tbuckley/cabot-search huggingface dataset:
Lymphocytes and Leukemia Viruses: Tropism and Transtropism of Murine Leukemia Virus<xref ref-type="fn" rid="fn2">2</xref>
Authors: Syamal K. Datta, C. J. M. Melief, Robert S. Schwartz
Journal: JNCI Journal of the National Cancer Institute (1975)

The tropism of naturally occurring murine leukemia virus (MuLV) was investigated in short-term lymphocyte cultures. The tropism of MuLV was readily defined in fibroblast cultures, but not in lymphocyte cultures. Lymphocytes free of infectious MuLV could be infected across the tropism barrier by partially purified MuLv or by in vitro contact with MuLV-producing lymphocytes. Stimulation of lymphocytes was not required for this cross-infection and replication of MuLV. When cross-infected lymphocytes and was specifically associated with lymphocytes were stimulated in vitro by allogeneic cells, they facilitated MuLV infection of ordinarily non-permissive fibroblasts. This phenomenon (transtropism) required antigenically stimulated lymphocytes and was specifically associated with infection of the lymphocyte by MuLV across the tropism barrier. Thus in contrast with the resting lymphocyte, the transformed lymphocyte acquired the ability to disseminate infectious MuLV to nonpermissive cells. These findings suggest a novel relationship between lymphocytes and leukemia viruses. They indicate one mechanism whereby antigenic stimulation may enhance the development of virus-induced lymphoid neoplasms.
Thymomas Induced by Simple Alkylating Agents in C57BL/Cbi Mice: Kinetics of the Dose Response&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: Jaroslav V. Frei, Philip D. Lawley
Journal: JNCI Journal of the National Cancer Institute (1980)

Journal Article Thymomas Induced by Simple Alkylating Agents in C57BL/Cbi Mice: Kinetics of the Dose Response Get access Jaroslav V. Frei, Jaroslav V. Frei 4Department of Pathology, University of Western Ontario, London, Ontario, N6A 5Cl, Canada. Search for other works by this author on: Oxford Academic PubMed Google Scholar Philip D. Lawley Philip D. Lawley 5Chester Beatty Research Institute, Pollards Wood Research Station, Chalfont St. Giles, Buck, HP8 4SP, England. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 64, Issue 4, April 1980, Pages 845–856, https://doi.org/10.1093/jnci/64.4.845 Published: 01 April 1980 Article history Received: 01 June 1979 Accepted: 08 August 1979 Published: 01 April 1980
Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in Podocytes
Authors: Hossam Hassan, Xuefei Tian, Kazunori Inoue, Nathan Chai, Chang Liu, Keita Soda, Gilbert Moeckel, Alda Tufro, Ann-Hwee Lee, Stefan Somlo, Sorin Fedeles, Shuta Ishibe
Journal: Journal of the American Society of Nephrology (2015)

Podocytes are terminally differentiated epithelial cells that reside along the glomerular filtration barrier. Evidence suggests that after podocyte injury, endoplasmic reticulum stress response is activated, but the molecular mechanisms involved are incompletely defined. In a mouse model, we confirmed that podocyte injury induces endoplasmic reticulum stress response and upregulated unfolded protein response pathways, which have been shown to mitigate damage by preventing the accumulation of misfolded proteins in the endoplasmic reticulum. Furthermore, simultaneous podocyte-specific genetic inactivation of X-box binding protein-1 (Xbp1), a transcription factor activated during endoplasmic reticulum stress and critically involved in the untranslated protein response, and Sec63, a heat shock protein-40 chaperone required for protein folding in the endoplasmic reticulum, resulted in progressive albuminuria, foot process effacement, and histology consistent with ESRD. Finally, loss of both Sec63 and Xbp1 induced apoptosis in podocytes, which associated with activation of the JNK pathway. Collectively, our results indicate that an intact Xbp1 pathway operating to mitigate stress in the endoplasmic reticulum is essential for the maintenance of a normal glomerular filtration barrier.
Risk Adjusting Survival Outcomes in Hospitals That Treat Patients With Cancer Without Information on Cancer Stage
Authors: David G. Pfister, David M. Rubin, Elena B. Elkin, Ushma S. Neill, Elaine Duck, Mark Radzyner, Peter B. Bach
Journal: JAMA Oncology (2015)

Instituting widespread measurement of outcomes for cancer hospitals using administrative data is difficult owing to lack of cancer-specific information such as disease stage.To evaluate the performance of hospitals that treat patients with cancer using Medicare data for outcome ascertainment and risk adjustment and to assess whether hospital rankings based on these measures are altered by the addition of cancer-specific information.Risk-adjusted cumulative mortality rates of patients with cancer were captured in Medicare claims data from 2005 through 2009 nationally and assessed at the hospital level. Similar analyses were conducted using Surveillance, Epidemiology, and End Results (SEER)-Medicare data for the subset of the United States covered by the SEER program to determine whether the inclusion of cancer-specific information (only available in cancer registries) in risk adjustment altered measured hospital performance. Data were from 729 279 fee-for-service Medicare beneficiaries treated for cancer in 2006 at hospitals treating 10 or more patients with each of the following cancers, according to Medicare claims: lung, prostate, breast, colon, and other. An additional sample of 18 677 similar patients were included from the SEER-Medicare administrative data.Risk-adjusted mortality overall and by cancer category, stratified by type of hospital; measures of correlation and agreement between hospital-level outcomes risk adjusted using Medicare data alone and Medicare data with SEER data.There were large survival differences between different types of hospitals that treat Medicare patients with cancer. At 1 year, mortality for patients treated by hospitals exempt from the Medicare prospective payment system was 10% lower than at community hospitals (18% vs 28%) across all cancers, and the pattern persisted through 5 years of follow-up and within specific cancer categories. Performance ranking of hospitals was consistent with or without SEER-Medicare disease stage information (weighted κ ≥ 0.81).Potentially important outcome differences exist between different types of hospitals that treat patients with cancer after risk adjustment using information in Medicare administrative data. This type of risk adjustment may be adequate for evaluating hospital performance, since the additional adjustment for data available only in cancer registries does not seem to appreciably alter measures of performance.
The role of IL-18 level and genetic polymorphism in patients with bronchial asthma and its relation to disease severity
Authors: Abeer Kassem, Nermin Hossam
Journal: European Respiratory Journal (2012)

Background: Asthma is a complex multifactorial disease with an obvious genetic predisposition, immunological aberration, and involvement of environmental factors. Interleukin -18(IL-18) is a unique cytokine that enhances innate immunity and both Th1- and Th2-driven immune responses. Objective: The aim of this case control study was to evaluate the role of IL-18 and genetic polymorphism in asthmatic patients, its relation to asthma severity. Subjects and Methods: Thirty patients with bronchial asthma and Thirty normal control subjects were enrolled in this study and were subjected to asthma questionnaire, spirometric studies, measurements of serum IL-18 using Human IL-18 Enzyme-linked Immunosorbent Assay kit and IL- 18 polymorphism was analyzed using allele specific polymerase chain reaction (PCR), at positions -607 in the promoter of the IL-18 gene. Results: There was statistical significant increase in serum IL-18 in severe asthmatic patients in relation to the other two asthmatic groups and control group (F=1105.259P=0.0001*).There was no significant difference between asthmatic patients and control group in−607C>A IL18 Allele distribution or frequencies. No significant association was observed with various disease characteristics. Conclusion: Although the−607C>A IL-18 Allele genetic analysis were insignificant between asthmatic and control, we found significant increase in serum IL-18 and degree of asthma severity. So our results need to be replicated by further studies possibly with other IL-18 genetic variants.
Use of radial endobronchial ultrasound for diagnosing peripheral lung lesions - A tertiary centre experience
Authors: Adrian Chan, Anantham Devanand, Mariko Koh
Journal: European Respiratory Journal (2012)

Introduction:  Small peripheral lung lesions continue to pose a diagnostic dilemma for pulmonologists. Flexible bronchoscopy with fluoroscopy has a limited diagnostic sensitivity (31-56%) for such lesions. Radial endobronchial ultrasound (EBUS) is a relatively new technique that has been used to improve yield, although diagnostic performance has been reported to vary considerably. We describe the characteristics of patients who underwent radial EBUS and outcomes in our centre.  Methods:  Retrospective review was performed for 123 patients from Singapore General Hospital with peripheral lung lesions who underwent brochoscopic evaluation with radial EBUS guidance from August 2008 to December 2011.  Results:  Median patient age was 64 years. Overall diagnostic yield was 68.3% with no difference for malignant (68.5%) or non-malignant (68%) lesions (p=0.954). Year-on-year diagnostic yield generally improved with increasing experience: in 2008, yield was 42.9% as compared to 2011 (80%). Data for ultrasound probe location was available for 93 patients. Yield was higher if the probe was within the lesion (78.3%) than when the probe was adjacent to the lesion (40%) (p=0.001). Data for lesion size was available for 118 patients. 40 patients had lesions less than 20mm diameter. Diagnostic yield of such lesions (77.5%) was higher than for larger lesions (64.1%), although this did not reach statistical significance (p=0.169).  Conclusion:  Radial EBUS is useful for evaluating peripheral lesions of less than 20mm diameter. Training and experience is important to improve diagnostic yield. We recommend that the ultrasound probe be positioned within the lesion before attempting bronchoscopic biopies.
Transplantable Mouse Plasma Cell Tumors in Experimental Chemotherapy&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Morris N. Teller, David Abraham, Matthew Bowie, Paul P. Carbone
Journal: JNCI Journal of the National Cancer Institute (1969)

The mouse plasma cell tumors LPC-1, MOPC-70A, and RPC-20, which synthesize different abnormal proteins, were transplanted intraperitoneally in BALB/c ♀ mice. By day 13, the blood of mice bearing LPC-1 showed significant decreases in red blood cells and hemoglobin and a significant increase in white blood cells; the lymphocyte/polymorpho-nuclear leukocyte ratio had shifted from 3:1-1:1. During this period, serum proteins with γ-mobility increased from 5% on day 0 to 14% on day 13. Of 10 drugs tested, aniline mustard, 5-fluorouracil, and cyclophosphamide were effective against the 3 tumors, and consistently doubled median survival times. MOPC-70A was more sensitive than LPC-1 and RPC-20 to nitrogen mustard and chlorambucil. Amethopterin was the least effective compound. The order of ability to control the synthesis of abnormal protein was: cyclophosphamide>5-fluorouracil>aniline mustard. The plasma cell mouse tumors, because of their similarity to human myeloma, are advantageous models for experimental chemotherapy.
IgE sensitisation to food allergens relates to increased airway and systemic inflammation in asthmatic children - Results from the MIDAS study
Authors: Andrei Malinovschi, Christer Janson, Malin Berthold, Magnus Borres, Kjell Alving, Lennart Nordvall
Journal: European Respiratory Journal (2012)

Food allergy is common among children with allergic asthma and has been linked to asthma severity. However, the relation between IgE sensitisation to food allergens and local airways inflammation or systemic inflammation in subjects with allergic asthma has been little studied.

Within the frame of an industry-academy collaboration on minimally-invasive diagnostics (MIDAS), fraction of NO in exhaled air (FeNO), serum eosinophil cationic protein (sECP) and IgE against aero- or food allergen mix was measured in 151 asthmatic children aged 10-18 years. Three asthma groups were defined: non-atopic (n=31, median age 15 yrs), IgE-sensitised to only aeroallergens (n=59, median age 15 yrs) and IgE-sensitised to both aero- and food allergens (n=61, median age 14 yrs).

FeNO levels were 8.9 ppb (7.1, 11.1) in non-atopic asthmatics, 14.2 ppb (11.7, 17.2) in aeroallergen-sensitised asthmatics and 23.4 ppb (19.4, 28.3) in asthmatics sensitised to both aero- and food allergens (p<0.01 for all comparisons). Corresponding sECP levels for the three groups were: 9.6 ng/mL (7.9, 11.8), 11.9 ng/mL (9.7, 14.5) (p=0.55 vs. non-atopic asthma), 21.9 ng/mL (18.6, 25.7) (p<0.001 vs. each of the other two groups). Asthmatic subjects sensitized to both aero- and food allergens had higher levels of FeNO and sECP than non-sensitised or aeroallergens-sensitised subjects, after adjustments for gender, age, height, lung function, total IgE.

In conclusion, sensitisation to food allergens is common among children with allergic asthma and is related to increased local as well as systemic inflammation. The clinical implications of these findings warrant further studies.
Neovascularisation in asthma: Altered angiogenic potential of ASM cells from asthmatic patients
Authors: Laura Keglowich, Michael Roth, Maria Philippova, Thérèse J. Resink, Michael Tamm, Peter Borger
Journal: European Respiratory Journal (2012)

Background: Airway remodeling is a key pathology in asthma with increasing changes of the airway wall structure, including thickening of airway smooth muscle (ASM) bundles and increased vascularisation. ASM cells require oxygen and nutritions which are delivered via blood vessels. Understanding the mechanism of neo-vascularisation may therefore lead to novel strategies to counteract remodeling. Methods: The capacity of ASM cells of asthmatics and non-asthmatics to induce sprouting was determined with a sprouting assay. To get broad insight into the factors which may be involved we used an angiogenesis array. Some of the 43 analyzed proteins are of further interest and their concentration was measure by ELISA. Results: Conditioned Medium (CM) from ASM cells was applied to a spheroid assay. In this assay the CM of ASM cells derived from asthmatics lead to more sprout outgrowth compared to CM derived from controls. Analyzing the CM with an commercial available angiogenesis array revealed that several angiogenic factors are elevated. The CXC-Chemokines ENA-78, GRO-alpha and IL-8 have been further analyzed by ELISA and were confirmed to be upregulated in asthmatics. Conclusion: Our results indicate that the angiogenic potential of ASM cells from asthmatic patients is higher compared to that of control cells. The ELR-motif-containing chemokines ENA-78, GRO-alpha and IL-8 are upregulated in asthmatics and might therefore contribute to neo-vascularisation. Counteracting this process may lead to novel asthma therapies. Supported by SNF 320030_124905/1.
Cocaine-induced microvascular spasm in Yucatan miniature swine. In vivo and in vitro evidence of spasm.
Authors: B D Núñez, L Miao, Y Wang, M M Núñez, M A Klein, F W Sellke, J N Ross, V Susulic, G Y Paik, J P Carrozza
Journal: Circulation Research (1994)

The purpose of the present study was to determine the maximal coronary flow reserve (CFR) before and after the administration of successive cocaine doses (0.1, 0.5, 3, and 7 mg/kg IV) for 2 minutes at 10-minute intervals in eight miniature swine. CFR was assessed by the administration of adenosine (0.03, 0.3, and 3 mg IC). Hemodynamic and flow measurements were performed 3 minutes after each dose. Coronary flow (CF) was measured with a Doppler-tipped wire in the proximal left anterior descending coronary artery (LAD). Also, microvessels were dissected, and vessel diameters were measured by a videoelectronic dimension analyzer. In vivo, LAD CF increased fourfold, CFR increased twofold, and coronary vascular resistance (CVR) decreased fourfold after the administration of adenosine. In contrast, LAD CF decreased threefold, CFR decreased onefold, and CVR increased sixfold 3 minutes after the administration of cocaine. Adenosine (3 mg) was repeated 4 minutes after the administration of cocaine, and LAD CF increased 1.4-fold, CVR increased 2.5-fold, and CFR decreased onefold. Thus, adenosine partially reversed the potent cocaine constrictor effect. In vitro, 10(-9) mol/L cocaine decreased the diameter of the coronary microvessels from 129 +/- 12 to 127 +/- 12 microns, and 10(-4) mol/L cocaine decreased coronary microvessel diameter to 114 +/- 15 microns (P &lt; .05). In conclusion, cocaine in vivo decreases CFR, and consistent with the in vivo effect, cocaine in vitro produced constriction of vessels &lt; 200 microns. These results indicate that cocaine can produce profound microvascular spasm. This may contribute to the ischemia/infarction reported in patients who abuse cocaine and who are subsequently found to have normal epicardial coronary arteries.
Systemic mastocytosis in adults: 2012 Update on diagnosis, risk stratification, and management
Authors: Animesh Pardanani
Journal: American Journal of Hematology (2012)

Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extra-cutaneous organs.The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V.The prognostic relevance of the 2008 World Health Organization (WHO) classification of SM has recently been confirmed. Classification of SM patients into indolent (SM), aggressive SM (ASM), SM associated with a clonal non-MC lineage disease (SM-AHNMD) and mast cell leukemia (MCL) subgroups is a useful first step in establishing prognosis.SM treatment is generally palliative. ISM patients have a normal life expectancy and receive symptom-directed therapy; infrequently, cytoreductive therapy may be indicated for refractory symptoms. ASM patients have disease-related organ dysfunction; interferon-α (±corticosteroids) can control dermatological, hematological, gastrointestinal, skeletal, and mediator-release symptoms, but is hampered by poor tolerability. Similarly, cladribine has broad therapeutic activity, with particular utility when rapid MC debulking is indicated; the main toxicity is myelosuppression. Imatinib has a therapeutic role in the presence of an imatinib-sensitive KIT mutation or in KITD816-unmutated patients. Treatment of SM-AHNMD is governed primarily by the non-MC neoplasm; hydroxyurea has modest utility in this setting.Dasatinib's in vitro anti-KITD816V activity has not translated into significant therapeutic activity in most SM patients. In contrast, preliminary data suggest that Midostaurin may produce significant decreases in MC burden in some patients.
Development of Monoclonal Antibodies to the Human Breast Carcinoma Cell Line PMC42&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: P J Dempsey, F P Feleppa, R W Brown, T A de Kretser, R H Whitehead, D G Jose
Journal: JNCI Journal of the National Cancer Institute (1986)

In an attempt to identify antigens expressed during breast differentiation, three murine monoclonal antibodies, CIBr2, CIBr7, and CIBr18, were produced against the human pleomorphic breast carcinoma cell line PMC42. All three monoclonal antibodies reacted with previously undescribed antigenic determinants on the PMC42 cell line. Antibody CIBr18 reacted only with the immunizing cell line PMC42, whereas antibodies CIBr2 and CIBr7 showed minimal reactivity toward a panel of 34 human leukemia- and solid tumor-derived cell lines. The antigenic determinants detected by the three antibodies were distinct, and each showed variable expression in PMC42 monolayer and organoid cultures. The heterogeneity of staining seen on PMC42 cultures may reflect the fact that this cell line contains up to eight morphologically distinct cell types. Antigen expression correlated with cell type in some instances, whereas in other instances phenotypic subdivision within a cell type was apparent. Antigens recognized by antibodies CIBr7 and CIBr18 were characterized biochemically. In Western blotting, antibody CIBr7 identified a single band of an apparent molecular weight of 38,000 within PMC42 cell lysates. Sodium dodecyl sulfate-polyacrylamide gel analysis of polypeptides immunoprecipitated by antibody CIBr18 from [35S]methionine-labeled PMC42 cell lysates identified two glycoproteins of apparent molecular weights of 115,000 and 120,000, respectively. No biochemical data for the CIBr2 antigen are yet available. All three antigens were detected in human mammary epithelium and some non-breast tissues. The expression of these antigens in normal and neoplastic mammary epithelia is discussed in terms of antigen heterogeneity and changes in antigen expression upon conversion to the malignant state.
Low-Dose <sup>131</sup>I in Treatment of Graves' Disease
Authors: C P Lowdell, G S Spathis, D O Cosgrove, H J Dobbs, V R McCready, C L Harmer
Journal: Journal of the Royal Society of Medicine (1985)

One hundred and sixty-four patients with Graves' disease were treated with low-dose radioiodine (2 mCi), with a mean follow up of 4 1/2 years. At this time 74 (45%) were euthyroid having had a single dose, with a total of 131 (80%) being controlled with one or more doses. Three (2%) were still toxic but their mean follow up was only 3 years. Thirty (18%) were rendered hypothyroid, two-thirds of these after a single dose of 2 mCi 131I. The one-year incidence of hypothyroidism was 6%, with an incidence at 6 years of 20%. Previous surgery, medical treatment and thyroid antibody status appeared to have no influence on the outcome.
The role of the smoke-free legislation on emergency department admissions due to tobacco-related diseases in Kocaeli
Authors: Fusun Yildiz, Serap Baris, Ilknur Basyigit, Hasim Boyaci, Hasan Aydinlik, Pinar Sonmez
Journal: European Respiratory Journal (2011)

Aim:  The aim of the study was to evaluate the admissions to emergency department due to tobacco-related diseases before and after smoke-free legislation.   Method:  The number of admissions to emergency departments of 15 hospitals in Kocaeli was evaluated retrospectively before and after the implementation of smoke-free legislation published in 19 July 2009. ICD codes of smoking-related disease which were determined as bronchitis (BR), chronic obstructive pulmonary disease (COPD), asthma, nasopharingitis (NP), lower respiratory tract infections (LRTI), allergic rhinitis (AR) and myocardial infarction (MI) were recorded The data on January to June 2009 and 2010 were compared for the prevention of seasonal changes.   Results:  There was a 22.5% decline in all emergency admissions due to smoking-related diseases.  Total number of admissions due to above mentioned diseases was 83 089 in the first 6 months of 2009 while it was decreased to 64 314 in the first 6 months of 2010. There was a 39.8% reduction in the diagnosis of bronchitis, 4.3% of reduction in the lower respiratory tract infections, 61.9% reduction for allergic rhinitis and 21.2% reduction in the COPD exacerbations.   Conclusion:  The number of admissions to emergency department due to tobacco-related disease decreased after the implementation of smoke-free legislation. This finding might be interpreted as an achievement of smoke-free environment.