tbuckley/cabot-search huggingface dataset:
Human Cytotoxic T Cells Specific for Autologous Melanoma Cells: Successful Generation From Lymph Node Cells in Seven Consecutive Cases
Authors: C. L. Slingluff, T. Darrow, C. Vervaert, M. A. Quinn-Allen, H. F. Seigler
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Human Cytotoxic T Cells Specific for Autologous Melanoma Cells: Successful Generation From Lymph Node Cells in Seven Consecutive Cases Get access Craig L. Slingluff, Jr., Craig L. Slingluff, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar Timothy Darrow, Timothy Darrow Search for other works by this author on: Oxford Academic PubMed Google Scholar Carol Vervaert, Carol Vervaert Search for other works by this author on: Oxford Academic PubMed Google Scholar Mary Ann Quinn-Allen, Mary Ann Quinn-Allen Search for other works by this author on: Oxford Academic PubMed Google Scholar Hilliard F. Seigler Hilliard F. Seigler 3Department of Surgery, Duke University Medical CenterDurham, NC 27710. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 13, 7 September 1988, Pages 1016–1026, https://doi.org/10.1093/jnci/80.13.1016 Published: 07 September 1988 Article history Received: 05 February 1988 Revision received: 27 May 1988 Accepted: 09 June 1988 Published: 07 September 1988
House Dust Mite Facilitates Ovalbumin-specific Allergic Sensitization and Airway Inflammation
Authors: Ramzi Fattouh, Mahmoud A. Pouladi, David Alvarez, Jill R. Johnson, Tina D. Walker, Susanna Goncharova, Mark D. Inman, Manel Jordana
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Mouse models of allergic airway disease have greatly contributed to our understanding of disease induction and pathogenesis. Although these models typically investigate responses to a single antigen or allergen, humans are frequently exposed to a myriad of allergens, each with distinct antigenic potential.Given that airway exposure to ovalbumin (OVA), a prototypic innocuous antigen, induces inhalation tolerance, we wished to investigate how this response would be altered if OVA were encountered concurrently with a house dust mite extract (HDM), which we have recently shown is capable of eliciting a robust allergic airway inflammatory response that is mediated, at least in part, by granulocyte-macrophage colony-stimulating factor.Balb/c mice were exposed daily to HDM (intranasally) followed immediately by exposure to aerosolized OVA for 5 weeks. To allow the inflammatory response elicited by HDM to subside fully, mice were then allowed to rest, unexposed, for 8 weeks, at which time they were rechallenged with aerosolized OVA for 3 consecutive days.At this time, we observed a robust eosinophilic inflammatory response in the lung that was associated with an increase in bronchial hyperreactivity. Moreover, we documented significantly elevated serum levels of OVA-specific IgE and IgG(1) and increased production of the Th2 cytokines interleukin 4 (IL-4), IL-5, and IL-13 by splenocytes stimulated in vitro with OVA.Our data demonstrate the potential of a potent allergen such as HDM to establish a lung microenvironment that fosters the development of allergic sensitization to otherwise weak or innocuous antigens, such as OVA.
Deficiency of the Cysteine Protease Cathepsin S Impairs Microvessel Growth
Authors: G.-P. Shi, G.K. Sukhova, M. Kuzuya, Q. Ye, J. Du, Y. Zhang, J.-H. Pan, M.L. Lu, X.W. Cheng, A. Iguchi, S. Perrey, A.M.-E. Lee, H.A. Chapman, P. Libby
Journal: Circulation Research (2003)

During angiogenesis, microvascular endothelial cells (ECs) secrete proteinases that permit penetration of the vascular basement membrane as well as the interstitial extracellular matrix. This study tested the hypothesis that cathepsin S (Cat S) contributes to angiogenesis. Treatment of cultured ECs with inflammatory cytokines or angiogenic factors stimulated the expression of Cat S, whereas inhibition of Cat S activity reduced microtubule formation by impairing cell invasion. ECs from Cat S–deficient mice showed reduced collagenolytic activity and impaired invasion of collagens type I and IV. Cat S–deficient mice displayed defective microvessel development during wound repair. This abnormal angiogenesis occurred despite normal vascular endothelial growth factor and basic fibroblast growth factor levels, implying an essential role for extracellular matrix degradation by Cat S during microvessel formation. These results demonstrate a novel function of endothelium-derived Cat S in angiogenesis.
Phase III Study of Gemcitabine Plus Docetaxel Compared With Capecitabine Plus Docetaxel for Anthracycline-Pretreated Patients With Metastatic Breast Cancer
Authors: Stephen Chan, Gilles Romieu, Jens Huober, Thierry Delozier, Michele Tubiana-Hulin, Andreas Schneeweiss, Ana Lluch, Antonio Llombart, Andreas du Bois, Rolf Kreienberg, Jose Ignacio Mayordomo, Antonio Antón, Mark Harrison, Alison Jones, Eva Carrasco, A. Thareau Vaury, Bente Frimodt-Moller, Pierre Fumoleau
Journal: Journal of Clinical Oncology (2009)

Purpose Patients with metastatic breast cancer who are pretreated with anthracyclines frequently receive taxane-based combinations. This phase III study compared the efficacy and safety of gemcitabine-docetaxel (GD) with capecitabine-docetaxel (CD) in advanced breast cancer. Patients and Methods Patients were randomly assigned to GD (G 1,000 mg/m 2 days 1 and 8; D 75 mg/m 2 day 1) or CD (C 1,250 mg/m 2 twice daily days 1 through 14; D 75 mg/m 2 day 1) every 21 days. Comparison of progression-free survival (PFS) was the primary objective. Results Patient characteristics were balanced between arms (N = 305). Median PFS was 8.05 months (95% CI, 6.60 to 8.71) for GD and 7.98 (95% CI, 6.93 to 8.77) for CD (log-rank P = .121). Overall response rate (ORR) was 32% in both arms, and overall survival (OS) was not different between arms (P = .983). Time to treatment failure (TTF; defined as discontinuation, progressive disease, death as a result of any cause, or the start of a new anticancer therapy) was superior in the GD arm (P = .059). Hematologic toxicity was similar in both arms, except for grades 3 to 4 leukopenia (GD, 78%; CD, 66%; P = .025) and transfusions (GD, 17%; CD, 7%; P = .0051). Grades 3 to 4 diarrhea, mucositis, and hand-and-foot syndrome were significantly higher in the CD arm. Fewer patients in the GD arm discontinued because of drug-related adverse events (13% v 27% in CD; P = .002). Conclusion No difference was observed between GD and CD arms in PFS, ORR, and OS. TTF was longer in the GD arm. These findings, combined with a nonhematologic toxicity profile that favors GD over approved doses of CD, suggest that gemcitabine may be a better option than capecitabine in combination with docetaxel in this clinical setting.
Sudden death recorded during Holter monitoring.
Authors: G Nikolic, R L Bishop, J B Singh
Journal: Circulation (1982)

Six instances of sudden death were recorded by Holter monitoring, which showed ventricular fibrillation in five and a bradyarrhythmia in one. Complex ventricular ectopic activity preceded cardiac arrest in five patients, including the one with the bradyarrhythmic arrest. Two patients with chronic bifascicular block arrested as a result of ventricular fibrillation. Fifteen cases reports from the literature are reviewed. The composite profile includes advanced myocardial disease (present in all cases), complex ventricular ectopic activity, R-on-T initiation of the terminal rhythm except in patients with prolonged QT interval, and variations in cycle length preceeding the onset of ventricular tachycardia or fibrillation. The role of supraventricular mechanisms in sudden death is uncertain.
Malignant effects of multiple rare variants in sarcomere genes on the prognosis of patients with hypertrophic cardiomyopathy
Authors: Jizheng Wang, Yilu Wang, Yubao Zou, Kai Sun, Zhimin Wang, Hu Ding, Jinqing Yuan, Wei Wei, Qing Hou, Hu Wang, Xuan Liu, Hongju Zhang, Yun Ji, Xianliang Zhou, Ravi K. Sharma, Daowen Wang, Ferhaan Ahmad, Rutai Hui, Lei Song
Journal: European Journal of Heart Failure (2014)
The Parkinson Disease Gene LRRK2: Evolutionary and Structural Insights
Authors: Ignacio Marín
Journal: Molecular Biology and Evolution (2006)

Mutations in the human leucine-rich repeat kinase 2 (LRRK2) gene are associated with both familial and sporadic Parkinson disease (PD). LRRK2 belongs to a gene family known as Roco. Roco genes encode for large proteins with several protein domains. Particularly, all Roco proteins have a characteristic GTPase domain, named Roc, plus a domain of unknown function called COR. In addition, LRRK2 and several other Roco proteins also contain a protein kinase domain. In this study, I use a combination of phylogenetic and structural analyses of the COR, Roc, and kinase domains present in Roco proteins to describe the origin and evolutionary history of LRRK2. Phylogenetic analyses using these domains demonstrate that LRRK2 emerged from a duplication that occurred after the protostome–deuterostome split. The duplication was followed by the acquisition by LRRK2 proteins of a specific type of N-terminal repeat, described here for the first time. This repeat is absent in the proteins encoded by the paralogs of LRRK2, called LRRK1 or in protostome LRRK proteins. These results suggest that Drosophila or Caenorhabditis LRRK genes may not be good models to understand human LRRK2 function. Genes in the slime mold Dictyostelium discoideum with structures very similar to those found in animal LRRK genes, including the protein kinase domain, have been described. However, phylogenetic analyses suggest that this structural similarity is due to independent acquisitions of distantly related protein kinase domains. Finally, I confirm in an extensive sequence analysis that the Roc GTPase domain is related but still substantially different from small GTPases, such as Rab, Ras, or Rho. Modeling based on known kinase structures suggests that mutations in LRRK2 that cause familiar PD may alter the local 3-dimensional folding of the LRRK2 protein without affecting its overall structure.
Cardiac Benefits of Fish Consumption May Depend on the Type of Fish Meal Consumed
Authors: Dariush Mozaffarian, Rozenn N. Lemaitre, Lewis H. Kuller, Gregory L. Burke, Russell P. Tracy, David S. Siscovick
Journal: Circulation (2003)

Background— Few studies have examined associations of fish consumption with ischemic heart disease (IHD) risk among older adults or how different types of fish meals relate to IHD risk. Methods and Results— In a population-based prospective cohort study, usual fish consumption was ascertained at baseline among 3910 adults aged ≥65 years and free of known cardiovascular disease in 1989 and 1990. Consumption of tuna and other broiled or baked fish correlated with plasma phospholipid long-chain n-3 fatty acids, whereas consumption of fried fish or fish sandwiches (fish burgers) did not. Over 9.3 years’ mean follow-up, there were 247 IHD deaths (including 148 arrhythmic deaths) and 363 incident nonfatal myocardial infarctions (MIs). After adjustment for potential confounders, consumption of tuna or other broiled or baked fish was associated with lower risk of total IHD death ( P for trend=0.001) and arrhythmic IHD death ( P =0.001) but not nonfatal MI ( P =0.44), with 49% lower risk of total IHD death and 58% lower risk of arrhythmic IHD death among persons consuming tuna/other fish 3 or more times per week compared with less than once per month. In similar analyses, fried fish/fish sandwich consumption was not associated with lower risk of total IHD death, arrhythmic IHD death, or nonfatal MI but rather with trends toward higher risk. Conclusions— Among adults aged ≥65 years, modest consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower risk of IHD death, especially arrhythmic IHD death. Cardiac benefits of fish consumption may vary depending on the type of fish meal consumed.
Human Immunodeficiency Virus Infection and Kidney Transplantation in the Era of Highly Active Antiretroviral Therapy and Modern Immunosuppression
Authors: Kevin C. Abbott, S. John Swanson, Lawrence Y.C. Agodoa, Paul L. Kimmel
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Before the era of highly active antiretroviral therapy, kidney transplant recipients infected with HIV had increased risk of death compared with HIV-uninfected recipients. More recent single-center reports have indicated improved results, but this has not been assessed in a national population. Therefore, a retrospective cohort study of US adult deceased donor kidney transplant recipients from January 1, 1996, to May 31, 2001 was conducted; patients were followed until October 31, 2001. A total of 27,851 patients had valid recipient HIV serology. Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss, respectively, adjusted for other factors, including comorbid conditions from Centers for Medicare and Medicaid Studies Form 2728. Factors independently associated with HIV infection were also assessed by logistic regression analysis. Only 12.8% of HIV-infected recipients were black, compared with 27.6% in the entire study cohort. HIV-infected kidney transplant recipients were significantly less likely to be black in logistic regression analysis (adjusted OR, 0.29; 95% CI, 0.08 to 0.99; P = 0.049), which was the only factor independently associated with HIV infection. It was found that HIV-infected recipients had improved survival compared with HIV-uninfected recipients, although this was not statistically significant in adjusted analysis (adjusted HR, 0.36; 95% CI, 0.05 to 2.53; P = 0.31). Kidney transplantation in HIV-infected patients is plausible and ongoing, but HIV-infected candidates who underwent kidney transplantation in the United States during the course of the study were demographically unrepresentative of HIV-infected candidates generally.
Serial pulmonary function tests in progressive systemic sclerosis.
Authors: L R Bagg, D T Hughes
Journal: Thorax (1979)

Serial pulmonary function tests were performed on nine patients with progressive systemic sclerosis over a mean period of ten years. Abnormality was seen to develop both early and late in the course of the disease, and the earliest abnormality observed was impairment of the transfer factor. Deterioration of some aspect of pulmonary function was noted in each case, evidence of restriction or air trapping being seen with equal frequency. Two patients died, both of causes unrelated to their pulmonary involvement, and even pronounced early involvement of the lungs did not necessarily imply a bad prognosis.
Use of leikotriene modifiers promotes to decrease bronchial hyperreactivity in bronchial asthma patients
Authors: Liudmyla Iashyna, Yuriy Feshchenko, Maryna Polianska, Inna Zvol, Svitlana Ishchuk, Liudmyla Savelieva, Alena Potochniak
Journal: European Respiratory Journal (2012)

Background: Clinical studies proved, that leikotriene modifiers have mild and variable broncholytic effect, decrease symptoms, improve lung function and decrease asthma exacerbations.  Objectives: This study aimed to investigate the influence of leikotriene modifiers (antagonists of CysL-R1 – montelukast) on bronchial hyperreactivity in steriod-naive bronchial asthma patients.  Methods: 30 steroid-naive (didn9t receive ICS more then 3 months before study) patients, male 9, female 21, in the age (53,4 ± 2,3) years, with ACT score   Results: Bronchial hyperreactivity (BHR), which revealed in fall of FEV1 on >10% vs basic data after 5 – 30 min after the end of physial load, was revealed in 12 patients. Initially FEV1 falled on 16% on the 5 min after the end of test, with maximal decrease (19,3%) on the 15 min. In 30 min after the end of physsical load FEV1 didn9t return to the basic data – difference was 9,5%. At the end of study treatment course BHR was revealed only in 9 patients, with maximal fall 11,5% on 15 min after the test, with recovery within 30 min.Correlative analysis shoved, that risk of BHR decreased after the impermanent course of montelukast therapy, but without stasistical significance.  Conclusion: use of leikotriene modifiers (antagonists of CysL-R1 – montelukast (Lukast)) decrease BHR in steriod-naive BA patients.
Pulmonary hypertension (PH) in chronic hemodialysis (CHD) patients is associated with inflammatory markers and volume overload
Authors: Hugo Bok Yoo, Luis Cuadrado Martin, Roberto dos Reis, Wagner Telini, Lidiane Rodrigues-Telini, João Carlos Hueb, Pasqual Barretti, Thais Thomaz Queluz
Journal: European Respiratory Journal (2013)

Introduction:  PH in CHD patients has been related to higher mortality and to micro inflammatory state. There is evidence that the micro inflammatory state can be induced by water and sodium overload. Recently was demonstrated an association between hypervolemia and PH.   Aim:  To verify the association between hypervolemia, inflammation and PH in CHD patients.   Methods:  Cross-sectional study assessing patients >18 yrs in CHD treatment for at least 3 months. PH was defined as a systolic pulmonary arterial pressure ≥ 35 mmHg in the echocardiography. Based on it, 2 groups were formed: PH or non-PH. Bioimpedance, C-reactive protein (CRP), α-1 acid glycoprotein (AGP), and BNP were evaluated. Comparisons between groups were considered significant at P    Results:  84 patients, 49 men and 35 women, with mean age of 59±13 yrs, were studied. Median of HD treatment = 31 months; 16 patients had PH (19%). The groups were homogeneous in terms of age, gender, and time in HD. However, they differed on inflammatory markers, left atrium size, and total body water as follow:   Conclusion:  PH in CHD patients is associated with both inflammatory markers and parameters of volume overload, suggesting that the control of PH might improve by volume overload prevention with consequent reduction of the inflammatory status.
Acute mountain sickness: an unexpected management problem
Authors: F Bellis
Journal: British Journal of Sports Medicine (2002)

The Everest Marathon in the Nepal Himalayas has been run every 18 months since 1987, from Gorak Shep near Everest Base Camp to Namche Bazaar. This is a 26.2 mile marathon run from a starting altitude of 5184 m above sea level down to 3664 m over exceptionally difficult terrain. The route is predominantly downhill, although there are two steep uphill sections, with the ground underfoot varying from snow and ice and stony scree to boulders on glacial terminal moraine. To acclimatise properly there is a 17 day trek up to the starting point.

A team of medical staff …
Migration Inhibitory Factor Mediates Angiogenesis via Mitogen-Activated Protein Kinase and Phosphatidylinositol Kinase
Authors: M. Asif Amin, Olga V. Volpert, James M. Woods, Pawan Kumar, Lisa A. Harlow, Alisa E. Koch
Journal: Circulation Research (2003)

In this study, we investigated the effects of migration inhibitory factor (rhMIF) on angiogenesis-related signaling cascades and apoptosis in human endothelial cells (ECs). We show that in vitro rhMIF induces migration and tube formation in Matrigel of human dermal microvascular endothelial cells (HMVECs), with potency comparable to that of basic fibroblast growth factor. In vivo, rhMIF induces angiogenesis in Matrigel plugs and in the corneal bioassay. Using panels of relatively specific kinase inhibitors, antisense oligonucleotides, and dominant-negative mutants, we show that mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) are critical for MIF-dependent HMVEC migration, whereas Src and p38 kinases are nonessential. Moreover, we demonstrate that rhMIF induces time-dependent increases in phosphorylation levels of MEK1/2, Erk1/2, and Elk-1, as well as PI3K, and its effector kinase, Akt, in HMVECs. Studies with dominant-negative mutants and antisense oligonucleotides corroborate these effects in HMVECs. Furthermore, we demonstrate that rhMIF-induced angiogenesis in the rat cornea in vivo and in the ex vivo endothelial cell morphogenesis assay is also MAPK- and PI3K-dependent. Our findings support a role for MIF as an angiogenic factor and provide a rationale for the use of MIF as a therapeutic inducer of neovascularization in the development of collateral circulation in coronary artery disease.
The Parieto-Frontal Integration Theory (P-FIT) of intelligence: Converging neuroimaging evidence
Authors: Rex E. Jung, Richard J. Haier
Journal: Behavioral and Brain Sciences (2007)

Abstract “Is there a biology of intelligence which is characteristic of the normal human nervous system?” Here we review 37 modern neuroimaging studies in an attempt to address this question posed by Halstead (1947) as he and other icons of the last century endeavored to understand how brain and behavior are linked through the expression of intelligence and reason. Reviewing studies from functional (i.e., functional magnetic resonance imaging, positron emission tomography) and structural (i.e., magnetic resonance spectroscopy, diffusion tensor imaging, voxel-based morphometry) neuroimaging paradigms, we report a striking consensus suggesting that variations in a distributed network predict individual differences found on intelligence and reasoning tasks. We describe this network as the Parieto-Frontal Integration Theory (P-FIT). The P-FIT model includes, by Brodmann areas (BAs): the dorsolateral prefrontal cortex (BAs 6, 9, 10, 45, 46, 47), the inferior (BAs 39, 40) and superior (BA 7) parietal lobule, the anterior cingulate (BA 32), and regions within the temporal (BAs 21, 37) and occipital (BAs 18, 19) lobes. White matter regions (i.e., arcuate fasciculus) are also implicated. The P-FIT is examined in light of findings from human lesion studies, including missile wounds, frontal lobotomy/leukotomy, temporal lobectomy, and lesions resulting in damage to the language network (e.g., aphasia), as well as findings from imaging research identifying brain regions under significant genetic control. Overall, we conclude that modern neuroimaging techniques are beginning to articulate a biology of intelligence. We propose that the P-FIT provides a parsimonious account for many of the empirical observations, to date, which relate individual differences in intelligence test scores to variations in brain structure and function. Moreover, the model provides a framework for testing new hypotheses in future experimental designs.
Preservation of post-transplant lung function with aerosol cyclosporin
Authors: T.E. Corcoran, G.C. Smaldone, J.H. Dauber, D.A. Smith, K.R. McCurry, G.J. Burckart, A. Zeevi, B.P. Griffith, A.T. Iacono
Journal: European Respiratory Journal (2004)

Post-lung transplant use of aerosol cyclosporin (ACsA) is considered by examining the relationship between deposited aerosol dose and effect. In a sub-study of placebo controlled trials of ACsA as a rejection prophylaxis, 15 drug subjects received aerosol dose quantification tests to gage their ability to effectively deposit the nebulised drug in their transplanted lung(s). A total of seven placebo subjects received mock deposition tests. The deposited doses and mock doses were compared to changes in the forced expiratory volume in one second, at six time points during the 2‐yr trial period (ACsA was started within 6 weeks post-transplant). Linear relationships were demonstrated between deposited dose and improvement in lung function in the drug subjects at all intervals. Mock dose data from placebo subjects did not demonstrate similar correlation. Based on these results, subjects were grouped by dose and compared. Subjects depositing ≥5 mg of the drug in the periphery of their transplant(s) had improving pulmonary function on average. Low-dose and placebo subjects demonstrated declines, more A2–A4 rejection events in the latter portion of the trial, and more chronic rejection beyond the end of the trial. A dose-to-effect relationship is demonstrated for aerosol cyclosporin in terms of pulmonary function and biopsy proven rejection.