tbuckley/cabot-search huggingface dataset:
INFLUENZA
Authors: Henry Pinkerton, Donald Greiff, Herman T. Blumenthal, Richard Hensley
Journal: The Journal of Experimental Medicine (1950)

In addition to the cycles of growth shown by the influenza A virus during the first 24 hours of its residence in the fertile egg, cycles separated by longer time intervals have been noted between the 24th and 96th hours. These longer cycles are best seen when the eggs are incubated at 40 degrees C. Corresponding fairly accurately with these cycles of growth of the virus, wide cyclic variations in the rates of increase in oxygen consumption of the infected eggs have been found to occur. These variations are in striking contrast to the uniformity of increase noted in uninfected eggs. The variations in infectivity may be caused by periodic interference with virus multiplication by accumulated inactive virus particles. The variations in oxygen consumption probably are correlated with variations in the concentration of virus toxins.
Seropositivity for human papillomavirus and incidence of subsequent squamous cell and basal cell carcinomas of the skin in patients with a previous nonmelanoma skin cancer
Authors: A. Paradisi, T. Waterboer, F. Sampogna, S. Tabolli, S. Simoni, M. Pawlita, D. Abeni
Journal: British Journal of Dermatology (2011)

Infection with human papillomaviruses (HPVs) is a risk factor for several epithelial cancers, but its relationship with keratinocyte tumours has not yet been established. Objective In this prospective study we investigated the possible role of different HPVs in the incidence of a subsequent nonmelanoma skin cancer (NMSC).One hundred and fifty-three patients with squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) enrolled in a previous case-control study were re-contacted, and a follow-up visit was offered. Demographic and clinical data, date of first NMSC presentation, Fitzpatrick skin type and history of NMSC during the follow-up period were ascertained. Recurrences and new second cancers were considered together as 'outcomes' in time-to-event analyses and in Cox proportional hazard models.Clinical data were obtained in 107 patients. HPV seropositivity at baseline was strongly associated with the risk of developing a second SCC after 5 years for a number of beta and gamma HPV types. For example, HPV-24-seropositive patients with an SCC at baseline had a 4-fold increased risk of developing a subsequent SCC (hazard ratio 4·35, 95% confidence interval 1·2-15·6, P = 0·024). No association between serological status for any HPV type tested and an increased risk of BCC was found.We observed a consistent pattern of a positive association between seropositivity for beta and gamma HPV types and the risk of a subsequent SCC in patients with a previous SCC. Our data corroborate the results of previous case-control studies and may spur further prospective studies on the causal role of HPVs in NMSC.
Prognosis of occupational asthma
Authors: PL Paggiaro, B Vagaggini, E Bacci, L Bancalari, M Carrara, A Di Franco, D Giannini, FL Dente, C Giuntini
Journal: European Respiratory Journal (1994)

Several studies on the prognosis of occupational asthma have shown that a significant proportion of patients continue to experience asthmatic symptoms and nonspecific bronchial hyperresponsiveness after cessation of work. The determinants of this unfavourable prognosis of asthma are: long duration of exposure before the onset of asthma; long duration of symptoms before diagnosis; baseline airway obstruction; dual response after specific challenge test; and the persistence of markers of airway inflammation in bronchoalveolar lavage fluid and bronchial biopsy. The relevance of immunological markers in the outcome of occupational asthma has not yet been assessed. Further occupational exposure in sensitized subjects leads to persistence and sometimes to progressive deterioration of asthma, irrespective of the reduction of exposure to the specific sensitizer, and only the use of particular protective devices effectively prevents the progression of the disease. A long-term follow-up study of toluene diisocyanate (TDI)-induced asthma showed that the improvement in bronchial hyperresponsiveness to methacholine occurred in a small percentage of subjects and only a long time after work cessation. Bronchial sensitivity to TDI may disappear, but non-specific bronchial hyperresponsiveness often persists unchanged, suggesting a permanent deregulation of airway tone. Steroid treatment significantly reduces nonspecific bronchial hyperresponsiveness only when started immediately after diagnosis.
Cytokine Levels Correlate with a Radiologic Score in Active Pulmonary Tuberculosis
Authors: MASSIMO CASARINI, FRANCO AMEGLIO, LUCILLA ALEMANNO, PROFETA ZANGRILLI, PAOLO MATTIA, GREGORINO PAONE, ALBERTO BISETTI, SANDRO GIOSUÈ
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Pulmonary tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. This microorganism is capable of inducing a delayed hypersensitivity reaction in the lung, with subsequent expression of the disease. This reaction depends on the presence of different cytokines that exert specific functions. The aim of this study was to evaluate the presence and the concentrations of nine different modulators in bronchoalveolar lavage fluid (BALF). For this purpose, 15 patients with active pulmonary tuberculosis were enrolled at the time of diagnosis, prior to institution of antituberculous therapy. All the patients demonstrated M. tuberculosis in the sputum, and their disease extention was defined by high-resolution computed tomography (HRCT) using a score which included the presence of six findings: miliary nodules, nodules < 10 mm, consolidation, ground glass, cavity and bronchial wall thickening. This score was more sensitive than an equivalent score calculated on the basis of chest radiology. HRCT score was calculated for each area of the two lungs in order to define the more and the less affected lung for each patient. The bronchoalveolar lavage (BAL) was performed in the more affected area for each lung. The HRCT total score for each washed area ranged between 1 and 15, and showed more significant differences between the more and less affected lungs (p = 0.0004) than those obtained with the individual radiologic findings (p ranged between 0.60 and 0. 004). The BAL concentrations of the nine cytokines evaluated for the more and less affected lungs were compared: interleukin-6 (IL-6), IL-8, IL-12, tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) showed significant differences (p ranged between 0. 016 and 0.0007). In addition, each cytokine concentration was correlated with the HRCT score. Significant correlations were found with IL-12, IL-6, IL-8, IL-2, and TNF-alpha. The correlations between cytokines and HRCT total score were better than those observed with the individual radiologic findings. A correlation matrix for the different cytokines evaluated one against each other, has also been added to show common behavior of these modulators. A similar analysis was also performed for the radiologic abnormalities.
Endogenous Sex Hormones and the Development of Type 2 Diabetes in Older Men and Women: the Rancho Bernardo Study
Authors: Jee-Young Oh, Elizabeth Barrett-Connor, Nicole M. Wedick, Deborah L. Wingard
Journal: Diabetes Care (2002)

OBJECTIVE—To determine the prospective association between endogenous sex hormones and the development of type 2 diabetes in older men and women. RESEARCH DESIGN AND METHODS—A standardized medical history was obtained, an oral glucose tolerance test was performed, and plasma samples for sex hormones and covariates were collected from ambulatory, community-dwelling men and women at baseline from 1984 to 1987. Approximately 8 years later (1992–1996), another medical history was obtained, an oral glucose tolerance test was performed, fasting and 2-h insulin levels were measured, and the homeostasis model assessment for insulin resistance (HOMA-IR) was evaluated. This report is based on the 294 men and 233 women, aged 55–89 years, who completed both visits and who did not have diabetes as determined by history or glucose tolerance test at baseline, as well as women who were postmenopausal and not taking replacement estrogen. RESULTS—In age-adjusted correlation analyses, total testosterone was inversely and significantly related to subsequent levels of fasting and postchallenge glucose and insulin in men, whereas bioavailable testosterone and bioavailable estradiol were positively and significantly related to fasting and postchallenge glucose and insulin in women (all P &amp;lt;0.05). There was similar significant association with insulin resistance (HOMA-IR) in unadjusted and multiply adjusted analyses (P &amp;lt;0.05). There were 26 men and 17 women with new (incident) diabetes. The odds for new diabetes were 2.7 (95% CI 1.1–6.6) for men in the lowest quartile of total testosterone and 2.9 (1.1–8.4) for women in the highest quartile of bioavailable testosterone. CONCLUSIONS—Low testosterone levels in men and high testosterone levels in women predict insulin resistance and incident type 2 diabetes in older adults.
Inactivation of Myc in Murine Two-Hit B lymphomas Causes Dormancy with Elevated Levels of Interleukin 10 Receptor and CD20: Implications for Adjuvant Therapies
Authors: Duonan Yu, Michael Dews, Andrea Park, John W. Tobias, Andrei Thomas-Tikhonenko
Journal: Cancer Research (2005)

Abstract Overexpression of c-Myc and inactivation of p53 are hallmarks of human Burkitt's lymphomas. We had previously showed that transduction of murine p53-null bone marrow cells with a Myc-encoding retrovirus is sufficient for B lymphomagenesis. To address the role of Myc in tumor sustenance, we generated lymphomas induced by the Myc-estrogen receptor fusion protein (MycER). Engrafted hosts were continuously treated with the ER ligand 4-hydroxytamoxifen (4-OHT) to allow tumor formation. Subsequent inactivation of MycER via 4-OHT deprivation resulted in tumor stasis but only partial regression. At the cellular level, dormant neoplastic lymphocytes withdrew from mitosis and underwent further B-cell differentiation. Concomitantly, they up-regulated genes involved in lymphocyte proliferation and survival, most notably interleukin 10 receptor α (IL10Rα) and CD20, the target for antibody therapy with Rituxan. We found that overexpression of IL10Rα affords significant proliferative advantages and in 4-OHT–deprived animals correlates with eventual tumor relapse. Both dormant and relapsing tumors maintain IL10Rα expression suggesting that they might be sensitive to emerging drugs targeting the IL-10 pathway. Up-regulation of CD20 following Myc inactivation was also observed in immortalized human lymphocytes. Importantly, in this system, MycOFFCD20HIGH cells were more prone to Rituxan-induced apoptosis than MycONCD20MED. Thus, targeting Myc, while moderately effective on its own, shapes the phenotype of dormant neoplastic cells and sensitizes them to adjuvant molecular therapies.
Identification of BACE1 cleavage sites in human voltage-gated sodium channel beta 2 subunit
Authors: Manuel T Gersbacher, Doo Yeon Kim, Raja Bhattacharyya, Dora M Kovacs
Journal: Molecular Neurodegeneration (2010)

Abstract Background The voltage-gated sodium channel β2 subunit (Navβ2) is a physiological substrate of BACE1 (β-site APP cleaving enzyme) and γ-secretase, two proteolytic enzymes central to Alzheimer's disease pathogenesis. Previously, we have found that the processing of Navβ2 by BACE1 and γ-secretase regulates sodium channel metabolism in neuronal cells. In the current study we identified the BACE1 cleavage sites in human Navβ2. Results We found a major (147-148 L↓M, where ↓ indicates the cleavage site) and a minor (144145 L↓Q) BACE1 cleavage site in the extracellular domain of human Navβ2 using a cell-free BACE1 cleavage assay followed by mass spectrometry. Next, we introduced two different double mutations into the identified major BACE1 cleavage site in human Navβ2: 147LM/VI and 147LM/AA. Both mutations dramatically decreased the cleavage of human Navβ2 by endogenous BACE1 in cell-free BACE1 cleavage assays. Neither of the two mutations affected subcellular localization of Navβ2 as confirmed by confocal fluorescence microscopy and subcellular fractionation of cholesterol-rich domains. Finally, wildtype and mutated Navβ2 were expressed along BACE1 in B104 rat neuroblastoma cells. In spite of α-secretase still actively cleaving the mutant proteins, Navβ2 cleavage products decreased by ~50% in cells expressing Navβ2 (147LM/VI) and ~75% in cells expressing Navβ2 (147LM/AA) as compared to cells expressing wildtype Navβ2. Conclusion We identified a major (147-148 L↓M) and a minor (144-145 L↓Q) BACE1 cleavage site in human Navβ2. Our in vitro and cell-based results clearly show that the 147-148 L↓M is the major BACE1 cleavage site in human Navβ2. These findings expand our understanding of the role of BACE1 in voltage-gated sodium channel metabolism.
Toxic Chemicals in Marine Sediment and Biota From Mukilteo, Washington: Relationships With Hepatic Neoplasms and Other Hepatic Lesions in English Sole (&lt;italic&gt;Parophrys vetulus&lt;/italic&gt;)&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: D C Malins, M M Krahn, D W Brown, L D Rhodes, M S Myers, B B McCain, S L Chan
Journal: JNCI Journal of the National Cancer Institute (1985)

Journal Article Toxic Chemicals in Marine Sediment and Biota From Mukilteo, Washington: Relationships With Hepatic Neoplasms and Other Hepatic Lesions in English Sole (Parophrys vetulus) Get access Donald C. Malins, Donald C. Malins Search for other works by this author on: Oxford Academic PubMed Google Scholar Margaret M. Krahn, Margaret M. Krahn Search for other works by this author on: Oxford Academic PubMed Google Scholar Donald W. Brown, Donald W. Brown Search for other works by this author on: Oxford Academic PubMed Google Scholar Linda D. Rhodes, Linda D. Rhodes Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark S. Myers, Mark S. Myers Search for other works by this author on: Oxford Academic PubMed Google Scholar Bruce B. McCain, Bruce B. McCain Search for other works by this author on: Oxford Academic PubMed Google Scholar Sin-Lam Chan Sin-Lam Chan Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 74, Issue 2, February 1985, Pages 487–494, https://doi.org/10.1093/jnci/74.2.487 Published: 01 February 1985 Article history Received: 13 June 1984 Accepted: 19 September 1984 Published: 01 February 1985
Randomized Trial of High-Dose Chemotherapy With Autologous Peripheral-Blood Stem-Cell Support Compared With Standard-Dose Chemotherapy in Women With Metastatic Breast Cancer: NCIC MA.16
Authors: Michael Crump, Stefan Gluck, Dongsheng Tu, Doug Stewart, Mark Levine, Peter Kirkbride, Janet Dancey, Susan O'Reilly, Tsiporah Shore, Stephen Couban, Caroline Girouard, Susan Marlin, Lois Shepherd, Kathleen I. Pritchard
Journal: Journal of Clinical Oncology (2007)

We conducted a multicenter, randomized trial to compare progression-free survival (PFS), overall survival (OS), and quality of life in women with metastatic breast cancer (MBC) receiving high-dose chemotherapy plus autologous stem-cell transplantation (ASCT; HDCT) compared with standard-dose therapy.Between April 1997 and December 2000, 386 women with MBC and no prior chemotherapy for metastatic disease were registered. After initial response to anthracycline- or taxane-based induction chemotherapy, 224 patients were randomly assigned: 112 to high-dose cyclophosphamide, mitoxantrone, and carboplatin chemotherapy and ASCT (HDCT), and 112 to standard therapy (ST). Median age was 47 years (range, 25 to 67 years). Thirty two percent of women randomly assigned had estrogen and progesterone receptor-negative breast cancer, 42% had visceral metastases, and 58% had bone metastases. Complete remission rates before random assignment were 11% for those receiving HDCT and 12% for those receiving ST.After a median follow-up of 48 months, 79 deaths were observed in the HDCT arm and 77 deaths were observed in the ST arm; seven patients (6%) in the HDCT arm died as a result of toxicity. The median OS was 24 months for the HDCT arm (95% CI, 21 to 35 months) and 28 months for ST (95% CI, 22 to 33 months; hazard ratio [HR], 0.9; 95% CI, 0.6 to 1.2; P = .43). PFS was 11 months for HDCT and 9 months for ST (HR, 0.6 in favor of HDCT; 95% CI, 0.5 to 0.9; P = .006).HDCT did not improve OS in women with MBC when used as consolidation after response to induction chemotherapy.
Increased serum trypsinogen 2 and trypsin 2-α<sub>1</sub>antitrypsin complex values identify endoscopic retrograde cholangiopancreatography induced pancreatitis with high accuracy
Authors: E Kemppainen, J Hedström, P Puolakkainen, J Halttunen, V Sainio, R Haapiainen, E Kivilaakso, U-H Stenman
Journal: Gut (1997)

Aims —To evaluate the clinical utility of two new tests for serum trypsinogen 2 and trypsin 2-α 1 antitrypsin complex (trypsin 2-AAT) in diagnosing and assessing the severity of acute pancreatitis (AP) induced by endoscopic retrograde cholangiopancreatography (ERCP). Patients —Three hundred and eight consecutive patients undergoing ERCP at Helsinki University Central Hospital in 1994 and 1995. Methods —Patients were followed prospectively for pancreatitis and clinical outcome. They were tested for serum trypsinogen 2, trypsin 2-AAT, and amylase in samples obtained before and one, six, and 24 hours after ERCP. Results —Pancreatitis developed in 31 patients (10%). Their median serum trypsinogen 2 increased 26-fold to 1401 μg/l at six hours after the procedure and trypsin 2-AAT showed an 11-fold increase to 88 μg/l at 24 hours. The increase in both markers was stronger in severe than in mild pancreatitis, and in patients without pancreatitis there was no significant increase. Baseline trypsinogen 2 and trypsin 2-AAT concentrations were elevated in 29% and 32% of patients, respectively. The diagnostic accuracy of a threefold elevation over the baseline value was therefore analysed. The sensitivity and specificity of these parameters in the diagnosis of post-ERCP pancreatitis was 93% and 91%, respectively, for serum trypsinogen 2 at six hours after the examination, and 93% and 90%, for trypsin 2-AAT at 24 hours. Conclusions —Serum trypsinogen 2 and trypsin 2-AAT reflect pancreatic injury after ERCP. High concentrations are associated with severe pancreatic damage. The delayed increase in trypsin 2-AAT compared with trypsinogen 2 appears to reflect the pathophysiology of AP. A greater than threefold increase in trypsinogen 2 six hours after ERCP is an accurate indicator of pancreatitis.
Respiratory abnormalities due to craniovertebral junction compression in rheumatoid disease.
Authors: R S Howard, F Henderson, N P Hirsch, J M Stevens, B E Kendall, H A Crockard
Journal: Annals of the Rheumatic Diseases (1994)

To assess the extent and severity of respiratory insufficiency associated with severe rheumatoid atlantoaxial dislocation and its relation to compression of the neuraxis.Twelve patients with severe atlantoaxial dislocation due to rheumatoid disease were studied. Detailed clinical, CT myelography and respiratory assessment including nocturnal oximetry, were performed on all patients.All patients were severely disabled by their underlying disease but none had symptoms of hypoventilation. All the patients with C1 compression had myelopathic features. Those with medullary deformation (moulding and/or stretch) had abnormal noctural oximetry whilst no significant desaturations were seen in the remaining patients. Post-operative studies showed resolution of noctural desaturations.This study suggests that clinically unsuspected respiratory insufficiency may be common in patients with severe medullary compression associated with rheumatoid atlantoaxial dislocation. It emphasises the importance of careful respiratory monitoring including nocturnal oxygen saturation in patients with major atlantoxial dislocation due to rheumatoid disease.
Homeostasis of Peripheral B Cells in the Absence of B Cell Influx from the Bone Marrow
Authors: Zhenyue Hao, Klaus Rajewsky
Journal: The Journal of Experimental Medicine (2001)

To study homeostasis of peripheral B lymphocytes in the absence of B cell influx from the bone marrow, we generated a mouse mutant in which the recombination-activating gene (RAG)-2 can be inducibly deleted. When RAG-2 was deleted at the age of 8-10 wk, splenic naive follicular B cells were gradually lost over a year of observation, with a half-life of approximately 4.5 mo. By contrast, the pool of marginal zone B cells in the spleen and of B-1 cells in the peritoneal cavity were kept at normal level. In lymph nodes, approximately 90% of the B cells were lost within 4 mo, and B cell numbers remained constant thereafter. Mice in which RAG-2 was deleted at birth maintained a small population of activated B cells with an increased proportion of marginal zone B cells. Additionally, an increase of the pool of IgM secreting cells and B-1a cells was observed.
Cardiovascular effects associated with antidiuretic activity of vasopressin after blockade of its vasoconstrictor action in dehydrated dogs.
Authors: J F Liard
Journal: Circulation Research (1986)

In view of our previous findings that a specific antidiuretic (V2) agonist, 4-valine-8-D-arginine vasopressin, acutely increased cardiac output and heart rate in dogs, we examined the hypothesis that interaction with V2-like receptors might contribute to the hemodynamic response seen after blockade of the vasoconstrictor (V1) effect of arginine-vasopressin in dehydrated dogs. After 48 hours of water restriction which increased plasma vasopressin to 10.6 +/- 2.0 pg/ml, the V1 antagonist 1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid) 2-(O-methyl)tyrosine arginine-vasopressin, 10 micrograms/kg, was injected intravenously into six conscious dogs, and the combined V1 + V2 antagonist 1-(beta-mercapto-beta,beta,cyclopentamethylene propionic acid) 2-(O-ethyl)-D-tyrosine, 4-valine arginine-vasopressin, 10 micrograms/kg, was administered to another six dogs. Mean arterial pressure, cardiac output (electromagnetic flowmeter), and regional blood flows (radioactive microspheres) were measured before and 20-30 minutes after antagonist administration. Mean arterial pressure did not change significantly in either instance. Cardiac output increased by 31.0 +/- 7.1% after V1 blockade, but by only 10.8 +/- 2.1% following V1 + V2 blockade. Blood flow increased significantly and to a similar extent in the skin, the skeletal muscles, and the fat following both antagonists. Conversely, kidney, arterial liver, and bone blood flow increased only after V1 blockade. In six additional, normally hydrated conscious dogs, it was shown that the V1 + V2 antagonist had no significant hemodynamic effects, a finding previously established for the V1 antagonist. The V1 + V2 antagonist completely prevented the hemodynamic effects associated with administration of the V2 agonist 4-valine-8-D-arginine vasopressin, 200 ng/kg, whereas the V1 antagonist did not. Both antagonists had similar effects on the hemodynamic changes induced by nitroprusside infusion, namely a potentiation of the blood pressure lowering action. These results suggest that part of the hemodynamic response to blockade of the vasoconstrictor action of vasopressin in dehydration is caused by unmasking cardiovascular effects linked to the antidiuretic activity of the arginine-vasopressin molecule.