tbuckley/cabot-search huggingface dataset:
The MRC OX-22- CD4+ T cells that help B cells in secondary immune responses derive from naive precursors with the MRC OX-22+ CD4+ phenotype.
Authors: F Powrie, D Mason
Journal: The Journal of Experimental Medicine (1989)

CD4+ T cells in the rat can be divided into two nonoverlapping subsets by their reactivity with the mAb MRC OX-22, which binds some of the high molecular weight forms of the CD45 antigen. The lineage relationship between subsets of CD4+ T cells expression different forms of CD45 has been a controversial issue for some time. Experiments described in this paper address this question using in vivo assays of T cell reactivity. Analysis of primary antibody responses in vivo show that it is MRC OX-22+ CD4+ T cells that are active in these assays, whereas antigen-primed T cells that provide helper activity for secondary antibody responses in vivo have the MRC OX-22- CD4+ phenotype. It is demonstrated that these memory T cells derive from MRC OX-22+ CD4+ T cell precursors and not from a putative separate lineage. It is concluded that with respect to the provision of help for B cells, MRC OX-22+ CD4+ T cells are precursors of memory cells with the phenotype MRC OX-22- CD4+.
Monitoring the potential introduction of the Swedish Chlamydia trachomatis variant (swCT) in the Netherlands
Authors: S A Morré, A Catsburg, I M de Boer, J Spaargaren, H JC de Vries, J Schirm, P HM Savelkoul, J van Steenbergen, C M Swaan
Journal: Eurosurveillance (2007)

This report describes the actions of public health experts in cooperation with specialists in sexually transmitted diseases (STD), epidemiologists and (molecular) microbiologists to investigate the possible introduction of the swCT variant in the Netherlands: 1. Investigating trends in CT epidemiology Result: STD surveillance and laboratory surveillance did not show any evidence of the introduction of the swCT variant in Holland. 2. Retesting samples by TaqMan PCR Result: Roche CT-negative samples suspected to be CT-positive on the basis of the clinical picture were retested by swCT TaqMan but did not harbour the swCT variant 3. Screening sample pools for the presence of the swCT variant Result: Four different sample pools covering a wide geographical range were tested by specific swCT Taqman assay, but the swCT variant was not detected in any of them. In conclusion, to date the swCT variant has not been found in the Netherlands. However, ongoing monitoring is needed until Roche and Abbott have adapted their CT nucleic acid amplification tests (NAATs) to detect the new variant.
Low Locoregional Recurrence Rate Among Node-Negative Breast Cancer Patients With Tumors 5 cm or Larger Treated by Mastectomy, With or Without Adjuvant Systemic Therapy and Without Radiotherapy: Results From Five National Surgical Adjuvant Breast and Bowel Project Randomized Clinical Trials
Authors: Alphonse G. Taghian, Jong-Hyeon Jeong, Eleftherios P. Mamounas, David S. Parda, Melvin Deutsch, Joseph P. Costantino, Norman Wolmark
Journal: Journal of Clinical Oncology (2006)

Lymph node (LN) -negative breast cancer tumors > or = 5 cm occur infrequently, and their optimal management is not well defined. In this study, we assess patterns of locoregional failure (LRF) in LN-negative patients who underwent mastectomy, either with or without adjuvant chemotherapy or hormonal therapy and without postmastectomy radiation therapy (PMRT).Of 8,878 breast cancer patients enrolled onto National Surgical Adjuvant Breast and Bowel Project B-13, B-14, B-19, B-20, and B-23 node-negative trials, 313 had tumors that were 5 cm or larger (median, 5.5 cm; range, 5.0 to 15.5 cm) at pathology and were treated by mastectomy. Median follow-up time was 15.1 years. Therapy included adjuvant chemotherapy in 34.2% of patients; tamoxifen in 21.1%; chemotherapy plus tamoxifen in 19.2%; and no systemic therapy in 25.5%.Twenty-eight patients experienced LRF. The overall 10-year cumulative incidences of isolated LRF, LRF with and without distant failure (DF), and DF alone as first event were 7.1%, 10.0%, and 23.6%, respectively. Cumulative incidences for isolated LRF as first event for patients with tumors of 5 cm or more than 5 cm were 7.0% and 7.2%, respectively (P = .9). For patients who underwent no systemic treatment, chemotherapy alone, tamoxifen alone, or chemotherapy plus tamoxifen, the incidences were 12.6%, 5.6%, 4.6%, and 5.3%, respectively (P = .2). The majority of failures occurred on the chest wall (24 of 28 patients). Multivariate analysis did not identify significant prognostic factors for LRF.In patients with LN-negative tumors > or = 5 cm who are treated by mastectomy with or without adjuvant systemic therapy and no PMRT, LRF as first event remains low. PMRT should not be routinely used for these patients.
CONTROLLED TRIALS OF TWO ORAL ANTIPRURITIC DRUGS, TRIMEPRAZINE AND METHDILAZINE.
Authors: M. A. SMITH, M. P. CURWEN
Journal: British Journal of Dermatology (1961)

Journal Article CONTROLLED TRIALS OF TWO ORAL ANTIPRURITIC DRUGS, TRIMEPRAZINE AND METHDILAZINE. Get access M. A. SMITH, M. A. SMITH St. Bartholomew's Hospital, London Search for other works by this author on: Oxford Academic Google Scholar M. P. CURWEN M. P. CURWEN St. Bartholomew's Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 73, Issue 10, 1 October 1961, Pages 351–358, https://doi.org/10.1111/j.1365-2133.1961.tb14395.x Published: 01 October 1961
In search of common foundations for cortical computation
Authors: William A. Phillips, Wolf Singer
Journal: Behavioral and Brain Sciences (1997)

It is worthwhile to search for forms of coding, processing, and learning common to various cortical regions and cognitive functions. Local cortical processors may coordinate their activity by maximizing the transmission of information coherently related to the context in which it occurs, thus forming synchronized population codes. This coordination involves contextual field (CF) connections that link processors within and between cortical regions. The effects of CF connections are distinguished from those mediating receptive field (RF) input; it is shown how CFs can guide both learning and processing without becoming confused with the transmission of RF information. Simulations explore the capabilities of networks built from local processors with both RF and CF connections. Physiological evidence for synchronization, CFs, and plasticity of the RF and CF connections is described. Coordination via CFs is related to perceptual grouping, the effects of context on contrast sensitivity, amblyopia, implicit influences of color in achromotopsia, object and word perception, and the discovery of distal environmental variables and their interactions through self-organization. Cortical computation could thus involve the flexible evaluation of relations between input signals by locally specialized but adaptive processors whose activity is dynamically associated and coordinated within and between regions through specialized contextual connections.
FK506 (tacrolimus) and endothelin combined treatment induces mobility of melanoblasts: new insights into follicular vitiligo repigmentation induced by topical tacrolimus on sun-exposed skin
Authors: C.-C.E. Lan, C.-S. Wu, G.-S. Chen, H.-S. Yu
Journal: British Journal of Dermatology (2010)

Topical tacrolimus (FK506) has been considered as a treatment option for treating vitiligo, a dermatosis characterized by disappearance of melanocytes (MCs). Previous reports have shown that a significant portion of treated patients demonstrated follicular repigmentation, indicating that the activation of MC precursor cells residing in the outer root sheath of hair follicles played an important role during the tacrolimus-induced repigmentation process.To investigate the mechanisms involved in follicular pigmentation induced by topical tacrolimus.As stem cells of MC lineage are identified in the lower portion of mouse hair follicles throughout the hair cycle, immature mouse melanoblasts (MBs) derived from neural crest cells (NCCmelb4) were used for this study. Relevant maturation parameters were evaluated.Our results revealed that FK506 stimulated the expressions of protein kinase A, protein kinase C and phosphorylated p38 mitogen-activated protein kinase. However, cell motility, a parameter associated with MB differentiation, was not enhanced by FK506 treatment. Endothelin (ET)-3, a prodifferentiation factor of MBs, also failed to promote NCCmelb4 cell locomotion. Combining ET-3 and FK506, however, stimulated cell mobility. ET B receptor, which was not present in NCCmelb4 cells, was induced after FK506 treatment.In summary, we have shown that FK506 is an efficient differentiation-stimulating agent, especially for cells of neural origin. The clinical efficacy of topical tacrolimus on vitiligo may be enhanced by combination with ET-3.
Overview of High Throughput Sequencing Technologies to Elucidate Molecular Pathways in Cardiovascular Diseases
Authors: Jared M. Churko, Gary L. Mantalas, Michael P. Snyder, Joseph C. Wu
Journal: Circulation Research (2013)

High throughput sequencing technologies have become essential in studies on genomics, epigenomics, and transcriptomics. Although sequencing information has traditionally been elucidated using a low throughput technique called Sanger sequencing, high throughput sequencing technologies are capable of sequencing multiple DNA molecules in parallel, enabling hundreds of millions of DNA molecules to be sequenced at a time. This advantage allows high throughput sequencing to be used to create large data sets, generating more comprehensive insights into the cellular genomic and transcriptomic signatures of various diseases and developmental stages. Within high throughput sequencing technologies, whole exome sequencing can be used to identify novel variants and other mutations that may underlie many genetic cardiac disorders, whereas RNA sequencing can be used to analyze how the transcriptome changes. Chromatin immunoprecipitation sequencing and methylation sequencing can be used to identify epigenetic changes, whereas ribosome sequencing can be used to determine which mRNA transcripts are actively being translated. In this review, we will outline the differences in various sequencing modalities and examine the main sequencing platforms on the market in terms of their relative read depths, speeds, and costs. Finally, we will discuss the development of future sequencing platforms and how these new technologies may improve on current sequencing platforms. Ultimately, these sequencing technologies will be instrumental in further delineating how the cardiovascular system develops and how perturbations in DNA and RNA can lead to cardiovascular disease.
Wegner's “illusion” anticipated: Jonathan Edwards on the will
Authors: Ryan D. Tweney, Amy B. Wachholtz
Journal: Behavioral and Brain Sciences (2004)

Wegner's The Illusion of Conscious Will (2002) ignores an important aspect of the history of the concept: the determinism of Jonathan Edwards (1754) and the later response to this determinism by William James and others. We argue that Edwards's formulation, and James's resolution of the resulting dilemma, are superior to Wegner's.
Comparison of nasal and tracheobronchial clearance by similar techniques in normal subjects.
Authors: A B Millar, J E Agnew, S P Newman, M T Lopez-Vidriero, D Pavia, S W Clarke
Journal: Thorax (1986)

Nasal and tracheobronchial mucociliary clearance have been compared in 10 healthy subjects. Nasal clearance was measured by monitoring the rate of removal of 2 microns diameter Teflon particles, labelled with 99mTc, which had been placed in the anterior part of the nose. Tracheobronchial clearance was measured with an objective radioaerosol technique, 5 microns diameter polystyrene particles being used. With these comparable techniques there was a close correlation between the nasal mucociliary clearance rate and both the area under the tracheobronchial clearance curve from 0 to 6 hours after radioaerosol inhalation (rs = -0.94, p less than 0.001) and the area under the tracheobronchial clearance curve from 0 to 2.5 hours after inhalation (rs = -0.79, p less than 0.01). The rate of clearance of small particles from the nose may thus be a useful guide to tracheobronchial clearance in healthy individuals.
A Comparison of Three Chemotherapeutic Regimens in the Treatment of Advanced Pancreatic and Gastric Carcinoma
Authors: Stephen A. Cullinan, Charles G. Moertel, Thomas R. Fleming, Joseph R. Rubin, James E. Krook, Lloyd K. Everson, Harry E. Windschitl, Donald I. Twito, Robert F. Marschke, John F. Foley, Del M. Pfeifle, John F. Barlow
Journal: JAMA (1985)

Three hundred five patients with advanced pancreatic and gastric carcinoma were randomly assigned to treatment with fluorouracil, fluorouracil plus doxorubicin (Adriamycin) (FA), or fluorouracil plus doxorubicin plus mitomycin (mitomycin C) (FAM). All regimens were equivalent with regard to patient survival. There is no reasonable likelihood that either the FA or FAM regimen could produce a meaningful survival advantage over fluorouracil alone. Interval to disease progression, objective response rates, and palliative effects (improved performance, body weight, or symptoms) were essentially equivalent among the three regimens. With regard to toxicity, the FAM regimen produced more anorexia, nausea, vomiting, leukopenia, thrombocytopenia, and cumulative bone marrow suppression. Fluorouracil alone produced more stomatitis and diarrhea. Because of a failure to produce improved survival or palliation, unrewarded toxicity, and excessive cost, neither the FA nor FAM regimen can be recommended for the treatment of advanced pancreatic or gastric cancer. (<i>JAMA</i>1985;253:2061-2067)
The heparin infusion prior to stenting (HIPS) trial: procedural, in-hospital, 30 day, and six month clinical, angiographic and IVUS results
Authors: R.L. Wilensky, J.-F. Tanguay, S. Ito, A.L. Bartorelli, J. Moses, D.O. Williams, T.A. Bucher, P. Gallant, H. Wu, J.J. Popma, N. Weismann, G.S. Mintz, A.V. Kaplan, M.B. Leon
Journal: Journal of the American College of Cardiology (1998)
Promise and Challenge of RNA Interference–Based Therapy for Cancer
Authors: Fabio Petrocca, Judy Lieberman
Journal: Journal of Clinical Oncology (2010)

Cancer therapeutics still fall far short of our goals for treating patients with locally advanced or metastatic disease. Until recently, almost all cancer drugs were crude cytotoxic agents that discriminate poorly between cancer cells and normally dividing cells. The development of targeted biologics that recognize tumor cell surface antigens and of specific inhibitors of pathways dysregulated in cancer cells or normal cellular pathways on which a cancer cell differentially depends has provided hope for converting our increasing understanding of cellular transformation into intelligently designed anticancer therapeutics. However, new drug development is painfully slow, and the pipeline of new therapeutics is thin. The discovery of RNA interference (RNAi), a ubiquitous cellular pathway of gene regulation that is dysregulated in cancer cells, provides an exciting opportunity for relatively rapid and revolutionary approaches to cancer drug design. Small RNAs that harness the RNAi machinery may become the next new class of drugs for treating a variety of diseases. Although it has only been 9 years since RNAi was shown to work in mammalian cells, about a dozen phase I to III clinical studies have already been initiated, including four for cancer. So far there has been no unexpected toxicity and suggestions of benefit in one phase II study. However, the obstacles for RNAi-based cancer therapeutics are substantial. This article will discuss how the endogenous RNAi machinery might be harnessed for cancer therapeutics, why academic researchers and biotech and pharmaceutical companies are so excited, and what the obstacles are and how they might be overcome.
Control of Methadone Dosage by Patients
Authors: Avram Goldstein
Journal: JAMA (1975)

Patients in a methadone clinic were given knowledge and control of their own dosages. Dosages could be changed by 5 mg/week, but if more than 50 mg was used, no take-home privileges were allowed. The maximum dosage permitted was 120 mg. Plasma methadone levels were determined for some patients. The result of the study was that there was little dosage change, with the median dosage increasing from 40 to 50 mg at the end of six months. A small group of patients did raise their dosages systematically, and these patients tended to decrease illicit opiate use. There was no indication that these patients had abnormally low plasma methadone levels. At the end of six months, patients and staff overwhelmingly preferred an open-dose self-adjustment system over the usual procedure of dosage management by professional staff and dosage changes achieved by negotiation. (<i>JAMA</i>234:734-737, 1975)
Early use of immunosuppressives or TNF antagonists for the treatment of Crohn's disease: time for a change
Authors: I. Ordas, B. G. Feagan, W. J. Sandborn
Journal: Gut (2011)

Crohn9s disease is a chronic inflammatory disorder that follows a progressive and destructive course. Ultimately, uncontrolled inflammation leads to bowel damage from disease-related complications such as strictures, fistulas and abscesses and surgical resection. Conventional 'step-care', whereby corticosteroids and immunosuppressives are prescribed sequentially, is an incremental approach to treatment that does not prevent disease progression and conveys an important risk of adverse events from repeated courses of corticosteroids. Although the immunosuppressives azathioprine, 6-mercaptopurine and methotrexate are corticosteroid-sparing, they are not highly effective for inducing mucosal healing or preventing disease progression. Tumour necrosis factor antagonists induce and maintain mucosal healing and reduce surgery and hospitalisation rates. This holds out the possibility that long-term use of these agents may prevent bowel damage. Combination therapy with immunosuppressives and tumour necrosis factor antagonists is likely the best strategy for achieving optimal outcomes in patients at high risk of disease progression. However, accurate prognostic markers must be identified to guide patient selection. Long-term prospective studies with robust outcomes are still needed to establish definitively the efficacy and safety of early combination therapy to prevent bowel damage, loss of gastrointestinal tract function and permanent disability.
PATHOGENESIS OF INFLAMMATION
Authors: Richard C. Graham, Robert H. Ebert, Oscar D. Ratnoff, John M. Moses
Journal: The Journal of Experimental Medicine (1965)

Activated Hageman factor, when injected into the rabbit ear chamber, produces a delayed and prolonged inflammatory response characterized by prominent sticking and emigration of leucocytes. In contrast, preformed bradykinin evokes an immediate and more transient response in which leucocytic emigration occurs less frequently. It is concluded that either Hageman factor produces its inflammatory effects by mechanisms other than kinin release, or bradykinin released endogenously has effects quite different from those resulting from a single injection of the exogenous material.
Beta-amyloid increases the expression level of ATBF1 responsible for death in cultured cortical neurons
Authors: Cha-Gyun Jung, Kyung-Ok Uhm, Yutaka Miura, Takashi Hosono, Hirofumi Horike, Kum Khanna, Mi-Jeong Kim, Makoto Michikawa
Journal: Molecular Neurodegeneration (2011)

Recently, several lines of evidence have shown the aberrant expression of cell-cycle-related proteins and tumor suppressor proteins in vulnerable neurons of the Alzheimer's disease (AD) brain and transgenic mouse models of AD; these proteins are associated with various paradigms of neuronal death. It has been reported that ATBF1 induces cell cycle arrest associated with neuronal differentiation in the developing rat brain, and that gene is one of the candidate tumor suppressor genes for prostate and breast cancers in whose cells overexpressed ATBF1 induces cell cycle arrest. However, the involvement of ATBF1 in AD pathogenesis is as yet unknown. We found that ATBF1 was up-regulated in the brains of 17-month-old Tg2576 mice compared with those of age-matched wild-type mice. Moreover, our in vitro studies showed that Aβ1-42 and DNA-damaging drugs, namely, etoposide and homocysteine, increased the expression ATBF1 level in primary rat cortical neurons, whereas the knockdown of ATBF1 in these neurons protected against neuronal death induced by Aβ1-42, etoposide, and homocysteine, indicating that ATBF1 mediates neuronal death in response to these substances. In addition, we found that ATBF1-mediated neuronal death is dependent on ataxia-telangiectasia mutated (ATM) because the blockage of ATM activity by treatment with ATM inhibitors, caffeine and KU55933, abolished ATBF1 function in neuronal death. Furthermore, Aβ1-42 phosphorylates ATM, and ATBF1 interacts with phosphorylated ATM. To the best of our knowledge, this is the first report that Aβ1-42 and DNA-damaging drugs increased the ATBF1 expression level in primary rat cortical neurons; this increase, in turn, may activate ATM signaling responsible for neuronal death through the binding of ATBF1 to phosphorylated ATM. ATBF1 may therefore be a suitable target for therapeutic intervention of AD.
Sulindac. Trials of a new anti-inflammatory drug.
Authors: E.C Huskisson, J Scott
Journal: Annals of the Rheumatic Diseases (1978)

Trials in patients with rheumatoid arthritis and osteoarthritis showed sulindac to be an analgesic with anti-inflammatory properties and at least as effective as aspirin. It was effective within 24 hours in doses of 300-400 mg daily. It had the advantages of twice daily administration and a lower incidence of gastric side effects than aspirin. Constipation, usually mild, occurred in 20-30% of cases. Like other anti-inflammatory drugs, it was effective in only a proportion of the patients.
Bayesian Adaptive Randomized Trial Design for Patients With Recurrent Glioblastoma
Authors: Lorenzo Trippa, Eudocia Q. Lee, Patrick Y. Wen, Tracy T. Batchelor, Timothy Cloughesy, Giovanni Parmigiani, Brian M. Alexander
Journal: Journal of Clinical Oncology (2012)

To evaluate whether the use of Bayesian adaptive randomized (AR) designs in clinical trials for glioblastoma is feasible and would allow for more efficient trials.