tbuckley/cabot-search huggingface dataset:
Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes
Authors: A Mahmood, A J FitzGerald, T Marchbank, E Ntatsaki, D Murray, S Ghosh, R J Playford
Journal: Gut (2006)

Zinc carnosine (ZnC) is a health food product claimed to possess health-promoting and gastrointestinal supportive activity. Scientific evidence underlying these claims is, however, limited.To examine the effect of ZnC on various models of gut injury and repair, and in a clinical trial.In vitro studies used pro-migratory (wounded monolayer) and proliferation ([(3)H]-thymidine incorporation) assays of human colonic (HT29), rat intestinal epithelial (RIE) and canine kidney (MDCK) epithelial cells. In vivo studies used a rat model of gastric damage (indomethacin/restraint) and a mouse model of small-intestinal (indomethacin) damage. Healthy volunteers (n = 10) undertook a randomised crossover trial comparing changes in gut permeability (lactulose:rhamnose ratios) before and after 5 days of indomethacin treatment (50 mg three times a day) with ZnC (37.5 mg twice daily) or placebo coadministration.ZnC stimulated migration and proliferation of cells in a dose-dependent manner (maximum effects in both assays at 100 micromol/l using HT29 cells), causing an approximate threefold increase in migration and proliferation (both p<0.01). Oral ZnC decreased gastric (75% reduction at 5 mg/ml) and small-intestinal injury (50% reduction in villus shortening at 40 mg/ml; both p<0.01). In volunteers, indomethacin caused a threefold increase in gut permeability in the control arm; lactulose:rhamnose ratios were (mean (standard error of mean)) 0.35 (0.035) before indomethacin treatment and 0.88 (0.11) after 5 days of indomethacin treatment (p<0.01), whereas no significant increase in permeability was seen when ZnC was coadministered.ZnC, at concentrations likely to be found in the gut lumen, stabilises gut mucosa. Further studies are warranted.
Lymphatic and venous function in lipoedema
Authors: C. A. HARWOOD, R. H. BULL, J. EVANS, P. S. MORTIMER
Journal: British Journal of Dermatology (1996)

Journal Article Lymphatic and venous function in lipoedema Get access C. A. HARWOOD, C. A. HARWOOD Departments of Dermatology, London SW17 OQT, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. H. BULL, R. H. BULL Departments of Dermatology, London SW17 OQT, U.K. Search for other works by this author on: Oxford Academic Google Scholar J. EVANS, J. EVANS Vascular Surgery. St George's Hospital, London SW17 OQT, U.K. Search for other works by this author on: Oxford Academic Google Scholar P. S. MORTIMER P. S. MORTIMER Departments of Dermatology, London SW17 OQT, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 134, Issue 1, 1 January 1996, Pages 1–6, https://doi.org/10.1046/j.1365-2133.1996.d01-741.x Published: 01 January 1996 Article history Accepted: 14 March 1995 Published: 01 January 1996
IN VITRO STUDIES ON STRAIN-DEPENDENT PRODUCTION OF THYMUS-SPECIFIC AUTOANTIBODIES
Authors: H. Fuji, F. Milgrom
Journal: The Journal of Experimental Medicine (1973)

In vitro cultures of spleen cells (S) from normal 8–10-wk-old DBA/2J mice were shown to develop a small number of plaque-forming cells (PFC) that released antibodies lytic to syngenic and autologous thymus cells as well as to syngenic lymphoma L5178Y cells used as the target in the PFC assay. A marked increase in the number of PFC detectable on L5178Y target cells was demonstrated on day 4 in the cultures of S cells to which syngenic or autologous thymus cells had been added (S+T) at time 0, whereas the PFC detectable on thymus cells in such cultures remained at a level similar to that in S cultures. This suggested that two populations of PFC participated in the observed phenomena. No PFC developed in the culture of thymus cells (T). The addition of the cell-free supernatants of 24-h cultures of T or of L5178Y cells to syngenic S cultures also caused a specific increase in the number of the PFC detectable on L5178Y, which suggested that certain immunogenic factors released from the T cells stimulated the response observed in the S+T cultures. Antibodies of IgM nature were detected in the supernatants of S+T cultures by means of cytolysis in agar of L5178Y cells. Although such antibodies did not cause lysis of thymus cells, they could be completely removed by absorption with normal adult or fetal thymus cells of syngenic origin. Still, the absorbing capacity of L5178Y was much higher than that of thymus cells. The absorption was more efficient at 4°C than at 22°C, and hardly any absorption occurred at 37°C. The tissue distribution of the antigen under study seemed to be restricted to thymus cells since no other murine tissue cells tested removed the antibodies. The thymic antigen under study was not restricted to strain DBA/2J and could be demonstrated on thymus cells of all other strains tested. On the other hand, the ability of spleen cells to respond in vitro to this antigen has thus far been observed only in DBA/2J mice. Spleen cells of strains C57BL/6J and NZB/BINJ as well as (DBA/2 x NZB)F1 failed to show any significant increase in the PFC response detectable on the L5178Y target when syngenic thymus cells or DBA/2J thymus cells were added. An intravenous injection of syngenic thymus cells to DBA/2J mice also caused the appearance in their spleens of PFC detectable on the L5178Y target. The described in vitro system may provide a good means of studying the cellular basis of generation of self-tolerance and of its breakdown.
Hemodialysis Vintage, Black Ethnicity, and Pretransplantation Antidonor Cellular Immunity in Kidney Transplant Recipients
Authors: Joshua J. Augustine, Emilio D. Poggio, Michael Clemente, Mark I. Aeder, Kenneth A. Bodziak, James A. Schulak, Peter S. Heeger, Donald E. Hricik
Journal: Journal of the American Society of Nephrology (2007)

Prolonged exposure to dialysis before transplantation and black ethnicity are known risk factors for acute rejection and graft loss in kidney transplant recipients. Because the strength of the primed antidonor T cell repertoire before transplantation also is associated with rejection and graft dysfunction, this study sought to determine whether hemodialysis (HD) vintage and/or black ethnicity affected donor-directed T cell immunity. An enzyme-linked immunosorbent spot (ELISPOT) assay was used to measure the frequency of peripheral T cells that expressed IFN-gamma in response to donor stimulator cells before transplantation in 100 kidney recipients. Acute rejection occurred in 38% of ELISPOT (+) patients versus 14% of ELISPOT (-) patients (P = 0.008). The median (HD) vintage was 46 mo (0 to 125 mo) in ELISPOT (+) patients versus 24 mo (0 to 276 mo) in ELISPOT (-) patients (P = 0.009). Black recipients had a greater median HD vintage (55 versus 14 mo in nonblack recipients; P < 0.001). Black recipients with less HD exposure had a low incidence of an ELISPOT (+) test, similar to nonblack recipients. Among variables examined, only HD vintage remained a significant positive correlate with an ELISPOT (+) result (odds ratio per year of HD 1.3; P = 0.003). These data suggest that the risk for developing cross-reactive antidonor T cell immunity increases with longer HD vintage, providing an explanation for the previously observed relationship between increased dialysis exposure and worse posttransplantation outcome. Longer HD vintage may also explain the increased T cell alloreactivity that previously was observed in black kidney recipients.
No Effect of the 1α,25-Dihydroxyvitamin D3 on β-Cell Residual Function and Insulin Requirement in Adults With New-Onset Type 1 Diabetes
Authors: Markus Walter, Thomas Kaupper, Kerstin Adler, Johannes Foersch, Ezio Bonifacio, Anette-G. Ziegler
Journal: Diabetes Care (2010)

OBJECTIVE To determine whether daily intake of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] is safe and improves β-cell function in patients with recently diagnosed type 1 diabetes. RESEARCH DESIGN AND METHODS Safety was assessed in an open study of 25 patients aged 18–39 years with recent-onset type 1 diabetes who received 0.25 μg 1,25(OH)2D3 daily for 9 months. An additional 40 patients were randomly assigned to 0.25 μg 1,25(OH)2D3 or placebo daily for 9 months and followed for a total of 18 months for safety, β-cell function, insulin requirement, and glycemic control. RESULTS Safety assessment showed values in the normal range in nearly all patients, regardless of whether they received 1,25(OH)2D3 or placebo. No differences in AUC C-peptide, peak C-peptide, and fasting C-peptide after a mixed-meal tolerance test between the treatment and placebo groups were observed at 9 and 18 months after study entry, with ∼40% loss for each parameter over the 18-month period. A1C and daily insulin requirement were similar between treatment and placebo groups throughout the study follow-up period. CONCLUSIONS Treatment with 1,25(OH)2D3 at a daily dose of 0.25 μg was safe but did not reduce loss of β-cell function.
FOXO3a Is a Major Target of Inactivation by PI3K/AKT Signaling in Aggressive Neuroblastoma
Authors: Evan E. Santo, Peter Stroeken, Peter V. Sluis, Jan Koster, Rogier Versteeg, Ellen M. Westerhout
Journal: Cancer Research (2013)

Abstract Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway in neuroblastoma is correlated with poor patient prognosis, but the precise downstream effectors mediating this effect have not been determined. Here we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma. FOXO3a expression was elevated in low-stage neuroblastoma tumors and normal embryonal neuroblasts, but reduced in late-stage neuroblastoma. Inactivation of FOXO3a by AKT was essential for neuroblastoma cell survival. Treatment of neuroblastoma cells with the dual PI3K/mTOR inhibitor PI-103 activated FOXO3a and triggered apoptosis. This effect was rescued by FOXO3a silencing. Conversely, apoptosis induced by PI-103 or the AKT inhibitor MK-2206 was potentiated by FOXO3a overexpression. Furthermore, levels of total or phosphorylated FOXO3a correlated closely with apoptotic sensitivity to MK-2206. In clinical specimens, there was an inverse relationship between gene expression signatures regulated by PI3K signaling and FOXO3a transcriptional activity. Moreover, high PI3K activity and low FOXO3a activity were each associated with an extremely poor prognosis. Our work indicates that expression of FOXO3a and its targets offer useful prognostic markers as well as biomarkers for PI3K/AKT inhibitor efficacy in neuroblastoma. Cancer Res; 73(7); 2189–98. ©2013 AACR.
EFFECT OF PHAGOCYTOSIS ON MEMBRANE TRANSPORT OF NONELECTROLYTES
Authors: Min-Fu Tsan, Richard D. Berlin
Journal: The Journal of Experimental Medicine (1971)

The activities of specific transport systems were determined before and after large portions of the surface membrane had been interiorized by phagocytosis of inert particles. In five separate transport systems in rabbit polymorphonuclear leukocytes (adenosine and two adenine transport systems) and alveolar macrophages (adenosine and lysine transport systems), the rate of transport was unaffected even after an estimated 35–50% of the membrane had been internalized. Studies of the kinetics of lysine and adenosine transport, exchange diffusion of lysine transport in alveolar macrophages, and the specificities of adenine transport in polymorphonuclear leukocytes indicate that the nature of the membrane transport systems is not altered by phagocytosis. Therefore the constancy of transport indicates that the number of carriers remains the same before and after phagocytosis. It was also shown that this constancy of transport did not depend on the introduction into the surface of new transport sites during phagocytosis. Therefore transport sites are preserved on the surface during the internalization of membrane which accompanies phagocytosis. The results are best explained by the concept that the membrane is mosaic in character with geographically separate transport and phagocytic sites.
Decreased insulin secretion in islets from protein malnourished rats is associated with impaired glutamate dehydrogenase function: effect of leucine supplementation
Authors: Priscilla Muniz Ribeiro da Silva, Thiago Martins Batista, Rosane Aparecida Ribeiro, Claudio Cesar Zoppi, Antonio Carlos Boschero, Everardo Magalhães Carneiro
Journal: Metabolism (2011)
Long-term culture of human antigen-specific cytotoxic T-cell lines.
Authors: S Gillis, P E Baker, F W Ruscetti, K A Smith
Journal: The Journal of Experimental Medicine (1978)

Long-term cultures of human cytotoxic T-cell lines (H-CTLL) were established. H-CTLL cells were strictly dependent on growth upon a T-cell growth factor (TCGF) produced by phytohemagglutinin-stimulated normal human peripheral blood lymphocytes. H-CTLL cells were maintained in TCGF-dependent exponential proliferative culture for over 4 mo during which time they continued to mediate stimulator antigen-specific cytotoxicity as measured by a 4-h 51Cr-release assay. H-CTLL cells recovered from cryopreserved stocks and re-established in long-term culture demonstrated similar high levels of antigen-specific cytotoxicity. H-CTLL cells were 95--100% E-rosette positive and expressed normal T and Ia-like cell surface markers. The ability to sustain differentiated antigen-specific T-effector cells in long-term culture may provide a new means for the study of both the mechanism and regulation of T-cell-mediated immunity.
Quality of health regulator's data is questioned after trust is slammed for poor standards
Authors: A. O'Dowd
Journal: BMJ (2009)

The quality of the data available on NHS trusts’ performance and standards has been called into question after a highly critical report into an Essex trust.

The Care Quality Commission, the regulatory body of NHS trusts in England, and Monitor, the independent regulator of foundation trusts, have taken joint action because of concerns they have over standards at Basildon and Thurrock University Hospitals NHS Foundation Trust.

The regulators are now coordinating their powers to force the trust to improve what have been described as “serious failings,” and a task force of experts is to be sent to the trust to sort out its affairs.

However, measures of standards published on the commission’s website say that the quality of services at the trust is “good.” The website ranks the trust’s safety and cleanliness as 13 out of …
Government will not know for years whether consultants' contract has paid off
Authors: Adrian O'Dowd
Journal: BMJ (2007)

The government has admitted that it will have to wait years before it discovers whether there are real productivity gains from the new consultants' contract.NHS leaders also told the House of Commons Committee of Public Accounts last week that lessons had been learnt from mistakes made when the contract was introduced, such as not piloting it before implementation.They were giving evidence as part of the committee's inquiry into the consultants' contract.The session was prompted by the publication earlier this month of a report from the government's
Is Decreased Prefrontal Cortical Sensitivity to Monetary Reward Associated With Impaired Motivation and Self-Control in Cocaine Addiction?
Authors: Rita Goldstein
Journal: American Journal of Psychiatry (2007)

Objective: This study attempted to examine the brain's sensitivity to monetary rewards of different magnitudes in cocaine abusers and to study its association with motivation and self-control. Method: Sixteen cocaine abusers and 13 matched healthy comparison subjects performed a forced-choice task under three monetary value conditions while brain activation was measured with functional magnetic resonance imaging. Objective measures of state motivation were assessed by reaction time and accuracy, and subjective measures were assessed by self-reports of task engagement. Measures of trait motivation and self-control were assessed with the Multidimensional Personality Questionnaire. Results: The cocaine abusers demonstrated an overall reduced regional brain responsivity to differences between the monetary value conditions. Also, in comparison subjects but not in cocaine abusers, reward-induced improvements in performance were associated with self-reports of task engagement, and money-induced activations in the lateral prefrontal cortex were associated with parallel activations in the orbitofrontal cortex. For cocaine abusers, prefrontal cortex sensitivity to money was instead associated with motivation and self-control. Conclusions: These findings suggest that in cocaine addiction 1) activation of the corticolimbic reward circuit to gradations of money is altered; 2) the lack of a correlation between objective and subjective measures of state motivation may be indicative of disrupted perception of motivational drive, which could contribute to impairments in self-control; and 3) the lateral prefrontal cortex modulates trait motivation and deficits in self-control, and a possible underlying mechanism may encompass a breakdown in prefrontal-orbitofrontal cortical communication.
Combination of Vascular Endothelial Growth Factor Receptor/Platelet-Derived Growth Factor Receptor Inhibition Markedly Improves Radiation Tumor Therapy
Authors: Carmen Timke, Heike Zieher, Alexandra Roth, Kai Hauser, Kenneth E. Lipson, Klaus J. Weber, Jürgen Debus, Amir Abdollahi, Peter E. Huber
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Investigations on the combination of radiotherapy with vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) antiangiogenic agents, which has the potential to improve the clinical outcome in cancer patients. Experimental Design: Here, we analyze the combined VEGF (SU5416) and PDGF (SU6668) receptor tyrosine kinase inhibition with irradiation in human endothelium (HUVEC), prostate cancer (PC3), and glioblastoma (U87) in vitro and in vivo. Results: Combined inhibition of VEGF and PDGF signaling resulted in enhanced apoptosis, reduced cell proliferation, and clonogenic survival as well as reduced endothelial cell migration and tube formation compared with single pathway inhibition. These effects were further enhanced by additional irradiation. Likewise, in PC3 and U87 tumors growing s.c. on BALB/c nu/nu mice, dual inhibition of VEGF and PDGF signaling significantly increased tumor growth delay versus each monotherapy. Interestingly, radiation at ∼20% of the dose necessary to induce local tumor control exerts similar tumor growth-inhibitory effects as the antiangiogenic drugs given at their maximum effective dose. Addition of radiotherapy to both mono- as well as dual-antiangiogenic treatment markedly increased tumor growth delay. With respect to tumor angiogenesis, radiation further decreased microvessel density (CD31 count) and tumor cell proliferation (Ki-67 index) in all drug-treated groups. Of note, the slowly growing PC3 tumor responded better to the antiangiogenic drug treatments than the faster-growing U87 tumor. In addition to the beneficial effect of abrogating VEGF survival signaling when combined with radiation, we identified here a novel mechanism for the tumor escape from radiation damage. We found that radiation induced up-regulation of all four isoforms of PDGF (A-D) in endothelial cells supporting adjacent smooth muscle cells resulting in a prosurvival effect of radiation. The addition of SU6668 attenuated this undesirable paracrine radiation effect, which may rationalize the combined application of radiation with PDGF signaling inhibition to increase antitumor effects. Conclusion: A relative low radiation dose markedly enhances local antitumor effects of combined VEGF and PDGF signaling inhibition, suggesting a promising combination regimen for local tumor treatment with radiotherapy remaining an essential element.
Rapid Prototyping
Authors: Michael S. Kim, Adam R. Hansgen, Onno Wink, Robert A. Quaife, John D. Carroll
Journal: Circulation (2008)

As the appreciation of structural heart disease in children and adults has increased and as catheter-based closure procedures are now being performed in clinical practice, cardiovascular physicians have multiple compelling new reasons to better understand cardiac anatomic and spatial relationships. Current 2-dimensional imaging techniques remain limited both in their ability to represent the complex 3-dimensional relationships present in structural heart disease and in their capacity to adequately facilitate often complex corrective procedures. This review discusses the cardiovascular applications of rapid prototyping, a new technology that may not only play a significant role in the planning of catheter-based interventions but also may serve as a valuable educational tool to enhance the medical community's understanding of the many forms of structural heart disease.
Integrative Biology Identifies Shared Transcriptional Networks in CKD
Authors: Sebastian Martini, Viji Nair, Benjamin J. Keller, Felix Eichinger, Jennifer J. Hawkins, Ann Randolph, Carsten A. Böger, Crystal A. Gadegbeku, Caroline S. Fox, Clemens D. Cohen, Matthias Kretzler
Journal: Journal of the American Society of Nephrology (2014)

A previous meta-analysis of genome-wide association data by the Cohorts for Heart and Aging Research in Genomic Epidemiology and CKDGen consortia identified 16 loci associated with eGFR. To define how each of these single-nucleotide polymorphisms (SNPs) could affect renal function, we integrated GFR-associated loci with regulatory pathways, producing a molecular map of CKD. In kidney biopsy specimens from 157 European subjects representing nine different CKDs, renal transcript levels for 18 genes in proximity to the SNPs significantly correlated with GFR. These 18 genes were mapped into their biologic context by testing coregulated transcripts for enriched pathways. A network of 97 pathways linked by shared genes was constructed and characterized. Of these pathways, 56 pathways were reported previously to be associated with CKD; 41 pathways without prior association with CKD were ranked on the basis of the number of candidate genes connected to the respective pathways. All pathways aggregated into a network of two main clusters comprising inflammation- and metabolism-related pathways, with the NRF2-mediated oxidative stress response pathway serving as the hub between the two clusters. In all, 78 pathways and 95% of the connections among those pathways were verified in an independent North American biopsy cohort. Disease-specific analyses showed that most pathways are shared between sets of three diseases, with closest interconnection between lupus nephritis, IgA nephritis, and diabetic nephropathy. Taken together, the network integrates candidate genes from genome-wide association studies into their functional context, revealing interactions and defining established and novel biologic mechanisms of renal impairment in renal diseases.
Breakdown of simple female genital fistula repair after 7 day versus 14 day postoperative bladder catheterisation: a randomised, controlled, open-label, non-inferiority trial
Authors: Mark A Barone, Mariana Widmer, Steven Arrowsmith, Joseph Ruminjo, Armando Seuc, Evelyn Landry, Thierno Hamidou Barry, Dantani Danladi, Lucien Djangnikpo, Tagie Gbawuru-Mansaray, Issoufa Harou, Alyona Lewis, Mulu Muleta, Dolorès Nembunzu, Robert Olupot, Ileogben Sunday-Adeoye, Weston Khisa Wakasiaka, Sihem Landoulsi, Alexandre Delamou, Lilian Were, Vera Frajzyngier, Karen Beattie, A Metin Gülmezoglu
Journal: The Lancet (2015)