tbuckley/cabot-search huggingface dataset:
Changing Physical Activity Behavior in Type 2 Diabetes
Authors: Leah Avery, Darren Flynn, Anna van Wersch, Falko F. Sniehotta, Michael I. Trenell
Journal: Diabetes Care (2012)

OBJECTIVE Behavioral interventions targeting “free-living” physical activity (PA) and exercise that produce long-term glycemic control in adults with type 2 diabetes are warranted. However, little is known about how clinical teams should support adults with type 2 diabetes to achieve and sustain a physically active lifestyle. RESEARCH DESIGN AND METHODS We conducted a systematic review of randomized controlled trials (RCTs) (published up to January 2012) to establish the effect of behavioral interventions (compared with usual care) on free-living PA/exercise, HbA1c, and BMI in adults with type 2 diabetes. Study characteristics, methodological quality, practical strategies for increasing PA/exercise (taxonomy of behavior change techniques), and treatment fidelity strategies were captured using a data extraction form. RESULTS Seventeen RCTs fulfilled the review criteria. Behavioural interventions showed statistically significant increases in objective (standardized mean difference [SMD] 0.45, 95% CI 0.21–0.68) and self-reported PA/exercise (SMD 0.79, 95% CI 0.59–0.98) including clinically significant improvements in HbA1c (weighted mean difference [WMD] –0.32%, 95% CI –0.44% to –0.21%) and BMI (WMD –1.05 kg/m2, 95% CI –1.31 to –0.80). Few studies provided details of treatment fidelity strategies to monitor/improve provider training. Intervention features (e.g., specific behavior change techniques, interventions underpinned by behavior change theories/models, and use of ≥10 behaviour change techniques) moderated effectiveness of behavioral interventions. CONCLUSIONS Behavioral interventions increased free-living PA/exercise and produced clinically significant improvements in long-term glucose control. Future studies should consider use of theory and multiple behavior change techniques associated with clinically significant improvements in HbA1c, including structured training for care providers on the delivery of behavioural interventions.
Different contributions of ASIC channels 1a, 2, and 3 in gastrointestinal mechanosensory function
Authors: A J Page
Journal: Gut (2005)

Members of the acid sensing ion channel (ASIC) family are strong candidates as mechanical transducers in sensory function. The authors have shown that ASIC1a has no role in skin but a clear influence in gastrointestinal mechanotransduction. Here they investigate further ASIC1a in gut mechanoreceptors, and compare its influence with ASIC2 and ASIC3.Expression of ASIC1a, 2, and 3 mRNA was found in vagal (nodose) and dorsal root ganglia (DRG), and was lost in mice lacking the respective genes. Recordings of different classes of splanchnic colonic afferents and vagal gastro-oesophageal afferents revealed that disruption of ASIC1a increased the mechanical sensitivity of all afferents in both locations. Disruption of ASIC2 had varied effects: increased mechanosensitivity in gastro-oesophageal mucosal endings, decreases in gastro-oesophageal tension receptors, increases in colonic serosal endings, and no change in colonic mesenteric endings. In ASIC3-/- mice, all afferent classes had markedly reduced mechanosensitivity except gastro-oesophageal mucosal receptors. Observations of gastric emptying and faecal output confirmed that increases in mechanosensitivity translate to changes in digestive function in conscious animals.These data show that ASIC3 makes a critical positive contribution to mechanosensitivity in three out of four classes of visceral afferents. The presence of ASIC1a appears to provide an inhibitory contribution to the ion channel complex, whereas the role of ASIC2 differs widely across subclasses of afferents. These findings contrast sharply with the effects of ASIC1, 2, and 3 in skin, suggesting that targeting these subunits with pharmacological agents may have different and more pronounced effects on mechanosensitivity in the viscera.
Human deficiency of the eighth component of complement. The requirement of C8 for serum Neisseria gonorrhoeae bactericidal activity.
Authors: B H Petersen, J A Graham, G F Brooks
Journal: Journal of Clinical Investigation (1976)

The serum of a 23-yr-old woman with prolonged disseminated gonococcal infection syndrome failed to normally promote hemolysis of sensitized sheep red blood cells (RBC). The patient's serum was deficient in the eight component of complement (C8) as determined by functional assays, immunoelectrophoresis, and quantitative immunoprecipitation. Functional titers of each of her other complement components were normal. No serum inhibitors of C8 were detected. The patient's serum supported activation of both the classical and alternate complement pathways. Her fresh serum lacked any bactericidal activity against Neisseria gonorrhoeae, but addition of purified C8 or complement donor serum restored bactericidal activity as well as RBC hemolytic activity. Her serum gave normal opsonization of yeast particles and staphylococci and had normal capacity to coat sensitized RBC with C8 and C4 and to generate chemotactic activity. No defects were observed in the patient's blood coagulation mechanisms. Complement-mediated bacterial lysis may be important in human defense against bacteremic Neisseria infections.
Molecular Testing in Breast Cancer
Authors: Costanza Paoletti, Daniel F. Hayes
Journal: Annual Review of Medicine (2014)

Tumor biomarker tests are critical to implementation of personalized medicine for patients at risk for or affected by breast cancer. A tumor biomarker test must have high analytical validity and clinical utility to be used to guide clinical care in standard practice. Few tumor biomarkers meet these high standards. These include germline DNA single-nucleotide polymorphisms in the BRCA1 and -2 genes to determine high risk in unaffected women, selected tissue-based markers to determine prognosis and predict benefit from therapy, and circulating MUC1, CEA and perhaps tumor cells to monitor patients with metastatic disease. Efforts to discover biomarkers that predict therapeutic toxicity are promising but not yet successful. Further research is needed to enhance the number of tumor biomarker tests so that patients with breast cancer can get the correct treatment at the appropriate time.
Gas chromatography-mass spectrometry analysis of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in urine and feces.
Authors: M D Friesen, L Garren, J C Béréziat, F Kadlubar, D Lin
Journal: Environmental Health Perspectives (1993)

A method has been developed to measure levels of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) excreted in urine and feces. The method involves organic solvent extraction, derivatization to form electron-capturing bis-pentafluorobenzyl derivatives, and analysis by gas chromatography-negative ion chemical ionization mass spectrometry using a deuterium-labeled internal standard. The method can detect PhIP at levels of less than 1 ng/g in rat urine (5 ng/24 hr) and 5 ng/g (wet weight) in rat feces (50 ng/24 hr). Sprague-Dawley rats given a single 50 micrograms dose of PhIP by gavage excreted an average of 0.6% of the dose in the urine and 25% of the dose in the feces as unchanged PhIP, in the first 4 days after treatment. To make this method applicable for the analyses of biological fluids of PhIP-exposed human subjects, it is now being improved by using immunoaffinity chromatography.
Alcoholism in the Elderly
Authors: Yank D. Coble
Journal: JAMA (1996)

ATTITUDES toward alcoholism and the elderly on the part of the patient, the physician, and the family can be formidable obstacles to identification, diagnosis, and treatment. Differentiating between alcoholism and other psychiatric disorders is often required because of the frequent occurrence of the latter in elderly problem drinkers, particularly those who are hospitalized. The medical consequences of prolonged or heavy alcohol use can be severe in the older patient and often require immediate attention and acute care. Physicians need to become more active in the prevention, diagnosis, and treatment of alcoholism and alcohol-related problems in the elderly. In 1979, the American Medical Association (AMA) Council on Scientific Affairs endorsed guidelines for the treatment of alcoholism and urged physicians to equip themselves at least to make a diagnosis and refer alcoholic patients for treatment.<sup>1</sup>In the nearly two decades since then, physicians have become increasingly aware that alcoholism is a
Trends in sexually transmitted infections in general practice 1990-2000: population based study using data from the UK general practice research database
Authors: Jackie A Cassell, Catherine H Mercer, Lorna Sutcliffe, Irene Petersen, Amir Islam, M Gary Brook, Jonathan D Ross, George R Kinghorn, Ian Simms, Gwenda Hughes, Azeem Majeed, Judith M Stephenson, Anne M Johnson, Andrew C Hayward
Journal: BMJ (2006)

To describe the contribution of primary care to the diagnosis and management of sexually transmitted infections in the United Kingdom, 1990-2000, in the context of increasing incidence of infections in genitourinary medicine clinics.Population based study.UK primary care.Patients registered in the UK general practice research database.Incidence of diagnosed sexually transmitted infections in primary care and estimation of the proportion of major such infections diagnosed in primary care.An estimated 23.0% of chlamydia cases in women but only 5.3% in men were diagnosed and treated in primary care during 1998-2000, along with 49.2% cases of non-specific urethritis and urethral discharge in men and 5.7% cases of gonorrhoea in women and 2.9% in men. Rates of diagnosis in primary care rose substantially in the late 1990s.A substantial and increasing number of sexually transmitted infections are diagnosed and treated in primary care in the United Kingdom, with sex ratios differing from those in genitourinary medicine clinics. Large numbers of men are treated in primary care for presumptive sexually transmitted infections.
Positron Emission Tomography of Herpes Simplex Virus 1 Oncolysis
Authors: Darshini Kuruppu, Anna-Liisa Brownell, Aijun Zhu, Meixiang Yu, Xukui Wang, Yakup Kulu, Bryan C. Fuchs, Hiroshi Kawasaki, Kenneth K. Tanabe
Journal: Cancer Research (2007)

Abstract Viral oncolysis, the destruction of cancer cells by replicating viruses, is under clinical investigation for cancer therapy. Lytic viral replication in cancer cells both destroys the cells and liberates progeny virion to infect adjacent cancer cells. The safety and efficacy of this approach are dependent on selective and robust viral replication in cancer cells rather than in normal cells. Methods to detect and quantify viral replication in tissues have relied on organ sampling for molecular analyses. Preclinical and clinical studies of viral oncolysis will benefit significantly from development of a noninvasive method to repetitively measure viral replication. We have shown that positron emission tomography (PET) allows for in vivo detection of herpes simplex virus (HSV)-1 replication in tumor cells using 9-(4-[18F]-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]FHBG) as the substrate for HSV thymidine kinase (HSV-TK). As expected, phosphorylated [18F]FHBG is initially trapped within HSV-1–infected tumor cells and is detectable as early as 2 h following virus administration. MicroPET images reveal that [18F]FHBG accumulation in HSV-1–infected tumors peaks at 6 h. However, despite progressive accumulation of HSV-1 titers and HSV-TK protein in the tumor as viral oncolysis proceeds, tumor cell degradation resulting from viral oncolysis increases over time, which limits intracellular retention of [18F]FHBG. These observations have important consequences with regard to strategies to use [18F]FHBG PET for monitoring sites of HSV-TK expression during viral oncolysis. [Cancer Res 2007;67(7):3295–300]
An introduction to death receptors in apoptosis
Authors: R. Kumar, P.E. Herbert, A.N. Warrens
Journal: International Journal of Surgery (2005)

Apoptosis is a source of much research interest across many fields, including developmental biology, immunology and oncology. As the exact pathways of this process are identified, so too are potential avenues for therapeutic application. Death receptors are important in inducing apoptosis and together with their ligands have become a source of attention as potential therapeutic agents. This review provides an introduction to the role of death receptors in apoptosis, together with a look at possible areas where this information may be applied therapeutically.
Single-dose desloratadine and montelukast and allergen-induced late airway responses
Authors: B. E. Davis, C. Illamperuma, G. M. Gauvreau, R. M. Watson, P. M. O'Byrne, F. Deschesnes, L. P. Boulet, D. W. Cockcroft
Journal: European Respiratory Journal (2009)

Montelukast and desloratadine synergistically inhibit the allergen-induced early asthmatic response. Montelukast also suppresses the allergen-induced late asthmatic response, but there are no reports on the effect of desloratadine or the combination on the allergen-induced late asthmatic response. Atopic asthmatics (n = 10) completed a multicentric randomised double-blind crossover study comparing single-dose placebo, 5 mg desloratadine, 10 mg montelukast and the combination administered 2 h prior to allergen inhalation challenge. Methacholine challenges were performed 24 h before and after allergen challenge. Exhaled nitric oxide measurements and sputum inflammatory cell counts were also carried out. All active treatments significantly decreased the late asthmatic response area under the curve. Combination therapy provided the greatest inhibition compared to desloratadine and montelukast. Montelukast was nonsignificantly better than desloratadine but not as effective as the combination. There was a trend towards a decrease in airway responsiveness following montelukast and combination. Montelukast, but not desloratadine or the combination, decreased exhaled NO levels 24 h after allergen. The allergen-induced increase in sputum eosinophil numbers was significantly suppressed at 7 h with desloratadine and combination therapy, and at 24 h with montelukast and combination therapy. Single-dose co-administration of desloratadine and montelukast 2 h prior to allergen inhalation clinically abolished the late asthmatic response and eosinophil recruitment.
Screening mammography and risk of breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study
Authors: Steven A Narod, Jan Lubinski, Parviz Ghadirian, Henry T Lynch, Pal Moller, William D Foulkes, Barry Rosen, Charmaine Kim-Sing, Claudine Isaacs, Susan Domcheck, Ping Sun
Journal: The Lancet Oncology (2006)
Homocysteine Induces Expression and Secretion of Monocyte Chemoattractant Protein-1 and Interleukin-8 in Human Aortic Endothelial Cells
Authors: Ranjana Poddar, Natarajan Sivasubramanian, Patricia M. DiBello, Killian Robinson, Donald W. Jacobsen
Journal: Circulation (2001)

Proinflammatory cytokines play key roles in atherogenesis and disease progression. Because hyperhomocysteinemia is an independent risk factor for cardiovascular disease, we hypothesized that homocysteine could be atherogenic by altering the expression of specific cytokines in vascular endothelial cells.Northern blot and RNase protection assays showed that DL-homocysteine induced mRNA expression of the proinflammatory cytokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in cultured human aortic endothelial cells (HAECs). Homocysteine had no effect on expression of other cytokines, namely tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, interleukin-1beta, and transforming growth factor-beta. MCP-1 mRNA expression increased 1 hour after homocysteine treatment, reached a maximum within 2 to 4 hours, and declined to basal levels over the next 24 hours. Induction of mRNA expression for both chemokines was observed with as little as 10 micromol/L DL-homocysteine, and maximal expression was achieved with 50 micromol/L DL-homocysteine. Homocysteine also triggered the release of MCP-1 and IL-8 protein from HAECs into the culture medium. The induction was specific for homocysteine, because equimolar concentrations of L-homocystine, L-cysteine, and L-methionine had no effect on mRNA levels and protein release. Furthermore, L-homocysteine induced chemokine expression, but D-homocysteine did not, thus demonstrating enantiomeric specificity. The culture medium from homocysteine-treated HAECs promoted chemotaxis in human peripheral blood monocytes and U937 cells. Anti-human recombinant MCP-1 antibody blocked the migration.Pathophysiological levels of L-homocysteine alter endothelial cell function by upregulating MCP-1 and IL-8 expression and secretion. This suggests that L-homocysteine may contribute to the initiation and progression of vascular disease by promoting leukocyte recruitment.
Sleep {middle dot} 7: Positive airway pressure therapy for obstructive sleep apnoea/hypopnoea syndrome
Authors: P Gordon
Journal: Thorax (2004)

The use of continuous positive airway pressure (CPAP) in treating symptoms associated with OSAHS is reviewed. Although it is an imperfect intervention, it continues to evolve and improve in such a way that patients who would not have been able to use this treatment even in the recent past can benefit from it today.
Interferon-γ Is Essential for Destruction of β Cells and Development of Insulin-dependent Diabetes Mellitus
Authors: Matthias G. von Herrath, Michael B.A. Oldstone
Journal: The Journal of Experimental Medicine (1997)

Autoimmune mediated destruction of β cells of the islets of Langerhans leads to insulin-dependent diabetes mellitus (IDDM). Rat insulin promoter (RIP) lymphocytic choriomeningitis virus (LCMV) transgenic mice that express the nucleoprotein (NP) or glycoprotein (GP) of LCMV under control of the RIP in their β cells develop IDDM after infection with LCMV and serve as a model for virus-induced IDDM. Recently, Kagi et al. (Kagi, D., B. Odermatt, P. Ohashi, R.M. Zinkernagel, and H. Hengartner. 1996. J. Exp. Med. 183:2143–2149) showed, using RIP LCMV perforin-deficient mice, that IDDM does not occur in the absence of perforin. They concluded that perforin-mediated killing by cytotoxic T lymphocytes (CTLs) is the main factor needed for β cell injury and destruction. Here we provide evidence that killing of β cells is more complex and multifactorial. By the use of our RIP LCMV model, we show that in perforin competent but interferon-γ (IFN-γ)–deficient mice, β cell injury is limited and IDDM does not occur. For these studies, double transgenic mice were generated that were genetically deficient in the production of IFN-γ and express LCMV NP or GP in their β cells. In such mice, IDDM was aborted despite the generation of LCMV-specific antiself CTLs that displayed normal cytolytic activity in vitro and in vivo and entered the pancreas. However, mononuclear infiltration into the islets did not occur, and upregulation of class I and II molecules usually found in islets of RIP LCMV single transgenic mice after LCMV infection preceding the onset of clinical IDDM was not present in these bigenic mice. Our findings indicate that in addition to perforin, β cell destruction, development of insulitis, and IDDM also depend on the cytokine INF-γ, presumably through enhancement of major histocompatibility complex expression and antigen presentation.
The Rights of the Mentally Retarded and Mandatory Screening for the AIDS Virus
Authors: V. K. Warren Tashjian
Journal: JAMA (1987)

To the Editor.—  In the Oct 3, 1986, JAMA article regarding the ethics of proposed screening programs for the acquired immunodeficiency syndrome (AIDS), 1 it appears the authors relied on myths and misinformation in writing that people with mental retardation may be candidates for mandatory screening.  This suggestion is offensive even after examining rational arguments. The authors refer to various groups that should not be screened for antibody to the human immunodeficiency virus (HIV) (the AIDS virus), because screening could cause the group to be stigmatized or isolated by society. In addition, they argue that screening violates human rights in a free society. The authors give ethical or practical grounds for not requiring screening for soldiers, criminals in prison, and prostitutes—groups without full autonomy or whose activity is not protected by the law.  Bayer et al then express the opinion that individuals with mental retardation and those living in residential
The Vitamin E Analogue α-TEA Stimulates Tumor Autophagy and Enhances Antigen Cross-Presentation
Authors: Yuhuan Li, Tobias Hahn, Kendra Garrison, Zhi-Hua Cui, Andrew Thorburn, Jacqueline Thorburn, Hong-Ming Hu, Emmanuel T. Akporiaye
Journal: Cancer Research (2012)

The semisynthetic vitamin E derivative alpha-tocopheryloxyacetic acid (α-TEA) induces tumor cell apoptosis and may offer a simple adjuvant supplement for cancer therapy if its mechanisms can be better understood. Here we report that α-TEA also triggers tumor cell autophagy and that it improves cross-presentation of tumor antigens to the immune system. α-TEA stimulated both apoptosis and autophagy in murine mammary and lung cancer cells and inhibition of caspase-dependent apoptosis enhanced α-TEA-induced autophagy. Cell exposure to α-TEA generated double-membrane-bound vesicles indicative of autophagosomes, which efficiently cross-primed antigen-specific CD8(+) T cells. Notably, vaccination with dendritic cells pulsed with α-TEA-generated autophagosomes reduced lung metastases and increased the survival of tumor-bearing mice. Taken together, our findings suggest that both autophagy and apoptosis signaling programs are activated during α-TEA-induced tumor cell killing. We suggest that the ability of α-TEA to stimulate autophagy and enhance cross-priming of CD8(+) T cells might be exploited as an adjuvant strategy to improve stimulation of antitumor immune responses.
Reconstruction of Brachial Artery Pressure From Noninvasive Finger Pressure Measurements
Authors: Willem Jan W. Bos, Jeroen van Goudoever, Gert A. van Montfrans, Anton H. van den Meiracker, Karel H. Wesseling
Journal: Circulation (1996)

Background Pulse wave distortions, mainly caused by reflections, and pressure gradients, caused by flow in the resistive vascular tree, may cause differences between finger and brachial artery pressures. These differences may limit the use of finger pressure measurements. We investigated whether brachial artery pressure waves could be reconstructed from finger pressure measurements by correcting for the pressure gradient in addition to correction for pulse wave distortion with a previously described filter. Methods and Results Finger artery pressure (with Finapres), intra-arterial brachial artery pressure (BAP), Riva-Rocci/Korotkoff (RRK), oscillometric, and return-to-flow (RTF) measurements were simultaneously performed in 57 healthy elderly subjects and patients with vascular disease and/or hypertension. A generalized waveform filter was used to correct for pulse wave distortions. Correction equations for the pressure gradient, based on finger pressure, RRK, RTF, or oscillometric measurements, were obtained in 28 randomly selected subjects and tested in 29. Before reconstruction, Finapres underestimated mean and diastolic BAP (finger pressure minus BAP: systolic, −3.2±16.9 mm Hg; mean, −13.0±10.5 mm Hg; diastolic, −8.4±9.0 mm Hg [mean±SD]). After filtering, reconstructed BAP waves were similar to actual BAP in shape but not in pressure level. Optimal correction for the pressure gradient with an equation based on RTF measurements reduced the pressure differences to meet American Association for the Advancement of Medical Instrumentation criteria (reconstructed finger pressure minus BAP: systolic, 3.7±7.0 mm Hg; mean, 0.7±4.6 mm Hg; and diastolic, 1.0±4.9 mm Hg). Conclusions BAP waves can be reconstructed from noninvasive finger pressure registrations when finger pressure waves are corrected for pulse wave distortion and individual pressure gradients.