tbuckley/cabot-search huggingface dataset:
In Vivo Cytotoxic T Lymphocyte Elicitation by Mycobacterial Heat Shock Protein 70 Fusion Proteins Maps to a Discrete Domain and Is Cd4+ T Cell Independent
Authors: Qian Huang, Joan F.L. Richmond, Kimiko Suzue, Herman N. Eisen, Richard A. Young
Journal: The Journal of Experimental Medicine (2000)

To gain insights into the mechanisms by which soluble heat shock protein (hsp) fusions can elicit CD8+ cytotoxic T lymphocytes (CTLs) against the fusion partner, mycobacterial (Mycobacterium tuberculosis) hsp70 was dissected to ascertain whether a particular hsp domain is necessary, and knockout mice were used to determine whether the fusion protein's immunogenicity is dependent on CD4+ T lymphocytes. We found that the ability to elicit CD8+ CTLs depends on a discrete 200–amino acid protein domain, indicating that the fusion protein's immunogenicity for CD8+ T cells does not require coupled chaperone function or peptide binding. Further, we found that ovalbumin (OVA).hsp70 fusion protein elicited anti-OVA CD8+ CTLs about equally well in CD4 knockout and wild-type C57BL/6 mice, and also when the hsp70 was of murine (self) origin. The ability of hsp70 fusion proteins to elicit CD4-independent CTL responses suggests that hsp70 fusion proteins may be useful for immunological prophylaxis and therapy against disease in CD4+ T cell–deficient individuals.
Adjuvant Chemotherapy After Potentially Curative Resection of Metastases From Colorectal Cancer: A Pooled Analysis of Two Randomized Trials
Authors: Emmanuel Mitry, Anthony L.A. Fields, Harry Bleiberg, Roberto Labianca, Guillaume Portier, Dongsheng Tu, Donato Nitti, Valter Torri, Dominique Elias, Chris O'Callaghan, Bernard Langer, Giancarlo Martignoni, Olivier Bouché, Franck Lazorthes, Eric Van Cutsem, Laurent Bedenne, Malcolm J. Moore, Philippe Rougier
Journal: Journal of Clinical Oncology (2008)

Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials.After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m(2) administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m(2) [FFCD] x 5 days or FU 370 mg/m(2) plus l-leucovorin 100 mg/m(2) IV x 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm).A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis.This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus-based regimen after complete resection of colorectal cancer metastases.
Appearance of superoxide anion radical in cerebral extracellular space during increased prostaglandin synthesis in cats.
Authors: H A Kontos, E P Wei, E F Ellis, L W Jenkins, J T Povlishock, G T Rowe, M L Hess
Journal: Circulation Research (1985)

When increased prostaglandin synthesis was induced in anesthetized cats equipped with cranial windows by topical application of arachidonate (200 micrograms/ml) or bradykinin (20 micrograms/ml), there was reduction of nitroblue tetrazolium, resulting in deposition of the reduced insoluble form of this dye on the brain surface. The amount of reduced nitroblue tetrazolium deposited on the brain surface was measured spectrophotometrically after fixation of the brain by perfusion with aldehydes to eliminate interference from hemoglobin. Topical application of 56 U/ml superoxide dismutase or 20 micrograms/ml indomethacin inhibited nitroblue tetrazolium reduction by 76.5%-82.5% and by 78%-85.5%, respectively. These results show that most of the nitroblue tetrazolium reduction was accounted for by superoxide anion radical generated in the course of arachidonate metabolism via the cyclooxygenase pathway. No superoxide production could be detected in the absence of arachidonate or bradykinin. Histological examination showed no evidence of parenchymal cellular damage or vascular damage and no accumulation of leukocytes. Pronounced leukocyte accumulation occurred 24 hours after topical arachidonate in rabbits with chronically implanted cranial windows. Superoxide appearance was reduced severely by 4,4'-diisothiocyano-2,2'-stilbene disulfonate and phenylglyoxal, two specific inhibitors of the anion channel. The most likely explanation for these findings is that increased metabolism of exogenous or endogenous arachidonate via cyclooxygenase results in the appearance of superoxide anion radical in cerebral extracellular space. Superoxide crosses the membrane of undamaged cells via the anion channel.
New criteria for impaired fasting glucose and screening for diabetes in cystic fibrosis
Authors: C. Mueller-Brandes, R. W. Holl, M. Nastoll, M. Ballmann
Journal: European Respiratory Journal (2005)

Cystic fibrosis-related diabetes mellitus (CFRD) is the most frequent comorbidity in cystic fibrosis. Its clinical relevance is stressed by the association with increased mortality, and decreased pulmonary and nutritional status. An annual oral glucose tolerance test (OGTT) is recommended as a screening test for CFRD, but this is often not realised because of its time- and resource-consuming nature. Therefore, alternative approaches are welcome. In 2003, the American Diabetes Association (ADA) lowered the cut-off point separating normal from elevated fasting plasma glucose from &lt;6.1 mmol·L −1 to &lt;5.6 mmol·L −1 , suggesting the performance of an OGTT only in those with impaired fasting glucose (IFG; range 5.6–6.0 mmol·L −1 ). The current authors tested whether this approach was reliable for the early identification of patients with CFRD. OGTTs from 1,128 patients (53% males; 47% females; median age 17.1 yrs) were available for analysis. A total of 101 (8.9%) OGTTs were classified as diabetic. The new ADA criteria for IFG increased the sensitivity to 82% ( versus 65%) and decreased the specificity to 70% ( versus 94%) compared with the old criteria used to identify patients with diabetic OGTTs. In conclusion, the American Diabetes Association approach of using impaired fasting glucose as an indication for performing selective oral glucose tolerance tests is definitely unsuitable when aiming at the early identification of patients with cystic fibrosis-related diabetes mellitus, and it cannot replace annual oral glucose tolerance tests.
Unusual Case of Recurrent Extraneural Metastatic Medulloblastoma in a Young Adult: Durable Complete Remission With Ewing Sarcoma Chemotherapy Regimen and Consolidation With Autologous Bone Marrow Transplantation and Local Radiation
Authors: Jincy Clement, John Varlotto, Witold Rybka, Elizabeth Frauenhoffer, Joseph J. Drabick
Journal: Journal of Clinical Oncology (2013)
Immune Function Abnormalities in Peripheral Blood Mononuclear Cell Cytokine Expression Differentiates Stages of Cutaneous T-Cell Lymphoma/Mycosis Fungoides
Authors: Benjamin F. Chong, Adam J. Wilson, Heather M. Gibson, Mikehl S. Hafner, Yu Luo, Carrie J. Hedgcock, Henry K. Wong
Journal: Clinical Cancer Research (2008)

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma (CTCL) characterized by neoplastic skin-homing T cells. To better understand the immunopathogenesis of MF, we analyzed the functional ability of peripheral blood mononuclear cells (PBMC) from early and late MF/CTCL patients to express cytokine genes. In late stage MF/CTCL, patients were separated into those with blood involvement (+B) and without blood involvement (-B).We analyzed T(H)1 (interleukin 2 (IL-2), IFN-gamma), T(H)2 (IL-4, IL-5, IL-10, IL-13), and T(H)17 (IL-17) cytokine gene expression from activated PBMCs from normal (n = 12), psoriasis (n = 6), early MF/CTCL (n = 11), and late MF/CTCL+B (n = 4) and MF/CTCL-B (n = 3) by quantitative real-time PCR.PBMCs from early MF/CTCL and psoriasis showed higher induction of IL-2, IL-4, and IFN-gamma genes than those from normal and late MF/CTCL-B and MF/CTCL+B (P < 0.05) in descending order. PBMCs from late MF/CTCL-B exhibited generally the highest level of IL-5, IL-10, IL-13, and IL-17 expression compared with the other groups. PBMCs from early MF/CTCL and late MF/CTCL-B had similarly elevated IL-13 and IL-17. Of all groups, PBMCs from late MF/CTCL+B had the lowest levels of IL-2 (P < 0.05), IL-4, IFN-gamma, IL-13, and IL-17.The different pattern of cytokine gene expression suggests a change in immune function in MF/CTCL from early MF/CTCL to late MF/CTCL-B to late MF/CTCL+B. These stages are consistent with localized disease associated with an anti-tumor immune response and late MF/CTCL associated with a loss of immune function mediated by malignant T cells that share regulatory T cell-like properties.
Implementing a State-Based Cardiovascular Disease and Diabetes Prevention Program
Authors: Karl K. Vanderwood, Taryn O. Hall, Todd S. Harwell, Marcene K. Butcher, Steven D. Helgerson
Journal: Diabetes Care (2010)

To evaluate weight loss and cardiometabolic risk reduction achieved through an adapted Diabetes Prevention Program intervention among adults at high risk for cardiovascular disease (CVD) and diabetes.Eight health care facilities implemented a group-based lifestyle intervention beginning in 2008. Participants attended 16 weekly core sessions followed by 6 monthly after core sessions.A total of 1,003 participants were enrolled, 816 (81%) completed the core and 578 (58%) completed the after core. Of participants completing the core and after core, 45 and 49% achieved the 7% weight loss goal, respectively. There were significant improvements in blood pressure, fasting glucose, and LDL cholesterol among participants completing the intervention.Our findings indicate it is feasible for state-coordinated CVD and diabetes prevention programs to achieve significant weight loss and improve cardiometabolic risk.
Dog Exposure at Birth through Age 3 Reduces the Risk of Asthma at Age 6
Authors: N.A. Hallett, K.A. Roberg, E.L. Anderson, L.E.P. Salazar, R.A. Grabher, D.F. DaSilva, J.D. Bufford, K.T. Sullivan Dillie, R. Gangnon, M.D. Evans, J.E. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2007)
Clonal expansion of abnormal B cells in old NZB mice.
Authors: M F Seldin, J Conroy, A D Steinberg, L A D'Hoosteleare, E S Raveche
Journal: The Journal of Experimental Medicine (1987)

The spleens of old NZB mice have an abnormal population of B cells with extra chromosomes. These hyperdiploid B cells manifest increased proliferative capacity; they grow in (NZB X DBA/2)F1 spleens after intravenous injections. Molecular analysis of individual old NZB and F1 passaged spleens demonstrate that hyperdiploid cells represent a clonal or oligoclonal expansion of B cells. All spleens with at least 10% hyperdiploid cells demonstrated both heavy and kappa light chain immunoglobulin gene rearrangements by Southern blot hybridization. None of the hyperdiploid spleens from old NZB mice had lambda rearrangements and only one of five showed evidence of clonal rearrangement of the TCR-beta gene. One also had a VK10 clonal rearrangement. Elevated p53 oncogene protein was observed in NZB hyperdiploid spleen cells; however, no p53 or other oncogene rearrangements or amplifications were seen. Hyperdiploid cells were IgM-bright, IgD-dull, Ia+, dull B220, Thy-1-, and Ly-1-dull. Spleens with hyperdiploid B cells had increased percentages of Ly-1 B cells. The data suggest that hyperdiploid cells in old NZB mice represent clonal expansion of B cells and that they may represent an intermediate stage between autoimmunity and malignancy.
Anticandidal low molecular compounds from higher plants with special reference to compounds from essential oils
Authors: A. Pauli
Journal: Medicinal Research Reviews (2005)

Abstract The most active low molecular weight compounds from higher plants against Candida species are compiled from a database of antimicrobials (Amicbase) to find out new hints on their mechanism of action. The selected compounds possess strong inhibitory activities in vitro against Candida species either in the agar diffusion test, bioautography, agar dilution test, serial dilution test, or activity in the vapour phase. The test conditions are listed thoroughly and aspects of the different methods and recent developments in the testing of anticandidal drugs are discussed. The anticandidal spectra of drugs, antiseptics, and disinfectants licensed on the major markets are given for comparision of activities with compounds from natural sources. So far known mechanisms of action are described and some new structure–activity relationships are deduced from relationships between biological activities and chemical and physical parameters. Main specific targets of natural anticandidals are the ergosterol pathway, respiratory chain, and chitin biosynthesis. © 2005 Wiley Periodicals, Inc. Med Res Rev
Use of SM-1 monoclonal antibody and human complement in selective killing of small cell carcinoma of the lung.
Authors: M Mabry, J A Speak, J D Griffin, R A Stahel, S D Bernal
Journal: Journal of Clinical Investigation (1985)

SM-1 is a murine monoclonal antibody strongly reactive with a cell membrane antigen of small cell carcinoma (SCC) of the lung but unreactive with the membrane of most other carcinomas and normal tissues including normal bone marrow. We have found that in the presence of human complement, SM-1 antibody is highly cytotoxic to SCC cells. Using three treatments with antibody and complement, more than 99% of SCC cells in culture were lysed, as determined by the chromium release and clonogenic assays. Similar efficiency of SCC cell lysis was observed when one SM-1 antibody treatment was followed by three treatments with human complement. In contrast, there was little antibody-dependent lysis of non-small cell lung cancer cells, other carcinomas, and leukemia cell lines. The amount of chromium released from normal bone marrow cells treated with SM-1 antibody and complement was minimal and was mainly due to the effect of complement alone. Clonogenic assays, including colony-forming unit-granulocytic/monocytic, erythroid burst-forming unit, and colony-forming unit-granulocytic/erythroid/monocytic/megakaryocytic, also showed no significant SM-1 antibody-dependent cytotoxicity on normal bone marrow precursors. Since SM-1 antibody is selectively cytotoxic to SCC cells in the presence of human complement, it is a potentially useful agent for the selective eradication of tumor cell contamination in marrows of patients with metastatic small cell lung cancer and possibly for in vivo serotherapy.
Complement as a multifaceted modulator of kidney transplant injury
Authors: Paolo Cravedi, Peter S. Heeger
Journal: Journal of Clinical Investigation (2014)

Improvements in clinical care and immunosuppressive medications have positively affected outcomes following kidney transplantation, but graft survival remains suboptimal, with half-lives of approximately 11 years. Late graft loss results from a confluence of processes initiated by ischemia-reperfusion injury and compounded by effector mechanisms of uncontrolled alloreactive T cells and anti-HLA antibodies. When combined with immunosuppressant toxicity, post-transplant diabetes and hypertension, and recurrent disease, among other factors, the result is interstitial fibrosis, tubular atrophy, and graft failure. Emerging evidence over the last decade unexpectedly identified the complement cascade as a common thread in this process. Complement activation and function affects allograft injury at essentially every step. These fundamental new insights, summarized herein, provide the foundation for testing the efficacy of various complement antagonists to improve kidney transplant function and long-term graft survival.
Age-related expression of naive (CD45RA/62L) and activation (HLA DR/CD38) surface markers on CD4+ and CD8+ T-cell in normal children (birth to 18 years)
Authors: WT Shearer, HM Rosenblatt, S Spector, E Richard Stiehm, D Wara, Sd Douglas, K Luzuriaga, E McFarland, R Yogev, M Rathore
Journal: Journal of Allergy and Clinical Immunology (2002)
BMA meeting: Doctors reject calls for national ban on drinking on public transport
Authors: N. Hawkes
Journal: BMJ (2010)

<h3>ABSTRACT</h3> Many species are shifting their ranges being forced to rapidly respond to novel stressful environmental conditions. Colonizing individuals experience strong selective forces that favor the expression of life history traits notably affecting dispersal and reproductive rates in newly invaded habitats. Limited information is currently available on trait variation within the invasive range despite being critical for understanding ecological and evolutionary factors that drive the process of range expansion of invasive species. Here we evaluated life history shifts of the widely introduced Asian clam <i>Corbicula</i>, within its invaded range. Through an exhaustive literature search, we obtained data for 17 invasive <i>Corbicula</i> populations from different ecosystems worldwide. We tested the relationship between population and individual parameters relevant to the process of range expansion. Our main results are that recently introduced <i>Corbicula</i> populations were characterized by (i) low density and low rate of population increase, (ii) clams reproduced earlier in slow-growing populations, and (iii) density had no effect on population increase. All <i>Corbicula</i> populations analyzed in this study, which are fixed for one genotype (lineage Form A/R), experienced different selective environments in the introduced range. These findings support the perspective that adaptive phenotypic plasticity favored the expression of traits that maximize fitness in recently established populations, which faced stronger <i>r</i>-selective forces relative to long-established ones. We discuss the role of plasticity in facilitating rapid adaptation and increasing the likelihood of populations to overcome difficulties associated with low densities and low population increase in newly invaded areas.
Relationship of postprandial serum gastrin response to sex, body weight, blood group status, familial dyspepsia, duration, and age of onset of ulcer symptoms in duodenal ulcer.
Authors: S K Lam, G B Ong
Journal: Gut (1980)

Integrated postprandial serum gastrin levels were studied in a prospective series of 144 Chinese patients with duodenal ulcer in relation to sex, total body weight, age of onset and duration of ulcer symptoms, blood group status, and positivity for familial dyspepsia. Postprandial gastrin was unrelated to sex, total body weight, duration of symptoms, and blood group status. Patients whose onset age was in the first two decades (early onset group) had significantly higher postprandial gastrin than those with onset age in the 4th and 6th decades (P less than 0.01). This was found to be associated with the presence in the early onset group (n = 35) of a high proportion of patients with positive family history of ulcer dyspepsia (n = 24), in whom postprandial gastrin was significantly higher than those without such history (P less than 0.01). These results suggest that early onset patients who are positive for family history of ulcer dyspepsia segregate to form one subgroup of duodenal ulcer. They also offer a clue that familial hypergastrinaemia may be one marker for familial duodenal ulcer.
Alternative ion channel splicing in mesial temporal lobe epilepsy and Alzheimer's disease
Authors: Erin L Heinzen, Woohyun Yoon, Michael E Weale, Arjune Sen, Nicholas W Wood, James R Burke, Kathleen A Welsh-Bohmer, Christine M Hulette, Sanjay M Sisodiya, David B Goldstein
Journal: Genome biology (2007)

Abstract Background Alternative gene transcript splicing permits a single gene to produce multiple proteins with varied functions. Bioinformatic investigations have identified numerous splice variants, but whether these transcripts are translated to functional proteins and the physiological significance of these alternative proteins are largely unknown. Through direct identification of splice variants associated with disease states, we can begin to address these questions and to elucidate their roles in disease predisposition and pathophysiology. This work specifically sought to identify disease-associated alternative splicing patterns in ion channel genes by comprehensively screening affected brain tissue collected from patients with mesial temporal lobe epilepsy and Alzheimer's disease. New technology permitting the screening of alternative splice variants in microarray format was employed. Real time quantitative PCR was used to verify observed splice variant patterns. Results This work shows for the first time that two common neurological conditions are associated with extensive changes in gene splicing, with 25% and 12% of the genes considered having significant changes in splicing patterns associated with mesial temporal lobe epilepsy and Alzheimer's disease, respectively. Furthermore, these changes were found to exhibit unique and consistent patterns within the disease groups. Conclusion This work has identified a set of disease-associated, alternatively spliced gene products that represent high priorities for detailed functional investigations into how these changes impact the pathophysiology of mesial temporal lobe epilepsy and Alzheimer's disease.