tbuckley/cabot-search huggingface dataset:
P43 Cellular protein cyclophilin A is involved in hepatitis B virus replication and its inhibition with DEB025 (alisporivir) or NIM811 demonstrates antiviral activity in vitro
Authors: S. Chokshi, S. Phillips, A. Riva, N. Naoumov
Journal: Gut (2011)

<h3>Introduction</h3> Cyclophilins are ubiquitously expressed intracellular proteins that have enzymatic activity—peptidyl-prolyl cis-trans isomerase, and are involved in regulation of mitochondrial/cytosolic transport in the cells. DEB025 (Alisporivir) and NIM811 are non-immunosuppressive cyclophilin inhibitors that efficiently block hepatitis C virus replication by targeting host rather than viral proteins, however the potential impact of cyclophillin inhibition on hepatitis B virus (HBV) life cycle is poorly understood. <h3>Aim</h3> In the present study we employed a panel of liver cell lines to investigate the ability of cyclophilin inhibitors DEB025 (Alisporivir) and NIM811 to affect HBV replication and viral particle secretion from the cells. <h3>Method</h3> HepG2215 cells, stably transfected with the full HBV genome and supporting the production of both infectious virions and HBsAg particles, and the parent cells (HepG2) were cultured for 7 days (baseline), prior to treatment with DEB025 or NIM811 at 0.25; 1.0 and 5.0 mg/ml. The cells and supernatants were harvested separately at baseline; 6, 24, 48 and 72 h after addition of cyclophilin inhibitors. HBV DNA levels - both intracellular and in culture supernatants—were quantitated by Taqman qPCR (ABI7500). Western blot and ELISA were used to assess intracellular and secreted HBsAg, respectively. PLC/PRF/5 cells, expressing only HBsAg, were also tested. Cyclophilin expression in the cells was silenced by transfection separately with siRNA for cyclophilins A, B, C or D to determine the role of individual cyclophilins in HBV replication. <h3>Results</h3> Cyclophilin inhibition with either DEB025 or NIM811 significantly reduced cytoplasmic core-particle associated HBV DNA levels in the cells, between 2 and 10-fold as compared with the control cells. The most pronounced reduction of intracellular HBV DNA (by 10-fold at 72 h) was observed with DEB025 5 mg/ml, which was greater than the reduction observed with NIM811. Similarly, DEB025 (at 1 and 5 mg/ml) showed a greater impact in reducing HBV virion secretion in the supernatants, compared with NIM811. HBsAg secretion from the cells was also reduced by up to 50% when compared to controls. Cyclophilin-A expression was markedly reduced after transfection with corresponding siRNA, which led to a rapid decrease of intracellular HBV DNA by 2 logs. HBV-DNA was reduced further when the cyclophillin-A silenced cultures were treated with NIM811 or DEB025. <h3>Conclusion</h3> These results demonstrate that cyclophilin A is directly involved in HBV replication. Cyclophilin inhibition by DEB025 or NIM811 interferes with HBV replication within liver cells and reduces the secretion of infectious virions and HBsAg particles from the cells, with DEB025 having a greater antiviral activity than NIM811.
Part 2: Answer: Haemorrhagic mesenteric cyst
Authors: T Vanassche, F M Vanhoenacker, I Pilate, M Ruppert
Journal: British Journal of Sports Medicine (2010)

The lesion was surgically removed. At microscopic analysis, the cyst wall contained fibrous tissue without an epithelial lining, consistent with a haemorrhagic mesenteric cyst of non-neoplastic origin (non-pancreatic pseudocyst).

Mesenteric cysts form a heterogeneous group of rare intra-abdominal cystic lesions, situated in or near the mesentery and without connection to retroperitoneal structures. Incidence varies from 1/20 000 to 1/100 000 hospital admissions according to the age of the patient, with more frequent diagnosis in younger patients.1 Various classifications have been proposed based on the aetiology of the cystic structure, distinguishing embryonic and developmental cysts from lesions of traumatic, neoplastic and infectious origin. As most of these older classifications are confusing, the current classification of mesenteric cysts is essentially based on histopathological characteristics of the tissue or structure from which they derive.2 Cysts …
Investigation of polymorphisms in the PADI4 gene in determining severity of inflammatory polyarthritis
Authors: A Barton
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> A functional haplotype of the peptidylarginine deiminase 4 (<i>PADI4</i>) gene has recently been identified as a rheumatoid arthritis susceptibility gene in a Japanese but not in a UK population. One possible explanation for this disparity is that the gene determines severity of rather than susceptibility to inflammatory polyarthritis (IP) and that the UK and Japanese cohorts differed in terms of outcome. <b>Aim:</b> To examine the association between individual <i>PADI4</i> single nucleotide polymorphisms (SNPs) and haplotypes, with the development and severity of erosions by five years in patients with IP. <b>Methods:</b> 438 patients from the NOAR inception cohort of patients with IP were <i>x</i> rayed five years after presentation with early IP. Association with four exonic SNPs (padi4_89*G/A, padi4_90*T/C, padi4_92*G/C, and padi4_104*T/C), mapping to the <i>PADI4</i> gene and defining a haplotype previously reported to be associated with rheumatoid arthritis, was investigated. Patients were compared for the presence, extent, and progression of erosions by five years and the presence of antibodies to citrullinated peptide (anti-CCP antibodies). <b>Results:</b> There was no association between individual <i>PADI4</i> SNPs or haplotypes and the development or extent of erosions by five years. Restricting analysis to patients who satisfied ACR criteria for rheumatoid arthritis by five years did not alter the conclusions. No association with presence of anti-CCP antibodies was detected. <b>Conclusions:</b> No evidence was found for association of the <i>PADI4</i> gene with severity as assessed by erosive outcome at five years or with presence of anti-CCP antibodies in patients with IP.
Cyclophosphamide in Treatment of Disseminated Malignant Disease
Authors: C. J. Anders, N. H. Kemp
Journal: BMJ (1961)

BmISH ~~~~~~~~~~~~~~~~~MmlC.#LJOu"M cord haemoglobin level suggests and early exchange transfusion is indicated.'There were, in addition to the 80 pairs of cases described, 50 infants with cord haemoglobin values over 11.5 g./100 ml.but who were treated within the first nine hours of life.Evidence has already been presented indicating that exchange transfusion was performed in the first nine hourg in some of these either because the cord haemoglobin value was relatively low or because early jaundice developed.In many, however, the time of exchange transfusion and whether or not the case was paired was determined by chance.The subsequent course in these cases did not differ from either of the paired groups.The same proportion developed severe jaundice, a similar number required additional transfusion, and only one infant died, not from haemolytic disease but from hyaline membrane disease.Six of the 50 infants were upset by the transfusion itself, a slightly higher proportion than in either of the other two groups.Even where haemolytic disease of the newborn has not been predicted.relatively severe disease should be diagnosed within 24 hours of birth, and if prompt exchange transfusion is carried out satisfactory results should be achieved.Summary During 1958, 1959, and 1960 we performed exchange transfusion between 9 and 24 hours in 80 infants in whom the cord haemoglobin values exceeded 11.5 g./ 100 ml.From the same period we selected 80 infants treated between one and nine hours but who were otherwise similar with regard to birth weight and cord haemoglobin and cord bilirubin levels.Although jaundice was more common in the group treated after nine hours, the frequency of severe jaundice or bilirubinaemia exceeding 15 mg./ 100 ml. was the same in the two groups, as was the need for subsequent exchange transfusion.There was a suggestion that the infants treated later tolerated the procedure better.No death' attributed to haemolytic disease of the newborn occurred in either group.We conclude that if the cord haemoglobin value exceeds 11.5 g./100 ml. in the absence of clinical or other evidence of severe haemolytic disease exchange transfusion may safely be delayed up to 16 hours of life.
DISTINCT EVENTS IN THE IMMUNE RESPONSE ELICITED BY TRANSFERRED MARROW AND THYMUS CELLS
Authors: G. M. Shearer, G. Cudkowicz
Journal: The Journal of Experimental Medicine (1969)

Marrow cells and thymocytes of unprimed donor mice were transplanted separately into X-irradiated syngeneic hosts, with or without sheep erythrocytes (SRBC). Antigen-dependent changes in number or function of potentially immunocompetent cells were assessed by retransplantation of thymus-derived cells with fresh bone marrow cells and SRBC; of marrow-derived cells with fresh thymocytes and SRBC; and of thymus-derived with marrow-derived cells and SRBC. Plaque-forming cells (PFC) of the direct (IgM) and indirect (IgG) classes were enumerated in spleens of secondary host mice at the time of peak responses. By using this two-step design, it was shown (a) that thymus, but not bone marrow, contained antigen-reactive cells (ARC) capable of initiating the immune response to SRBC (first step), and (b) that the same antigen complex that activated thymic ARC was required for the subsequent interaction between thymus-derived and marrow cells and/or for PFC production (second step). Thymic ARC separated from marrow cells but exposed to SRBC proliferated and generated specific inducer cells. These were the cells that interacted with marrow precursors of PFC to form the elementary units for plaque responses to SRBC, i.e. the class- and specificity-restricted antigen-sensitive units. It was estimated that each ARC generated 80-800 inducer cells in 4 days by way of a minimum of 6-10 cell divisions. On the basis of the available evidence, a simple model was outlined for cellular events in the immune response to SRBC.
Applications of polymeric smart materials to environmental problems.
Authors: H N Gray, D E Bergbreiter
Journal: Environmental Health Perspectives (1997)

New methods for the reduction and remediation of hazardous wastes like carcinogenic organic solvents, toxic materials, and nuclear contamination are vital to environmental health. Procedures for effective waste reduction, detection, and removal are important components of any such methods. Toward this end, polymeric smart materials are finding useful applications. Polymer-bound smart catalysts are useful in waste minimization, catalyst recovery, and catalyst reuse. Polymeric smart coatings have been developed that are capable of both detecting and removing hazardous nuclear contaminants. Such applications of smart materials involving catalysis chemistry, sensor chemistry, and chemistry relevant to decontamination methodology are especially applicable to environmental problems.
Abstract 357: Nonclinical tumor efficacy studies of [18F]AH113804, a novel PET imaging agent with high affinity for the human c-Met receptor
Authors: Paul M. Evans, Mark Battle, Gareth Getvoldsen, Graeme McRobbie, Roger Bjerke, Matthew Morrison, Edvin Johannesen, Grethe T. Dalsgaard
Journal: Cancer Research (2012)

Abstract c-Met, the tyrosine-kinase receptor for hepatocyte growth factor (HGF)/scatter factor, is involved in tumour growth, invasion and metastasis in many human cancers of epithelial origin. Various tumour types are reported to overexpress c-Met, whilst expression in most normal tissues is relatively low. [18F]AH113804 is a peptide-based molecular imaging agent being developed by GE Healthcare for the in vivo evaluation of tumour and metastatic c-Met expression by PET imaging. In vitro affinity studies with fluorescently labelled analogues confirmed that whilst the AH113804 peptide had high affinity for human c-Met (hc-Met), there was limited or no affinity for dog or rodent c-Met, respectively. In mice, relatively high uptake of [18F]AH113804 was observed in human xenograft tumours known to express high levels of hc-Met, with rapid clearance from key background tissues such as muscle (tumour to muscle ratio of &amp;gt;5 achieved by 30 minutes post-injection). This biodistribution profile allowed the tumour to be clearly visualised by micro-PET imaging. Tumour uptake was significantly reduced by co-administration of excess non-radioactive peptide, confirming tumour uptake was specific. Tumour uptake of [18F]AH113804 was also shown to correlate with expression of hcMet, with a relative retention of 2.0±0.1, 1.2±0.2 and 0.7±0.2% retained dose per gram normalised for body weight (% rd/g/100g bw) 60 minutes post-injection in xenograft tumours with relatively high (HT-29 tumours), lower (U87 tumours) and no (LLC tumours) expression of hc-Met respectively (as assayed by ELISA). Finally, 111InCl3 was used in a dual tumour model as a non-specific marker of blood pool to confirm differences in tumour uptake were not related to differences in tumour blood pool or delivery. There was a significant difference in [18F]AH113804 uptake between HT-29 (2.2±0.8% rd/g/100 g bw) and LLC (0.9±0.2% rd/g/100 g bw) tumours (p&amp;lt;0.001) 30 minutes post-injection, whilst uptake of 111InCl3 was similar for the two tumour types (HT-29; 0.9±0.2% rd/g/100 g bw, LLC; 1.1±0.2% rd/g/100 g bw). Overall, these results confirmed that [18F]AH113804 has desirable properties for a c-Met targeted molecular imaging agent. Since there are a number of anti-c-Met therapies in clinical development, [18F]AH113804 has potential to be used as an aid in therapy selection and/or monitoring. Furthermore, [18F]AH113804 may be of use in patient stratification and prediction of patient outcome for specific cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 357. doi:1538-7445.AM2012-357
Air pollution effects on the gut microbiota
Authors: Saad Y Salim, Gilaad G Kaplan, Karen L Madsen
Journal: Gut Microbes (2013)

Global incidence rates for inflammatory bowel disease (IBD) have gradually risen over the past 20 years. Genome-wide association studies (GWAS) have identified over 160 genetic loci associated with IBD; however, inherited factors only account for a partial contribution to the disease risk. We have recently shown that urban airborne particulate matter (PM) ingested via contaminated food can alter gut microbiome and immune function under normal and inflammatory conditions. In this addendum, we will discuss how PM can modify the gut microbial form and function, provide evidence on changes seen in intestinal barrier, and suggest a working hypothesis of how pollutants affect the gastrointestinal tract. The significance of the work presented could lead to identifying airborne pollutants as potential risk factors and thus provide better patient care management.
A Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer
Authors: Michael H. Kershaw, Jennifer A. Westwood, Linda L. Parker, Gang Wang, Zelig Eshhar, Sharon A. Mavroukakis, Donald E. White, John R. Wunderlich, Silvana Canevari, Linda Rogers-Freezer, Clara C. Chen, James C. Yang, Steven A. Rosenberg, Patrick Hwu
Journal: Clinical Cancer Research (2006)

Abstract Purpose: A phase I study was conducted to assess the safety of adoptive immunotherapy using gene-modified autologous T cells for the treatment of metastatic ovarian cancer. Experimental Design: T cells with reactivity against the ovarian cancer–associated antigen α-folate receptor (FR) were generated by genetic modification of autologous T cells with a chimeric gene incorporating an anti-FR single-chain antibody linked to the signaling domain of the Fc receptor γ chain. Patients were assigned to one of two cohorts in the study. Eight patients in cohort 1 received a dose escalation of T cells in combination with high-dose interleukin-2, and six patients in cohort 2 received dual-specific T cells (reactive with both FR and allogeneic cells) followed by immunization with allogeneic peripheral blood mononuclear cells. Results: Five patients in cohort 1 experienced some grade 3 to 4 treatment-related toxicity that was probably due to interleukin-2 administration, which could be managed using standard measures. Patients in cohort 2 experienced relatively mild side effects with grade 1 to 2 symptoms. No reduction in tumor burden was seen in any patient. Tracking 111In-labeled adoptively transferred T cells in cohort 1 revealed a lack of specific localization of T cells to tumor except in one patient where some signal was detected in a peritoneal deposit. PCR analysis showed that gene-modified T cells were present in the circulation in large numbers for the first 2 days after transfer, but these quickly declined to be barely detectable 1 month later in most patients. An inhibitory factor developed in the serum of three of six patients tested over the period of treatment, which significantly reduced the ability of gene-modified T cells to respond against FR+ tumor cells. Conclusions: Large numbers of gene-modified tumor-reactive T cells can be safely given to patients, but these cells do not persist in large numbers long term. Future studies need to employ strategies to extend T cell persistence. This report is the first to document the use of genetically redirected T cells for the treatment of ovarian cancer.
Immunogenicity and IgE Blocking Capacity Of a Mixture Of Depigmented and Chemically Modified Allergens From Different Homologous Groups
Authors: Victor Miguel Iraola, José Ramón Leonor, María Morales, Raquel Moya, M. Angeles López Matas, Ma Teresa Gallego, Jerónimo Carnés
Journal: Journal of Allergy and Clinical Immunology (2014)
The Incidence Rate of Acquired Immunodeficiency Syndrome in Selected Populations
Authors: Ann M. Hardy
Journal: JAMA (1985)

Population figures were obtained, and incidence rates of acquired immunodeficiency syndrome (AIDS) for the 12 months from June 1, 1983, to May 31, 1984, were estimated for single (never-married) men aged 15 years or older, intravenous (IV) drug users, Haitians living in the United States, persons with hemophilia A and B, female sexual contacts of male IV drug users, and blood transfusion recipients. Single men in San Francisco and Manhattan, IV drug users in New York City and New Jersey, hemophilia A patients, and recent Haitian entrants had the highest rates of disease (82.0 to 268.9 per 100,000). Male IV drug users and male Haitians were two to four times as likely to experience development of AIDS as were females in each group. Persons with hemophilia A had six times the incidence rate of AIDS as did those with hemophilia B. Persons with severe hemophilia A had three times the rate of those with moderate and seven times the rate of those with mild clotting factor deficiency. Although blood transfusion recipients and female sexual contacts of male IV drug users had much lower average yearly rates than did persons in the four other groups (0.4 to 9.4 per 100,000), they still had a higher incidence rate of AIDS than did persons not belonging to any of these groups (0.1 per 100,000).
Failure to fire after an electrical injury – a complex syndrome in a soldier
Authors: FMH Ahmad, KVS Hari Kumar
Journal: Military Medical Research (2015)

Complex regional pain syndrome (CRPS) is a disorder characterized by an intractable, disabling pain of the affected limb. It is triggered by various injuries and is often resistant to standard therapy. We report a young soldier with CRPS of the right hand sustained from an electrical injury, who had improvement in resting pain with Zoledronic acid. In this report, we discuss the therapeutic options and the role of bisphosphonates in CRPS.
The Monomeric Guanosine Triphosphatase rab4 Controls an Essential Step on the Pathway of Receptor-mediated Antigen Processing in B Cells
Authors: Deborah A. Lazzarino, Peter Blier, Ira Mellman
Journal: The Journal of Experimental Medicine (1998)

Each member of the rab guanosine triphosphatase protein family assists in the regulation of a specific step within the biosynthetic or endocytic pathways. We have found that the early endosome-associated rab4 protein controls a step critical for receptor-mediated antigen processing in a murine A20 B cell line. Expression of the dominant negative rab4N121I mutant dramatically inhibited the processing and presentation of ovalbumin, λ cI repressor, or rabbit immunoglobulin G internalized as antigens by B cell antigen receptors or transfected Fc receptors. This defect did not reflect a block in antigen endocytosis or degradation, and transfected cells remained completely capable of presenting exogenously added ovalbumin and λ repressor peptides. Most remarkably, rab4N121I-expressing cells were undiminished in their ability to present each of these antigens when whole proteins were internalized at high concentration by fluid-phase endocytosis. Thus, expression of the rab4N121I selectively inactivated a portion of the endocytic pathway required for the processing of receptor-bound, but not nonspecifically internalized, antigens. These results suggest that elements of the early endosome-recycling pathway play an important and selective role in physiologically relevant forms of antigen processing in B cells.
Management of Acute Epiglottitis
Authors: Craig Willert
Journal: JAMA (1982)

To the Editor.—  The extensive experience with epiglottitis in pediatric patients has generated several important principles concerning the management of epiglottitis that were not well delineated in the article by Ossoff and Wolff entitled Acute Epiglottitis in Adults (1980;244:2639).  First, the advisability of manipulation of the patient with suspected epiglottitis by indirect laryngoscopy must be questioned. Although we could find no reports of morbidity or mortality associated with this procedure, manipulation of the pharynx with a tongue blade in children has been associated with sudden total airway obstruction. An endolateral neck roentgenogram is the preferred initial diagnostic procedure in patients with suspected epiglottitis. In our series of 19 patients with epiglottitis at Children's Memorial Hospital during a four-year period, the endolateral roentgenogram demonstrated the abnormal epiglottis in all cases. This degree of accuracy was also found in a recent series of adults with epiglottitis. 1   Expectant management of patients with