase monotonically with increasing dose levels, but likely plateau after they reach maximal toxicity or efficacy. Here, we propose a phase I-II trial design to assess both toxicity and efficacy to find the best dose as well as a good dose.We propose a 2-step dose-finding trial for assessing both toxicity and efficacy for a targeted agent. The 1st step uses a traditional phase I trial design. This step only assesses toxicity and finds the maximal tolerated dose (MTD). For the 2nd step, we propose a modified phase II selection design for 2 or 3 dose levels at and below the MTD to determine efficacy and evaluate each dose level by both efficacy and toxicity.Simulation studies are done on several combinations of toxicity and efficacy scenarios to assess the operating statistics of our proposed trial design. We then compare our results with a traditional phase I trial followed by a single-arm phase II trial using the same total sample size. The proposed design does better in most cases than a traditional design using the same overall sample size. This design allows assessing a few dose levels more closely for both efficacy and toxicity and provides greater certainty of having correctly determined the best dose level before launching into a large efficacy trial.
Cross hepatotoxicity between tricyclic antidepressants.
Authors: D Larrey, B Rueff, D Pessayre, G Danan, M Algard, J Geneve, J P Benhamou
Journal: Gut (1986)

Cross hepatotoxicity between drugs in very uncommon. We report the case of a patient in whom acute hepatitis was induced by a tricyclic antidepressant, amineptine, and recurred early after administration of another tricyclic antidepressant, clomipramine. This observation suggests that the tricyclic ring is involved in the mechanism of the deleterious effect of both drugs to the liver.
Spontaneous dissection of the oesophagus.
Authors: G N Morritt, P R Walbaum
Journal: Thorax (1980)

Spontaneous rupture of the oesophagus is a well-known entity. Partial or intramural rupture of the oesophagus has been described but is not so well known, and the purpose of this paper is to draw attention to this condition. The clinical presentation, radiological appearances, and treatment of two such cases are described.
Open access to specialist opinion is preferable
Authors: L. O'Toole, A. Oates, K. S Channer
Journal: BMJ (1995)

EDITOR,--C M Francis and colleague's report on open access echocardiography1 highlights the fears of many cardiologists about open access services.2 The principal aim of the author's service—the identification of patients with left ventricular dysfunction so that treatment with an angiotensin converting enzyme inhibitor could be started—occurred in only 50 (19%) of 259 patients, while valve disease was identified in 12. In a similar study of an open access exercise electrocardiography service McClements et al identified ischaemic heart disease in only 18% of the 192 patients tested.3 It is argued that a negative result of the test is reassuring, but many patients remain symptomatic despite reassurance.4 Furthermore, screening a low risk population …
Endothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression
Authors: Masaki Ieda, Keiichi Fukuda, Yasuyo Hisaka, Kensuke Kimura, Haruko Kawaguchi, Jun Fujita, Kouji Shimoda, Eiko Takeshita, Hideyuki Okano, Yukiko Kurihara, Hiroki Kurihara, Junji Ishida, Akiyoshi Fukamizu, Howard J. Federoff, Satoshi Ogawa
Journal: Journal of Clinical Investigation (2004)

The cardiac sympathetic nerve plays an important role in regulating cardiac function, and nerve growth factor (NGF) contributes to its development and maintenance. However, little is known about the molecular mechanisms that regulate NGF expression and sympathetic innervation of the heart. In an effort to identify regulators of NGF in cardiomyocytes, we found that endothelin-1 specifically upregulated NGF expression in primary cultured cardiomyocytes. Endothelin-1-induced NGF augmentation was mediated by the endothelin-A receptor, Gibetagamma, PKC, the Src family, EGFR, extracellular signal-regulated kinase, p38MAPK, activator protein-1, and the CCAAT/enhancer-binding protein delta element. Either conditioned medium or coculture with endothelin-1-stimulated cardiomyocytes caused NGF-mediated PC12 cell differentiation. NGF expression, cardiac sympathetic innervation, and norepinephrine concentration were specifically reduced in endothelin-1-deficient mouse hearts, but not in angiotensinogen-deficient mice. In endothelin-1-deficient mice the sympathetic stellate ganglia exhibited excess apoptosis and displayed loss of neurons at the late embryonic stage. Furthermore, cardiac-specific overexpression of NGF in endothelin-1-deficient mice overcame the reduced sympathetic innervation and loss of stellate ganglia neurons. These findings indicate that endothelin-1 regulates NGF expression in cardiomyocytes and plays a critical role in sympathetic innervation of the heart.
Singular value decomposition-based regression identifies activation of endogenous signaling pathways in vivo
Authors: Zhandong Liu, Min Wang, James V Alvarez, Megan E Bonney, Chien-chung Chen, Celina D'Cruz, Tien-chi Pan, Mahlet G Tadesse, Lewis A Chodosh
Journal: Genome biology (2008)

The ability to detect activation of signaling pathways based solely on gene expression data represents an important goal in biological research. We tested the sensitivity of singular value decomposition-based regression by focusing on functional interactions between the Ras and transforming growth factor beta signaling pathways. Our findings demonstrate that this approach is sufficiently sensitive to detect the secondary activation of endogenous signaling pathways as it occurs through crosstalk following ectopic activation of a primary pathway.
Mature natural killer cell and lymphoid tissue–inducing cell development requires Id2-mediated suppression of E protein activity
Authors: Markus D. Boos, Yoshifumi Yokota, Gerard Eberl, Barbara L. Kee
Journal: The Journal of Experimental Medicine (2007)

The Id2 transcriptional repressor is essential for development of natural killer (NK) cells, lymphoid tissue–inducing (LTi) cells, and secondary lymphoid tissues. Id2 was proposed to regulate NK and LTi lineage specification from multipotent progenitors through suppression of E proteins. We report that NK cell progenitors are not reduced in the bone marrow (BM) of Id2−/− mice, demonstrating that Id2 is not essential for NK lineage specification. Rather, Id2 is required for development of mature (m) NK cells. We define the mechanism by which Id2 functions by showing that a reduction in E protein activity, through deletion of E2A, overcomes the need for Id2 in development of BM mNK cells, LTi cells, and secondary lymphoid tissues. However, mNK cells are not restored in the blood or spleen of Id2−/−E2A−/− mice, suggesting a role for Id2 in suppression of alternative E proteins after maturation. Interestingly, the few splenic mNK cells in Id2−/− and Id2−/−E2A−/− mice have characteristics of thymus-derived NK cells, which develop in the absence of Id2, implying a differential requirement for Id2 in BM and thymic mNK development. Our findings redefine the essential functions of Id2 in lymphoid development and provide insight into the dynamic regulation of E and Id proteins during this process.
The Prediction of Major Outcomes of Type 1 Diabetes: a 12-Year Prospective Evaluation of Three Separate Definitions of the Metabolic Syndrome and Their Components and Estimated Glucose Disposal Rate
Authors: Georgia Pambianco, Tina Costacou, Trevor J. Orchard
Journal: Diabetes Care (2007)

The metabolic syndrome has been shown to confer an increased risk of cardiovascular disease in both the general and type 2 diabetic populations, but few studies have assessed the metabolic syndrome in type 1 diabetic patients. In a type 1 diabetic cohort, we assessed the prevalence and value of the metabolic syndrome in improving the prediction of major complication outcomes compared with its components and a surrogate measure of insulin resistance, estimated glucose disposal rate (eGDR).A total of 514 (78%) subjects participating in the Pittsburgh Epidemiology of Diabetes Complications Study with complete 12-year follow-up clinical data were classified by baseline metabolic syndrome status according to three definitions: those of the National Cholesterol Education Program Adult Treatment Panel III (modified by the American Heart Association), the International Diabetes Federation (IDF), and the World Health Organization (WHO). The complication outcomes included coronary artery disease, renal failure, diabetes-related death, and the aggregate of these three major outcomes of diabetes (MOD).Metabolic syndrome prevalence ranged from 8% (IDF) to 21% (WHO). All definitions showed reasonable specificity (> or = 83%) for each outcome, while the WHO definition had the highest sensitivity for all outcomes except renal failure, for which eGDR was most sensitive. However, the components of each definition predicted better than the overall syndrome. Microalbuminuria was clearly the strongest predictor of all individual measures, yielding hazard ratios of 9 and 6 for mortality and MOD, respectively.Though the three metabolic syndrome classifications predict major complication outcomes in type 1 diabetes, their individual components predict better. Of the variables studied, including HbA1, microalbuminuria appears to be the best single predictor of MOD.
H-2 compatibility is required for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus.
Authors: P C Doherty, R M Zinkernagel
Journal: The Journal of Experimental Medicine (1975)

Maximal cell-mediated lysis of targets infected with lymphocytic choriomeningitis virus occurs only within a H-2 compatible system. Syngeneic immune spleen cells are at least 100 times as effective as are allogeneic lymphocytes. Reciprocal restriction of cytotoxic T-cell activity has been shown to operative between H-2k, H-2d, and H-2b. Experiments with cogenic mice have localized the effect to the H-2 gene complex. Furthermore, the observation that lymphocytes from H-2a mice cause high specific 51Cr release from either H-2d virus-infected cells, indicates that identity at either the K or the D end of the H-2 gene complex is sufficient for this lytic interaction.
Human embryotoxicity of pyrrolizidine-containing drugs
Authors: Ryan J. Huxtable
Journal: Hepatology (1989)

Hepatic veno-occlusive disease is the most frequent cause of hepatic vein obstruction in children. Only the small and medium veins are involved. The initial vascular lesion is endothelial edema, followed by phlebosclerosis and occlusion of the small vessels, leading to secondary necrosis of liver cells, progressive fibrosis, and ultimately cirrhosis. The disease was first recognized in Jamaica in 1954, and subsequently reported from other parts of the world. It arises from the ingestion of pyrrolizidine alkaloids found in various herbal medicines and in poorly winnowed wheat. Several plants have been implicated, in particular the genera Senecio, Crotalaria, and Heliotropium. More recently, similar pathologic changes have been observed after hepatic irradiation, bone marrow transplantation, and use of chemotherapeutic drugs. We report a newborn infant with fatal hepatic vaso-occlusive disease. Pyrrolizidine alkaloids were identified in the herbal medicine bought by the mother at a pharmacy and consumed daily during the entire pregnancy.
Tumor-Reactive CD8+ T Cells in Metastatic Gastrointestinal Cancer Refractory to Chemotherapy
Authors: Simon Turcotte, Alena Gros, Eric Tran, Chyi-Chia R. Lee, John R. Wunderlich, Paul F. Robbins, Steven A. Rosenberg
Journal: Clinical Cancer Research (2013)

Abstract Purpose: To evaluate whether patients with metastatic gastrointestinal adenocarcinomas refractory to chemotherapy harbor tumor-reactive cytotoxic T cells. Experimental Design: Expansion of CD8+ tumor-infiltrating lymphocytes (TIL) and cancer cell lines was attempted from gastrointestinal cancer metastases in 16 consecutive patients for the study of antitumor immune recognition. Retroviral transduction of genes encoding T-cell receptors (TCR) was used to define HLA-restriction elements and specific reactivity. Results: TIL were expanded from metastases in all patients, and new tumor cell lines were generated in 5 patients. Autologous tumor recognition without cross-reactivity against allogeneic HLA-matched gastrointestinal tumors was found in CD8+ TIL from 3 of these 5 patients. In a patient with gastric cancer liver metastases, the repertoire of CD8+ TIL was dominated by cytolytic sister clones reactive to 2 out of 4 autologous cancer cell lines restricted by HLA-C*0701. From the same patient, a rare CD8+ TIL clone with a distinct TCR recognized all four cancer cell lines restricted by HLA-B*4901. In a patient with bile duct cancer, two distinct antitumor cytolytic clones were isolated from a highly polyclonal CD8+ TIL repertoire. TCRs isolated from these clones recognized epitopes restricted by HLA-A*0201. In a third patient, CD8+ TIL reactivity was progressively lost against an autologous colon cancer cell line that displayed loss of HLA haplotype. Conclusions: This study provides a basis for the development of immunotherapy for patients with advanced gastrointestinal malignancies by first establishing the presence of naturally occurring tumor-reactive CD8+ TIL at the molecular level. Clin Cancer Res; 20(2); 331–43. ©2013 AACR.
Identification and characterization of autoantibodies against the nuclear envelope lamin B receptor from patients with primary biliary cirrhosis.
Authors: J C Courvalin, K Lassoued, H J Worman, G Blobel
Journal: The Journal of Experimental Medicine (1990)

We have identified autoantibodies from two patients with primary biliary cirrhosis (PBC) that recognize the nuclear envelope of mammalian cells on indirect immunofluorescence microscopy. These antibodies bind to a 58-kD integral membrane protein (p58) of the turkey erythrocyte nuclear envelope, which has been previously identified as a membrane receptor for lamin B (Worman, H. J., J. Yuan, G. Blobel, and S. D. Georgatos. 1988. Proc. Natl. Acad. Sci. USA. 85:8531). The antibodies also bind to a 61-kD integral membrane protein (p61) of the rat liver nuclear envelope. Affinity-purified antibodies eluted from turkey p58 bind to rat p61, showing that the two proteins share an epitope(s) and that p61 is likely the rat liver lamin B receptor. In human nuclear envelopes, the antigen recognized has an apparent molecular mass close to that of avian protein. These findings, along with the previous discovery of autoantibodies against an integral membrane glycoprotein (gp210) of the nuclear pore membrane in patients with PBC, suggest that antibodies against integral membrane proteins of the nuclear envelope are characteristic of a subset of patients with PBC.