tbuckley/cabot-search huggingface dataset:
Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients
Authors: Joseph A. Kovacs, Richard A. Lempicki, Igor A. Sidorov, Joseph W. Adelsberger, Irini Sereti, William Sachau, Grace Kelly, Julia A. Metcalf, Richard T. Davey, Judith Falloon, Michael A. Polis, Jorge Tavel, Randy Stevens, Laurie Lambert, Douglas A. Hosack, Marjorie Bosche, Haleem J. Issaq, Stephen D. Fox, Susan Leitman, Michael W. Baseler, Henry Masur, Michele Di Mascio, Dimiter S. Dimitrov, H. Clifford Lane
Journal: Journal of Clinical Investigation (2005)

HIV infection leads to decreases in the number of CD4 T lymphocytes and an increased risk for opportunistic infections and neoplasms. The administration of intermittent cycles of IL-2 to HIV-infected patients can lead to profound increases (often greater than 100%) in CD4 cell number and percentage. Using in vivo labeling with 2H-glucose and BrdU, we have been able to demonstrate that, although therapy with IL-2 leads to high levels of proliferation of CD4 as well as CD8 lymphocytes, it is a remarkable preferential increase in survival of CD4 cells (with half-lives that can exceed 3 years) that is critical to the sustained expansion of these cells. This increased survival was time-dependent: the median half-life, as determined by semiempirical modeling, of labeled CD4 cells in 6 patients increased from 1.7 weeks following an early IL-2 cycle to 28.7 weeks following a later cycle, while CD8 cells showed no change in the median half-life. Examination of lymphocyte subsets demonstrated that phenotypically naive (CD27+CD45RO-) as well as central memory (CD27+CD45RO+) CD4 cells were preferentially expanded, suggesting that IL-2 can help maintain cells important for host defense against new antigens as well as for long-term memory to opportunistic pathogens.
Limitation of infarct expansion and ventricular remodeling by late reperfusion. Study of time course and mechanism in a rat model.
Authors: M P Boyle, H F Weisman
Journal: Circulation (1993)

Reperfusion of acutely infarcted myocardium may be beneficial in limiting infarct expansion and ventricular remodeling even if established after the time that salvage of ischemic myocardium is possible.To examine the permanency, time course, and mechanism of this effect of late reperfusion, 200 rats were randomized into one of four groups: (1) infarction with reperfusion after 1 to 2 hours, (2) infarction with reperfusion after 6 to 8 hours, (3) infarction without reperfusion, and (4) sham operation. Surviving rats were killed at either 7 days, when infarct expansion has plateaued, or 21 days, when infarct healing is complete. In both 7- and 21-day analyses, late reperfusion did not reduce infarct size or degree of transmural necrosis but significantly limited infarct expansion, as measured by an index based on infarct endocardial segment lengthening and infarct wall thinning (expansion index at 7 days: no reperfusion, 2.73 +/- 0.25, n = 13; reperfusion after 1 to 2 hours, 1.56 +/- 0.13, n = 23, P < .001; reperfusion after 6 to 8 hours, 1.78 +/- 0.15, n = 16, P = .002; at 21 days: no reperfusion, 3.45 +/- 0.39, n = 13; reperfusion after 1 to 2 hours, 2.21 +/- 0.24, n = 15, P = .01; reperfusion after 6 to 8 hours, 2.02 +/- 0.20, n = 9, P = .01). Reperfusion after 6 to 8 hours was equally effective in limiting expansion as reperfusion after 1 to 2 hours. Late reperfusion also significantly reduced ventricular remodeling at 21 days, as measured by an index based on left ventricular cavity dilatation and noninfarcted myocardial hypertrophy (remodeling index at 21 days: no reperfusion, 2.67 +/- 0.15, n = 13; reperfusion after 1 to 2 hours, 2.20 +/- 0.15, n = 15, P = .035; reperfusion after 6 to 8 hours, 2.12 +/- 0.10, n = 9, P = .012). Histological examination revealed that reperfusion accelerated the clearance of residual dead myofibrils, suggesting an increase in the rate of healing, and increased the degree of myocytolysis but did not change the final degree of infarct healing, tissue density, or viable subepicardial cells.Late reperfusion causes a permanent reduction in postinfarction expansion that is present even after complete infarct healing. The time after coronary occlusion in which reperfusion is of benefit in reducing subsequent expansion and remodeling is substantially longer than previously established. The mechanism by which late reperfusion limits expansion may involve changing the rate of healing and the nature of myocardial necrosis but does not involve preserving subepicardial cells.
Ornithine decarboxylase is a target for chemoprevention of basal and squamous cell carcinomas in Ptch1+/– mice
Authors: Xiuwei Tang, Arianna L. Kim, David J. Feith, Anthony E. Pegg, Justin Russo, Hong Zhang, Michelle Aszterbaum, Levy Kopelovich, Ervin H. Epstein, David R. Bickers, Mohammad Athar
Journal: Journal of Clinical Investigation (2004)

Solar ultraviolet B (UVB) radiation induces cutaneous ornithine decarboxylase (ODC), the first enzyme in the polyamine-biosynthesis pathway, which drives continued proliferation and clonal expansion of initiated (mutated) cells, leading to tumorigenesis. Therefore ODC is a potentially important target for chemoprevention of basal cell carcinomas (BCCs), the majority of which have mutations in the tumor-suppressor gene known as patched (PTCH). To assess this possibility, we first overexpressed ODC in the skin of Ptch1+/– mice using a keratin 6 (K6) promoter that directs constitutive ODC expression in the outer root sheath of the hair follicle. UVB irradiation of these mice accelerated induction of BCCs as compared with their Ptch1+/– littermates. To further verify the role of ODC in BCC tumorigenesis, we used an antizyme (AZ) approach to inhibit ODC activity in the Ptch1+/– mice. Ptch1+/– mice with AZ overexpression driven by the K6 promoter were resistant to the induction of BCCs by UVB. Furthermore, oral administration of the suicidal ODC inhibitor α-difluoromethylornithine reduced UVB-induced BCCs in Ptch1+/– mice. These results demonstrate the crucial importance of ODC for the induction of BCCs and indicate that chemopreventive strategies directed at inhibiting this enzyme may be useful in reducing BCCs in human populations.
Energy intake and weight are increased by antibiotics in children with cystic fibrosis
Authors: S D West
Journal: Thorax (2003)

Background: The 1997 BTS/RCP national audit of acute care of chronic obstructive pulmonary disease (COPD) found wide variations in mortality between hospitals which were only partially explained by known audit indicators of outcome.It was hypothesised that some of the unexplained variation may result from differences in hospital type, organisation and resources.This pilot study examined the hypothesis as a factor to be included in a future national audit programme.Methods: Thirty hospitals in England and Wales were randomly selected by geographical region and hospital type (teaching, large district general hospital (DGH), small DGH).Data on process and outcome of care (death and length of stay) were collected retrospectively at 90 days on all prospectively identified COPD admissions over an 8 week period.Each centre completed a questionnaire relating to organisation and resources available for the care of COPD patients.Results: Eleven teaching hospitals, nine large DGHs, and 10 small DGHs provided data on 1274 cases.Mortality was high (14%) with wide variation between centres (IQR 9-19%).Small DGHs had a higher mortality (17.5%) than teaching hospitals (11.9%) and large DGHs (11.2%).When corrected for confounding factors, an excess of deaths in small DGHs was still observed (OR 1.56 (CI 1.04 to 2.35)) v teaching hospitals.Analysis of resource and organisational factors suggested higher mortality was associated with fewer doctors (OR 1.5) and with fewer patients being under the care of a specialist physician (OR 1.8).Small DGHs had fewest resources.Conclusion: Significant differences in mortality may exist between hospital types.The findings justify further study in a proposed national audit.. . . . .
Performance of magnetic resonance elastography and diffusion-weighted imaging for the staging of hepatic fibrosis: A meta-analysis
Authors: Qing-Bing Wang, Hui Zhu, Hai-Ling Liu, Bei Zhang
Journal: Hepatology (2012)

A meta-analysis was performed to assess and compare the accuracies of magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) for the staging of hepatic fibrosis. Online journal databases and a manual search from January 2000 to May 2011 were used. We identified 41 studies, but only 14 met the criteria to perform a meta-analysis assessing MRE (five trials) or DWI (10 trials). Fibrosis was categorized by redistribution into five stages according to histopathological description. A bivariate binomial model was used to combine the sensitivity and specificity and their 95% confidence intervals (CIs), from which diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (sROC) were derived to indicate the diagnostic accuracy of imaging modalities. With MRE, the sensitivity, specificity, DOR, PLR, NLR, and area under sROC curve (with 95% CIs) for staging F0 ˜ F1 versus F2 ˜ F4 and F0 ˜ F2 versus F3 ˜ F4 were 0.94 (0.81-0.98), 0.95 (0.87-0.98), 20 (7-57), 0.06 (0.02-0.22), 317 (55-1,796), 0.98 (0.97-0.99) and 0.92 (0.85-0.96), 0.96 (0.91-0.98), 21 (10-45), 0.08 (0.04-0.16), 251 (103-609), and 0.98 (0.96-0.99), respectively; and with DWI, these values were 0.77 (0.71-0.82), 0.78 (0.69-0.85), 3 (2-5), 0.30 (0.22-0.40), 12 (6-21), 0.83 (0.79-0.86) and 0.72 (0.60-0.81), 0.84 (0.77-0.89), 5 (3-7), 0.34 (0.23-0.50), 13 (6-29), and 0.86 (0.83-0.89), respectively. A z test demonstrated that MRE had a significantly higher accuracy than DWI in those indicators ( P &lt; 0.05). Conclusion : MRE is more reliable for staging hepatic fibrosis, compared with DWI, with a high combination of sensitivity, specificity, likelihood ratios, DOR, and area under sROC curve. (HEPATOLOGY 2012;56:239–247)
TUBERCULOSIS OF RABBITS INDUCED BY DROPLET NUCLEI INFECTION
Authors: H. L. Ratcliffe, W. F. Wells
Journal: The Journal of Experimental Medicine (1948)

At intervals from 2 to 11 weeks after normal rabbits had inhaled small numbers of virulent bovine tubercle bacilli as separated cells in droplet nuclei, groups of these animals received a single exposure to reinfection during which each animal inhaled about 20,000 separated bacilli. Normal control rabbits which inhaled this large number of bacilli died within 4 weeks thereafter. Their deaths were attributed to destruction of the lungs by developing initial tubercles. Eleven of 12 rabbits which were reinfected within 4 weeks after initial infection seemed to respond as normal animals. Their lungs were largely replaced by developing reinfection tubercles when they died or were killed within 32 days after reinfection. The inflammatory response of the reinfection tubercles was not consistently different from that of initial tubercles, although reinfection tubercles contained fewer bacilli than initial lesions of the same age. Within 5 weeks after initial infection rabbits apparently had developed immunity to reinfection with virulent bovine tubercle bacilli inhaled as separated cells in droplet nuclei. In some of them, however, exposure to massive inhaled reinfection seemed to stimulate the progress of initial infection. It is suggested that in rabbits the development of resistance to tubercle bacilli does not bear a linear relationship to time, but progresses in steps and within 5 weeks after small initial infection by inhalation is adequate to prevent the growth of separated bacilli when these are deposited upon alveolar walls. It is suggested also that the basic effect of acquired resistance of rabbits to tubercle bacilli is inhibition of multiplication of the bacilli.
Force-Velocity and Series Elastic Characteristics of Smooth Muscle from the Hog Carotid Artery
Authors: JEREMIAH T. HERLIHY, RICHARD A. MURPHY
Journal: Circulation Research (1974)

The force-velocity and series elastic characteristics of vascular strips from the media of hog carotid arteries were determined using the method of quick release to a known afterload. Shortening velocity was a function of load, and the data could be fitted by a rectangular hyperbola using the Hill equation, (P + a) V = b (P o - P), where P is the load, P o is the maximum isometric force developed at the optimum muscle length (L o ), V is velocity, and a and b are constants. The following dynamic constants were obtained for the electrically stimulated strips: estimated maximum shortening velocity for the unloaded muscle (V max ) = 0.12 L o /sec, b = 0.02 L o /sec, P o = 1.80 kg-wt/cm 2 = 1.76 x 10 6 dynes/cm 2 , and a/P o = 0.18. Maximum power output occurred at a load of 0.28 P o . The stress-strain curve for the series elastic component could be approximated by the simple exponential equation, stress = 0.034e 058 strain . The extension of the series elastic component at P o was 7.2% of L o .
T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma
Authors: Axel Trautmann, Peter Schmid-Grendelmeier, Katja Krüger, Reto Crameri, Mübeccel Akdis, Ahmet Akkaya, Eva-B. Bröcker, Kurt Blaser, Cezmi A. Akdis
Journal: Journal of Allergy and Clinical Immunology (2002)
Omics and Drug Response
Authors: Urs A. Meyer, Ulrich M. Zanger, Matthias Schwab
Journal: The Annual Review of Pharmacology and Toxicology (2011)

A new generation of technologies commonly named omics permits assessment of the entirety of the components of biological systems and produces an explosion of data and a major shift in our concepts of disease. These technologies will likely shape the future of health care. One aspect of these advances is that the data generated document the uniqueness of each human being in regard to disease risk and treatment response. These developments have reemphasized the concept of personalized medicine. Here we review the impact of omics technologies on one key aspect of personalized medicine: the individual drug response. We describe how knowledge of different omics may affect treatment decisions, namely drug choice and drug dose, and how it can be used to improve clinical outcomes.
Sentinel Lymph Node Biopsy and Melanoma Biology
Authors: Richard Essner
Journal: Clinical Cancer Research (2006)

Abstract Minimally invasive intraoperative lymphatic mapping and sentinel node biopsy has become the standard approach for staging the regional lymph nodes for early-stage melanoma. The procedure requires close collaboration of surgeon, pathologist, and nuclear medicine physician. The strength of lymphatic mapping and sentinel node biopsy is its accuracy of detecting occult lymph node metastases. Reverse transcriptase-PCR (RT-PCR) analyses of either fresh-frozen or paraffin-embedded sections of the sentinel lymph nodes have been found to be more sensitive than H&amp;E staining or immunohistochemistry techniques, but lack of specificity and limits in the availability of tissue specimens make this technique impractical for routine use. Three randomized clinical trials are examining the therapeutic value of lymphatic mapping and sentinel node biopsy for melanoma. Preliminary results of the Multicenter Lymphadenectomy Trial I show the high level of accuracy and low morbidity of lymphatic mapping and sentinel node biopsy done through an international working group. The therapeutic value of lymphatic mapping and sentinel node biopsy is still unclear. Multicenter Lymphadenectomy Trial II will test the clinical significance of lymph nodes evaluated by RT-PCR and the value of completion lymph node dissection for patients found to have tumor-positive sentinel lymph nodes by H&amp;E, immunohistochemistry, or RT-PCR. The Sunbelt Melanoma Trial examines the therapeutic value of completion dissection and benefits of Intron A. The ability to detect occult nodal metastases and evaluate the interaction of primary tumor with the regional lymph nodes may provide for better understanding of the metastatic process in patients with melanoma and help to determine the function of the regional lymph nodes as markers of metastases or incubators of tumor cells in the metastatic cascade.
Autoantibodies against interleukin 1alpha in rheumatoid arthritis: association with long term radiographic outcome
Authors: N A Graudal
Journal: Annals of the Rheumatic Diseases (2002)

<b>Objectives:</b> To investigate the possible association of interleukin 1α autoantibodies (IL1α aAb) with the long term course of joint erosion in patients with rheumatoid arthritis (RA). <b>Methods:</b> Serum samples from 176 patients with RA included in a prospective study over 30 years were analysed for IL1α aAb by binding to human [<sup>125</sup>I]IL1α. Erosions of 19 diarthrodial joints were radiographically scored by the Larsen method. <b>Results:</b> The relative risk (RR) of early IL1α aAb positive patients developing at least 30% of maximum radiographic joint destruction was significantly lower than for IL1α aAb negative patients, RR=0.29 (p=0.04). In rheumatoid factor positive patients RR was only 0.18 (p=0.02). Patients who seroconverted more than two years after the onset of RA showed the most aggressive development of joint erosion, with a relative risk of at least 40% of maximum radiographic joint destruction of 2.56 (p=0.048) <b>Conclusions:</b> The progression of radiographic joint destruction in patients with RA is associated with, and perhaps modified by, circulating IL1α aAb, suggesting that IL1α or IL1α aAb, or both, have a role in the erosive processes. IL1α aAb appear to be of prognostic significance in RA.
Genomic Landscape of Human Papillomavirus–Associated Cancers
Authors: Maria Rusan, Yvonne Y. Li, Peter S. Hammerman
Journal: Clinical Cancer Research (2015)

Recent next-generation sequencing studies have generated a comprehensive overview of the genomic landscape of human papillomavirus (HPV)-associated cancers. This review summarizes these findings to provide insight into the tumor biology of these cancers and potential therapeutic opportunities for HPV-driven malignancies. In addition to the tumorigenic properties of the HPV oncoproteins, integration of HPV DNA into the host genome is suggested to be a driver of the neoplastic process. Integration may confer a growth and survival advantage via enhanced expression of viral oncoproteins, alteration of critical cellular genes, and changes in global promoter methylation and transcription. Alteration of cellular genes may lead to loss of function of tumor suppressor genes, enhanced oncogene expression, loss of function of DNA repair genes, or other vital cellular functions. Recurrent integrations in RAD51B, NR4A2, and TP63, leading to aberrant forms of these proteins, are observed in both HPV-positive head and neck squamous cell carcinoma (HNSCC) and cervical carcinoma. Additional genomic alterations, independent of integration events, include recurrent PIK3CA mutations (and aberrations in other members of the PI3K pathway), alterations in receptor tyrosine kinases (primarily FGFR2 and FGFR3 in HPV-positive HNSCC, and ERBB2 in cervical squamous cell carcinoma), and genes in pathways related to squamous cell differentiation and immune responses. A number of the alterations identified are potentially targetable, which may lead to advances in the treatment of HPV-associated cancers.
Gemcitabine–docetaxel versus cisplatin–vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin
Authors: J.-L. Pujol, J.-L. Breton, R. Gervais, P. Rebattu, A. Depierre, J.-F. Morère, B. Milleron, D. Debieuvre, D. Castéra, P.-J. Souquet, D. Moro-Sibilot, E. Lemarié, R. Kessler, H. Janicot, D. Braun, D. Spaeth, X. Quantin, C. Clary
Journal: Annals of Oncology (2005)
Mechanism of the Effects of Furosemide on Renin Secretion in Anesthetized Dogs
Authors: ARTHUR J. VANDER, JOYCE CARLSON
Journal: Circulation Research (1969)

Furosemide was administered to anesthetized dogs in priming doses of 0.1, 0.5, or 2.5 mg/kg followed by the same amounts per hour as infusion. When sodium and water balances were maintained constant by the continuous replacement of urinary losses with isotonic saline, the renal venous renin activity (and renin release) was not altered by the 0.1 mg/kg dose but was significantly increased by the two larger doses. This increase was manifest within 5 to 10 minutes. The larger doses also increased mean arterial pressure but did not change plasma sodium or glomerular filtration rate. Renal plasma flow was increased by the 2.5 mg/kg dose but not by the 0.5 mg/kg. In another group of dogs in which salt depletion was allowed to occur, 0.1 mg/kg produced an increased renin release within 30 minutes; this increase was completely reversed by the replacement of sodium and water losses. In this group of dogs, the glomerular filtration rate decreased and then returned to control values after restoration of fluid balance. It is hypothesized that the two higher doses of furosemide stimulated renin release by directly inhibiting macula densa sodium transport, and that the reported effects of all natriuretics can be explained in terms of a single macula densa theory.
A Multidimensional Twin Study of Mental Health in Women
Authors: Kenneth S. Kendler, John M. Myers, Michael C. Neale
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: While researchers have increasing insight into the role of genetic and environmental factors in the etiology of psychiatric and substance use disorders, they know much less about how such factors influence the dimensions of healthy psychological functioning. METHOD: In a population-based sample of 794 female-female twin pairs, the authors examined, by using multivariate structural equation modeling, six dimensions of mental health: perceived physical health, nonconflictual interpersonal relationships, anxious-depressive symptoms, substance use, social support, and self-esteem. RESULTS: The best-fit model was complex and constituted five common factors (two genetic, one family environmental, and two unique environmental); variable-specific genetic effects for physical health, substance use, and social support; and variable-specific family environmental effects for interpersonal relationships and substance use. Genetic effects were seen for all six dimensions; total heritabilities ranged from 16% to 49%. Family environment was an important influence on interpersonal relationships, substance use, and social support. CONCLUSIONS: Mental health is a complex phenotype that is influenced by a diverse array of genetic and environmental factors. While genetic factors appear to be of moderate etiologic importance in all major dimensions of mental health, the family environment is an important influence on only interpersonal relations, social support, and substance use.