tbuckley/cabot-search huggingface dataset:
Ret oncogene activation in human thyroid neoplasms is restricted to the papillary cancer subtype.
Authors: M Santoro, F Carlomagno, I D Hay, M A Herrmann, M Grieco, R Melillo, M A Pierotti, I Bongarzone, G Della Porta, N Berger
Journal: Journal of Clinical Investigation (1992)

We have recently reported the activation of a new oncogene in human papillary thyroid carcinomas. This oncogene, papillary thyroid carcinoma (PTC), is a novel rearranged version of the ret tyrosine-kinase protooncogene. Thyroid neoplasms include a broad spectrum of malignant tumors, ranging from well-differentiated tumors to undifferentiated anaplastic carcinomas. To determine the frequency of ret oncogene activation, we analyzed 286 cases of human thyroid tumors of diverse histologic types. We found the presence of an activated form of the ret oncogene in 33 (19%) of 177 papillary carcinomas. By contrast, none of the other 109 thyroid tumors, which included 37 follicular, 15 anaplastic, and 18 medullary carcinomas, and 34 benign lesions, showed ret activation.
Cellular phagocytic studies in rheumatoid arthritis patients treated with levamisole.
Authors: K M Wynne, P A Dieppe, J Scott, E C Huskisson
Journal: Annals of the Rheumatic Diseases (1981)

A simple method is described which allows sequential monitoring of the endocytic activity of blood and synovial fluid cells from rheumatoid arthritis patients undergoing therapy with levamisole. Evidence of immediate (24 hours) and long-term (5-7 weeks) cellular phagocytic enhancement is presented.
Paraprofessional-Delivered Home-Visiting Intervention for American Indian Teen Mothers and Children: 3-Year Outcomes From a Randomized Controlled Trial
Authors: Allison Barlow, Britta Mullany, Nicole Neault, Novalene Goklish, Trudy Billy, Ranelda Hastings, Sherilynn Lorenzo, Crystal Kee, Kristin Lake, Cleve Redmond, Alice Carter, John T. Walkup
Journal: American Journal of Psychiatry (2014)

The Affordable Care Act provides funding for home-visiting programs to reduce health care disparities, despite limited evidence that existing programs can overcome implementation and evaluation challenges with at-risk populations. The authors report 36-month outcomes of the paraprofessional-delivered Family Spirit home-visiting intervention for American Indian teen mothers and children.Expectant American Indian teens (N=322, mean age=18.1 years) from four southwestern reservation communities were randomly assigned to the Family Spirit intervention plus optimized standard care or optimized standard care alone. Maternal and child outcomes were evaluated at 28 and 36 weeks gestation and 2, 6, 12, 18, 24, 30, and 36 months postpartum.At baseline the mothers had high rates of substance use (>84%), depressive symptoms (>32%), dropping out of school (>57%), and residential instability (51%). Study retention was ≥83%. From pregnancy to 36 months postpartum, mothers in the intervention group had significantly greater parenting knowledge (effect size=0.42) and parental locus of control (effect size=0.17), fewer depressive symptoms (effect size=0.16) and externalizing problems (effect size=0.14), and lower past month use of marijuana (odds ratio=0.65) and illegal drugs (odds ratio=0.67). Children in the intervention group had fewer externalizing (effect size=0.23), internalizing (effect size=0.23), and dysregulation (effect size=0.27) problems.The paraprofessional home-visiting intervention promoted effective parenting, reduced maternal risks, and improved child developmental outcomes in the U.S. population subgroup with the fewest resources and highest behavioral health disparities. The methods and results can inform federal efforts to disseminate and sustain evidence-based home-visiting interventions in at-risk populations.
Renal Function Following Three Distinct Weight Loss Dietary Strategies During 2 Years of a Randomized Controlled Trial
Authors: Amir Tirosh, Rachel Golan, Ilana Harman-Boehm, Yaakov Henkin, Dan Schwarzfuchs, Assaf Rudich, Julia Kovsan, Georg M. Fiedler, Matthias Blüher, Michael Stumvoll, Joachim Thiery, Meir J. Stampfer, Iris Shai
Journal: Diabetes Care (2013)

OBJECTIVE This study addressed the long-term effect of various diets, particularly low-carbohydrate high-protein, on renal function on participants with or without type 2 diabetes. RESEARCH DESIGN AND METHODS In the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT), 318 participants (age, 51 years; 86% men; BMI, 31 kg/m2; mean estimated glomerular filtration rate [eGFR], 70.5 mL/min/1.73 m2; mean urine microalbumin-to-creatinine ratio, 12:12) with serum creatinine &amp;lt;176 μmol/L (eGFR ≥30 mL/min/1.73 m2) were randomized to low-fat, Mediterranean, or low-carbohydrate diets. The 2-year compliance was 85%, and the proportion of protein intake significantly increased to 22% of energy only in the low-carbohydrate diet (P &amp;lt; 0.05 vs. low-fat and Mediterranean). We examined changes in urinary microalbumin and eGFR, estimated by Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration formulas. RESULTS Significant (P &amp;lt; 0.05 within groups) improvements in eGFR were achieved in low-carbohydrate (+5.3% [95% CI 2.1–8.5]), Mediterranean (+5.2% [3.0–7.4]), and low-fat diets (+4.0% [0.9–7.1]) with similar magnitude (P &amp;gt; 0.05) across diet groups. The increased eGFR was at least as prominent in participants with (+6.7%) or without (+4.5%) type 2 diabetes or those with lower baseline renal function of eGFR &amp;lt;60 mL/min/1.73 m2 (+7.1%) versus eGFR ≥60 mL/min/1.73 m2 (+3.7%). In a multivariable model adjusted for age, sex, diet group, type 2 diabetes, use of ACE inhibitors, 2-year weight loss, and change in protein intake (confounders and univariate predictors), only a decrease in fasting insulin (β = −0.211; P = 0.004) and systolic blood pressure (β = −0.25; P &amp;lt; 0.001) were independently associated with increased eGFR. The urine microalbumin-to-creatinine ratio improved similarly across the diets, particularly among participants with baseline sex-adjusted microalbuminuria, with a mean change of −24.8 (P &amp;lt; 0.05). CONCLUSIONS A low-carbohydrate diet is as safe as Mediterranean or low-fat diets in preserving/improving renal function among moderately obese participants with or without type 2 diabetes, with baseline serum creatinine &amp;lt;176 μmol/L. Potential improvement is likely to be mediated by weight loss–induced improvements in insulin sensitivity and blood pressure.
Chronic cough and phlegm in young adults
Authors: I. Cerveri, S. Accordini, A. Corsico, M.C. Zoia, L. Carrozzi, L. Cazzoletti, M. Beccaria, A. Marinoni, G. Viegi, R. de Marco
Journal: European Respiratory Journal (2003)

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines underline that the presence of chronic cough and sputum production before airflow obstruction offers a unique opportunity to identify subjects at risk of chronic obstructive pulmonary disease for an early intervention. Current epidemiological data on these subjects are scant. Between 1998–2000, the authors evaluated the prevalence and characteristics of these symptoms by a multicentre cross-sectional survey of Italian people aged between 20–44 yrs from the general population (Italian Study on Asthma in Young Adults (ISAYA)). Besides the questions on asthma, more than 18,000 subjects answered the question: “Have you had cough and phlegm on most days for as much as 3 months per year and for at least two successive years?” The adjusted prevalence of subjects with chronic cough and phlegm was 11.9%, being 11.8% in males and 12.0% in females. From these subjects ∼20% reported coexisting asthma and ∼30%, predominately females, were nonsmokers. The survey showed thatsex (female), smoking and low socioeconomic status were significantly and independently associated with chronic cough and phlegm, current smoking playing the major role. The prevalence of subjects with chronic cough and phlegm is startlingly high among young adults. Further follow-up studies are needed to establish how many of them will go on to develop chronic obstructive pulmonary disease.
Erythropoietin priming improves the vasculogenic potential of G-CSF mobilized human peripheral blood mononuclear cells
Authors: Jeehoon Kang, Ji-Yeon Yun, Jin Hur, Jin-A Kang, Jae-Il Choi, Seung Bum Ko, Jaewon Lee, Ju-Young Kim, In-Chang Hwang, Young-Bae Park, Hyo-Soo Kim
Journal: Cardiovascular Research (2014)

AimsFrom our previous clinical trials, intracoronary infusion of granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (mobPBMCs) proved to be effective in improving myocardial contractility and reducing infarct volume in acute myocardial infarction. We tested the effect of priming mobPBMCs with erythropoietin (EPO) to augment its therapeutic efficacy.
Mimicry of the a determinant of hepatitis B surface antigen by an antiidiotypic antibody. I. Evaluation in hepatitis B surface antigen responder and nonresponder strains.
Authors: M W Pride, A Thakur, Y Thanavala
Journal: The Journal of Experimental Medicine (1993)

B and T cell responses of several strains of mice, immunized with a monoclonal antiidiotype (anti-Id) that mimics the a determinant of hepatitis B surface antigen (HBsAg), were studied to determine if the immune response to the anti-Id was regulated by H-2-linked immune response genes as has been previously observed for HBsAg. We report that immunization with anti-Id could elicit HBsAg-specific antibodies in mice of the H-2d,q, or f haplotype and in an outbred wild mouse strain (Mus spretus), thus circumventing the H-2 haplotype restriction pattern observed when immunizing with HBsAg in H-2f mice. Purified lymph node T cells from mice of the H-2d or q haplotype and M. spretus that were primed in vivo with HBsAg or anti-Id could be stimulated in vitro with either HBsAg or anti-Id but not with an irrelevant antibody of the same subclass as the anti-Id. However, purified lymph node T cells from H-2f mice that were primed in vivo with the anti-Id could only be stimulated in vitro with anti-Id. No in vitro stimulation whatsoever was observed in H-2f mice immunized with HBsAg. The effect of processing and presentation of the anti-Id by antigen-presenting cells (APC) was studied in mice of the H-2d haplotype. Stimulation of purified lymph node T cells by HBsAg and anti-Id was shown to be strictly dependent on APC and restricted by major histocompatibility complex class II antigens at the I-A locus. Treatment of APC with paraformaldehyde or chloroquine abrogated the T cell response to all antigens except for a nine-amino acid synthetic peptide representing a partial analogue of the group a determinant of HBsAg S(139-147). The significance of these results is discussed in the context of understanding the mechanism of mimicry elicited by the anti-Id.
A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits
Authors: M O Osman, J U Kristensen, N O Jacobsen, S B Lausten, B Deleuran, M Deleuran, B Gesser, K Matsushima, C G Larsen, S L Jensen
Journal: Gut (1998)

Background —Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis. Aims —To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbit model of severe acute pancreatitis. Methods —Acute pancreatitis was induced by retrograde injection of 5% chenodeoxycholic acid into the pancreatic duct and duct ligation. Twenty rabbits were divided equally into two groups: acute pancreatitis controls received physiological saline and the treated group received WS-4, 30 minutes before induction of acute pancreatitis. Results —Pretreatment of animals with WS-4 resulted in significant down regulation of serum IL-8 and tumour necrosis factor α (TNF-α) from three to six hours after induction of acute pancreatitis (p=0.011 and 0.047 for IL-8 and 0.033 and 0.022 for TNF-α, respectively). In addition, a significant reduction in the CD11b and CD18 positive cells and the amount of interstitial neutrophil infiltration in the lungs from WS-4 treated animals was seen. In contrast, WS-4 did not alter the amount of pancreatic necrosis and the serum concentrations of amylase, lipase, calcium, and glucose. Conclusion —WS-4 cannot change the amount of pancreatic necrosis induced by injection of 5% bile acid, but does reduce the acute lung injury, presumably through inhibition of circulating IL-8 and TNF-α, and CD11b/CD18 in lung tissue. Therefore, a role of IL-8 in the progression of acute pancreatitis and the development of its systemic complications is suggested.
Bevacizumab (Avastin®) aerosol therapy (AT) inhibits primary and metastatic tumor growth in a murine model with human non-small cell lung cancer (NSCLC)
Authors: Yehuda Schwarz, Alex Starr, Alexandra Litinsky, Lilah Israeli, Ofer Merimsky
Journal: European Respiratory Journal (2012)

Rationale: Avastin is used by systemic delivery only in lung cancer treatment, although the potential AT administration exists. AT of Avastin may increase drug concentration in the tumor and so augment the drug efficacy. Objectives: to evaluate the effect of Avastin AT using mouse models of human (H1299) NSCLC. Methods: An animal model of advanced disseminated NSCLC by orthotopically inoculation of cultivated human NSCLC cells into animal-lung was developed in our lab. AT was performed 5 times a week from day 5 to day 21 after inoculation using a jet nebulizer and a cage specially constructed for the inhalations. The dosages used were 0.05 mg/kg and 0.005 mg/kg of Avastin. The effect of nebulization on Avastin was assessed in terms of in vitro inhibition of tumor cell growth (XTT assay). In vitro growth of H1299 cells was mildly inhibited by AT Avastin (10-20%). Results: 40% reduction of lung/tumor weight and 50% inhibition of regional metastases was seen with Avastin AT. It was well tolerated by the animals without any gross pathological or histological changes in the heart, kidney, liver or spleen. Histological examination of the lungs showed congestion and hemorrhage in the 0.05 mg/kg treated animal, but only minimal findings were seen in the 0.005 mg/kg treated group. Hematological and blood biochemical examination were normal in the treated mice. Conclusions: we demonstrated efficacy of Avastin aerosol treatment in animal model of NSCLC with minimal side effects. The study opens a new therapeutic approach by aerosolizing Avastin to treat patients with advanced disseminated lung cancer.
A Cancer Stem Cell Model for Studying Brain Metastases From Primary Lung Cancer
Authors: Sara M. Nolte, Chitra Venugopal, Nicole McFarlane, Olena Morozova, Robin M. Hallett, Erin O’Farrell, Branavan Manoranjan, Naresh K. Murty, Paula Klurfan, Edward Kachur, John P. Provias, Forough Farrokhyar, John A. Hassell, Marco Marra, Sheila K. Singh
Journal: JNCI Journal of the National Cancer Institute (2013)

Brain metastases are most common in adults with lung cancer, predicting uniformly poor patient outcome, with a median survival of only months. Despite their frequency and severity, very little is known about tumorigenesis in brain metastases. We applied previously developed primary solid tumor-initiating cell models to the study of brain metastases from the lung to evaluate the presence of a cancer stem cell population. Patient-derived brain metastases (n = 20) and the NCI-H1915 cell line were cultured as stem-enriching tumorspheres. We used in vitro limiting-dilution and sphere-forming assays, as well as intracranial human–mouse xenograft models. To determine genes overexpressed in brain metastasis tumorspheres, we performed comparative transcriptome analysis. All statistical analyses were two-sided. Patient-derived brain metastasis tumorspheres had a mean sphere-forming capacity of 33 spheres/2000 cells (SD = 33.40) and median stem-cell frequency of 1/60 (range = 0–1/141), comparable to that of primary brain tumorspheres (P = .53 and P = .20, respectively). Brain metastases also expressed CD15 and CD133, markers suggestive of a stemlike population. Through intracranial xenotransplantation, brain metastasis tumorspheres were found to recapitulate the original patient tumor heterogeneity. We also identified several genes overexpressed in brain metastasis tumorspheres as statistically significant predictors of poor survival in primary lung cancer. For the first time, we demonstrate the presence of a stemlike population in brain metastases from the lung. We also show that NCI-H1915 tumorspheres could be useful in studying self-renewal and tumor initiation in brain metastases. Our candidate genes may be essential to metastatic stem cell populations, where pathway interference may be able to transform a uniformly fatal disease into a more localized and treatable one.
Fibrosing Interstitial Lung Disease. A Practical High-Resolution Computed Tomography–based Approach to Diagnosis and Management and a Review of the Literature
Authors: Philip A. Hodnett, David P. Naidich
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Establishing the etiology of fibrosing interstitial lung disease (FILD) remains a clinical challenge. This is because many disorders resulting in lung fibrosis may be similar in their initial clinical and radiographic appearances. High-resolution computed tomography (HRCT) studies are now almost always obtained for patients who present with otherwise nonspecific clinical symptoms and chest radiographic findings. In the majority of cases presenting with FILD, differential diagnosis typically requires differentiating among three most commonly encountered clinical entities: idiopathic pulmonary fibrosis with usual interstitial pneumonia, nonspecific interstitial pneumonia, and chronic hypersensitivity pneumonitis. As a consequence, the development of a simplified diagnostic algorithmic approach initially focusing on the interpretation of HRCT findings may prove of considerable value provided thorough familiarity with optimal HRCT techniques and methods of interpretation. For this purpose, in patients with FILD in whom an underlying etiology is not initially apparent, the recently proposed American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines for the diagnosis of IPF have been modified to create a straightforward, clinically practicable algorithmic approach to clinical management based on the initial interpretation and classification of HRCT findings.
Diagnosis and Epidemiology of Condyloma Acuminatum-Reply
Authors: Willard Cates
Journal: JAMA (1984)

<h3>In Reply.—</h3> We thank Drs Katz and Weiss for elaborating on the epidemiology and diagnosis of condyloma and their relationship to HPV. We agree entirely that the NDTI data on the incidence of condyloma acuminatum are<i>minimum</i>estimates of sexually transmitted HPV infections. If we were to add the diagnoses of flat condyloma, cervical intraepithelial neoplasia (CIN), and other genital neoplasms to the spectrum of HPV lesions, the incidence would be much greater. Thus, we concur that HPV is a very common—and probably the most neglected—sexually transmitted infection. Even though the NDTI data minimized both the spectrum and the magnitude of HPV infections, we believe that they accurately reflect<i>trends</i>of condyloma acuminatum during the past 15 years. They demonstrate that the incidence of HPV lesions has dramatically increased. This rise is consistent with trends in other STDs, such as genital herpes and<i>Chlamydia trachomatis</i>, for which we have inadequate
Relation Between Crossbridge Structure and Actomyosin ATPase Activity in Rat Heart
Authors: Andrea Weisberg, Saul Winegrad
Journal: Circulation Research (1998)

Abstract —Cardiac myofilaments contain proteins that regulate the interaction between actin and myosin. In the thick filament, there are several proteins that may contribute to the regulation of the contraction. The myosin binding protein C, or C protein, has 4 sites that can be phosphorylated by a Ca 2+ -calmodulin–controlled kinase, protein kinase A or protein kinase C. Using electron microscopy and optical diffraction, we examined the structure of thick filaments isolated from rat ventricles with either the α or β isoform of myosin heavy chain (MHC) and the effect of specific phosphorylation of C protein on the structure. In thick filaments with α-MHC, crossbridges were clearly visible. Phosphorylation of C protein by protein kinase A extended the crossbridges from the backbone of the filament, changed their orientation, increased the degree of order of the crossbridges, and decreased the flexibility of the crossbridges. Crossbridges in filaments with β-MHC were less ordered and apparently more flexible. Phosphorylation of C protein in β-MHC–containing filaments did not extend the crossbridges and did not alter degree of order or flexibility. The relative flexibility of the crossbridges inferred from the optical diffraction pattern correlated well with the rate of ATP hydrolysis by actomyosin. These results suggest that (1) crossbridge flexibility is an important parameter in setting the rate of crossbridge cycling, and (2) C protein–mediated control of the position and flexibility of crossbridges may regulate actomyosin ATPase activity by modifying the kinetics of crossbridge cycling.
Disseminated tuberculosis following unrelated cord blood transplantation for refractory peripheral T-cell lymphoma: Clinical role of serum procalcitonin levels
Authors: J. Koya, Y. Nannya, T. Yoshizato, K. Ono, S. Seo, M. Nakagawa, M. Ichikawa, M. Kurokawa
Journal: Journal of Infection (2011)
C-Reactive Protein, the Metabolic Syndrome, and Risk of Incident Cardiovascular Events
Authors: Paul M Ridker, Julie E. Buring, Nancy R. Cook, Nader Rifai
Journal: Circulation (2003)

The metabolic syndrome describes a high-risk population having 3 or more of the following clinical characteristics: upper-body obesity, hypertriglyceridemia, low HDL, hypertension, and abnormal glucose. All of these attributes, however, are associated with increased levels of C-reactive protein (CRP).We evaluated interrelationships between CRP, the metabolic syndrome, and incident cardiovascular events among 14 719 apparently healthy women who were followed up for an 8-year period for myocardial infarction, stroke, coronary revascularization, or cardiovascular death; 24% of the cohort had the metabolic syndrome at study entry. At baseline, median CRP levels for those with 0, 1, 2, 3, 4, or 5 characteristics of the metabolic syndrome were 0.68, 1.09, 1.93, 3.01, 3.88, and 5.75 mg/L, respectively (P(trend) <0.0001). Over the 8-year follow-up, cardiovascular event-free survival rates based on CRP levels above or below 3.0 mg/L were similar to survival rates based on having 3 or more characteristics of the metabolic syndrome. At all levels of severity of the metabolic syndrome, however, CRP added prognostic information on subsequent risk. For example, among those with the metabolic syndrome at study entry, age-adjusted incidence rates of future cardiovascular events were 3.4 and 5.9 per 1000 person-years of exposure for those with baseline CRP levels less than or greater than 3.0 mg/L, respectively. Additive effects for CRP were also observed for those with 4 or 5 characteristics of the metabolic syndrome. The use of different definitions of the metabolic syndrome had minimal impact on these findings.These prospective data suggest that measurement of CRP adds clinically important prognostic information to the metabolic syndrome.