tbuckley/cabot-search huggingface dataset:
Protection from cytomegalovirus after transplantation is correlated with immediate early 1–specific CD8 T cells
Authors: Torsten Bunde, Alexander Kirchner, Bodo Hoffmeister, Dirk Habedank, Roland Hetzer, Georgy Cherepnev, Susanna Proesch, Petra Reinke, Hans-Dieter Volk, Hans Lehmkuhl, Florian Kern
Journal: The Journal of Experimental Medicine (2005)

T cells are crucial for the control of cytomegalovirus (CMV) in infected individuals. Although CMV-specific T cells can be quantified by various methods, clear correlates of protection from CMV disease have not been defined. However, responses to the pp65 protein are believed to play an important role. Here, the proportions of interferon γ–producing T cells following ex vivo activation with pools of overlapping peptides representing the pp65 and immediate early (IE)-1 proteins were determined at multiple time points and related to the development of CMV disease in 27 heart and lung transplant recipients. Frequencies of IE-1–specific CD8 T cells above 0.2 and 0.4% at day 0 and 2 wk, respectively, or 0.4% at any time during the first months discriminated patients who did not develop CMV disease from patients at risk, 50–60% of whom developed CMV disease. No similar distinction between risk groups was possible based on pp65-specific CD8 or CD4 T cell responses. Remarkably, CMV disease developed exclusively in patients with a dominant pp65-specific CD8 T cell response. In conclusion, high frequencies of IE-1 but not pp65-specific CD8 T cells correlate with protection from CMV disease. These results have important implications for monitoring T cell responses, adoptive cell therapy, and vaccine design.
Differential expression of A and B laminin chains during rat liver regeneration
Authors: América Giménez, Joaquim Hostench, Stamatis C. Stamatoglou, Carlos Enrich
Journal: Hepatology (1995)

We have studied the distribution and expression of laminin during rat liver regeneration by immunofluorescence and immunoblotting using affinity-purified laminin antibodies. Laminin was localized on sinusoidal surfaces in normal and regenerating hepatic parenchyma, but enhanced expression was detected during regeneration from 6 hours to 7 days after a partial hepatectomy. A and B laminin chains were specifically detected by Western blotting in highly purified plasma membrane fractions derived from the sinusoidal domain of hepatocytes. Analysis of laminin expression in whole homogenates from hepatectomized rats showed a differential expression of A and B laminin chains during regeneration: The A chain showed a progressive increase, whereas the B chain exhibited an early, prereplicative increase and then gradually declined to control levels at the end of restorative growth. The results suggest differential temporal requirements for A and B laminin chains during hepatic growth and tissue formation.
Hepatosplanchnic haemodynamics and renal blood flow and function in rats with liver failure
Authors: P Javlé, J Yates, H G Kynaston, K F Parsons, S A Jenkins
Journal: Gut (1998)

Background —Massive liver necrosis, characteristic of acute liver failure, may affect hepatosplanchnic haemodynamics, and contribute to the alterations in renal haemodynamics and function. Aims —To investigate the relation between hepatosplanchnic haemodynamics, including portal systemic shunting, and renal blood flow and function in rats with acute liver failure. Methods —Liver failure was induced in male Wistar rats by intraperitoneal injection of 1.1 g/kg of d (+)-galactosamine hydrochloride. The parameters assessed included: systemic, hepatosplanchnic, and renal blood flow ( 57 Co microsphere method); portal-systemic shunting and intrarenal shunting (consecutive intrasplenic, intraportal, or renal arterial injections of 99m Tc methylene diphosphonate and 99m Tc albumin microspheres); arterial blood pressure and portal pressure; renal function; and liver function (liver function tests and 14 C aminopyrine breath test). Results —Progressive liver dysfuntion was accompanied by the development of a hyperdynamic circulation, a highly significant decrease in renal blood flow and function, and an increase in intrarenal shunting 36, 42, and 48 hours after administration of d -galactosamine. The alterations in renal blood flow and function were accompanied by significant increases in portal pressure, portal venous inflow, and intrahepatic portal systemic shunting in galactosamine treated rats compared with controls. There was a significant correlation between changes in renal blood flow and changes in portal pressure, intrahepatic portal systemic shunting, and deterioration in liver function ( r =0.8, p&lt;0.0001). Conclusions —The results of this study suggest that both increased intrahepatic portal systemic shunting and hepatocyte impairment may contribute to alterations in renal haemodynamics and function.
Epigenetics of cervical cancer. An overview and therapeutic perspectives
Authors: Alfonso Dueñas-González, Marcela Lizano, Myrna Candelaria, Lucely Cetina, Claudia Arce, Eduardo Cervera
Journal: Molecular Cancer (2005)

Abstract Cervical cancer remains one of the greatest killers of women worldwide. It is difficult to foresee a dramatic increase in cure rate even with the most optimal combination of cytotoxic drugs, surgery, and radiation; therefore, testing of molecular targeted therapies against this malignancy is highly desirable. A number of epigenetic alterations occur during all stages of cervical carcinogenesis in both human papillomavirus and host cellular genomes, which include global DNA hypomethylation, hypermetylation of key tumor suppressor genes, and histone modifications. The reversible nature of epigenetic changes constitutes a target for transcriptional therapies, namely DNA methylation and histone deacetylase inhibitors. To date, studies in patients with cervical cancer have demonstrated the feasibility of reactivating the expression of hypermethylated and silenced tumor suppressor genes as well as the hyperacetylating and inhibitory effect upon histone deacetylase activity in tumor tissues after treatment with demethylating and histone deacetylase inhibitors. In addition, detection of epigenetic changes in cytological smears, serum DNA, and peripheral blood are of potential interest for development of novel biomolecular markers for early detection, prediction of response, and prognosis.
The Spleen in Friend Leukemia. I. Prolonged Survival of Leukemic Mice After Auto-implantation of Spleen Tissue 2 3
Authors: Stuart B. Levy, Carole B. Rubenstein, Charlotte Friend
Journal: JNCI Journal of the National Cancer Institute (1976)

Friend virus infection of susceptible mice led rapidly to fulminant erythroleukemia and death. Subcutaneous implantation of leukemic spleen bits into splenectomized normal animals led to their early death from Friend leukemia. In contrast, bits of leukemic spleen implanted sc into splenectomized leukemic mice prolonged the survival of these animals. Concomitant with this survival was a reversal of the virus-induced immunosuppression and an increase in the levels of circulating, neutralizing, antivirus activity. This marked difference in response to leukemic spleen implants by leukemic as compared to normal mice reflected previous contact of the former with Friend virus. Our studies indicated that the Friend virus-infected mouse mounted a resistance to the virus infection, which under certain conditions is capable of reversing the disease process.
p210BCR-ABL inhibits SDF-1 Chemotactic Response via Alteration of CXCR4 Signaling and Down-regulation of CXCR4 Expression
Authors: Jean-Francois Geay, Dorothée Buet, Yanyan Zhang, Adlen Foudi, Peggy Jarrier, Magali Berthebaud, Ali G. Turhan, William Vainchenker, Fawzia Louache
Journal: Cancer Research (2005)

Abstract It has been shown that p210BCR-ABL significantly impairs CXCR4 signaling. We report here that the migratory response to SDF-1 was profoundly altered in blast crisis, whereas chronic-phase CD34+ cells migrated normally to this chemokine. This migratory defect was associated with a low CXCR4 membrane expression. In vitro STI-571 treatment of CD34+ cells from patients in blast crisis markedly increased the CXCR4 transcript and CXCR4 membrane expression. Because p210BCR-ABL frequently increases with disease progression, we determined the effects of high and low p210BCR-ABL expression on CXCR4 protein in the granulocyte macrophage colony-stimulating factor–dependent human cell line MO7e. p210BCR-ABL expression distinctly alters CXCR4 protein through two different mechanisms depending on its expression level. At low expression, a signaling defect was detected with no modification of CXCR4 expression. However, higher p210BCR-ABL expression induced a marked down-regulation of CXCR4 that is related to its decreased transcription. The effect of p210BCR-ABL required its tyrosine kinase activity. Collectively, these data indicate that p210BCR-ABL could affect CXCR4 by more than one mechanism and suggest that down-regulation of CXCR4 may have important implications in chronic myelogenous leukemia pathogenesis.
PMO-054 Laparoscopic silastic ring loop gastric bypass (SR-LGBP): a single centre experience
Authors: M Clarke, L Pearless, M Booth
Journal: Gut (2012)

<h3>Introduction</h3> Laparoscopic loop gastric bypass (LGBP) may represent a simpler alternative procedure to Roux-en-Y gastric bypass. Placement of a silastic ring (SR) may minimise weight regain. This study reports upto 5-year outcomes following laparoscopic SR-LGBP. <h3>Methods</h3> Retrospective analysis of consecutive patients undergoing SR-LGBP between August 2005 and January 2008. A 15–20 ml lesser-curve gastric pouch was created with 32Fr orogastric bougie, handsewn gastroenterostomy 150–200 cm distal to the ligament of Treitz and a 6.5–7 cm silastic ring around the gastric pouch. <h3>Results</h3> 156 patients (78% female, 22% male) with a mean (range) age of 44 (18–63) years, pre-op weight of 129 (83–197) kg and BMI of 46 (35–64) kg/m<sup>2</sup> underwent surgery. 87% had pre-operative comorbidities and median (range) follow-up was 35 (6–72) months. Mean (SD) % excess weight loss (EWL) at 6, 12, 24, 36 and 60 months was 74.6 (19.5), 93.4 (21.1), 98.8 (27.6), 93.5 (20.1) and 89 (16.1) respectively. 37% had complete resolution of comorbidities and 67.3% required vitamin/mineral supplementation. Overall 90 (57.7%) patients; 12 (7.7%) early and 78 (50%) late, reported minor complications, the commonest being reflux (10%) or vomiting/dysphagia/food intolerance (16%). 39 (25%) patients; 4 (2.6%) early and 35 (22.4%) late, reported major complications requiring hospitalisation. Marginal ulcer and anastomotic stenosis were seen in 7.7% and 9.6% respectively. 16 (10.3%) patients required reoperation: 6 (3.8%) bile reflux, 3 (1.9%) ring removal, 2 (1.3%) perforation and 5 (3.2%) other. There were no deaths. <h3>Conclusion</h3> SR-LGBP achieves excellent EWL with low mortality. While vomiting, food intolerance, reflux, stricture and stomal ulceration were relatively common, only 10% required reoperation. <h3>Competing interests</h3> None declared.
Decrease in Depression Symptoms Is Associated With Longer Survival in Patients With Metastatic Breast Cancer: A Secondary Analysis
Authors: Janine Giese-Davis, Kate Collie, Kate M.S. Rancourt, Eric Neri, Helena C. Kraemer, David Spiegel
Journal: Journal of Clinical Oncology (2010)

Numerous studies have examined the comorbidity of depression with cancer, and some have indicated that depression may be associated with cancer progression or survival. However, few studies have assessed whether changes in depression symptoms are associated with survival.In a secondary analysis of a randomized trial of supportive-expressive group therapy, 125 women with metastatic breast cancer (MBC) completed a depression symptom measure (Center for Epidemiologic Studies-Depression Scale [CES-D]) at baseline and were randomly assigned to a treatment group or to a control group that received educational materials. At baseline and three follow-up points, 101 of 125 women completed a depression symptom measure. We used these data in a Cox proportional hazards analysis to examine whether decreasing depression symptoms over the first year of the study (the length of the intervention) would be associated with longer survival.Median survival time was 53.6 months for women with decreasing CES-D scores over 1 year and 25.1 months for women with increasing CES-D scores. There was a significant effect of change in CES-D over the first year on survival out to 14 years (P = .007) but no significant interaction between treatment condition and CES-D change on survival. Neither demographic nor medical variables explained this association.Decreasing depression symptoms over the first year were associated with longer subsequent survival for women with MBC in this sample. Further research is necessary to confirm this hypothesis in other samples, and causation cannot be assumed based on this analysis.
The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand.
Authors: J O'Connell, G C O'Sullivan, J K Collins, F Shanahan
Journal: The Journal of Experimental Medicine (1996)

Tumors escape immunological rejection by a diversity of mechanisms. In this report, we demonstrate that the colon cancer cell SW620 expresses functional Fas ligand (FasL), the triggering agent of Fas receptor (FasR)-mediated apoptosis within the immune system. FasL mRNA and cell surface FasL were detected in SW620 cells using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining, respectively. We show that SW620 kills Jurkat T cells in a Fas-mediated manner. FasR-specific antisense oligonucleotide treatment, which transiently inhibited FasR expression, completely protected Jurkat cells from killing by SW620. FasL-specific antisense oligonucleotide treatment of SW620 inhibited its Jurkat-killing activity. FasL has recently been established as a mediator of immune privilege in mouse retina and testis. Our finding that colon cancer cells express functional FasL suggests it may play an analogous role in bestowing immune privilege on human tumors. HT29 and SW620 colon cancer cells were found to express FasR mRNA and cell surface FasR using RT-PCR and immunofluorescence flow cytometry, respectively. However, neither of these cells underwent apoptosis after treatment by the anti-FasR agonistic monoclonal antibody CH11. Our results therefore suggest a Fas counterattack model for immune escape in colon cancer, whereby the cancer cells resist Fas-mediated T cell cytotoxicity but express functional FasL, an apoptotic death signal to which activated T cells are inherently sensitive.
IODINE IN SURGICAL TUBERCULOUS DISEASE
Authors: W. A. Tatchell
Journal: BMJ (1909)

IODINE IN SURGICAL TUBERCULOUS DISEASE.[ TMzrcBJouTn 39who are prevented by chronic ill-health from doing effec- tive work.Again, it is a disease to be fought because so many of our children with the best brains are attacked by it.If ever a teacher says to me that such and such a boy is the sharpest in the school, I always notice the lungs with extra care.Early Symptoms and Signs.The following remarks do not refer to cases in an advanced stage, children definitely ill, nor need I allude to the classical types of the tuberculous.Night swveating is a symptom concerning which one of my colleagues has no faith.He says that they all say they sweat.That seems to me only saying that " all men are liars," and needs qualification.There are certain distinctions to be made:1.If the sweating has existed all the child's life, it is probable the original cause was rickets.If it has started recently, or has existed in infancy, stopped, and started again, it has weight.2. If the sweating is not constant, but occurs from time to time, whenever the child catches cold (of course excluding the results of hot drinks at night).3. The sweating must be on the forehead or round the neck.It may he elsewhere as well, but, if the forehead is always dry, I am sceptical. 4. The sweating must be worse in cold weather. 5. Must not be due to heavy bedclothes.
Arginase Inhibition Protects against Allergen-induced Airway Obstruction, Hyperresponsiveness, and Inflammation
Authors: Harm Maarsingh, Annet B. Zuidhof, I. Sophie T. Bos, Marcel van Duin, Jean-Luc Boucher, Johan Zaagsma, Herman Meurs
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

In a guinea pig model of allergic asthma, using perfused tracheal preparations ex vivo, we demonstrated that L-arginine limitation due to increased arginase activity underlies a deficiency of bronchodilating nitric oxide (NO) and airway hyperresponsiveness (AHR) after the allergen-induced early and late asthmatic reaction.Using the same animal model, we investigated the acute effects of the specific arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) and of L-arginine on AHR after the early and late reaction in vivo. In addition, we investigated the protection of allergen-induced asthmatic reactions, AHR, and airway inflammation by pretreatment with the drug.Airway responsiveness to inhaled histamine was measured in permanently instrumented, freely moving guinea pigs sensitized to ovalbumin at 24 hours before allergen challenge and after the allergen-induced early and late asthmatic reactions by assessing histamine PC(100) (provocative concentration causing a 100% increase of pleural pressure) values.Inhaled ABH acutely reversed AHR to histamine after the early reaction from 4.77 +/- 0.56-fold to 2.04 +/- 0.34-fold (P < 0.001), and a tendency to inhibition was observed after the late reaction (from 1.95 +/- 0.56-fold to 1.56 +/- 0.47-fold, P < 0.10). Quantitatively similar results were obtained with inhaled l-arginine. Remarkably, after pretreatment with ABH a 33-fold higher dose of allergen was needed to induce airway obstruction (P < 0.01). Consequently, ABH inhalation 0.5 hour before and 8 hours after allergen challenge protected against the allergen-induced early and late asthmatic reactions, AHR and inflammatory cell infiltration.Inhalation of ABH or l-arginine acutely reverses allergen-induced AHR after the early and late asthmatic reaction, presumably by attenuating arginase-induced substrate deficiency to NO synthase in the airways. Moreover, ABH considerably reduces the airway sensitivity to inhaled allergen and protects against allergen-induced bronchial obstructive reactions, AHR, and airway inflammation. This is the first in vivo study indicating that arginase inhibitors may have therapeutic potential in allergic asthma.
Phase I Safety and Pharmacokinetic Study of Bavituximab, a Chimeric Phosphatidylserine-Targeting Monoclonal Antibody, in Patients with Advanced Solid Tumors
Authors: David E. Gerber, Alison T. Stopeck, Lucas Wong, Lee S. Rosen, Philip E. Thorpe, Joseph S. Shan, Nuhad K. Ibrahim
Journal: Clinical Cancer Research (2011)

Bavituximab is a chimeric immunoglobulin G1 phosphatidylserine-targeting monoclonal antibody that triggers vascular disruption and enhances antitumor immune response. This phase I study assessed the safety and pharmacokinetics of bavituximab in patients with advanced solid tumors.Patients with refractory advanced solid tumors were enrolled into four sequential dose-escalation cohorts (0.1, 0.3, 1, or 3 mg/kg bavituximab weekly) with two dosing schedules. Patients in the 0.1 and 0.3 mg/kg cohorts received bavituximab on days 0, 28, 35, and 42. Patients in the 1 and 3 mg/kg cohorts were administered bavituximab on days 0, 7, 14, and 21. Safety, pharmacokinetics, and tumor response were assessed.Twenty-six patients were accrued. No maximum tolerated dose was reached. Six serious adverse events occurred in five patients, including one pulmonary embolism at 3 mg/kg, which was the only dose-limiting toxicity (DLT) in the study. Bavituximab half-life ranged from 37 to 47 hours, with no accumulation seen following administration of multiple doses. Activated partial thromboplastin time was modestly prolonged in vitro at the highest dose tested. As assessed on day 56, a total of 18 patients were evaluable for efficacy, of whom 10 had disease progression and none had an objective response.Bavituximab was well tolerated at doses ranging up to 3 mg/kg weekly. Pharmacokinetic studies support a weekly dosing regimen. Additional phase I and II clinical trials are in progress to investigate bavituximab in combination with chemotherapy and other molecularly targeted agents.
Regulation of D6 chemokine scavenging activity by ligand- and Rab11-dependent surface up-regulation
Authors: Raffaella Bonecchi, Elena M. Borroni, Achille Anselmo, Andrea Doni, Benedetta Savino, Massimiliano Mirolo, Monica Fabbri, Venkatakrishna R. Jala, Bodduluri Haribabu, Alberto Mantovani, Massimo Locati
Journal: Blood (2008)
Von Willebrand factor levels predict clinical outcome in patients with cirrhosis and portal hypertension
Authors: V. La Mura, J. C. Reverter, A. Flores-Arroyo, S. Raffa, E. Reverter, S. Seijo, J. G. Abraldes, J. Bosch, J. C. Garcia-Pagan
Journal: Gut (2011)

<h3>Background and aims</h3> Endothelial dysfunction is a major determinant of the increased hepatic vascular tone of cirrhotic livers. Von Willebrand factor (vWF), P-selectin and 8-iso-PGF2α (isoprostanes), surrogate markers of endothelial dysfunction, are increased in patients with cirrhosis. This study was aimed at exploring in patients with cirrhosis and portal hypertension the relation of these endothelial factors with systemic and hepatic haemodynamics and their possible clinical prognostic value. <h3>Methods</h3> 42 consecutive patients with cirrhosis and portal hypertension had measurement of the hepatic venous pressure gradient (HVPG), cardiopulmonary pressures and vWF, P-selectin and isoprostane levels in blood samples from hepatic and peripheral veins. Patients were followed up to 2 years, death or liver transplantation and any clinical event were recorded. <h3>Results</h3> vWF, P-selectin and isoprostanes were increased in patients with cirrhosis compared with controls (p&lt;0.001). vWF levels significantly correlated with HVPG, Child–Pugh score and MELD. Cox model analysis disclosed an independent indirect association of peripheral vWF with survival free of portal hypertension-related events and of transplantation. The vWF cut-off value of 216 U/dl (Youden index) disclosed two different populations of patients with cirrhosis with a highly different probability of survival free of portal hypertension-related events and transplantation (87% vs 22%, p=0.001). The prognostic role of vWF persisted after adjusting for parameters of liver dysfunction and for HVPG. <h3>Conclusions</h3> In patients with cirrhosis and portal hypertension vWF levels correlate with liver function and HVPG and independently predict clinical outcome.
An antagonist peptide mediates positive selection and CD4 lineage commitment of MHC class II–restricted T cells in the absence of CD4
Authors: Henry Kao, Paul M. Allen
Journal: The Journal of Experimental Medicine (2005)

The CD4 coreceptor works together with the T cell receptor (TCR) to deliver signals to the developing thymocyte, yet its specific contribution to positive selection and CD4 lineage commitment remains unclear. To resolve this, we used N3.L2 TCR transgenic, RAG-, and CD4-deficient mice, which are severely impaired in positive selection, and asked whether altered peptide ligands can replace CD4 function in vivo. Remarkably, in the presence of antagonist ligands that normally deleted CD4+ T cells in wild-type mice, we induced positive selection of functional CD4 lineage T cells in mice deficient in CD4. We show that the kinetic threshold for positive and negative selection was lowered in the absence of CD4, with no evident skewing toward the CD8 lineage with weaker ligands. These results suggest that CD4 is dispensable as long as the affinity threshold for positive selection is sustained, and strongly argue that CD4 does not deliver a unique instructional signal for lineage commitment.