tbuckley/cabot-search huggingface dataset:
Acquired resistance to Listeria monocytogenes is mediated by Lyt-2+ T cells independently of the influx of monocytes into granulomatous lesions.
Authors: M E Mielke, G Niedobitek, H Stein, H Hahn
Journal: The Journal of Experimental Medicine (1989)

Facultative intracellular bacteria induce specific T cell responses of both the CD4+ and the CD8+ subsets. The immunohistological study of the tissue responses to Listeria monocytogenes in T cell subset-depleted, Listeria-primed mice revealed that CD4+ cells not only represent the predominant lymphocyte population in granulomatous lesions but mediate the attraction and accumulation of blood-borne monocytes into inflammatory foci. On the other hand, CD8+ T cells are able to mediate protection in the absence of CD4+ T cells, invading monocytes, and granulomatous inflammation, and therefore appear to activate resident macrophages for listericidal activity.
Rho GDP Dissociation Inhibitor 2 Suppresses Metastasis via Unconventional Regulation of RhoGTPases
Authors: Konstadinos Moissoglu, Kevin S. McRoberts, Jeremy A. Meier, Dan Theodorescu, Martin A. Schwartz
Journal: Cancer Research (2009)

Rho GDP dissociation inhibitor 2 (RhoGDI2) has been identified as a metastasis suppressor in bladder and possibly other cancers. This protein is a member of a family of proteins that maintain Rho GTPases in the cytoplasm and inhibit their activation and function. To understand the mechanism of metastasis suppression, we compared effects of RhoGDI1 and RhoGDI2. Despite showing much stronger inhibition of metastasis, RhoGDI2 is a weak inhibitor of Rho GTPase membrane targeting and function. However, point mutants that increase or decrease the affinity of RhoGDI2 for GTPases abolished its ability to inhibit metastasis. Surprisingly, metastasis suppression correlates with increased rather than decreased Rac1 activity. These data show that RhoGDI2 metastasis inhibition works through Rho GTPases but via a mechanism distinct from inhibition of membrane association.
Availability of digital dermoscopy in daily practice dramatically reduces the number of excised melanocytic lesions: results from an observational study
Authors: I. Tromme, L. Sacré, F. Hammouch, C. Legrand, L. Marot, P. Vereecken, I. Theate, P. van Eeckhout, P. Richez, J.F. Baurain, L. Thomas, N. Speybroeck
Journal: British Journal of Dermatology (2012)

Digital dermoscopy has been shown to permit an earlier detection of melanoma. However, few studies have investigated its added value in reducing unnecessary excisions in everyday clinical practice.To compare, in daily practice, the efficiency of three dermoscopy methods: dermoscopy alone with little training, dermoscopy alone with adequate training and dermoscopy with adequate training and access to digital dermoscopy, and to confirm the safety of this latter approach.Thirty-six dermatologists working without digital dermoscopy were divided into two groups according to their training in dermoscopy. The third group constituted of two dermatologists working in a pigmented lesion clinic with access to the digital dermoscopy technique and eight additional dermatologists working in the same dermatology department. These 46 dermatologists included all presumed melanocytic lesions excised over a period of 1 year. The primary endpoint was the melanoma/nonmelanoma ratio (M/NM-R); secondary endpoints were the ratio of 'problem' naevi to common naevi (PN/CN-R), specificity and sensitivity for the diagnosis of melanoma, in situ/invasive melanoma ratio, and the mean Breslow thickness.In total, 1865 excised lesions, including 231 melanomas, were included. In the digital dermoscopy availability group (DD-G) the M/NM-R was significantly better (1/2.43), as was the PN/CN-R (1/1.48) (P < 0.001 in both cases). The specificity was significantly higher in the DD-G and significantly higher for trained examiners as compared with examiners with little training. More that one-third of all melanomas discovered by digital dermoscopy were in situ, and the mean Breslow thickness was 0.32 mm for the invasive ones.The reduction of unnecessary excisions when using digital dermoscopy compared with dermoscopy alone in our study suggests that access to digital dermoscopy offers a better management of pigmented lesions in daily practice. The high number of early lesions diagnosed by this technique confirms that its use is safe.
Sequential vs Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer: Randomized Phase III Trial RTOG 9410
Authors: W. J. Curran, R. Paulus, C. J. Langer, R. Komaki, J. S. Lee, S. Hauser, B. Movsas, T. Wasserman, S. A. Rosenthal, E. Gore, M. Machtay, W. Sause, J. D. Cox
Journal: JNCI Journal of the National Cancer Institute (2011)

The combination of chemotherapy with thoracic radiotherapy (TRT) compared with TRT alone has been shown to confer a survival advantage for good performance status patients with stage III non–small cell lung cancer. However, it is not known whether sequential or concurrent delivery of these therapies is the optimal combination strategy. A total of 610 patients were randomly assigned to two concurrent regimens and one sequential chemotherapy and TRT regimen in a three-arm phase III trial. The sequential arm included cisplatin at 100 mg/m 2 on days 1 and 29 and vinblastine at 5 mg/m 2 per week for 5 weeks with 60 Gy TRT beginning on day 50. Arm 2 used the same chemotherapy regimen as arm 1 with 60 Gy TRT once daily beginning on day 1. Arm 3 used cisplatin at 50 mg/m 2 on days 1, 8, 29, and 36 with oral etoposide at 50 mg twice daily for 10 weeks on days 1, 2, 5, and 6 with 69.6 Gy delivered as 1.2 Gy twice-daily fractions beginning on day 1. The primary endpoint was overall survival, and secondary endpoints included tumor response and time to tumor progression. Kaplan–Meier analyses were used to assess survival, and toxic effects were examined using the Wilcoxon rank sum test. All statistical tests were two-sided. Median survival times were 14.6, 17.0, and 15.6 months for arms 1–3, respectively. Five-year survival was statistically significantly higher for patients treated with the concurrent regimen with once-daily TRT compared with the sequential treatment (5-year survival: sequential, arm 1, 10% [20 patients], 95% confidence interval [CI] = 7% to 15%; concurrent, arm 2, 16% [31 patients], 95% CI = 11% to 22%, P = .046; concurrent, arm 3, 13% [22 patients], 95% CI = 9% to 18%). With a median follow-up time of 11 years, the rates of acute grade 3–5 nonhematologic toxic effects were higher with concurrent than sequential therapy, but late toxic effects were similar. Concurrent delivery of cisplatin-based chemotherapy with TRT confers a long-term survival benefit compared with the sequential delivery of these therapies.
The transpulmonary pressure gradient for the diagnosis of pulmonary vascular disease
Authors: Robert Naeije, Jean-Luc Vachiery, Patrick Yerly, Rebecca Vanderpool
Journal: European Respiratory Journal (2012)

The transpulmonary pressure gradient (TPG), defined by the difference between mean pulmonary arterial pressure (P(pa)) and left atrial pressure (P(la); commonly estimated by pulmonary capillary wedge pressure: P(pcw)) has been recommended for the detection of intrinsic pulmonary vascular disease in left-heart conditions associated with increased pulmonary venous pressure. In these patients, a TPG of >12 mmHg would result in a diagnosis of "out of proportion" pulmonary hypertension. This value is arbitrary, because the gradient is sensitive to changes in cardiac output and both recruitment and distension of the pulmonary vessels, which decrease the upstream transmission of P(la). Furthermore, pulmonary blood flow is pulsatile, with systolic P(pa) and mean P(pa) determined by stroke volume and arterial compliance. It may, therefore, be preferable to rely on a gradient between diastolic P(pa) and P(pcw). The measurement of a diastolic P(pa)/P(pcw) gradient (DPG) combined with systemic blood pressure and cardiac output allows for a step-by-step differential diagnosis between pulmonary vascular disease, high output or high left-heart filling pressure state, and sepsis. The DPG is superior to the TPG for the diagnosis of "out of proportion" pulmonary hypertension.
Pituitary Adenylate Cyclase–Activating Polypeptide Stimulates Renin Secretion via Activation of PAC1 Receptors
Authors: Matthias Hautmann, Ulla G. Friis, Michael Desch, Vladimir Todorov, Hayo Castrop, Florian Segerer, Christiane Otto, Gu[Combining Diaeresis]nther Schu[Combining Diaeresis]tz, Frank Schweda
Journal: Journal of the American Society of Nephrology (2007)

Besides of its functional role in the nervous system, the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in the regulation of cardiovascular function. Therefore, PACAP is a potent vasodilator in several vascular beds, including the renal vasculature. Because the kidney expresses both PACAP and PACAP-binding sites, it was speculated that PACAP might regulate cardiovascular function by direct vascular effects and indirectly by regulating renin release from the kidneys. PACAP (1-27) stimulated renin secretion from isolated perfused kidneys of rats 4.9-fold with a half-maximum concentration of 1.9 nmol/L. In addition, PACAP stimulated renin release and enhanced membrane capacitance of isolated juxtaglomerular cells, indicating a direct stimulation of exocytotic events. The effect of PACAP on renin release was mediated by the specific PACAP receptors (PAC1), because PACAP (1-27) applied in concentrations in the physiologic range (10 and 100 pmol/L) did not enhance renin release from isolated kidneys of PAC1 receptor knockout mice (PAC1-/-), whereas it stimulated renin release 1.38- and 2.5-fold in kidneys from wild-type mice. Moreover, plasma renin concentration was significantly lower in PAC1-/- compared with their wild-type littermates under control conditions as well as under a low- or high-salt diet and under treatment with the angiotensin-converting enzyme inhibitor ramipril, whereas no differences in plasma renin concentration between the genotypes were detectable after water deprivation. These data show that PACAP acting on PAC1 receptors potently stimulates renin release, serving as a tonic enhancer of the renin system in vivo.
Pyogenic arthritis due to bacteroides complicating rheumatoid arthritis.
Authors: M J Dodd, I D Griffiths, R Freeman
Journal: Annals of the Rheumatic Diseases (1982)

Two cases of anaerobic, pyogenic arthritis complicating rheumatoid disease due to bacteroides are described. The relative well-being of the patients and indolence of the affected joints are emphasised, and the effective role of metronidazole in the treatment of septic arthritis due to bacteroides is discussed.
The Viral Load of Epstein–Barr Virus (EBV) DNA in Peripheral Blood Predicts for Biological and Clinical Characteristics in Hodgkin Lymphoma
Authors: Stefan Hohaus, Rosaria Santangelo, Manuela Giachelia, Barbara Vannata, Giuseppina Massini, Annarosa Cuccaro, Maurizio Martini, Valeriana Cesarini, Tonia Cenci, Francesco D'Alo, Maria Teresa Voso, Giovanni Fadda, Giuseppe Leone, Luigi M Larocca
Journal: Clinical Cancer Research (2011)

The Epstein-Barr virus (EBV) is present in the malignant Hodgkin/Reed-Sternberg (HRS) cells of 20% to 40% cases of Hodgkin lymphoma (HL) in Western countries. We were interested in the detection and quantification of cell-free plasma EBV-DNA as an indicator of biological and clinical characteristics in EBV-associated HL.EBV was detected in peripheral blood compartments (whole blood, plasma, and mononuclear cells) at diagnosis by real-time PCR for the EBNA (EB nuclear antigen) region (n = 93) and in HRS cells by in situ hybridization for EBV-encoded small RNAs (EBER; n = 63). These data were correlated to histological and clinical characteristics, EBV serology, circulating cell-free DNA, and interleukin (IL)-6 levels.Detection of EBV-DNA in plasma had a high specificity (90%), but a relatively low sensitivity (65%) to predict for EBV association. The viral load was higher in patients with advanced stage disease, older age in the presence of B-symptoms, and international prognostic score more than 2. The presence of EBV in HRS cells and higher plasma EBV-DNA copy numbers correlated to an increased frequency of tumor-infiltrating CD68+ macrophages in lymph node biopsies. Plasma EBV-DNA load correlated to circulating cell-free DNA and IL-6 levels, and inversely correlated to lymphocyte counts and EBNA1 antibody titers.Although the presence of EBV-DNA in peripheral blood cannot be regarded as a surrogate marker for EBER, the plasma EBV-DNA load at HL diagnosis is an indicator of disease activity and biological characteristics associated with negative prognosis. Moreover, the inverse correlation to EBNA1 antibody titers and lymphocyte counts may indicate a reduction in immunosurveillance, favoring the expansion of EBV-HRS cells in HL.
Investigation of association of the DLG5 gene with psoriatic arthritis
Authors: P. Ho, J. Worthington, I. N Bruce, A. Barton
Journal: Annals of the Rheumatic Diseases (2006)

Psoriatic arthritis (PsA) is defined as “an inflammatory arthritis associated with psoriasis which is usually negative for rheumatoid factor” and is the second most common cause of inflammatory joint disease after rheumatoid arthritis.1 A strong genetic component to disease aetiology has been shown, with the sibling recurrence risk (λs) estimated to be 27.2 Patients with Crohn’s disease have an increased risk of developing both PsA and psoriasis.3,4 Crohn’s disease and PsA are also both cytokine driven and both respond to anti-tumour necrosis factor α treatment. We therefore hypothesised that common genetic factors may underlie these two conditions. Indeed, the major Crohn’s disease susceptibility gene, CARD15 , has been reported to be associated with PsA in …
PATIENT REACTIONS TO THE "OPEN DOOR"
Authors: NATHAN WISEBORD, HERMAN C. B. DENBER, FREDERICK B. CHARATAN, JOHN H. TRAVIS
Journal: American Journal of Psychiatry (1958)

Fifty-five of 86 patients were interviewed concerning their attitudes to the "open door" as a function of the therapeutic community in the research division ward. The patients generally agreed that the "open door" had played a beneficial role in their strivings towards successful reintegration and adaptation.
Dietary Sodium Restriction Reverses Vascular Endothelial Dysfunction in Middle-Aged/Older Adults With Moderately Elevated Systolic Blood Pressure
Authors: Kristen L. Jablonski, Matthew L. Racine, Candace J. Geolfos, Phillip E. Gates, Michel Chonchol, Matthew B. McQueen, Douglas R. Seals
Journal: Journal of the American College of Cardiology (2012)
Chronic Ethanol Consumption Disturbs G–Protein Expression and Inhibits Cyclic Amp-Dependent Signaling in Regenerating Rat Liver
Authors: Anna Mae Diehl, Shi Qi Yang, Piera Cote, Gary S. Wand
Journal: Hepatology (1992)

Evidence suggests that ethanol desensitizes hepatocytes to the trophic effects of hormones. Cyclic AMP-dependent signals are important regulators of intermediary metabolism, cellular proliferation and differentiation, and modulate liver growth during hepatic regeneration. The events leading to cyclic AMP accumulation after partial hepatectomy were characterized in rats consistently fed ethanol-containing diets and compared with results in rats fed isocaloric amounts of nonethanol diet to determine whether altered cyclic AMP-dependent signal transduction contributes to ethanol-associated aberrations in hepatic growth regulation. Ethanol treatment significantly inhibited hepatic accumulation of cyclic AMP after partial hepatectomy. This was most likely the result of decreased synthesis of cyclic AMP because activation of adenylyl cyclase by agents acting through receptors (e.g., glucagon or isoproterenol), GTP-binding proteins (GTP-gamma-S) and directly on adenylyl cyclase (e.g., forskolin) was significantly inhibited in ethanol-fed rats. Both homologous and heterologous desensitization contributed to this effect. beta 1-Adrenergic receptors were relatively down-regulated 6 hr after partial hepatectomy in ethanol-fed rats, whereas glucagon receptor kinetics were similar in the two groups. Liver membrane expression of GTP-binding proteins differed markedly after partial hepatectomy in ethanol-fed and pair-fed rats. Ethanol significantly inhibited post-partial hepatectomy induction of the stimulatory G protein, Gs alpha but led to overexpression of the inhibitory, G(i)2 alpha, subunit. Steady-state messenger RNA levels of these G proteins were similar in ethanol-fed and pair-fed rats, suggesting that ethanol inhibits G protein expression posttranscriptionally.(ABSTRACT TRUNCATED AT 250 WORDS)
Molecular Cloning of NHE3 from LLC-PK1 Cells and Localization in Pig Kidney
Authors: CHRISTINE A. SHUGRUE, NICHOLAS OBERMÜLLER, SEBASTIAN BACHMANN, CAROLYN W. SLAYMAN, ROBERT F. REILLY
Journal: Journal of the American Society of Nephrology (1999)

LLC-PK1 cells, an established line from pig kidney, express basolateral and apical Na+/H+ exchangers that can be distinguished by their differing sensitivities to the amiloride analog N-ethyl-N-isopropylamiloride (EIPA). It has been shown previously that the basolateral exchanger is encoded by NHE1. In the present study, a combination of reverse transcription-PCR, 5' RACE, and genomic library screening was used to clone the coding region of the porcine NHE3 gene. There was significant homology between the LLC-PK1 sequence and the previously reported rabbit and rat NHE3 genes, with nucleotide and deduced amino acid identities of 87 and 85% in rabbit, and 85 and 87% in rat, respectively. To study expression patterns, Northern analysis was carried out using an NHE3 cDNA to probe poly(A)+ RNA isolated from LLC-PK1 cells, and from pig kidney cortex. In all three cases, a major transcript of 6.1 kb was detected along with two minor transcripts of 4.7 and 3.8 kb. In situ hybridization with two different NHE3 probes gave intense labeling of the distal convoluted tubule in pig kidney but (unexpectedly) no detectable labeling of the proximal tubule. These studies suggest that there are marked species differences in NHE3 expression in the distal nephron.
Livebirth after uterus transplantation
Authors: Mats Brännström, Liza Johannesson, Hans Bokström, Niclas Kvarnström, Johan Mölne, Pernilla Dahm-Kähler, Anders Enskog, Milan Milenkovic, Jana Ekberg, Cesar Diaz-Garcia, Markus Gäbel, Ash Hanafy, Henrik Hagberg, Michael Olausson, Lars Nilsson
Journal: The Lancet (2014)
Renal Function Following Fluorescein Angiography in Diabetic Patients With Chronic Kidney Disease
Authors: Yusuke Kameda, Tetsuya Babazono, Kensuke Haruyama, Yasuhiko Iwamoto, Shigehiko Kitano
Journal: Diabetes Care (2009)

Intravenous fluorescein angiography has been widely used in evaluating diabetic retinopathy. Diabetic patients in whom fluorescein angiography is crucial are likely to have chronic kidney disease (CKD) because retinopathy and nephropathy usually progress in parallel. Although numerous reports have been published concerning the development of adverse reactions after fluorescein angiography (1–3), to the best of our knowledge, it has never been debated in the literature whether fluorescein (noniodinated contrast media) induces nephropathy as does iodinated radiocontrast. Therefore, we conducted this hospital-based retrospective cohort study to determine whether fluorescein angiography is associated with deterioration of renal function in diabetic patients with CKD.

Among consecutive diabetic patients undergoing fluorescein angiography to assess retinopathy at the Department of Ophthalmology, …
Oscillating Cortical Thick Ascending Limb Cells at the Juxtaglomerular Apparatus
Authors: Peter Komlosi, Boglarka Banizs, Attila Fintha, Stacy Steele, Zhi-Ren Zhang, P. Darwin Bell
Journal: Journal of the American Society of Nephrology (2008)

While studying the intracellular calcium dynamics in cells of the macula densa, the observation was made that tubular epithelial cells located near the macula densa and associated with the renal arterioles exhibit spontaneous Ca2+ oscillations. In this study, the cortical thick ascending limb-distal tubule, with attached glomerulus, was isolated and perfused. At a low luminal sodium chloride concentration, Ca2+ oscillations at a frequency of 63 mHz were observed in tubular cells that were within 100 microm of the macula densa plaque using four-dimensional multiphoton microscopy and wide-field fluorescence microscopy with fura-2. The Ca2+ oscillations were absent in the macula densa cells. Spontaneous oscillations in basolateral membrane potential suggested that Ca2+ oscillations occurred, at least in part, through depolarization-induced increases in Ca2+ entry. The amplitude of these Ca2+ oscillations was significantly enhanced by the activation of the Ca2+-sensing receptor. Increasing the luminal sodium chloride concentration or luminal flow resulted in a significant increase in both the amplitude of Ca2+ oscillations and the intracellular Ca2+ concentration in perimacular cortical thick ascending limb cells. In addition, luminal furosemide attenuated the [NaCl]L-dependent changes in intracellular Ca2+ concentration, but hydrochlorothiazide had no effect. These findings demonstrate that tubular epithelial cells at the perimeter of the macula densa exhibit spontaneous oscillations in intracellular Ca2+ concentration, enhanced by tubular flow and luminal sodium chloride. These oscillatory patterns may play a role in juxtaglomerular signaling.
Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36
Authors: Terry K. Means, Eleftherios Mylonakis, Emmanouil Tampakakis, Richard A. Colvin, Edward Seung, Lindsay Puckett, Melissa F. Tai, Cameron R. Stewart, Read Pukkila-Worley, Suzanne E. Hickman, Kathryn J. Moore, Stephen B. Calderwood, Nir Hacohen, Andrew D. Luster, Joseph El Khoury
Journal: The Journal of Experimental Medicine (2009)

Receptors involved in innate immunity to fungal pathogens have not been fully elucidated. We show that the Caenorhabditis elegans receptors CED-1 and C03F11.3, and their mammalian orthologues, the scavenger receptors SCARF1 and CD36, mediate host defense against two prototypic fungal pathogens, Cryptococcus neoformans and Candida albicans. CED-1 and C03F11.1 mediated antimicrobial peptide production and were necessary for nematode survival after C. neoformans infection. SCARF1 and CD36 mediated cytokine production and were required for macrophage binding to C. neoformans, and control of the infection in mice. Binding of these pathogens to SCARF1 and CD36 was β-glucan dependent. Thus, CED-1/SCARF1 and C03F11.3/CD36 are β-glucan binding receptors and define an evolutionarily conserved pathway for the innate sensing of fungal pathogens.