tbuckley/cabot-search huggingface dataset:
Activation of the transcription factor NF-kappa B in human tracheobronchial epithelial cells by inflammatory stimuli
Authors: B Jany, R Betz, R Schreck
Journal: European Respiratory Journal (1995)

Recent studies have shown that surface epithelial cells play a major role in the defence and inflammatory reactions of the airways. How extracellular stimuli lead to increased gene expression in these epithelial cells is not well known. In this study, we asked whether the multiunit transcription factor, nuclear factor (NF)-kappa B, which regulates the expression of genes involved in defense and immune processes, is activated in airway epithelial cells following stimulation with inflammatory mediators and hydrogen peroxide. In addition, we studied whether this would be followed by upregulation of the NF-kappa B target gene product granulocyte-macrophage colony-stimulating factor (GM-CSF). Activation of NF-kappa B in the SV40 transformed human tracheobronchial epithelial cell line 1HAEo- was measured by electrophoretic mobility shift assays. GM-CSF concentrations in cell culture supernatants were determined by enzyme-linked immunosorbent assays. NF-kappa B was rapidly activated by exposure of cells to interleukin-1 beta (IL-1 beta), phorbol myristate acetate (PMA), and tumour necrosis factor-alpha (TNF). Exposure to H2O2 platelet activating factor (PAF) and lipopolysaccharide (LPS) did not lead to increased NF-kappa B activation. Co-stimulation of IL-1 beta with H2O2 led to augmentation and prolongation of the effect on NF-kappa B activation compared to stimulation with IL-1 beta alone. GM-CSF concentrations increased following stimulation with IL-1 beta and H2O2, and the effect of IL-1 beta/H2O2 co-stimulation on GM-CSF concentrations was additive. These results suggest that NF-kappa B may represent an important transcription factor, controlling the expression of cytokine genes in airway epithelial cells.
Reducing TMPRSS6 ameliorates hemochromatosis and β-thalassemia in mice
Authors: Shuling Guo, Carla Casu, Sara Gardenghi, Sheri Booten, Mariam Aghajan, Raechel Peralta, Andy Watt, Sue Freier, Brett P. Monia, Stefano Rivella
Journal: Journal of Clinical Investigation (2013)

β-Thalassemia and HFE-related hemochromatosis are 2 of the most frequently inherited disorders worldwide. Both disorders are characterized by low levels of hepcidin (HAMP), the hormone that regulates iron absorption. As a consequence, patients affected by these disorders exhibit iron overload, which is the main cause of morbidity and mortality. HAMP expression is controlled by activation of the SMAD1,5,8/SMAD4 complex. TMPRSS6 is a serine protease that reduces SMAD activation and blocks HAMP expression. We identified second generation antisense oligonucleotides (ASOs) targeting mouse Tmprss6. ASO treatment in mice affected by hemochromatosis (Hfe(-/-)) significantly decreased serum iron, transferrin saturation and liver iron accumulation. Furthermore, ASO treatment of mice affected by β-thalassemia (HBB(th3/+) mice, referred to hereafter as th3/+ mice) decreased the formation of insoluble membrane-bound globins, ROS, and apoptosis, and improved anemia. These animals also exhibited lower erythropoietin levels, a significant amelioration of ineffective erythropoiesis (IE) and splenomegaly, and an increase in total hemoglobin levels. These data suggest that ASOs targeting Tmprss6 could be beneficial in individuals with hemochromatosis, β-thalassemia, and related disorders.
AIDS-Related Burkitt's Lymphoma Versus Diffuse Large-Cell Lymphoma in the Pre–Highly Active Antiretroviral Therapy (HAART) and HAART Eras: Significant Differences in Survival With Standard Chemotherapy
Authors: Soon Thye Lim, Roksana Karim, Bharat N. Nathwani, Anil Tulpule, Byron Espina, Alexandra M. Levine
Journal: Journal of Clinical Oncology (2005)

To compare outcomes of patients with HIV-Burkitt's lymphoma (HIV-BL) and HIV-diffuse large-cell lymphoma (HIV-DLCL) after treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or M-BACOD (methotrexate, bleomycin, cyclophosphamide, etoposide) in pre-highly active antiretroviral therapy (HAART) versus HAART eras.Three hundred sixty-three patients with AIDS-related lymphoma diagnosed from 1982 to 2003 were reviewed retrospectively, including 262 in the pre-HAART (HIV-BL, 117; HIV-DLCL, 145) and 101 in the HAART era (HIV-BL, 18; HIV-DLCL, 83). Pre-HAART included those who did not receive HAART, and HAART era included those diagnosed after January 1997 who received HAART.There were no significant differences between groups in terms of age, sex, history of injection drug use, prior AIDS, lactate dehydrogenase level, and disease stage at diagnosis. Compared with HIV-BL, HIV-DLCL was associated with significantly lower CD4 counts in the pre-HAART but not the HAART era. Although the overall median survival was similar for both groups in the pre-HAART era (HIV-BL, 6.4 months v HIV-DLCL, 8.3 months; P = .43), survival was significantly worse in patients with HIV-BL in the HAART era (HIV-BL, 5.7 months v HIV-DLCL, 43.2 months; P = .0003). Failure to attain complete remission and CD4 count less than 100 cells/mm(3) independently predicted for poor survival in the pre-HAART era. In comparison, histology of HIV-BL and no attainment of complete remission were independent poor prognostic factors in the HAART era.Survival of patients with HIV-DLCL has improved in the HAART era, along with CD4 count, whereas survival of similarly treated patients with HIV-BL remained poor. The current practice of using the same regimen for both groups of patients should be re-evaluated.
Hypermethylation of CpG Islands in Primary and Metastatic Human Prostate Cancer
Authors: Srinivasan Yegnasubramanian, Jeanne Kowalski, Mark L. Gonzalgo, Marianna Zahurak, Steven Piantadosi, Patrick C. Walsh, G. Steven Bova, Angelo M. De Marzo, William B. Isaacs, William G. Nelson
Journal: Cancer Research (2004)

Aberrant DNA methylation patterns may be the earliest somatic genome changes in prostate cancer. Using real-time methylation-specific PCR, we assessed the extent of hypermethylation at 16 CpG islands in DNA from seven prostate cancer cell lines (LNCaP, PC-3, DU-145, LAPC-4, CWR22Rv1, VCaP, and C42B), normal prostate epithelial cells, normal prostate stromal cells, 73 primary prostate cancers, 91 metastatic prostate cancers, and 25 noncancerous prostate tissues. We found that CpG islands at GSTP1, APC, RASSF1a, PTGS2, and MDR1 were hypermethylated in >85% of prostate cancers and cancer cell lines but not in normal prostate cells and tissues; CpG islands at EDNRB, ESR1, CDKN2a, and hMLH1 exhibited low to moderate rates of hypermethylation in prostate cancer tissues and cancer cell lines but were entirely unmethylated in normal tissues; and CpG islands at DAPK1, TIMP3, MGMT, CDKN2b, p14/ARF, and CDH1 were not abnormally hypermethylated in prostate cancers. Receiver operator characteristic curve analyses suggested that CpG island hypermethylation changes at GSTP1, APC, RASSF1a, PTGS2, and MDR1 in various combinations can distinguish primary prostate cancer from benign prostate tissues with sensitivities of 97.3-100% and specificities of 92-100%. Hypermethylation of the CpG island at EDNRB was correlated with the grade and stage of the primary prostate cancers. PTGS2 CpG island hypermethylation portended an increased risk of recurrence. Furthermore, CpG island hypermethylation patterns in prostate cancer metastases were very similar to the primary prostate cancers and tended to show greater differences between cases than between anatomical sites of metastasis.
Renal Expression of Aquaporins in Liver Cirrhosis Induced by Chronic Common Bile Duct Ligation in Rats
Authors: PATRICIA FERNÁNDEZ-LLAMA, RACHEL TURNER, GERALD DIBONA, MARK A. KNEPPER
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Semiquantitative immunoblotting was used to investigate the expression levels of the four major renal aquaporins, the Na-K-2Cl cotransporter of the thick ascending limb, the type 3 Na-H exchanger, and the Na-K-ATPase in kidneys from rats with cirrhosis secondary to common bile duct ligation (CBDL). These rats had significant water retention and hyponatremia. In contrast to models of cirrhosis induced by carbon tetrachloride, aquaporin-2 expression in CBDL-induced cirrhosis was decreased. Thus, these results show that in the setting of extracellular fluid volume expansion, excessive water retention with hyponatremia can occur in the absence of increases in aquaporin-2 abundance. In addition, the expression levels of the two basolateral collecting duct aquaporins (aquaporin-3 and -4) were decreased in CBDL rats relative to sham-operated control rats. Similarly, the Na-K-2Cl cotransporter of the thick ascending limb and the type 3 Na-H exchanger showed decreases in expression. In contrast, the expression levels of aquaporin-1 and the α1 subunit of the Na-K-ATPase were not decreased. Thus, dysregulation of multiple water channels and ion transporters may play a role in water balance abnormalities associated with CBDL-induced cirrhosis in rats.
What does electrophoretic variation tell us about protein variation?
Authors: A. Barbadilla, L. M. King, R. C. Lewontin
Journal: Molecular Biology and Evolution (1996)

MCZ Laboratories, Harvard University Before the introduction of DNA sequencing meth- ods into population genetics by Kreitman (1983), the major source of information about genetic variation among organisms in natural populations came from electrophoretic studies of proteins. The amount of in- formation acquired during 25 years of major electro- phoretic activity is staggering and, for purely technical reasons, is likely to remain orders of magnitude greater in number of genes, number of individuals, and number of species examined than can be acquired from nucle- otide sequence data. It would be extremely desirable if this mass of data on electrophoretic phenotypes could be translated into data on patterns of amino acid varia- tion, using the information now available for a handful of cases where amino acid variation in natural popula- tions has been definitively ascertained from DNA se- quence variation. It is the purpose of this paper to show that while the total amount of amino acid variability can be inferred from electrophoretic data, the different pat- terns of electrophoretic class frequency distributions do not allow any other inferences, because those patterns can be generated by the simplest null model of the gen- eration of electrophoretic variation from amino acid variation, without the need to make any assumptions about selection or population structure. The charge-state model (or the stepwise mutation model) was originally proposed by Ohta and Kimura (1973) to deal with electrophoretic data. This model as- sumes that only amino acid changes resulting in signif- icant charge changes are clearly detectable. Hence gel electrophoresis ideally detects changes in net (integer) charge in a protein but not in fractions of charge. Al- though the model is somewhat simplistic, Brown, Mar- shall, and Weir (198 1) concluded after a review of the existing evidence that there was general support for the model, which can be considered at one end of the spec- trum of models describing electrophoretic variation. *
IMPROVING INSULIN THERAPY WITH NEOSTIGMINE
Authors: AMEDEO ESPOSITO, IRVING D. ROSENBERG
Journal: American Journal of Psychiatry (1961)

In insulin coma therapy, in those patients who regularly require intravenous injections of glucose to bring them out of coma, the intramuscular injection of 1 or 1½ mg. of neostigmine from 10 to 45 minutes before gavage with 1 quart of 40% sucrose resulted in a 100% elimination of intravenous injections required. This therefore is felt to be an important contribution to insulin coma therapy. In addition it may help materially in the re-establishment of insulin coma therapy at those mental hospitals where it was previously discontinued because of the greater number of personnel required to administer intravenous injections.
Plasma creatine kinase after the marathon--a diagnostic dilemma.
Authors: A. Young
Journal: British Journal of Sports Medicine (1984)

The mechanism of the protein leak from exercised muscle remains obscure, but may be related to depletion of intracellular high-energy phosphate and/or to mechanical disruption. The high levels of creatine kinase (CK) and other muscle proteins found in plasma for several days after marathon running, especially downhill running, are due to protein efflux from skeletal muscle. There is no evidence that marathon running damages the healthy, well-perfused myocardium, despite the fact that the plasma levels of total creatine kinase (CK), the isoenzyme CK-MB, CK-MB/total CK (%), myoglobin, aspartate transaminase, lactate dehydrogenase and tropomyosin may be the same as after myocardial infarction. These indices must be interpreted with the greatest caution when found in anyone who habitually undertakes strenuous exercise, especially if they have done so within the previous week.
Prognostic Value of Myocardial Viability in Medically Treated Patients With Global Left Ventricular Dysfunction Early After an Acute Uncomplicated Myocardial Infarction
Authors: Eugenio Picano, Rosa Sicari, Patrizia Landi, Lauro Cortigiani, Riccardo Bigi, Claudio Coletta, Alfonso Galati, Joanna Heyman, Roberto Mattioli, Mario Previtali, Wilson Mathias, Claudio Dodi, Giovanni Minardi, Jorge Lowenstein, Giovanni Seveso, Alessandro Pingitore, Alessandro Salustri, Mauro Raciti
Journal: Circulation (1998)

Background —Residual viable myocardium identified by dobutamine stress after myocardial infarction may act as an unstable substrate for further events such as subsequent angina and reinfarction. However, in patients with severe global left ventricular dysfunction, viability might be protective rather than detrimental. The aim of this study was to assess the impact on survival of echocardiographically detected viability in medically treated patients with global left ventricular dysfunction evaluated after acute uncomplicated myocardial infarction. Methods and Results —The data bank of the large-scale, prospective, multicenter, observational Echo Dobutamine International Cooperative (EDIC) study was interrogated to select 314 medically treated patients (271 men; age, 58±9 years) who underwent low-dose (≤10 μg · kg −1 · min −1 ) dobutamine for the detection of myocardial viability and high-dose dobutamine for the detection of myocardial ischemia (≤40 μg · kg −1 · min −1 with atropine ≤1 mg) performed 12±6 days after an acute uncomplicated myocardial infarction and showing a moderate to severe resting left ventricular dysfunction (wall motion score index [WMSI] &gt;1.6). Patients were followed up for 9±7 months. Low-dose dobutamine stress echocardiography identified myocardial viability in 130 patients (52%). Dobutamine-atropine stress echocardiography was positive for ischemia in 148 patients (47%) and negative in 166 patients (53%). During the follow-up, there were 12 cardiac deaths (3.8% of the total population). With the use of Cox proportional hazards model, delta low-dose WMSI (the variation between rest WMSI and low-dose WMSI) was shown to exert a protective effect by reducing cardiac death by 0.8 for each decrease in WMSI at low-dose dobutamine (coefficient, −0.2; hazard ratio, 0.8; P &lt;0.03); WMSI at peak stress was the best predictor of cardiac death in this set of patients (hazard ratio, 14.9; P &lt;0.0018). Conclusions —In medically treated patients with severe global left ventricular dysfunction early after acute uncomplicated myocardial infarction, the presence of myocardial viability identified as inotropic reserve after low-dose dobutamine is associated with a higher probability of survival. The higher the number of segments showing improvement of function, the better the impact is of myocardial viability on survival. The presence of inducible ischemia in this set of patients is the best predictor of cardiac death.
Renal Blood Flow and Renin Activity in Renal Venous Blood in Essential Hypertension
Authors: M. DONALD BLAUFOX, ARTHUR FROMOWITZ, HYO BOK LEE, CHIEN-HSING MENG, MILTON ELKIN
Journal: Circulation Research (1970)

The intrarenal distribution of blood flow measured by the 133 xenon washout method and the renin activity of renal venous blood were determined in 16 patients with early essential hypertension. None of the patients had evidence of systemic disease except for the elevation in blood pressure (&gt; 150/100 mm Hg). Fifteen of the subjects received a controlled sodium diet during 7 to 9 days before study, at the time of renal angiography. An inverse relationship was noted between the cortical component of the renal blood flow and renin activity of renal venous blood (r = 0.64, P &lt; 0.02). Renin secretion rates were also calculated in 12 patients confirming the inverse relationship between cortical distribution of blood flow and renin secretion (r = 0.763, P &lt; 0.01). The cortical renal blood flow in 10 patients on a low salt intake was 79.6% ± 2.6 (SE) of the total renal blood flow. The cortical blood flow in five patients on a high salt diet was 87.6% ± 1.9 (SE); the statistical difference between the two groups is significant ( P &lt; 0.05). A direct relationship was noted between cortical blood flow and the logarithm of the 24-hour urinary sodium excretion from the day preceding the study (r = 0.54, P &lt; 0.05). Renin secretion rate and renin in renal venous blood were directly correlated (r = 0.813, P &lt; 0.01). Changes in corticomedullary distribution of flow were inversely related to the changes in cortical distribution. The degree of reduction of cortical renal blood flow correlated with the degree of increase in renin secretion and in renin activity in renal venous blood. Our data are compatible with reduced cortical renal blood flow mediating renin release or vice versa. Either mechanism would result in more efficient conservation of salt and water by the kidney.
Magnetic resonance spectroscopy reveals that activated monocytes contribute to neuronal injury in SIV neuroAIDS
Authors: Kenneth Williams, Susan Westmoreland, Jane Greco, Eva Ratai, Margaret Lentz, Woong-Ki Kim, Robert A. Fuller, John P. Kim, Patrick Autissier, Prahbat K. Sehgal, Raymond F. Schinazi, Norbert Bischofberger, Michael Piatak, Jeffrey D. Lifson, Eliezer Masliah, R. Gilberto González
Journal: Journal of Clinical Investigation (2005)

Difficulties in understanding the mechanisms of HIV neuropathogenesis include the inability to study dynamic processes of infection, cumulative effects of the virus, and contributing host immune responses. We used H magnetic resonance spectroscopy and studied monocyte activation and progression of CNS neuronal injury in a CD8 lymphocyte depletion model of neuroAIDS in SIV-infected rhesus macaque monkeys. We found early, consistent neuronal injury coincident with viremia and SIV infection/activation of monocyte subsets and sought to define the role of plasma virus and monocytes in contributing to CNS disease. Antiretroviral therapy with essentially non-CNS-penetrating agents resulted in slightly decreased levels of plasma virus, a significant reduction in the number of activated and infected monocytes, and rapid, near-complete reversal of neuronal injury. Robust macrophage accumulation and productive virus replication were found in brains of infected and CD8 lymphocyte-depleted animals, but no detectable virus and few scattered infiltrating macrophages were observed in CD8 lymphocyte-depleted animals compared with animals not receiving antiretroviruses that were sacrificed at the same time after infection. These results underscore the role of activated monocytes and monocyte infection outside of the brain in driving CNS disease.
Targeting ALDHbright Human Carcinoma–Initiating Cells with ALDH1A1-Specific CD8+ T Cells
Authors: Carmen Visus, Yangyang Wang, Antonio Lozano-Leon, Robert L. Ferris, Susan Silver, Miroslaw J. Szczepanski, Randall E. Brand, Cristina R. Ferrone, Theresa L. Whiteside, Soldano Ferrone, Albert B. DeLeo, Xinhui Wang
Journal: Clinical Cancer Research (2011)

Cancer-initiating cells (CIC) are considered to represent the subpopulation of tumor cells that is resistant to conventional cancer treatments, highly tumorigenic in immunodeficient mice, and responsible for tumor recurrence and metastasis. Based on an elevated aldehyde dehydrogenase (ALDH) activity attributable to ALDH1/3 isoforms, ALDH(bright) cells have been identified and isolated from tumors and shown to have characteristics of CIC. The ALDH1A1 isoform was previously identified as a tumor antigen recognized by CD8(+) T cells. This study examines the ability of ALDH1A1-specific CD8(+) T cells to eliminate ALDH(bright) cells and control tumor growth and metastases.ALDH(bright) cells were isolated by flow cytometry using ALDEFLUOR from HLA-A2(+) human head and neck, breast, and pancreas carcinoma cell lines and tested for their tumorigenicity in immunodeficient mice. ALDH1A1-specific CD8(+) T cells were generated in vitro and tested for their ability to eliminate CICs in vitro and in vivo by adoptive transfer to immunodeficient mice bearing human tumor xenografts.ALDH(bright) cells isolated by flow cytometry from HLA-A2(+) breast, head and neck, and pancreas carcinoma cell lines at low numbers (500 cells) were tumorigenic in immunodeficient mice. ALDH(bright) cells present in these cell lines, xenografts, or surgically removed lesions were recognized by ALDH1A1-specific CD8(+) T cells in vitro. Adoptive therapy with ALDH1A1-specific CD8(+) T cells eliminated ALDH(bright) cells, inhibited tumor growth and metastases, or prolonged survival of xenograft-bearing immunodeficient mice.The results of this translational study strongly support the potential of ALDH1A1-based immunotherapy to selectively target CICs in human cancer.
Domestic mites from an acarologic perspective
Authors: F. Th. M. Spieksma
Journal: Allergy (1997)

Knowledge of the taxonomic, physiologic, biologic, and ecologic characteristics of allergenic domestic mites contributes to the understanding of the causation of many cases of allergic asthma, and to the measures to be taken to control excessive mite occurrence in homes. Domestic mites, i.e., the combined group of storage mites living in the home environment and of pyroglyphid house‐dust mites, belong to the subclass of the acari. This comprises also many other mites of medical and economic importance, together with thousands of free‐living mites. Because of some species‐specific properties of their allergenic products, it is important that the producing mite is always correctly identified. In spite of their small size (approx. 0.5 mm), domestic mites have well‐developed and elaborate systems of respiration, digestion, and water balance, enabling them to live and survive in the various habitats of the home environment. Knowledge of the effects of the various and changing ecologic conditions in the home environment is helpful in developing strategies to prevent the establishment and growth of large populations of allergenic domestic mites.
Enhanced dermal wound neovascularization by targeted delivery of endothelial progenitor cells using an RGD-g-PLLA scaffold
Authors: Koung Li Kim, Dong Keun Han, Kwideok Park, Sun-Hwa Song, Ji Yeon Kim, Jeong-Min Kim, Ho Yun Ki, Se Won Yie, Cheong-Rae Roh, Eun-Seok Jeon, Duk-Kyung Kim, Wonhee Suh
Journal: Biomaterials (2009)