tbuckley/cabot-search huggingface dataset:
Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection
Authors: Maria Moeller, Nicole M. Haynes, Michael H. Kershaw, Jacob T. Jackson, Michele W. L. Teng, Shayna E. Street, Loretta Cerutti, Stephen M. Jane, Joseph A. Trapani, Mark J. Smyth, Phillip K. Darcy
Journal: Blood (2005)
Cross sectional survey of multicentre clinical databases in the United Kingdom
Authors: Nick Black, Marian Barker, Mary Payne
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> To describe the multicentre clinical databases that exist in the United Kingdom, to report on their quality, to explore which organisational and managerial features are associated with high quality, and to make recommendations for improvements. <b>Design</b> Cross sectional survey, with interviews with database custodians and search of electronic bibliographic database (PubMed). <b>Studies reviewed</b> 105 clinical databases across the United Kingdom. <b>Results</b> Clinical databases existed in all areas of health care, but their distribution was uneven—cancer and surgery were better covered than mental health and obstetrics. They varied greatly in age, size, growth rate, and geographical areas covered. Their scope (and thus their potential uses) and the quality of the data collected also varied. The latter was not associated with any organisational characteristics. Despite impressive achievements, many faced substantial financial uncertainty. Considerable scope existed for improvements: greater use of nationally approved codes; more support from relevant professional organisations; greater involvement by nurses, allied health professionals, managers, and laypeople in database management teams; and more attention to data security and ensuring patient confidentiality. With some notable exceptions, the audit and research potential of most databases had not been realised: half the databases had each produced only four or fewer peer reviewed research articles. <b>Conclusions</b> At least one clinical database support unit is needed in the United Kingdom to provide assistance in organisation and management, information technology, epidemiology, and statistics. Without such an initiative, the variable picture of databases reported here is likely to persist and their potential not be realised.
Intravenous omeprazole rapidly raises intragastric pH.
Authors: R P Walt, J R Reynolds, M J Langman, H L Smart, G Kitchingman, K W Somerville, C J Hawkey
Journal: Gut (1985)

Twenty four hour intragastric acidity was measured in five duodenal ulcer patients studied at least three times. The effects of different dosage regimens of intravenous omeprazole was compared with placebo. Mean intragastric acidity from 1000 to 0800 was 34.3 +/- 4.3 mmol/l on placebo. After omeprazole 80 mg at 0900 and 40 mg at 1700 mean acidity was 2.1 +/- 0.9 mmol/l and after omeprazole 80 mg at 0900 and 80 mg at 1700 it was 0.7 +/- 0.2 mmol/l. pH remained above 4.0 for about 80% of recordings with these regimens and for only 5% with placebo. Three of the five patients also received omeprazole 80 mg at 0900, 40 mg at 1700 and 40 mg at 0100 when pH remained above 4.0 for 90% of recordings with 99% inhibition of acidity. Omeprazole rapidly raised intragastric pH in all patients and maintained a gastric pH of greater than 4.0 for most of the time. Large doses of IV omeprazole were required compared with studies using the oral compound.
Novel Pharmacological Approaches to Manage Interstitial Lung Fibrosis in the Twenty-First Century
Authors: Shri N. Giri
Journal: The Annual Review of Pharmacology and Toxicology (2003)

Pharmacological agents currently in use to treat interstitial lung fibrosis are either ineffective or too toxic in humans. This review addresses mechanistically based novel approaches that have the potential to minimize the accumulation of collagen in the lung, a hallmark of lung fibrosis. These approaches include maintaining the intracellular levels of NAD(+) and ATP, blocking the biological activities of TGF-beta and integrins, evaluating the effectiveness of PAF-receptor antagonists and NOS inhibitors, and developing a new generation of cysteine pro-drugs with an adequate degree of bioavailability. A critical analysis of each approach as it relates to management of IPF in humans is presented.
Psoriasis, psoriatic arthritis and risk of gout in US men and women
Authors: Joseph F Merola, Shaowei Wu, Jiali Han, Hyon K Choi, Abrar A Qureshi
Journal: Annals of the Rheumatic Diseases (2014)

Individuals with psoriasis have increased blood levels of uric acid. However, there is no prospective data on the association between psoriasis and uric acid levels and subsequent development of gout. In this study, we examined the risk of gout among individuals with psoriasis and psoriatic arthritis (PsA) in two cohorts of men and women, the Health Professionals Follow-up Study (HPFS) (1986-2010) and Nurses' Health Study (NHS) (1998-2010). 27 751 men and 71 059 women were included in the analysis. Lifetime history of physician-diagnosed incident psoriasis and PsA was confirmed by validated supplementary questionnaires. Incident gout diagnoses were confirmed based on the American College of Rheumatology survey criteria. We used Cox proportional hazards models controlling for potential risk factors to calculate the HRs with 95% CIs of incident gout while simultaneously adjusting for several common risk factors. We documented 2217 incident cases of gout during follow-up. Psoriasis was associated with an increased risk of subsequent gout with a multivariate HR of 1.71 (95% CI 1.36 to 2.15) in the pooled analysis. Risk of gout was substantially augmented among those with psoriasis and concomitant PsA (pooled multivariate HR: 4.95, 95% CI 2.72 to 9.01) when compared to participants without psoriasis. In this prospective study of US women and men, psoriasis and PsA were associated with an increased risk of gout.
Effectiveness of targeted falls prevention programme in subacute hospital setting: randomised controlled trial
Authors: Terry P Haines, Kim L Bennell, Richard H Osborne, Keith D Hill
Journal: BMJ (2004)

To assess the effectiveness of a targeted, multiple intervention falls prevention programme in reducing falls and injuries related to falls in a subacute hospital.Randomised controlled trial of a targeted multiple intervention programme implemented in addition to usual care compared with usual care alone.Three subacute wards in a metropolitan hospital specialising in rehabilitation and care of elderly patients.626 men and women aged 38 to 99 years (average 80 years) were recruited from consecutive admissions to subacute hospital wards.Falls risk alert card with information brochure, exercise programme, education programme, and hip protectors.Incidence rate of falls, injuries related to falls, and proportion of participants who experienced one or more falls during their stay in hospital.Participants in the intervention group (n = 310) experienced 30% fewer falls than participants in the control group (n = 316). This difference was significant (Peto log rank test P = 0.045) and was most obvious after 45 days of observation. In the intervention group there was a trend for a reduction in the proportion of participants who experienced falls (relative risk 0.78, 95% confidence interval 0.56 to 1.06) and 28% fewer falls resulted in injury (log rank test P = 0.20).A targeted multiple intervention falls prevention programme reduces the incidence of falls in the subacute hospital setting.
Prevalence and age-dependence of malignant mutations in the beta-myosin heavy chain and troponin t genes in hypertrophic cardiomyopathy
Authors: Michael J Ackerman, Sara L VanDriest, Steve R Ommen, Melissa L Will, Rick A Nishimura, A.Jamil Tajik, Bernard J Gersh
Journal: Journal of the American College of Cardiology (2002)
Molecular Determinants of Magnesium Homeostasis
Authors: R. Todd Alexander, Joost G. Hoenderop, Rene[Combining Acute Accent] J. Bindels
Journal: Journal of the American Society of Nephrology (2008)

The past decade has witnessed multiple advances in our understanding of magnesium (Mg<sup>2+</sup>) homeostasis. The discovery that mutations in claudin-16/paracellin-1 or claudin-19 are responsible for familial hypomagnesemia with hypercalciuria and nephrocalcinosis provided insight into the molecular mechanisms governing paracellular transport of Mg<sup>2+</sup>. Our understanding of the transcellular movement of Mg<sup>2+</sup> was similarly enhanced by the realization that defects in transient receptor potential melastatin 6 (TRPM6) cause hypomagnesemia with secondary hypocalcemia. This channel regulates the apical entry of Mg<sup>2+</sup> into epithelia. In so doing, TRPM6 alters whole-body Mg<sup>2+</sup> homeostasis by controlling urinary excretion. Consequently, investigation into the regulation of TRPM6 has increased. Acid-base status, 17β estradiol, and the immunosuppressive agents FK506 and cyclosporine affect plasma Mg<sup>2+</sup> levels by altering TRPM6 expression. A mutation in epithelial growth factor is responsible for isolated autosomal recessive hypomagnesemia, and epithelial growth factor activates TRPM6. A defect in the γ-subunit of the Na,K-ATPase causes isolated dominant hypomagnesemia by altering TRPM6 activity through a decrease in the driving force for apical Mg<sup>2+</sup> influx. We anticipate that the next decade will provide further detail into the control of the gatekeeper TRPM6 and, therefore, overall whole-body Mg<sup>2+</sup> balance.
Current Clinical Management of Pulmonary Arterial Hypertension
Authors: Roham T. Zamanian, Kristina T. Kudelko, Yon K. Sung, Vinicio de Jesus Perez, Juliana Liu, Edda Spiekerkoetter
Journal: Circulation Research (2014)

During the past 2 decades, there has been a tremendous evolution in the evaluation and care of patients with pulmonary arterial hypertension (PAH). The introduction of targeted PAH therapy consisting of prostacyclin and its analogs, endothelin antagonists, phosphodiesterase-5 inhibitors, and now a soluble guanylate cyclase activator have increased therapeutic options and potentially reduced morbidity and mortality; yet, none of the current therapies have been curative. Current clinical management of PAH has become more complex given the focus on early diagnosis, an increased number of available therapeutics within each mechanistic class, and the emergence of clinically challenging scenarios such as perioperative care. Efforts to standardize the clinical care of patients with PAH have led to the formation of multidisciplinary PAH tertiary care programs that strive to offer medical care based on peer-reviewed evidence-based, and expert consensus guidelines. Furthermore, these tertiary PAH centers often support clinical and basic science research programs to gain novel insights into the pathogenesis of PAH with the goal to improve the clinical management of this devastating disease. In this article, we discuss the clinical approach and management of PAH from the perspective of a single US-based academic institution. We provide an overview of currently available clinical guidelines and offer some insight into how we approach current controversies in clinical management of certain patient subsets. We conclude with an overview of our program structure and a perspective on research and the role of a tertiary PAH center in contributing new knowledge to the field.
Strengthening the reporting of genetic risk prediction studies: the GRIPS statement
Authors: A Cecile J W Janssens, John P A Ioannidis, Cornelia M van Duijn, Julian Little, Muin J Khoury
Journal: BMJ (2011)

The number of known genetic markers of risk is increasing but the interpretation of their clinical effect is hampered by poor reporting of prediction studies. These guidelines from the GRIPS group aim to ensure transparent reporting of prediction studies
Insulin-Like Growth Factor-I Regulation of Immune Function: A Potential Therapeutic Target in Autoimmune Diseases?
Authors: Terry J. Smith
Journal: Pharmacological Reviews (2010)

This topically limited review explores the relationship between the immune system and insulin-like growth factors (IGF-I and IGF-II) and the proteins through which they act, including IGF-I receptor (IGF-IR) and the IGF-I binding proteins. The IGF/IGF-IR pathway plays important and diverse roles in tissue development and function. It regulates cell cycle progression, apoptosis, and the translation of proteins. Many of the consequences ascribed to IGF-IR activation result from its association with several accessory proteins that are either identical or closely related to those involved in insulin receptor signaling. Relatively recent awareness that IGF-I and IGF-IR regulate immune function has cast this pathway in an unexpected light; it may represent an important switch governing the quality and amplitude of immune responses. IGF-I/IGF-IR signaling may also participate in the pathogenesis of autoimmune diseases, although its relationship with these processes seems complex and relatively unexplored. On the one hand, IGF-I seems to protect experimental animals from developing insulin-deficient diabetes mellitus. In contrast, activating antibodies directed at IGF-IR have been detected in patients with Graves9 disease, where the receptor is overexpressed by multiple cell types. The frequency of IGF-IR<sup>+</sup> B and T cells is substantially increased in patients with that disease. Potential involvement of IGF-I and IGF-IR in the pathogenesis of autoimmune diseases suggests that this pathway might constitute an attractive therapeutic target. IGF-IR has been targeted in efforts directed toward drug development for cancer, employing both small-molecule and monoclonal antibody approaches. These have been generally well-tolerated. Recognizing the broader role of IGF-IR in regulating both normal and pathological immune responses may offer important opportunities for therapeutic intervention in several allied diseases that have proven particularly difficult to treat.
Chronic β2-adrenergic receptor stimulation increases proliferation of human cardiac fibroblasts via an autocrine mechanism
Authors: N Turner
Journal: Cardiovascular Research (2003)

The aim of this study was to determine whether chronic beta-adrenergic receptor (beta-AR) stimulation induces proliferation of human cardiac fibroblasts and to investigate the mechanism(s) involved.In vitro cultures of human cardiac fibroblasts were established from biopsies of right atrial appendage. RT-PCR analysis and pharmacological studies demonstrated that these cells express predominantly the beta(2)-AR subtype coupled to activation of adenylyl cyclase and p44/42 mitogen-activated protein kinase (MAPK). Proliferation was determined by cell counting over a 6-day period in medium containing 2.5% fetal calf serum (control) or supplemented with the non-selective beta-AR agonist isoproterenol (ISO). ISO induced a concentration-dependent increase in cardiac fibroblast proliferation, which was maximal at 1 micromol/l. This increased proliferation was inhibited by the beta(2)-AR-selective antagonist ICI-118,551, but not the beta(1)-AR-selective antagonist atenolol. Direct activation of adenylyl cyclase alone (0.1-10 micromol/l forskolin) stimulated cyclic AMP production and MAPK activation, but did not induce cell proliferation. Since catecholamines are not considered to be 'classical' growth factors, we subsequently investigated whether beta(2)-AR stimulation results in secretion of growth factors that are able to stimulate proliferation in an autocrine manner. Conditioned medium obtained from cardiac fibroblasts treated with ISO for 48 h increased proliferation of parallel cultures of fibroblasts in the presence of the beta-AR antagonist alprenolol. Heat-treatment of this conditioned medium fully prevented the increase in cell proliferation, indicating that the autocrine factor(s) are heat-sensitive proteins.Chronic beta(2)-AR stimulation increases proliferation of human cardiac fibroblasts via a mechanism involving increased secretion of heat-sensitive growth factors.
THE FIBRINOLYTIC PATHWAY OF HUMAN PLASMA
Authors: Allen P. Kaplan, K. Frank Austen
Journal: The Journal of Experimental Medicine (1972)

The conversion of the plasminogen proactivator to plasminogen activator by activated Hageman factor or its fragments has been recognized as an essential step in the conversion of plasminogen to plasmin. The plasminogen proactivator has been completely separated from prekallikrein and pre-PTA, two other proenzyme substrates of activated Hageman factor or its fragments. Plasminogen proactivator, free of any contaminating proteins as assessed by disc gel electrophoresis or isoelectric focusing, revealed a single band with an isoelectric point of 8.9 corresponding in position to the Hageman factor activatable material eluted from replicate unstained gels. After conversion of plasminogen proactivator by Hageman factor fragments to the plasminogen activator, the active site of the plasminogen activator is not inhibited by C1INH and is thus readily distinguished from that of kallikrein or PTA. The plasminogen activator is susceptible to inactivation by DFP while the plasminogen proactivator is not, as has been the case for esterases having a serine in the active site. Its interaction with plasminogen is inhibited by ϵ-aminocaproic acid.
Role of APC and DNA mismatch repair genes in the development of colorectal cancers.
Authors: Satya Narayan, Deodutta Roy
Journal: Molecular Cancer (2003)

Colorectal cancer is the third most common cause of cancer-related death in both men and women in the western hemisphere. According to the American Cancer Society, an estimated 105,500 new cases of colon cancer with 57,100 deaths will occur in the U.S. in 2003, accounting for about 10% of cancer deaths. Among the colon cancer patients, hereditary risk contributes approximately 20%. The main inherited colorectal cancers are the familial adenomatous polyposis (FAP) and the hereditary nonpolyposis colorectal cancers (HNPCC). The FAP and HNPCC are caused due to mutations in the adenomatous polyposis coli (APC) and DNA mismatch repair (MMR) genes. The focus of this review is to summarize the functions of APC and MMR gene products in the development of colorectal cancers.
Molecular Basis for G2 Arrest Induced by 2′-<i>C</i>-Cyano-2′-Deoxy-1-β-<scp>d</scp>-<i>Arabino</i>-Pentofuranosylcytosine and Consequences of Checkpoint Abrogation
Authors: Xiaojun Liu, Ying Guo, Yexiong Li, Yingjun Jiang, Sherri Chubb, Atsushi Azuma, Peng Huang, Akira Matsuda, Walter Hittelman, William Plunkett
Journal: Cancer Research (2005)

Abstract 2′-C-cyano-2′-deoxy-1-β-d-arabino-pentofuranosylcytosine (CNDAC) is a nucleoside analogue with a novel mechanism of action that is currently being evaluated in clinical trials. Incorporation of CNDAC triphosphate into DNA and extension during replication leads to single-strand breaks directly caused by β-elimination. These breaks, or the lesions that arise from further processing, cause cells to arrest in G2. The purpose of this investigation was to define the molecular basis for G2 checkpoint activation and to delineate the sequelae of its abrogation. Cell lines derived from diverse human tissues underwent G2 arrest after CNDAC treatment, suggesting a common mechanism of response to the damage created. CNDAC-induced G2 arrest was instituted by activation of the Chk1-Cdc25C-Cdk1/cyclin B checkpoint pathway. Neither Chk2, p38, nor p53 was required for checkpoint activation. Inhibition of Chk1 kinase with 7-hydroxystaurosporine (UCN-01) abrogated the checkpoint pathway as indicated by dephosphorylation of checkpoint proteins and progression of cells through mitosis and into G1. Cell death was first evident in hematologic cell lines after G1 entry. As indicated by histone H2AX phosphorylation, DNA damage initiated by CNDAC incorporation was transformed into double-strand breaks when ML-1 cells arrested in G2. Some breaks were manifested as chromosomal aberrations when the G2 checkpoint of CNDAC-arrested cells was abrogated by UCN-01 but also in a minor population of cells that escaped to mitosis during treatment with CNDAC alone. These findings provide a mechanistic rationale for the design of new strategies, combining CNDAC with inhibitors of cell cycle checkpoint regulation in the therapy of hematologic malignancies.
Principles of Mechanical Ventilator Use in Respiratory Failure
Authors: J R Hinson, J J Marini
Journal: Annual Review of Medicine (1992)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Impaired polymorphonuclear leucocyte chemotaxis in rheumatoid arthritis.
Authors: D H Goddard, A P Kirk, J R Kirwan, G D Johnson, E J Holborow
Journal: Annals of the Rheumatic Diseases (1984)

This study has investigated the chemotactic activity of polymorphonuclear cells (PMNs) isolated from the blood of patients with either articular rheumatoid arthritis (RA) or RA with extra-articular manifestations. A double fluorochrome immunofluorescent staining test has been employed to identify cell-associated immunoglobulins, probably immune complexes. The results suggest an inverse relationship between PMN chemotaxis and staining for cell-associated immunoglobulins, either surface bound or internalised. PMNs from RA patients showed reduced chemotaxis, and this was further reduced when RA PMNs were incubated for 30 minutes in autologous serum. A similar reduction in chemotaxis of normal PMNs occurred after incubation in RA sera. Preincubation of both RA and normal PMNs in RA serum (but not normal serum) resulted in an increase in the number of cells in which cell-associated immunoglobulins were demonstrable. This further reduction in RA PMN chemotaxis after exposure to autologous serum, together with an increase in immunoglobulin staining, may indicate selection of certain PMNs at the time of venepuncture due to cell margination. Such a selection process would call for a re-evaluation of previous studies of RA PMN function in relation to the disease process.
Nonfinancial Barriers to Care for Children and Youth
Authors: N Halfon, M Inkelas, D Wood
Journal: Annual Review of Public Health (1995)

Public health and medical care interventions have produced dramatic changes in the health of children in the United States. Emerging new morbidities such as behavioral and learning disorders, and child abuse and neglect, highlight the lack of an integrated system of health. Children's developmental vulnerability, dependency, and unique morbidities have been underemphasized in the organization and delivery of health care. The Andersen and Aday model of health care utilization is used to describe financial and nonfinancial barriers to care for children that include family characteristics and organizational characteristics of the health system. Case studies of immunization delivery, children with chronic illness, and mobile populations of children reveal the mismatch between the health care system and children's basic health needs. Integrated service models for high-risk populations of children represent an essential mechanism for coordinating the delivery of medical, developmental, educational, and social services needed by children and families. Universal, coordinated public health and medical services of adequate scope and quality should be assured for children through market and health system reform.