tbuckley/cabot-search huggingface dataset:
Adrenal suppression in bronchiectasis and the impact of inhaled corticosteroids
Authors: J. Holme, J. W. Tomlinson, R. A. Stockley, P. M. Stewart, N. Barlow, A. L. Sullivan
Journal: European Respiratory Journal (2008)

The present study identified three patients with bronchiectasis receiving inhaled corticosteroids (ICSs) who had symptomatic adrenal suppression secondary to ICS. The prevalence of adrenal suppression is unknown in bronchiectasis. The frequency of adrenal suppression and the impact of ICS use in bronchiectasis patients were examined. In total, 50 outpatients (33 receiving ICSs) underwent a short Synacthen test and completed a St George's Respiratory Questionnaire (SGRQ). Symptoms of adrenal suppression, steroid use and lung function were compared between subjects who were suppressed and those who were not. Adrenal suppression was evident in 23.5% of subjects who did not receive ICSs and 48.5% of those who did. Basal cortisol and the increments by which cortisol increased 30 min after Synacthen were lower in suppressed than in nonsuppressed subjects. The incremental cortisol rise was negatively correlated with SGRQ impacts and total score, suggesting a worse quality of life in those who had an impaired adrenal response. The greatest frequency of generalised symptoms was seen in the suppressed group. A significant proportion of subjects with bronchiectasis have evidence of adrenal suppression, and this is increased when inhaled corticosteroids are also used. Impairment of the cortisol response to stimulation is associated with poorer health status.
Pyrophosphohydrolase activity and inorganic pyrophosphate content of cultured human skin fibroblasts. Elevated levels in some patients with calcium pyrophosphate dihydrate deposition disease.
Authors: L M Ryan, R L Wortmann, B Karas, M P Lynch, D J McCarty
Journal: Journal of Clinical Investigation (1986)

In calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, metabolic abnormalities favoring extracellular inorganic pyrophosphate (PPi) accumulation have been suspected. Elevations of intracellular PPi in cultured skin fibroblasts from a single French kindred with familial CPPD deposition (19) and elevated nucleoside triphosphate pyrophosphohydrolase activity (NTPPPH), which generates PPi in extracts of CPPD crystal-containing cartilages (14) favor this suspicion. To determine whether NTPPPH activity or PPi content of cells might be a disease marker expressed in extraarticular cells, human skin-derived fibroblasts were obtained from control donors and patients affected with the sporadic and familial varieties of CPPD (CPPD-S and CPPD-F) deposition. Intracellular PPi was elevated in both CPPD-S (P less than 0.05) and CPPD-F (P less than 0.01) fibroblasts compared with control fibroblasts. Ecto-NTPPPH activity was elevated in CPPD-S (P less than 0.01) but not CPPD-F. Intracellular PPi correlated with ecto-NTPPPH (P less than 0.01). Elevated PPi levels in skin fibroblasts may serve as a biochemical marker for patients with familial or sporadic CPPD crystal deposition disease; ecto-NTPPPH activity further separates the sporadic and familial disease types. Expression of these biochemical abnormalities in nonarticular cells implies a generalized metabolic abnormality.
Mobility Pathways for Vertebrate L1, L2, CR1, and RTE Clade Retrotransposons
Authors: K. Ichiyanagi, N. Okada
Journal: Molecular Biology and Evolution (2008)

Autonomous non–long terminal repeat retrotransposons (NLRs) are ubiquitous mobile genetic elements that insert their DNA copies at new locations by retrotransposition. In vertebrates, there are 4 NLR clades, L1, L2, CR1, and RTE, which diverged in the Precambrian era. It has been demonstrated that retrotransposition of L1 and L2 members proceeds via coordinated reactions of targeted DNA cleavage and reverse transcription catalyzed by the NLR-encoded proteins, which are followed by the joining of the 5′ (upstream) junction. However, the study on the mobility pathways for vertebrate NLRs is so far limited to L1 and L2. In this report, using target analysis of nested transposons for genomic copies, we studied retrotransposition pathways for a variety of vertebrate NLRs, including those of the L1, L2, CR1, and RTE clades in the human, cow, opossum, chicken, and zebrafish genomes. Thus, this study constitutes the first comprehensive analysis of NLR retrotransposition products in vertebrates. Our data revealed that these elements share similar mechanisms for the cleavages of the 2 target DNA strands and for the initiation of reverse transcription. Possible endonuclease-independent insertions were also identified. Overall, our results suggest the existence of multiple retrotransposition pathways that are conserved among the diverse NLR clades in various vertebrate hosts.
Effect of Herpes Simplex Suppression on Incidence of HIV among Women in Tanzania
Authors: Deborah Watson-Jones, Helen A. Weiss, Mary Rusizoka, John Changalucha, Kathy Baisley, Kokugonza Mugeye, Clare Tanton, David Ross, Dean Everett, Tim Clayton, Rebecca Balira, Louise Knight, Ian Hambleton, Jerome Le Goff, Laurent Belec, Richard Hayes
Journal: New England Journal of Medicine (2008)

Infection with herpes simplex virus type 2 (HSV-2) is associated with an increased risk of acquiring infection with the human immunodeficiency virus (HIV). This study tested the hypothesis that HSV-2 suppressive therapy reduces the risk of HIV acquisition.
Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1.
Authors: C Terai, R S Kornbluth, C D Pauza, D D Richman, D A Carson
Journal: Journal of Clinical Investigation (1991)

The mechanisms by which HIV-1 infection kills T lymphocytes are not clearly established. Apoptosis is an internally programmed cell death pathway that may regulate both T cell development and senescence, and that is characterized by cleavage of DNA at internucleosomal regions. The present experiments show that acute HIV-1 infection of MT2 lymphoblasts and activated normal peripheral blood mononuclear cells induces apoptosis. The addition of anti-gp120 neutralizing antibody, after HIV-1 infection of MT2 cells, permitted sustained high levels of viral replication, but blocked apoptosis and cell death. Apoptosis may account for the direct cytopathologic effects of HIV-1 in T cells.
Tumour necrosis factor microsatellites and HLA-DRB1*, HLA-DQA1*, and HLA-DQB1* alleles in Peruvian patients with rheumatoid arthritis
Authors: F Castro
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To study the association between rheumatoid arthritis (RA) and HLA and tumour necrosis factor (TNF) polymorphism in Peruvian mestizo patients in comparison with ethnically similar controls. <h3>METHODS</h3> Seventy nine patients with RA and 65 ethnically matched healthy controls were genotyped for HLA-DRB1, HLA-DQA1, HLA-DQB1, and TNFα and TNFβ alleles using PCR amplification. Clinical severity was assessed as mild, moderate, or severe in 35 of the patients. <h3>RESULTS</h3> TNFα6 showed the strongest association with disease susceptibility. The TNFα6 allele was more common in patients than in controls (p&lt;0.0076) and the proportion of patients with at least one copy of this allele was greater (p&lt;0.015, relative risk 2.35). Among the HLA-DRB1* alleles with the shared epitope sequence, only the DRB1*1402 allele was significantly increased in patients compared with controls (p&lt;0.0311), as was the proportion of patients with at least one copy of this allele (p&lt;0.0232, relative risk 2.74). In contrast, the overall frequency of alleles with the shared epitope was not different in patients and controls. The haplotype HLA-DRB1*1402-DQB1*0301-DQA1*0401 was significantly more common in patients. TNFα6 was more common in patients whether or not they had this haplotype. None of the 11 patients lacking the TNFα6 allele had severe disease. <h3>CONCLUSIONS</h3> This study shows for the first time that TNF gene polymorphism is associated with susceptibility to RA in a non-white population. TNFα6 and HLA-DRB1*1402 independently conferred significantly increased risk in Peruvian mestizo patients.
High expression of myocyte enhancer factor 2C (MEF2C) is associated with adverse-risk features and poor outcome in pediatric acute myeloid leukemia: a report from the Children’s Oncology Group
Authors: George S. Laszlo, Todd A. Alonzo, Chelsea J. Gudgeon, Kimberly H. Harrington, Alex Kentsis, Robert B. Gerbing, Yi-Cheng Wang, Rhonda E. Ries, Susana C. Raimondi, Betsy A. Hirsch, Alan S. Gamis, Soheil Meshinchi, Roland B. Walter
Journal: Journal of Hematology & Oncology (2015)

Recent studies have identified myocyte enhancer factor 2C (MEF2C) as cooperating oncogene in acute myeloid leukemia (AML) and suggested a contribution to the aggressive nature of at least some subtypes of AML, raising the possibility that MEF2C could serve as marker of poor-risk AML and, therefore, have prognostic significance. To test this hypothesis, we retrospectively quantified MEF2C expression in pretreatment bone marrow specimens in participants of the AAML0531 trial by reverse-transcriptase polymerase chain reaction and correlated expression levels with disease characteristics and clinical outcome. In all 751 available patient specimens, MEF2C messenger RNA (mRNA) was detectable and varied >3000-fold relative to β-glucuronidase. Patients with the highest relative MEF2C expression (4th quartile) less likely achieved a complete remission after one course of chemotherapy than the other patients (67 vs. 78 %, P = 0.005). They also had an inferior overall survival (P = 0.014; at 5 years 55 ± 8 vs. 67 ± 4 %), inferior event-free survival (P < 0.001; at 5 years 38 ± 7 vs. 54 ± 4 %), and higher relapse risk than patients within the lower 3 quartiles of MEF2C expression (P < 0.001; at 5 years 53 ± 9 vs. 35 ± 5 %). These differences were accounted for by lower prevalence of cytogenetically/molecularly defined low-risk disease (16 vs. 46 %, P < 0.001) and higher prevalence of standard-risk disease (68 vs. 42 %, P < 0.001) in patients with high MEF2C expression, suggesting that MEF2C cooperates with additional pathogenic abnormalities. High MEF2C expression identifies a subset of AML patients with adverse-risk disease features and poor outcome. With confirmation that high MEF2C mRNA expression leads to overexpression of MEF2C protein, these findings provide the rationale for therapeutic targeting of MEF2C transcriptional activation in AML.
Functional behavior and morphology of the coronary artery wall in patients with Kawasaki disease assessed by intravascular ultrasound
Authors: Atsuko Suzuki, Masakazu Yamagishi, Kouji Kimura, Hisashi Sugiyama, Yoshio Arakaki, Tetsuro Kamiya, Kunio Miyatake
Journal: Journal of the American College of Cardiology (1996)
Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology
Authors: C. Vancheri, M. Failla, N. Crimi, G. Raghu
Journal: European Respiratory Journal (2010)

Several clinical trials have recently targeted specific pathways implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, IPF remains plagued by a median survival of 3 yrs and emphasises the need for further research with new insights and perspectives. The prevailing pathogenic hypotheses assume that either an inflammatory process or an independent epithelial/fibroblastic disorder may propagate the disease process. Based on knowledge developed with considerable scientific evidence, we provide our perspectives with an alternative point of view that IPF be considered as a neoproliferative disorder of the lung. Genetic alterations, response to growth and inhibitory signals, resistance to apoptosis, myofibroblast origin and behaviour, altered cellular communications, and intracellular signalling pathways are all fundamental pathogenic hallmarks of both IPF and cancer. The concept of IPF as a lethal malignant disorder of the lung might extend beyond the pathogenic link between these two diseases and disclose new pathogenic mechanisms leading to novel therapeutic options, adopted from cancer biology. Moreover, this vision might dawn the awareness of the public, political and scientific community of this devastating disease from an angle different from the current perception and provoke new ideas and studies to get a better understanding to control the otherwise relentless progressive disease.
Disseminated Mycobacterium tuberculosis infection due to interferon deficiency. Response to replacement therapy
Authors: S. Luke Seneviratne, R. Doffinger, J. Macfarlane, L Ceron-Gutierrez, M R Amel Kashipaz, A Robbins, T Patel, P T Powell, D S Kumararatne, R. J Powell
Journal: Thorax (2006)

The case of a previously healthy HIV seronegative woman with disseminated <i>Mycobacterium tuberculosis</i> infection and markedly reduced interferon γ production is reported here. Complete healing of her disseminated lesions was seen only after addition of subcutaneous interferon γ to her tuberculosis treatment.
Familial endometrial cancer in female carriers of MSH6 germline mutations
Authors: Juul Wijnen, Wiljo de Leeuw, Hans Vasen, Heleen van der Klift, Pål Møller, Astrid Stormorken, Hanne Meijers-Heijboer, Dick Lindhout, Fred Menko, Sandra Vossen, Gabriela Möslein, Carli Tops, Annette Bröcker-Vriends, Ying Wu, Robert Hofstra, Rolf Sijmons, Cees Cornelisse, Hans Morreau, Riccardo Fodde
Journal: Nature Genetics (1999)
Removal of Distortion from Indicator Dilution Curves with Analog Computer
Authors: JAMES K. COOPER, J. ROBERT SCHWEIKERT, THOMAS G. ARNOLD, WILLIAM W. LACY
Journal: Circulation Research (1963)

A method has been developed for characterizing quantitatively, and for removing from indicator dilution curves, the distortion introduced by catheter sampling systems. The method involves a specially constructed cuvette and analog computer analysis of the curves recorded by densitometers placed at the entrance of the catheter and at points downstream. This method of correction of distortion is based on a general theory of function transformation which is applicable to all situations and not upon empirically established constants which are only valid in special situations. The geometry (coiling, bending) of the catheter has been found to affect the distortion. Disruption of the flow pattern by insertion of a braided wire in the lumen causes less variation of the distortion caused by bending and coiling. Distortion was not significantly affected by change in blood temperature in our system.
STUDIES ON EXPERIMENTAL SHIGELLOSIS
Authors: C. David McGuire, Thomas M. Floyd
Journal: The Journal of Experimental Medicine (1958)

Experimental Shigella flexneri 3 infections produced in normal mice have been described. The passage of viable Shigella through the stomach of orally infected animals, and the persistence of the organisms in the intestine for periods of 5 to 7 days, with an increase in bacterial numbers, indicated that true infection was produced. Blood culture studies showed that a Shigella bacteriemia occurred after either oral or parenteral administration of Shigella to normal mice. Mice infected orally revealed mild, but consistent pathological changes, including mesenteric hemorrhage, liver and spleen hypertrophy, and occasional diarrhea.
“I'm Not Ready for Hospice”: Strategies for Timely and Effective Hospice Discussions
Authors: David J. Casarett, Timothy E. Quill
Journal: Annals of Internal Medicine (2007)

Hospice programs offer unique benefits for patients who are near the end of life and their families, and growing evidence indicates that hospice can provide high-quality care. Despite these benefits, many patients do not enroll in hospice, and those who enroll generally do so very late in the course of their illness. Some barriers to hospice referral arise from the requirements of hospice eligibility, which will be difficult to eliminate without major changes to hospice organization and financing. However, the challenges of discussing hospice create other barriers that are more easily remedied. The biggest communication barrier is that physicians are often unsure of how to talk with patients clearly and directly about their poor prognosis and limited treatment options (both requirements of hospice referral) without depriving them of hope. This article describes a structured strategy for discussing hospice, based on techniques of effective communication that physicians use in other "bad news" situations. This strategy can make hospice discussions both more compassionate and more effective.
A case of weak muscles
Authors: N Sofat
Journal: Annals of the Rheumatic Diseases (2002)

Background: Gut involvement in inflammatory myositis is rare but causes significant morbidity and mortality. Case report: A case of eosinophilic gastroenteritis and polymyositis occurring in the same patient is described. The interface of visceral and striated muscle involvement is discussed. The pathophysiology of eosinophilic gastroenteritis and the spectrum of gastrointestinal involvement in inflammatory myositis are also discussed. Results: Both gastrointestinal and skeletal muscle symptoms improved with immunosuppression, suggesting a possible common underlying mechanism.
Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma
Authors: Diego F. Calvisi, Sara Ladu, Alexis Gorden, Miriam Farina, Ju-Seog Lee, Elizabeth A. Conner, Insa Schroeder, Valentina M. Factor, Snorri S. Thorgeirsson
Journal: Journal of Clinical Investigation (2007)

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, accounting for an estimated 600,000 deaths annually. Aberrant methylation, consisting of DNA hypomethylation and/or promoter gene CpG hypermethylation, is implicated in the development of a variety of solid tumors, including HCC. We analyzed the global levels of DNA methylation as well as the methylation status of 105 putative tumor suppressor genes and found that the extent of genome-wide hypomethylation and CpG hypermethylation correlates with biological features and clinical outcome of HCC patients. We identified activation of Ras and downstream Ras effectors (ERK, AKT, and RAL) due to epigenetic silencing of inhibitors of the Ras pathway in all HCC. Further, selective inactivation of SPRY1 and -2, DAB2, and SOCS4 and -5 genes and inhibitors of angiogenesis (BNIP3, BNIP3L, IGFBP3, and EGLN2) was associated with poor prognosis. Importantly, several epigenetically silenced putative tumor suppressor genes found in HCC were also inactivated in the nontumorous liver. Our results assign both therapeutic and chemopreventive significance to methylation patterns in human HCC and open the possibility of using molecular targets, including those identified in this study, to effectively inhibit HCC development and progression.
Allergic females have the lowest chance of recovery following early wheezing
Authors: Emma Goksör, Mainor Åmark, Bernt Alm, Göran Wennergren
Journal: European Respiratory Journal (2011)

Background:  We have previously reported on the outcome in childhood and adolescence in children hospitalized due to wheezing before the age of two. The aim of the present follow-up was to report on the prevalence of and risk factors for asthma at adult age.   Methods:  We have prospectively studied asthma development in 101 children hospitalized due to wheezing before the age of two. The cohort was re-investigated at age 25-29 years and tested for bronchial hyper-responsiveness and allergic sensitization. The response rate at adult age was 72%.   Results:  Current asthma was seen in 38% (28/73) and 50% of these had a moderate to severe asthma. In the asthmatics, symptoms triggered by exercise were reported in 79%, infection 36%, tobacco-smoke 25%, contact with pollen 32% and furred animals in 18%.  Current allergy (OR 9.8; 95% CI 2.8-34.4) and female gender (OR 3.3; 95% CI 1.1-10.3) increased the risk of adult asthma independently of each other. This is illustrated in a stratified Cox regression analysis where the females with current allergy have the lowest chance of recovery (Hazard ratio 0.1; 95% CI 0.04-0.3) compared to males without allergy.   Conclusion:  In subjects hospitalized due to early wheezing, current allergy and female gender increased the risk of adult asthma. Females with current allergy had the lowest chance of recovery.
EXPERIMENTAL STUDIES ON HETEROPLASTIC BONE FORMATION
Authors: Goichi Asami, William Dock
Journal: The Journal of Experimental Medicine (1920)

1. Bone formation in the rabbit kidney with ligated vessels takes place (a) through the activity of young fibroblasts which accumulate to form a membrane-like structure; (b) subsequently by direct ossification of hyaline connective tissue in continuity with preformed bone; and (c) through erosion of lime placques by granulating tissue and laying down of lamellar bone by cells derived from fibroblasts. 2. Bone formation in the rabbit kidney begins not in direct contact with calcium deposits, but in the loose vascular connective tissue close under the transitional epithelium of the calices. 3. With autotransplanted ear cartilage of the rabbit there is an active new formation of cartilage in the connective tissue which surrounds the transplants, and the bone is formed by the fibroblasts from the perichondrium which erode and invade the calcified areas in this new cartilage. 4. The process of bone formation in the kidney is similar to that found in normal membranous ossification, while with the transplanted ear cartilage the process is identical with endochondral ossification.
Weekly Trastuzumab and Paclitaxel Therapy for Metastatic Breast Cancer With Analysis of Efficacy by <i>HER2</i> Immunophenotype and Gene Amplification
Authors: Andrew D. Seidman, Monica N. Fornier, Francisco J. Esteva, Lee Tan, Stamatina Kaptain, Ariadne Bach, Katherine S. Panageas, Crispinita Arroyo, Vicente Valero, Violante Currie, Teresa Gilewski, Maria Theodoulou, Mary Ellen Moynahan, Mark Moasser, Nancy Sklarin, Maura Dickler, Gabriella D’Andrea, Massimo Cristofanilli, Edgardo Rivera, Gabriel N. Hortobagyi, Larry Norton, Clifford A. Hudis
Journal: Journal of Clinical Oncology (2001)

PURPOSE: This phase II study evaluated weekly trastuzumab and paclitaxel therapy in women with HER2-normal and HER2-overexpressing metastatic breast cancer. Efficacy was correlated with immunohistochemical and fluorescent in situ hybridization (FISH) assay results. PATIENTS AND METHODS: Eligible patients had bidimensionally measurable metastatic breast cancer. Up to three prior chemotherapy regimens, including prior anthracycline and taxane therapy, were allowed. Trastuzumab 4 mg/kg and paclitaxel 90 mg/m 2 were administered on week 1, with trastuzumab 2 mg/kg and paclitaxel 90 mg/m 2 administered on subsequent weeks. HER2 status was evaluated using four different immunohistochemical assays and FISH. RESULTS: Patients received a median of 25 weekly infusions (range, one to 85 infusions). Median delivered paclitaxel dose-intensity was 82 mg/m 2 /wk (range, 52 to 90 mg/m 2 /wk). The intent-to-treat response rate for all 95 patients enrolled was 56.8% (95% confidence interval, 47% to 67%). A response rate of 61.4% (4.5% complete response, 56.8% partial response) was observed in 88 fully assessable patients. In patients with HER2-overexpressing tumors, overall response rates ranged from 67% to 81% compared with 41% to 46% in patients with HER2-normal expression (ranges reflect the different assay methods used to assess HER2 status). Differences in response rates between patients with HER2-overexpressing tumors and those with normal HER2 expression were statistically significant for all assay methods, with CB11 and TAB250 antibodies and FISH having the strongest significance. Therapy was generally well tolerated, although three patients had serious cardiac complications. CONCLUSION: Weekly trastuzumab and paclitaxel therapy is active in women with metastatic breast cancer. Therapy was relatively well tolerated; however, attention to cardiac function is necessary.