tbuckley/cabot-search huggingface dataset:
Politicians must heed health effects of climate change
Authors: V. Lim, J. W Stubbs, N. Nahar, N. Amarasena, Z. U. Chaudry, S. C. K. Weng, B. Mayosi, Z. van der Spuy, R. Liang, K. N. Lai, G. Metz, G W. N Fitzgerald, B. Williams, N. Douglas, J. Donohoe, S. Darnchaivijir, P. Coker, I. Gilmore
Journal: BMJ (2009)

The report on climate change and health commissioned by University College London and the Lancet concludes: “Climate change is the biggest global health threat of the 21st century.”1 In this report, the authors emphasise not only the immediacy and gravity of this threat but also the directness: while the poorest in the world will be …
<i>When the Tumor Is Not the Target</i>: A Title Whose Time Is Up?
Authors: Raymond P. Abratt
Journal: Journal of Clinical Oncology (2003)

The Art of Oncology: When the Tumor Is Not the Target is a section within the Journal of Clinical Oncology.It has attracted a series of interesting and enjoyable articles.However, the title of the section refers to the divisions between biologic and nonbiologic care, rather than their integration, and likens biologic therapy to target eradication.Should the title be reconsidered?The title Simultaneous Care: Treatment and Palliative Care Throughout Disease 1 is representative of the theme and ethos of the articles within the section.It describes the improvement of patient well-being-be it biologic, psychological, social, or spiritual-at all stages of the course of disease.The article from which this title is quoted discusses integrated therapy, the communication between patients and doctors of the uncertainties associated with treatment outcome, and the role of clinical research.Many patients and fellow health professionals see oncologists as having a key responsibility in delivering and integrating care.The oncologist is in an authoritative position because of his or her knowledge and experience.Oncologists also understand the value of collaboration by the team of caregivers, as well as the influence of the doctor-patient relationship on all the aforementioned aspects of patient well-being.The title of the section should thus emphasize integration of therapies, rather than their divisions.The metaphor of target eradication for biologic therapy is military in nature and is not appropriate for therapy and healing.It arouses associations of victory or failure, collateral damage, and a "fight to the end."It is not an accurate reflection of conventional anticancer therapies, which have always included the need to make weighted decisions on the likely benefits and harms of therapy.In particular, it does not reflect developments in anticancer therapy, which is increasingly directed toward the understanding and regulation of biologic behavior.Are there alternative metaphors?The metaphor of art itself might be considered and the section titled The Art of Oncology only.Art is created through intelligent and skilful responses to the complexities of life and the world around us.It is vital and transforming.It is in a continuous process of development and study.It is individual but also resonates in the broader world.At its best, The Art Of Oncology will reflect the principles that emerge after working through the complexities of integrated patient care.Would such a metaphor add the much needed weight to nonbiologic aspects of patient care?It should, and one knows that the published articles will do so.Are there any other offers?
The Evolution and Functional Impact of Human Deletion Variants Shared with Archaic Hominin Genomes
Authors: Yen-Lung Lin, Pavlos Pavlidis, Emre Karakoc, Jerry Ajay, Omer Gokcumen
Journal: Molecular Biology and Evolution (2015)

Allele sharing between modern and archaic hominin genomes has been variously interpreted to have originated from ancestral genetic structure or through non-African introgression from archaic hominins. However, evolution of polymorphic human deletions that are shared with archaic hominin genomes has yet to be studied. We identified 427 polymorphic human deletions that are shared with archaic hominin genomes, approximately 87% of which originated before the Human-Neandertal divergence (ancient) and only approximately 9% of which have been introgressed from Neandertals (introgressed). Recurrence, incomplete lineage sorting between human and chimp lineages, and hominid-specific insertions constitute the remaining approximately 4% of allele sharing between humans and archaic hominins. We observed that ancient deletions correspond to more than 13% of all common (>5% allele frequency) deletion variation among modern humans. Our analyses indicate that the genomic landscapes of both ancient and introgressed deletion variants were primarily shaped by purifying selection, eliminating large and exonic variants. We found 17 exonic deletions that are shared with archaic hominin genomes, including those leading to three fusion transcripts. The affected genes are involved in metabolism of external and internal compounds, growth and sperm formation, as well as susceptibility to psoriasis and Crohn's disease. Our analyses suggest that these "exonic" deletion variants have evolved through different adaptive forces, including balancing and population-specific positive selection. Our findings reveal that genomic structural variants that are shared between humans and archaic hominin genomes are common among modern humans and can influence biomedically and evolutionarily important phenotypes.
Rhinology findings and their clinical usefulness for closer asthma fenotyping
Authors: Olga Ruzickova-Kirchnerova, Vladan Hrabe, Ivana Malkusova, Milan Terl, Petr Panzner, Jana Kuntscherova
Journal: European Respiratory Journal (2011)

Background:  Our previous study conducted on patients with severe persistent asthma documented a strong correlation between eosinophilic inflammation of upper and lower airways.The aim of presented study was to determine whether there are existing differences between the intensity of eosinophilia and/or polyp presentation in upper airways in patients with eosinophilic astma with no clinically significant allergy versus patients with eosinophilic and allergic asthma.   Methods:  32 patients with severe persistent asthma were included for evaluation. According to markers of eosinophilia (FeNO, ECP, eo in NM, BALTe, IS and FBC) and allergy (SPT, spec. IgE) we devided asthmatics into three groups: I. eosinophilic and allergic, II. eosinophilic but non-allergic and III. non-eosinophilic. We also focused on presence of perrenial allergy and NSAID intolerance. CT scan of paranasal sinuses, rhinology examination and operation history were included for evaluation of nasal polyps (NP) presentation.   Results:  Significant correlations were found in eosinophil counts in NM and NP presentation (p=0,0012). Intensity of NP correlated mostly with eosinophilic but non-allergic astma (0,0117). Intensity of eosinophilia in NM and presentation of NP correlated in the group I mostly with mould allergy, in the group II with NSAID intolerance (p   Conclusion:  We found presence of nasal polyps as an negativ prognostic factor in patients with severe asthma - in allergic asthmatics indicates the risk for mould allergy (and possible ABPA or SAFS), in non-allergic astmatics for NSAID intolerance. Previous study data were considered (ERS10L1_6353, ERJ, 2010, 36 Suppl. 54). Supp. by VZ MSM 0021620812 grant.
Outcome After Relapse Among Children With Standard-Risk Acute Lymphoblastic Leukemia: Children's Oncology Group Study CCG-1952
Authors: Suman Malempati, Paul S. Gaynon, Harland Sather, Mei K. La, Linda C. Stork
Journal: Journal of Clinical Oncology (2007)

Purpose The event-free survival (EFS) of children with standard-risk acute lymphoblastic leukemia (SR-ALL) is now more than 80%. However, prognosis after relapse continues to be poor. We examined postrelapse outcomes of children initially treated on the Children's Cancer Group CCG-1952 study. Patients and Methods We evaluated outcomes after bone marrow (BM) relapse and isolated extramedullary (EM) relapse for 347 patients with SR-ALL (WBC &lt; 50,000/μL; age, 1 to 9 years). The prognostic significance of several factors for EFS after relapse (EFS2) was assessed by Cox regression analysis. Stem-cell transplant (SCT) was compared with chemotherapy as salvage treatment. Results The mean ± SE times to isolated central nervous system relapse, BM relapse, and isolated testicular relapse were 23 ± 1 months (range, 1 to 88 months), 36 ± 1 months (range, 2 to 79 months), and 40 ± 2 months (range, 16 to 64 months), respectively. The estimated percent ± SE 3-year EFS2 and overall survival rates after BM relapse were 37% ± 4% and 46% ± 4%, respectively, and rates after isolated EM relapse were 57% ± 5% and 71% ± 5%, respectively. By multivariate analysis, we found the duration of first remission to be the most significant predictor of EFS2 for either BM relapse or isolated EM relapse. Outcome was equivalent with SCT or chemotherapy after early or late relapse of SR-ALL at any site. Conclusion Duration of first remission remains the most significant predictor of outcome after either BM or isolated EM relapse of SR-ALL. Prognosis after early BM relapse remains poor and is not improved with SCT in this cohort.
Recent Advances in the Chemistry and Immunochemistry of Human Chorionic Gonadotropin: Impact on Clinical Measurements*
Authors: JOHN F. O'CONNOR, STEVEN BIRKEN, JOYCE W. LUSTBADER, ALEXANDER KRICHEVSKY, YI CHEN, ROBERT E. CANFIELD
Journal: Endocrine Reviews (1994)

Journal Article Recent Advances in the Chemistry and Immunochemistry of Human Chorionic Gonadotropin: Impact on Clinical Measurements Get access John F. O'Connor, John F. O'Connor 1Columbia University College of Physicians and Surgeons, Irving Center for Clinical Research New York, New York 10032 *Address requests for reprints to: John F. O'Connor, Ph.D., Columbia University College of Physicians and Surgeons, Irving Center for Clinical Research, PH-10E 105-B, 630 West 168th Street, New York, New York 10032. Search for other works by this author on: Oxford Academic Google Scholar Steven Birken, Steven Birken 1Columbia University College of Physicians and Surgeons, Irving Center for Clinical Research New York, New York 10032 Search for other works by this author on: Oxford Academic Google Scholar Joyce W. Lustbader, Joyce W. Lustbader 1Columbia University College of Physicians and Surgeons, Irving Center for Clinical Research New York, New York 10032 Search for other works by this author on: Oxford Academic Google Scholar Alexander Krichevsky, Alexander Krichevsky 1Columbia University College of Physicians and Surgeons, Irving Center for Clinical Research New York, New York 10032 Search for other works by this author on: Oxford Academic Google Scholar Yi Chen, Yi Chen 1Columbia University College of Physicians and Surgeons, Irving Center for Clinical Research New York, New York 10032 Search for other works by this author on: Oxford Academic Google Scholar Robert E. Canfield Robert E. Canfield 1Columbia University College of Physicians and Surgeons, Irving Center for Clinical Research New York, New York 10032 Search for other works by this author on: Oxford Academic Google Scholar Endocrine Reviews, Volume 15, Issue 5, 1 October 1994, Pages 650–683, https://doi.org/10.1210/edrv-15-5-650 Published: 01 October 1994
Calcineurin and Beyond
Authors: Jeffery D. Molkentin
Journal: Circulation Research (2000)

In response to increased ventricular wall tension or neurohumoral stimuli, the myocardium undergoes an adaptive hypertrophy response that temporarily augments pump function. Although initially beneficial, sustained cardiac hypertrophy can lead to decompensation and cardiomyopathy. Recent studies have focused on characterizing the molecular mechanisms that underlie cardiac hypertrophy. An increasing number of signal transduction pathways have been identified as important regulators of the hypertrophic response, including the low-molecular weight GTPases (Ras, RhoA, and Rac), mitogen-activated protein kinases, protein kinase C, and calcineurin. This review will discuss an emerging body of evidence that implicates the calcium-calmodulin-activated protein phosphatase calcineurin as a physiological regulator of the cardiac hypertrophic response. Although the sufficiency of calcineurin to promote cardiomyocyte hypertrophy in vivo and in vitro is established, its overall necessity as a hypertrophic mediator is currently an area of ongoing debate. The use of the calcineurin-inhibitory agents cyclosporine A and FK506 have suggested a necessary role for calcineurin in many, but not all, animal models of hypertrophy or cardiomyopathy. The evidence implicating a role for calcineurin signaling in the heart will be weighed against a growing body of literature suggesting necessary roles for a diverse array of intracellular signaling pathways, highlighting the multifactorial nature of the hypertrophic program.
Mechanism of the inotropic action of inosine on canine myocardium
Authors: W. CZARNECKI, M. I M NOBLE
Journal: Cardiovascular Research (1983)

Journal Article Mechanism of the inotropic action of inosine on canine myocardium Get access WLODZIMIERZ CZARNECKI, WLODZIMIERZ CZARNECKI * From The Midhurst Medical Research Institute, Midhurst, WestSussex, GU290BL *Cardiovascular Laboratory, Medical Research Center, Polish Academy of Sciences, 00-784 Warsaw, Poland, Dworkowa 3. Search for other works by this author on: Oxford Academic PubMed Google Scholar MARK I M NOBLE MARK I M NOBLE From The Midhurst Medical Research Institute, Midhurst, WestSussex, GU290BL Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 17, Issue 12, December 1983, Pages 735–739, https://doi.org/10.1093/cvr/17.12.735 Published: 01 December 1983
Towards Stratifying Ischemic Components by Cardiac MRI and Multifunctional Stainings in a Rabbit Model of Myocardial Infarction
Authors: Yuanbo Feng, Feng Chen, Zhanlong Ma, Frederik Dekeyzer, Jie Yu, Yi Xie, Marlein Miranda Cona, Raymond Oyen, Yicheng Ni
Journal: Theranostics (2014)

Objectives: We sought to identify critical components of myocardial infarction (MI) including area at risk (AAR), MI-core and salvageable zone (SZ) by using cardiac magnetic resonance imaging (cMRI) and multifunctional stainings in rabbits.Materials and Methods: Fifteen rabbits received 90-min coronary artery (CA) ligation and reopening to induce reperfused MI.First-pass perfusion weighted imaging (PWI 90' ) was performed immediately before CA reperfusion.Necrosis avid dye Evans blue (EB) was intravenously injected for later MI-core detection.One-day later, cMRI with T2-weighted imaging (T2WI), PWI 24h and delayed enhancement (DE) T1WI was performed at a 3.0T clinical scanner.The heart was excised and CA was re-ligated with aorta infused by red-iodized-oil (RIO).The heart was sliced into 3-mm sections for digital radiography (DR), histology and planimetry with myocardial salvage index (MSI) and perfusion density rate (PDR) calculated.Results: There was no significant difference between MI-cores defined by DE-T1WI and EB-staining (31.13±8.55%vs 29.80±7.97%;p=0.74).The AAR was defined similarly by PWI 90' (39.93±9.51%),RIO (38.82±14.41%)and DR (38.17±15.98%),underestimated by PWI 24h (36.44±5.31%),but overestimated (p<0.01) by T2WI (56.93±8.87%).Corresponding MSI turned out to be 24.17±9.5% (PWI 90' ), 21.97±9.41%(DR) and 22.68±9.65%(RIO), which were significantly (p<0.01)higher and lower than that with PWI 24h (15.15±7.34%)and T2WI (45.52±7.5%)respectively.The PDR differed significantly (p<0.001) between normal myocardium (350.6±33.1%)and the AAR (31.2±15%), suggesting 11-times greater blood perfusion in normal myocardium over the AAR.Conclusion: The introduced rabbit platform and new staining techniques together with the use of a 3.0T clinical scanner for cMRI enabled visualization of MI components and may contribute to translational cardiac imaging research for improved theranostic management of ischemic heart disease.
Greater Dose-Ranging Effects on A1C Levels Than on Glucosuria With LX4211, a Dual Inhibitor of SGLT1 and SGLT2, in Patients With Type 2 Diabetes on Metformin Monotherapy
Authors: Julio Rosenstock, William T. Cefalu, Pablo Lapuerta, Brian Zambrowicz, Ike Ogbaa, Phillip Banks, Arthur Sands
Journal: Diabetes Care (2014)

OBJECTIVE To assess the dose-ranging efficacy and safety of LX4211, a dual inhibitor of sodium–glucose cotransporter (SGLT) 1 and SGLT2, in type 2 diabetes. RESEARCH DESIGN AND METHODS Type 2 diabetic patients inadequately controlled on metformin were randomly assigned to 75 mg once daily, 200 mg once daily, 200 mg twice daily, or 400 mg once daily of LX4211 or placebo. Primary end point was A1C change from baseline to week 12. Secondary end points included changes in blood pressure (BP) and body weight. RESULTS Baseline characteristics in 299 patients randomly assigned to LX4211 or placebo in this 12-week dose-ranging study were similar: mean age 55.9 years, A1C 8.1% (65 mmol/mol), BMI 33.1 kg/m2, and BP 124/79 mmHg. LX4211 significantly reduced A1C to week 12 in a dose-dependent manner by 0.42% (4.6 mmol/mol), 0.52% (5.7 mmol/mol), 0.80% (8.7 mmol/mol), and 0.92% (10.0 mmol/mol), respectively (P &amp;lt; 0.001 each), compared with 0.09% (1.0 mmol/mol) for placebo. Greater A1C reductions were produced by 400 mg once a day than 200 mg once a day LX4211 without higher urinary glucose excretion, suggesting a contribution of SGLT1 inhibition. Significant reductions were seen in body weight (−1.85 kg; P &amp;lt; 0.001) and systolic BP (−5.7 mmHg; P &amp;lt; 0.001), but diastolic BP was unchanged (−1.6; P = 0.164). Adverse events with LX4211 were mild to moderate and similar to placebo, including urinary tract infections and gastrointestinal-related events; genital infections were limited to LX4211 groups (0–5.0%). No hypoglycemia occurred. CONCLUSIONS Dual inhibition of SGLT1/SGLT2 with LX4211 produced significant dose-ranging improvements in glucose control without dose-increasing glucosuria and was associated with reductions in weight and systolic BP in metformin-treated patients with type 2 diabetes.
CELLULAR SITES OF FORMATION OF GAMMA GLOBULIN
Authors: L. G. Ortega, R. C. Mellors
Journal: The Journal of Experimental Medicine (1957)

The cellular sites of formation of gammaglobulin in lymphatic tissues of man and in a representative human lymphoid infiltrate have been studied by fluorescent antibody technique. The findings indicate that gamma-globulin is formed in the germinal centers of lymphatic nodules and in the cytoplasm of mature and immature plasma cells of two types-those with and those without Russell bodies. The germinal center cells that synthesize gamma-globulin have been designated "intrinsic" cells to distinguish them from the medium and large lymphocytes, and the primitive reticular cells that occur elsewhere and do not produce gamma-globulin. Unlike the plasma cells, which function as individual units, the intrinsic cells apparently form gamma-globulin only when they are arranged in discrete aggregations. The function, the blood supply, and the systematic cellular arrangement of germinal centers justifies the postulate that they are miniature organs of internal secretion of gamma-globulin. The release of gamma-globulin from its sites of formation appears to be accomplished by holocrine and apocrine secretion. Presumably, these secretory mechanisms are adaptations required for the production of antibody since they have not been described in parenchymal cells that form the other serum proteins. The cells found to form gamma-globulin appear to be identical with those previously shown to form specific antibody in response to a variety of antigens in the experimental animal. This evidence indicates that normal gamma-globulin, if it exists, originates in the same cells that produce antibody. It is suggested, also, that each of the 3 morphologically distinct categories of cells that synthesize gamma-globulin represents a response to a particular form of antigenic stimulation. Nuclear participation in the process of gamma-globulin synthesis was not detected by the technique employed.
Weight Loss in Combination With Physical Activity Improves Endothelial Dysfunction in Human Obesity
Authors: Angela Sciacqua, Mafalda Candigliota, Roberto Ceravolo, Angela Scozzafava, Flora Sinopoli, Andrea Corsonello, Giorgio Sesti, Francesco Perticone
Journal: Diabetes Care (2003)

OBJECTIVE—To test whether weight loss may improve endothelial dysfunction in human obesity, we recruited 28 healthy obese subjects, aged 30–46 years, with BMI 30–43 kg/m2. RESEARCH DESIGN AND METHODS—Endothelium-dependent and -independent vasodilation were investigated by intra-arterial infusion of increasing doses of acetylcholine (ACh; 7.5, 15, and 30 μg · ml−1 · min−1) and sodium nitroprusside (0.8, 1.6, and 3.2 μg · ml−1 · min−1). Insulin resistance was estimated by homeostasis model assessment (HOMA). Weight loss was obtained by caloric restriction and physical activity. RESULTS—We observed a significant reduction in BMI (from 33.1 ± 4.2 to 27.5 ± 4.5 kg/m2, −16.9%, P &amp;lt; 0.0001) and in waist circumference (from 108.2 ± 12.1 to 96.8 ± 12.9 cm, −10.5%, P &amp;lt; 0.0001). Weight loss was also associated with a significant increase in ACh-stimulated forearm blood flow (FBF), from 7.4 ± 2.8 to 12.9 ± 3.4 ml · 100 ml−1 of tissue · min−1 kg/m2 (P &amp;lt; 0.0001). Multivariate regression analysis demonstrated that the only independent predictor of FBF was HOMA, accounting for 44.5% of the variation, whereas the addition of BMI explained another 2.3% of the variation. CONCLUSIONS—Our data demonstrate that energy-restricted diet associated with physical activity induce a significant and clinically relevant improvement in ACh-stimulated vasodilation in obese healthy subjects.
Antikeratin antibodies: diagnostic and prognostic markers for early rheumatoid arthritis.
Authors: L Paimela, M Gripenberg, P Kurki, M Leirisalo-Repo
Journal: Annals of the Rheumatic Diseases (1992)

Antibodies to the stratum corneum of rat oesophagus (antikeratin antibodies) were assayed by indirect immunofluorescence in a prospective study of patients with early rheumatoid arthritis (RA). At the beginning of the study, antikeratin antibodies of IgG class were detected in serum samples from 27/71 (38%) patients compared with 1/20 (5%) control patients with reactive arthritis, and 1/38 (3%) healthy blood donors. At the end of the two year follow up, 27/67 (40%) patients with RA were positive for antikeratin antibodies. The patients with RA who were initially positive for antikeratin antibodies had a more active disease course than the patients negative for antikeratin antibodies as measured by clinical, laboratory, and radiological variables. The prevalence of positivity for antikeratin antibodies fluctuated during the follow up, the variation paralleling the disease activity. The occurrence of HLA-DR4 was similar in patients with RA who were positive and negative for antikeratin antibodies. Antikeratin antibodies were also found in seronegative patients with RA, confirming that antikeratin antibodies do not have rheumatoid factor activity. These results show that antikeratin antibodies are detectable at the time of the initial diagnosis of RA and that the positivity for antikeratin antibodies may have prognostic significance in early RA.