tbuckley/cabot-search huggingface dataset:
Increased number and frequency of group 3 innate lymphoid cells in nonlesional psoriatic skin
Authors: B. Dyring-Andersen, C. Geisler, C. Agerbeck, J.P.H. Lauritsen, S.D. Gúdjonsdottir, L. Skov, C.M. Bonefeld
Journal: British Journal of Dermatology (2013)

Psoriasis is a common immune-mediated inflammatory disease that affects the skin and joints. The interleukin (IL)-23/IL-17A axis and IL-22 play key roles in the pathogenesis of psoriasis. IL-23-responsive innate lymphoid cells (ILCs) with a high capacity to produce IL-17 and/or IL-22 have recently been identified and associated with inflammatory bowel diseases. The occurrence and role of ILCs in human skin are poorly understood.To describe the prevalence of the different ILC subpopulations in skin from healthy controls and patients with psoriasis or allergy to nickel.Skin biopsies were taken from healthy skin, nonlesional and lesional psoriatic skin, and nickel- and petrolatum-exposed skin from patients with contact allergy to nickel, and lymphocytes were isolated. The cells were stained and characterized by flow cytometry. Cytokine and ligand mRNA expression were measured by quantitative polymerase chain reaction.We found that members of the three groups of ILCs were present in human skin. Remarkably, the number and frequency of RORγt(+) CD56(+) ILC3s, which are known to produce IL-22, were elevated in both nonlesional and lesional skin from patients with psoriasis compared with healthy skin and skin from patients with contact allergy to nickel. Furthermore, skin ILCs expressed high levels of the natural killer receptor NKG2D. NKG2D binds to stress-induced ligands, including major histocompatibility complex class I-related chain A, which we found to be strongly upregulated in lesional skin from patients with psoriasis.These results show that ILCs are present in human skin and indicate that RORγt(+) CD56(+) ILC3 may be involved in the pathogenesis of psoriasis.
PARVOVIRUS B19 IN HUMAN DISEASE
Authors: K.E. Brown, MD, N.S. Young, MD
Journal: Annual Review of Medicine (1997)

▪ Abstract Parvovirus B19, the only known human pathogenic parvovirus, is associated with a wide range of disease manifestations. In healthy individuals, the major presentation of B19 infection is erythema infectiosum. In patients with underlying hemolytic disorders, infection is the primary cause of transient aplastic crisis. In immunosuppressed patients, persistent infection may develop that presents as pure red cell aplasia and chronic anemia. In utero infection may result in hydrops fetalis or congenital anemia. Diagnosis is based on examination of bone marrow and virologic studies. Much is known of the pathophysiology of the virus, and studies are in progress to develop a vaccine to prevent this widespread infection.
ACCF/ACR/AHA/ASE/ASNC/HRS/NASCI/RSNA/SAIP/SCAI/SCCT/SCMR 2008 Health Policy Statement on Structured Reporting in Cardiovascular Imaging
Authors: Pamela S. Douglas, Robert C. Hendel, Jennifer E. Cummings, John M. Dent, John McB. Hodgson, Udo Hoffmann, Robert J. Horn, W. Gregory Hundley, Charles E. Kahn, Gerard R. Martin, Frederick A. Masoudi, Eric D. Peterson, Geoffrey L. Rosenthal, Harry Solomon, Arthur E. Stillman, Shawn D. Teague, James D. Thomas, Peter L. Tilkemeier, Wm. Guy Weigold
Journal: Journal of the American College of Cardiology (2008)
Methylcyclopentadienyl manganese tricarbonyl: health risk uncertainties and research directions.
Authors: J M Davis
Journal: Environmental Health Perspectives (1998)

With the way cleared for increased use of the fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT) in the United States, the issue of possible public health impacts associated with this additive has gained greater attention. In assessing potential health risks of particulate Mn emitted from the combustion of MMT in gasoline, the U.S. Environmental Protection Agency not only considered the qualitative types of toxic effects associated with inhaled Mn, but conducted extensive exposure-response analyses using various statistical approaches and also estimated population exposure distributions of particulate Mn based on data from an exposure study conducted in California when MMT was used in leaded gasoline. Because of limitations in available data and the need to make several assumptions and extrapolations, the resulting risk characterization had inherent uncertainties that made it impossible to estimate health risks in a definitive or quantitative manner. To support an improved health risk characterization, further investigation is needed in the areas of health effects, emission characterization, and exposure analysis.
Posterior Reversible Encephalopathy Syndrome: More Than Meets the Eye
Authors: Javier Munoz, Vinodh A. Kumar, Jackson Hamilton, Lezlee Jean Pasche, Lauren A. Langford, Melissa W. Taggart, Carlos Kamiya-Matsuoka, Sudhakar Tummala, Stacy Moulder, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2013)
Depression and enhancement of baroreceptor pressor response in cats after intracerebroventricular injection of noradrenergic blocking agents: dependence on supracollicular areas of the brain.
Authors: A S Tadepalli, E Mills, S M Schanberg
Journal: Circulation Research (1976)

The alpha-adrenergic blocking drugs, phentolamine and Hydergine, both act centrally at different sites to depress and enhance the pressor and sympathetic nerve response to decreased baroreceptor afferent input in anesthetized cats. Depression of the rise in blood pressure and sympathetic nerve discharge during bilateral carotid occlusion (BCO) followed injection of the agents into the 4th cerebral ventricle when the brain was intact but not when connections were interrupted at the midcollicular level by transection or lesion. Enhancement of responses occurred when drug distribution was confined to the brain rostral to the midcollicular level via injection into the 3rd cerebral ventricle with the cerebral aqueduct cannulated. Both agents decreased resting blood pressure and Hydergine decreased heart rate in intact and decerebrate preparations but not in 3rd ventricle-cerebral aqueduct experiments. We found that pretreatment with the noradrenergic precursor. L-dopa consistently prevented depression by phentolamine but was less effective against Hydergine. The results indicate that mechanisms which enhance and suppress the baroreceptor pressor response are normally operative in anesthetized cats and, furthermore, that neural pathways mediating the effects are ones connecting the caudal brainstem with supracollicular levels of the brain. It is further suggested that the pathways may be noradrenergic.
Impaired Vascular Regulation in Patients with Obstructive Sleep Apnea
Authors: Kevin J. Reichmuth, John M. Dopp, Steven R. Barczi, James B. Skatrud, Piotr Wojdyla, Don Hayes, Barbara J. Morgan
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Impaired endothelium-dependent vasodilation has been documented in patients with sleep apnea. This impairment may result in blood flow dysregulation during apnea-induced fluctuations in arterial blood gases.To test the hypothesis that hypoxic and hypercapnic vasodilation in the forearm and cerebral circulation are impaired in patients with sleep apnea.We exposed 20 patients with moderate to severe sleep apnea and 20 control subjects, to isocapnic hypoxia and hyperoxic hypercapnia. A subset of 14 patients was restudied after treatment with continuous positive airway pressure.Cerebral flow velocity (transcranial Doppler), forearm blood flow (venous occlusion plethysmography), arterial pressure (automated sphygmomanometry), oxygen saturation (pulse oximetry), ventilation (pneumotachograph), and end-tidal oxygen and carbon dioxide tensions (expired gas analysis) were measured during three levels of hypoxia and two levels of hypercapnia. Cerebral vasodilator responses to hypoxia (-0.65 +/- 0.44 vs. -1.02 +/- 0.72 [mean +/- SD] units/% saturation; P = 0.03) and hypercapnia (2.01 +/- 0.88 vs. 2.57 +/- 0.89 units/mm Hg; P = 0.03) were smaller in patients versus control subjects. Hypoxic vasodilation in the forearm was also attenuated (-0.05 +/- 0.09 vs. -0.10 +/- 0.09 unit/% saturation; P = 0.04). Hypercapnia did not elicit forearm vasodilation in either group. Twelve weeks of continuous positive airway pressure treatment enhanced hypoxic vasodilation in the cerebral circulation (-0.83 +/- 0.32 vs. -0.46 +/- 0.29 units/% saturation; P = 0.01) and forearm (-0.19 +/- 0.15 vs. -0.02 +/- 0.08 units/% saturation; P = 0.003), and hypercapnic vasodilation in the brain showed a trend toward improvement (2.24 +/- 0.78 vs. 1.76 +/- 0.64 units/mm Hg; P = 0.06).Vasodilator responses to chemical stimuli in the cerebral circulation and the forearm are impaired in many patients with obstructive sleep apnea. Some of these impairments can be improved with continuous positive airway pressure.
Non–lineage/stage-restricted effects of a gain-of-function mutation in tyrosine phosphatase <i>Ptpn11</i> (Shp2) on malignant transformation of hematopoietic cells
Authors: Dan Xu, Xia Liu, Wen-Mei Yu, Howard J. Meyerson, Caiying Guo, Stanton L. Gerson, Cheng-Kui Qu
Journal: The Journal of Experimental Medicine (2011)

Activating mutations in protein tyrosine phosphatase 11 (Ptpn11) have been identified in childhood acute leukemias, in addition to juvenile myelomonocytic leukemia (JMML), which is a myeloproliferative disorder (MPD). It is not clear whether activating mutations of this phosphatase play a causal role in the pathogenesis of acute leukemias. If so, the cell origin of leukemia-initiating stem cells (LSCs) remains to be determined. Ptpn11(E76K) mutation is the most common and most active Ptpn11 mutation found in JMML and acute leukemias. However, the pathogenic effects of this mutation have not been well characterized. We have created Ptpn11(E76K) conditional knock-in mice. Global Ptpn11(E76K/+) mutation results in early embryonic lethality. Induced knock-in of this mutation in pan hematopoietic cells leads to MPD as a result of aberrant activation of hematopoietic stem cells (HSCs) and myeloid progenitors. These animals subsequently progress to acute leukemias. Intriguingly, in addition to acute myeloid leukemia (AML), T cell acute lymphoblastic leukemia/lymphoma (T-ALL) and B-ALL are evolved. Moreover, tissue-specific knock-in of Ptpn11(E76K/+) mutation in lineage-committed myeloid, T lymphoid, and B lymphoid progenitors also results in AML, T-ALL, and B-ALL, respectively. Further analyses have revealed that Shp2 (encoded by Ptpn11) is distributed to centrosomes and that Ptpn11(E76K/+) mutation promotes LSC development, partly by causing centrosome amplification and genomic instability. Thus, Ptpn11(E76K) mutation has non-lineage-specific effects on malignant transformation of hematopoietic cells and initiates acute leukemias at various stages of hematopoiesis.
Manual Thrombus-Aspiration Improves Myocardial Reperfusion
Authors: Francesco Burzotta, Carlo Trani, Enrico Romagnoli, Mario Attilio Mazzari, Antonio Giuseppe Rebuzzi, Maria De Vita, Barbara Garramone, Floriana Giannico, Giampaolo Niccoli, Giuseppe G.L. Biondi-Zoccai, Giovanni Schiavoni, Rocco Mongiardo, Filippo Crea
Journal: Journal of the American College of Cardiology (2005)
G Protein β3 Subunit 825T Allele and Enhanced Coronary Vasoconstriction on α <sub>2</sub> -Adrenoceptor Activation
Authors: Dietrich Baumgart, Christoph Naber, Michael Haude, Olaf Oldenburg, Raimund Erbel, Gerd Heusch, Winfried Siffert
Journal: Circulation Research (1999)

Recently, alpha(2)-adrenoceptor activation was shown to play an important role in the vasoconstriction of normal coronary arteries, whereas in the presence of atherosclerosis, the activation of both alpha(1)- and alpha(2)-adrenoceptors reduces coronary blood flow in humans. alpha(2)-Adrenoceptors activate pertussis toxin (PTX)-sensitive G proteins, whereas alpha(1)-adrenoceptors couple to PTX-insensitive G proteins. Thus, the 825T allele of the beta3 subunit of heterotrimeric G proteins, associated with enhanced PTX-sensitive G protein signaling, was expected to determine the alpha(2)-adrenoceptor-, but not the alpha(1)-adrenoceptor-, mediated reduction in coronary blood flow (CBF). Genotyping was performed on 48 individuals. Twelve of the 48 received the alpha(1)-adrenoceptor agonist methoxamine (MTX; 5 mg IC), and 12 received the alpha(2)-adrenoceptor agonist BHT 933 (BHT; 5 mg IC). Twenty-four additional individuals received both MTX and BHT during the same investigational procedure. CBF was calculated on the basis of coronary angiography and intracoronary Doppler flow velocity measurement. Drug-related ischemia was assessed on the basis of ST-segment changes and angina pectoris. In response to BHT, but not to MTX, CBF was reduced to a significantly greater extent in 825T allele carriers (58+/-4%, n=16) than in individuals homozygous for the C825 allele (28+/-4%, n=19, P=0.001). This finding was independent of cholesterol levels, mean arterial blood pressure, and the presence or absence of coronary artery disease. Ischemic events in response to BHT occurred more frequently in 825T allele carriers than in homozygous 825C allele carriers (P=0.01). alpha(2)-Adrenoceptor coronary vasoconstriction is genetically determined and significantly enhanced in GNB3 825T allele carriers.
A Review of Spatial Methods in Epidemiology, 2000–2010
Authors: Amy H. Auchincloss, Samson Y. Gebreab, Christina Mair, Ana V. Diez Roux
Journal: Annual Review of Public Health (2012)

Understanding the impact of place on health is a key element of epidemiologic investigation, and numerous tools are being employed for analysis of spatial health-related data. This review documents the huge growth in spatial epidemiology, summarizes the tools that have been employed, and provides in-depth discussion of several methods. Relevant research articles for 2000-2010 from seven epidemiology journals were included if the study utilized a spatial analysis method in primary analysis (n = 207). Results summarized frequency of spatial methods and substantive focus; graphs explored trends over time. The most common spatial methods were distance calculations, spatial aggregation, clustering, spatial smoothing and interpolation, and spatial regression. Proximity measures were predominant and were applied primarily to air quality and climate science and resource access studies. The review concludes by noting emerging areas that are likely to be important to future spatial analysis in public health.
Journals are inconsistent in their choice of articles to be fast-tracked
Authors: D. Spurgeon
Journal: BMJ (2002)

A study of accelerated publication versus the usual forms of publication in two leading medical journals shows that current practices for selecting articles to be “fast-tracked” are inconsistent.

Authors of the study, which appears in CMAJ , the Canadian Medical Association's journal (2002;166:1137-43), are from four Canadian universities and the University of Lausanne, Switzerland.

The researchers identified six articles from each of two journals—the New England Journal of Medicine and the Lancet —that were prereleased on the journals' websites, and they then matched them with 12 control articles, according to the journal, disease or procedure, theme area, and …
Thrombus Aspiration during Primary Percutaneous Coronary Intervention
Authors: Tone Svilaas, Pieter J. Vlaar, Iwan C. van der Horst, Gilles F.H. Diercks, Bart J.G.L. de Smet, Ad F.M. van den Heuvel, Rutger L. Anthonio, Gillian A. Jessurun, Eng-Shiong Tan, Albert J.H. Suurmeijer, Felix Zijlstra
Journal: New England Journal of Medicine (2008)

Primary percutaneous coronary intervention (PCI) is effective in opening the infarct-related artery in patients with myocardial infarction with ST-segment elevation. However, the embolization of atherothrombotic debris induces microvascular obstruction and diminishes myocardial reperfusion.We performed a randomized trial assessing whether manual aspiration was superior to conventional treatment during primary PCI. A total of 1071 patients were randomly assigned to the thrombus-aspiration group or the conventional-PCI group before undergoing coronary angiography. Aspiration was considered to be successful if there was histopathological evidence of atherothrombotic material. We assessed angiographic and electrocardiographic signs of myocardial reperfusion, as well as clinical outcome. The primary end point was a myocardial blush grade of 0 or 1 (defined as absent or minimal myocardial reperfusion, respectively).A myocardial blush grade of 0 or 1 occurred in 17.1% of the patients in the thrombus-aspiration group and in 26.3% of those in the conventional-PCI group (P<0.001). Complete resolution of ST-segment elevation occurred in 56.6% and 44.2% of patients, respectively (P<0.001). The benefit did not show heterogeneity among the baseline levels of the prespecified covariates. At 30 days, the rate of death in patients with a myocardial blush grade of 0 or 1, 2, and 3 was 5.2%, 2.9%, and 1.0%, respectively (P=0.003), and the rate of adverse events was 14.1%, 8.8%, and 4.2%, respectively (P<0.001). Histopathological examination confirmed successful aspiration in 72.9% of patients.Thrombus aspiration is applicable in a large majority of patients with myocardial infarction with ST-segment elevation, and it results in better reperfusion and clinical outcomes than conventional PCI, irrespective of clinical and angiographic characteristics at baseline. (Current Controlled Trials number, ISRCTN16716833.)
Restoration of Tissue Factor Pathway Inhibitor-2 in a Human Glioblastoma Cell Line Triggers Caspase-Mediated Pathway and Apoptosis
Authors: Joseph George, Christopher S. Gondi, Dzung H. Dinh, Meena Gujrati, Jasti S. Rao
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The induction of apoptotic pathways in cancer cells offers a novel and potentially useful approach to improve patient responses to conventional chemotherapy. Tissue factor pathway inhibitor-2 (TFPI-2) is a protease inhibitor that is abundant in the extracellular matrix and highly expressed in noninvasive cells but absent or undetectable in highly invasive human glioblastoma cells. Experimental Design: Using a recombinant adeno-associated viral vector carrying human TFPI-2 cDNA, we stably expressed TFPI-2 in U-251 cells, a highly invasive human glioblastoma cell line. Our previous studies showed that restoration of TFPI-2 in glioblastomas effectively prevents cell proliferation, angiogenesis, and tumor invasion. In this study, we determined whether TFPI-2 restoration could induce apoptosis through the caspase-mediated signaling pathway. Results: The results from nuclear chromatin staining, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay, and fluorescence-activated cell sorting analysis showed increased apoptosis in U-251 cells after restoration of TFPI-2. Caspase-9 and caspase-3 activity assays showed increased activity, indicating enhanced apoptosis. Immunofluorescence for cleaved caspase-9 and caspase-3 depicted increased expression and colocalization of both molecules. Western blot analysis showed increased transcriptional activities of Fas ligand, tumor necrosis factor-α, Bax, Fas-associated death domain, and tumor necrosis factor receptor 1–associated death domain as well as elevated levels of cleaved caspases and poly(ADP-ribose) polymerase. Semiquantitative reverse transcription-PCR depicted increased expression of tumor necrosis factor-α and Fas ligand and the related death domains tumor necrosis factor receptor 1–associated death domain and Fas-associated death domain. Conclusions: Taken together, these results show that restoration of TFPI-2 activates both intrinsic and extrinsic caspase-mediated, proapoptotic signaling pathways and induces apoptosis in U-251 cells. Furthermore, our study suggests that recombinant adeno-associated viral vector–mediated gene expression offers a novel tool for cancer gene therapy.
Dr. M. L. Thomson
Authors: H. E. Robson
Journal: British Journal of Sports Medicine (1981)

Background/aim: Geriatric oncology practice should be based on dedicated studies and real-world experience. Therefore, we evaluated survival outcomes after palliative thoracic radiotherapy in octogenarian patients with lung cancer and analyzed prognostic factors. Patients and Methods: We carried out a retrospective analysis of 51 patients with a median age of 83 years. Three different fractionation regimens were compared: two fractions of 8.5 Gy, 10 fractions of 3 Gy, and higher doses than 30 Gy (maximum biologically equivalent dose in 2-Gy fractions (EQD2) was always lower than 50 Gy). No concomitant chemotherapy was prescribed. Patients with incomplete radiotherapy (16%) were included, in line with the intention-to-treat principle, i.e. based on prescribed rather than accumulated dose. Results: Median survival was 3.4 months. We observed a relatively high proportion of patients who received radiotherapy in the last 30 days of life (24%). Nevertheless, approximately 10% of patients were alive 3-5 years after treatment. Prognosis was similar for those with stage III and IV disease. Multivariate analysis identified four significant prognostic factors for shorter survival: reduced performance status, serum C-reactive protein (CRP) ≥30 mg/l, leukocytosis, and prescribed radiation dose ≤30 Gy (EQD2=33 Gy). The three different radiotherapy regimens resulted in median survival of 2.4, 2.6 and 11.8 months, respectively. Conclusion: Survival outcomes were highly variable. Given that survival after 10 fractions of 3 Gy was indistinguishable from that after two fractions of 8.5 Gy, we suggest that the latter regimen should be considered for patients with poor prognosis. Patients with favorable prognostic factors should be treated with higher radiation doses, e.g. 15 fractions of 3 Gy.
Atypical PKC-ζ regulates SDF-1–mediated migration and development of human CD34+ progenitor cells
Authors: Isabelle Petit, Polina Goichberg, Asaf Spiegel, Amnon Peled, Chaya Brodie, Rony Seger, Arnon Nagler, Ronen Alon, Tsvee Lapidot
Journal: Journal of Clinical Investigation (2005)

The chemokine stromal cell–derived factor–1 (SDF-1) and its receptor, CXCR4, play a major role in migration, retention, and development of hematopoietic progenitors in the bone marrow. We report the direct involvement of atypical PKC-ζ in SDF-1 signaling in immature human CD34+-enriched cells and in leukemic pre-B acute lymphocytic leukemia (ALL) G2 cells. Chemotaxis, cell polarization, and adhesion of CD34+ cells to bone marrow stromal cells were found to be PKC-ζ dependent. Overexpression of PKC-ζ in G2 and U937 cells led to increased directional motility to SDF-1. Interestingly, impaired SDF-1–induced migration of the pre-B ALL cell line B1 correlated with reduced PKC-ζ expression. SDF-1 triggered PKC-ζ phosphorylation, translocation to the plasma membrane, and kinase activity. Furthermore we identified PI3K as an activator of PKC-ζ, and Pyk-2 and ERK1/2 as downstream targets of PKC-ζ. SDF-1–induced proliferation and MMP-9 secretion also required PKC-ζ activation. Finally, we showed that in vivo engraftment, but not homing, of human CD34+-enriched cells to the bone marrow of NOD/SCID mice was PKC-ζ dependent and that injection of mice with inhibitory PKC-ζ pseudosubstrate peptides resulted in mobilization of murine progenitors. Our results demonstrate a central role for PKC-ζ in SDF-1–dependent regulation of hematopoietic stem and progenitor cell motility and development.