tbuckley/cabot-search huggingface dataset:
Potential Roles of Apoptosis in Viral Pathogenesis
Authors: Mary Collins
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Apoptosis is a physiologic mechanism of cell death that is induced during development or reversible tissue expansion or after tissue damage to eliminate unwanted cells. Recently, viral gene products have been shown to either specifically induce or specifically inhibit apoptosis. In this review, our current understanding of the regulation of apoptosis is outlined. The mechanisms by which viruses can inhibit or induce apoptosis are described. The role of apoptosis in modulating the immune response to viral infection is discussed. Finally, the hypothesis is advanced that the balance between induction and inhibition of apoptosis is modulated by viruses to optimize the course of viral infection. Collins M. Potential roles of apoptosis in viral pathogenesis.
Subclinical Neuropathy Among Diabetes Control and Complications Trial Participants Without Diagnosable Neuropathy at Trial Completion
Authors: James W. Albers, William H. Herman, Rodica Pop-Busui, Catherine L. Martin, Patricia Cleary, Barbara Waberski
Journal: Diabetes Care (2007)

OBJECTIVE—We sought to evaluate the prevalence of subclinical neuropathy in intensive and conventional treatment groups at completion of the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS—We assessed neuropathy using nerve conduction results obtained at DCCT completion after stratifying the DCCT cohort to exclude subjects with progressively less severe degrees of diagnosable neuropathy. We began with those who had confirmed clinical neuropathy (the primary DCCT end point) and eventually excluded all subjects with any clinical or electrodiagnostic evidence of neuropathy. RESULTS—After excluding subjects with confirmed clinical neuropathy at DCCT completion, 8 of 10 nerve conduction measures (including all lower-extremity measures) were significantly improved in the intensive treatment group (O'Brien rank-sum test across all nerve conduction measures, P &amp;lt; 0.0001). Conduction velocity group differences were substantial, and the peroneal conduction velocity averaged 3.1 m/s faster in the intensive compared with the conventional treatment group (45.1 vs. 42.0 m/s, P &amp;lt; 0.0001). Numerous significant differences in median and peroneal motor conduction velocities favoring the intensive treatment group persisted, regardless of the exclusion criteria applied. CONCLUSIONS—Intensive and conventional treatment group subjects without diagnosable neuropathy at DCCT completion had significant differences in electrophysiologic measurements favoring the intensive treatment group. Differences in subsequent incident neuropathy between the original treatment groups may reflect, in part, their levels of subclinical neuropathy at DCCT completion, rather than persistent metabolic effects.
Diabetes Personal Trainer Outcomes
Authors: Tonja R. Nansel, Ronald J. Iannotti, Bruce G. Simons-Morton, Christopher Cox, Leslie P. Plotnick, Loretta M. Clark, Linda Zeitzoff
Journal: Diabetes Care (2007)

To assess the social-cognitive, behavioral, and physiological outcomes of a self-management intervention for youth with type 1 diabetes.A total of 81 youth with type 1 diabetes aged 11-16 years were randomized to usual care versus a "diabetes personal trainer" intervention, consisting of six self-monitoring, goal-setting, and problem-solving sessions with trained nonprofessionals. Assessments were completed at baseline and multiple follow-up intervals. A1C data were obtained from medical records. ANCOVA adjusting for age and baseline values were conducted for each outcome.At both short-term and 1-year follow-up, there was a trend for an overall intervention effect on A1C (short-term F = 3.71, P = 0.06; 1-year F = 3.79, P = 0.06) and a significant intervention-by-age interaction, indicating a great effect among older than younger youth (short-term F = 4.78, P = 0.03; 1-year F = 4.53, P = 0.04). Subgroup analyses demonstrated no treatment group difference among younger youth but a significant difference among the older youth. No treatment group differences in parent or youth report of adherence were observed.The diabetes personal trainer intervention demonstrated significant effects in A1C among middle adolescents.
Arginine Deiminase as a Novel Therapy for Prostate Cancer Induces Autophagy and Caspase-Independent Apoptosis
Authors: Randie H. Kim, Jodi M. Coates, Tawnya L. Bowles, Gregory P. McNerney, Julie Sutcliffe, Jae U. Jung, Regina Gandour-Edwards, Frank Y.S. Chuang, Richard J. Bold, Hsing-Jien Kung
Journal: Cancer Research (2009)

Abstract Arginine deprivation as an anticancer therapy has historically been met with limited success. The development of pegylated arginine deiminase (ADI-PEG20) has renewed interest in arginine deprivation for the treatment of some cancers. The efficacy of ADI-PEG20 is directly correlated with argininosuccinate synthetase (ASS) deficiency. CWR22Rv1 prostate cancer cells do not express ASS, the rate-limiting enzyme in arginine synthesis, and are susceptible to ADI-PEG20 in vitro. Interestingly, apoptosis by 0.3 μg/mL ADI-PEG20 occurs 96 hours posttreatment and is caspase independent. The effect of ADI-PEG20 in vivo reveals reduced tumor activity by micropositron emission tomography as well as reduced tumor growth as a monotherapy and in combination with docetaxel against CWR22Rv1 mouse xenografts. In addition, we show autophagy is induced by single amino acid depletion by ADI-PEG20. Here, autophagy is an early event that is detected within 1 to 4 hours of 0.3 μg/mL ADI-PEG20 treatment and is an initial protective response to ADI-PEG20 in CWR22Rv1 cells. Significantly, the inhibition of autophagy by chloroquine and Beclin1 siRNA knockdown enhances and accelerates ADI-PEG20–induced cell death. PC3 cells, which express reduced ASS, also undergo autophagy and are responsive to autophagy inhibition and ADI-PEG20 treatment. In contrast, LNCaP cells highly express ASS and are therefore resistant to both ADI-PEG20 and autophagic inhibition. These data point to an interrelationship among ASS deficiency, autophagy, and cell death by ADI-PEG20. Finally, a tissue microarray of 88 prostate tumor samples lacked expression of ASS, indicating ADI-PEG20 is a potential novel therapy for the treatment of prostate cancer. [Cancer Res 2009;69(2):700–8]
THE PRODUCTION OF ARTERIOSCLEROSIS AND GLOMERULONEPHRITIS IN THE RABBIT BY INTRAVENOUS INJECTIONS OF DIPHTHERIA TOXIN
Authors: C. H. Bailey
Journal: The Journal of Experimental Medicine (1917)

There may be produced in rabbits by the intravenous injection of large doses of diphtheria toxin a vascular degeneration involving the entire aorta, the carotids to the base of the skull, the subclavians, and iliacs, and, for a varying distance distally, the brachials, femorals, and large abdominal vessels. The first part of the pulmonary artery is sometimes affected. The lesion is practically diffuse throughout the aorta and vessels mentioned, consisting of a fatty degeneration and necrosis of the smooth muscle in a wide zone of the media and a crowding together of the elastic fibers in the region affected, resulting in an irregular thinning of the vessel walls and many small aneurysmal pouchings. In rabbits which received pituitrin with the diphtheria toxin extensive calcification occurred throughout this degenerated zone, both in the aorta and other large vessels. It is believed, however, that pituitrin is not essential to the calcification and that if it is of any importance it is because an extreme fatty degeneration is produced more quickly in the media of the vessels when it is administered simultaneously with the toxin. Diphtheria toxin, given in large doses intravenously, produces in the kidneys of the rabbit a pronounced vascular and parenchymatous degeneration. The former consists of a swelling and desquamation of the endothelial cells of the arterioles and small veins with the formation of fibrinous thrombi, a necrosis and thrombosis of the capillaries of the tufts with hemorrhage and the formation of fibrinous and hyaline masses, and in some of the affected glomeruli considerable collections of polymorphonuclear leukocytes.
Diesel Exhaust Exposure and Nasal Response to Attenuated Influenza in Normal and Allergic Volunteers
Authors: Terry L. Noah, Haibo Zhou, Hongtao Zhang, Katie Horvath, Carole Robinette, Matthew Kesic, Megan Meyer, David Diaz-Sanchez, Ilona Jaspers
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Diesel exhaust enhances allergic inflammation, and pollutants are associated with heightened susceptibility to viral respiratory infections. The effects of combined diesel and virus exposure in humans are unknown.Objectives: Test whether acute exposure to diesel modifies inflammatory responses to influenza virus in normal humans and those with allergies.Methods: We conducted a double-blind, randomized, placebo-controlled study of nasal responses to live attenuated influenza virus in normal volunteers and those with allergic rhinitis exposed to diesel (100 μg/m3) or clean air for 2 hours, followed by standard dose of virus and serial nasal lavages. Endpoints were inflammatory mediators (ELISA) and virus quantity (quantitative reverse-transcriptase polymerase chain reaction). To test for exposure effect, we used multiple regression with exposure group (diesel vs. air) as the main explanatory variable and allergic status as an additional factor.Measurements and Main Results: Baseline levels of mediators did not differ among groups. For most postvirus nasal cytokine responses, there was no significant diesel effect, and no significant interaction with allergy. However, diesel was associated with significantly increased IFN-γ responses (P = 0.02), with no interaction with allergy in the regression model. Eotaxin-1 (P = 0.01), eosinophil cationic protein (P < 0.01), and influenza RNA sequences in nasal cells (P = 0.03) were significantly increased with diesel exposure, linked to allergy.Conclusions: Short-term exposure to diesel exhaust leads to increased eosinophil activation and increased virus quantity after virus inoculation in those with allergic rhinitis. This is consistent with previous literature suggesting a diesel "adjuvant" effect promoting allergic inflammation, and our data further suggest this change may be associated with reduced virus clearance.Clinical trial registered with www.clinicaltrials.gov (NCT00617110).
Effect of distension and feeding on phasic changes in human proximal gastric tone.
Authors: N K Ahluwalia, D G Thompson, J Barlow
Journal: Gut (1996)

BACKGROUND: Proximal stomach by virtue of its property of accommodation acts as a reservoir for the ingested food, but its role in emptying and the factors modulating it remain unexplored. AIM: To assess the effects of distension and of feeding on proximal gastric tone. SUBJECTS: 14 healthy volunteers with no current or past history of any gastro-intestinal symptoms. METHODS: Isobaric changes in volume of the proximal stomach were recorded both during fasting and for the first 30 minutes after a meal. RESULTS: For a given degree of distension, the mean (SEM) intragastric pressure was consistently lower, immediately after meal ingestion (9.8 (1.1), mm Hg) than during fasting (12.9 (0.6) mm Hg; p &lt; 0.01). Proximal gastric tone was continuously variable with a frequency of fluctuation of 0.9-1.3/minute and an amplitude of 16.8 (2.2) ml, superimposed upon slower higher amplitude fluctuations in baseline tone. These variations in tone were unaffected by the degree of gastric distension or by food. CONCLUSIONS: While proximal gastric tone decreases after meal ingestions consistent with accommodation, the fluctuations in tone are not an importance factor in the modulation of nutrient emptying from the proximal stomach in the immediate postprandial period.
The treatment of 45 patients with cutaneous T-cell lymphoma with low doses of interferon-α2a and etretinate
Authors: B. DRENO, A. CLAUDY, J. MEYNADIER, J.L. VERRET, P. SOUTEYRAND, J.P. ORTONNE, B. KALIS, W.Y. GODEFROY, K. BEERBLOCK, L. THILL
Journal: British Journal of Dermatology (1991)

Summary Forty-five patients with cutaneous T-cell lymphomas (CTCL), 32 with mycosis fungoides (MF) and 13 with Sézary syndrome (SS), were treated with interferon-α2a (IFN-α2a) (6–9 ± 10IU daily) for 3 months. Those responding to treatment were then treated with interferon-α alone (6–9 ± 106 IU three times weekly), and non-responders received a combination of etretinate(0·5 mg/kg/day) and IFN-α2a in similar concentrations. After 12 months of treatment, 28/ 45 patients (62–2%) were in complete or partial (>50%) remission. Of these. 17 (60±7%) were receiving IFN-α alone and II the combined interferon–retinoid therapy. Of the patients with MF stage I and II,20/25 were responders (12 receiving IFN-α alone and eight on combined therapy), whereas only 8/20 with Stage IV or SS responded to treatment (five receiving IFN-α2a alone and three combined therapy). These results suggest that the association of etretinate with low-dose recombinant IFN-α2a is an effective means of treating epidermotropic CTCL, particularly in the early stages.
Molecular Basis and Enzymatic Properties of Glucose 6-Phosphate Dehydrogenase Volendam, Leading to Chronic Nonspherocytic Anemia, Granulocyte Dysfunction, and Increased Susceptibility to Infections
Authors: Dirk Roos, Rob van Zwieten, Juul T. Wijnen, Felix Gómez-Gallego, Martin de Boer, David Stevens, Claudia J. Pronk-Admiraal, Thea de Rijk, Cornelis J.F. van Noorden, Ron S. Weening, Tom J. Vulliamy, J. Eduard Ploem, Philip J. Mason, José M. Bautista, P. Meera Khan, Ernest Beutler
Journal: Blood (1999)
The Pharmacokinetics (PK), Safety and Tolerability of Fexofenadine HCl 6 mg/mL Suspension in Children with Allergic Rhinitis (AR): a Multicenter, Open-label, Single-dose Study
Authors: R.E. Grubbe, A.S. Nayak, B. Kittner, N. Segall
Journal: Journal of Allergy and Clinical Immunology (2007)
Acceleration of type 1 diabetes mellitus in proinsulin 2–deficient NOD mice
Authors: Karine Thébault-Baumont, Danielle Dubois-Laforgue, Patricia Krief, Jean-Paul Briand, Philippe Halbout, Karine Vallon-Geoffroy, Joëlle Morin, Véronique Laloux, Agnès Lehuen, Jean-Claude Carel, Jacques Jami, Sylviane Muller, Christian Boitard
Journal: Journal of Clinical Investigation (2003)

Accumulating evidence favors a role for proinsulin as a key autoantigen in diabetes. In the mouse, two proinsulin isoforms coexist. Most studies point to proinsulin 2 as the major isoform recognized by T cells in the NOD mouse. We studied mice in which a null proinsulin 2 mutation was transferred from proinsulin 2–deficient 129 mice onto the NOD background along with 16 genetic markers (including I-Ag7 MHC molecule) associated with diabetes. Intercross mice from the fourth backcross generation showed that proinsulin 2–/– mice develop accelerated insulitis and diabetes. The high prevalence of anti-insulin autoantibodies in proinsulin 2–/– mice indicates that diabetes acceleration relates to altered recognition of proinsulin. The prevalence of anti–glutamic acid decarboxylase autoantibodies and of sialitis is not increased in proinsulin 2–/– mice. We give evidence that proinsulin 2 expression leads to silencing of T cells specific for an epitope shared by proinsulin 1 and proinsulin 2. In the human, alleles located in the VNTR region flanking the insulin gene control β cell response to glucose and proinsulin expression in the thymus and are key determinants of diabetes susceptibility. Proinsulin 2–/– NOD mice provide a model to study the role of thymic expression of insulin in susceptibility to diabetes.
Substance Abuse in First-Episode Bipolar I Disorder: Indications for Early Intervention
Authors: Christopher Baethge, Ross J. Baldessarini, Hari-Mandir Kaur Khalsa, John Hennen, Paola Salvatore, Mauricio Tohen
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: This study clarified the early characteristics of substance use disorders in patients with first-episode bipolar I disorder. METHOD: The authors evaluated substance use disorders, associated factors, and clinical course, prospectively, in the first 2 years of DSM-IV bipolar I disorder with standardized methods. RESULTS: Baseline substance use disorder was found in 33% (37 of 112) of the patients at baseline and in 39% at 24 months. Anxiety disorders were more frequent in the patients with than without substance use disorder (30% and 13%, respectively). Associations of alcohol dependence with depressive symptoms and cannabis dependence with manic symptoms were suggested. Patients using two or more substances had worse outcomes. CONCLUSIONS: Since substance use disorders were frequent from the beginning of bipolar I disorder and were associated with anxiety disorders and poor outcome, early interventions for substance use disorder and anxiety might improve later outcome.
Escaping ALK Inhibition: Mechanisms of and Strategies to Overcome Resistance
Authors: Christine M. Lovly, William Pao
Journal: Science Translational Medicine (2012)

Mutated anaplastic lymphoma kinase (ALK) drives the development of multiple tumor types, and ALK tyrosine kinase inhibitors such as crizotinib have been validated as targeted therapeutics. Unfortunately, as with other oncogene-driven tumors, therapeutic resistance invariably develops. In Science Translational Medicine, two recent studies provide new insight into mechanisms of resistance to ALK tyrosine kinase inhibitors and possible strategies to overcome this resistance.
A co-productive health leadership model to support the liberation of the NHS
Authors: Edward Nicol, Bob Sang
Journal: Journal of the Royal Society of Medicine (2011)

Summary Following the recent white paper – Equity and Excellence: Liberating the NHS – we need a 21st-century model of leadership in the NHS that re-focuses on the centrality of the relationship between clinicians and patients. This paper argues the case for co-productive ‘Health Leadership’ that can meet the challenges set by the current Big Society agenda, Darzi and Wanless, so that we achieve a sustainable, high quality NHS, fit for the 21st century.
Protracted enteric cryptosporidial infection in selective immunoglobulin A and saccharomyces opsonin deficiencies.
Authors: M R Jacyna, J Parkin, R Goldin, J H Baron
Journal: Gut (1990)

Chronic cryptosporidial infection in man usually occurs in those who are immunocompromised. We report a patient with a one year history of bowel symptoms resulting from persistent cryptosporidial infection of the colon. Investigations showed underlying selective IgA and saccharomyces opsonin deficiencies but no evidence of cell mediated immune dysfunction. Both selective immunoglobulin A and opsonin deficiencies are relatively common in the general population and may be a cause of susceptibility to persistent cryptosporidial infection.
“Review”-ing Our New Opportunities for “Rapid Report”-ing
Authors: W. K. Alfred Yung
Journal: Neuro-Oncology (2008)

Now that we at Neuro-Oncology are well on our way with our more frequent publication schedule, we would like to take this opportunity to highlight a couple of meaningful opportunities this development presents for enhancing our editorial coverage. Perhaps most obviously, we can now begin to consider and publish Rapid Reports that are truly deserving of the name. In the past, we have used the heading to showcase articles that have undergone expedited review and relatively quick publication. However, in a quarterly journal, there was a built-in delay that no amount of hurrying on the editorial side could make up for.
Coffee Intake, Recurrence, and Mortality in Stage III Colon Cancer: Results From CALGB 89803 (Alliance)
Authors: Brendan J. Guercio, Kaori Sato, Donna Niedzwiecki, Xing Ye, Leonard B. Saltz, Robert J. Mayer, Rex B. Mowat, Renaud Whittom, Alexander Hantel, Al Benson, Daniel Atienza, Michael Messino, Hedy Kindler, Alan Venook, Frank B. Hu, Shuji Ogino, Kana Wu, Walter C. Willett, Edward L. Giovannucci, Jeffrey A. Meyerhardt, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2015)

Purpose Observational studies have demonstrated increased colon cancer recurrence in states of relative hyperinsulinemia, including sedentary lifestyle, obesity, and increased dietary glycemic load. Greater coffee consumption has been associated with decreased risk of type 2 diabetes and increased insulin sensitivity. The effect of coffee on colon cancer recurrence and survival is unknown. Patients and Methods During and 6 months after adjuvant chemotherapy, 953 patients with stage III colon cancer prospectively reported dietary intake of caffeinated coffee, decaffeinated coffee, and nonherbal tea, as well as 128 other items. We examined the influence of coffee, nonherbal tea, and caffeine on cancer recurrence and mortality using Cox proportional hazards regression. Results Patients consuming 4 cups/d or more of total coffee experienced an adjusted hazard ratio (HR) for colon cancer recurrence or mortality of 0.58 (95% CI, 0.34 to 0.99), compared with never drinkers (P trend = .002). Patients consuming 4 cups/d or more of caffeinated coffee experienced significantly reduced cancer recurrence or mortality risk compared with abstainers (HR, 0.48; 95% CI, 0.25 to 0.91; P trend = .002), and increasing caffeine intake also conferred a significant reduction in cancer recurrence or mortality (HR, 0.66 across extreme quintiles; 95% CI, 0.47 to 0.93; P trend = .006). Nonherbal tea and decaffeinated coffee were not associated with patient outcome. The association of total coffee intake with improved outcomes seemed consistent across other predictors of cancer recurrence and mortality. Conclusion Higher coffee intake may be associated with significantly reduced cancer recurrence and death in patients with stage III colon cancer.
Segmental uniparental disomy is a commonly acquired genetic event in relapsed acute myeloid leukemia
Authors: Manoj Raghavan, Lan-Lan Smith, Debra M. Lillington, Tracy Chaplin, Ioannis Kakkas, Gael Molloy, Claude Chelala, Jean-Baptiste Cazier, James D. Cavenagh, Jude Fitzgibbon, T. Andrew Lister, Bryan D. Young
Journal: Blood (2008)
Ethics and reproductive medicine
Authors: D Schafer
Journal: Human Reproduction Update (1996)

This article surveys relevant moral and ethical implications of reproductive medicine, excluding any aspects of contraception. To maintain the methodological priority of a moral perspective, it focuses on moral theory and ethics in general before looking at the impact of ethics on the different techniques applied in reproductive medicine. We suggest that discourse ethics should be centre-stage among the moral perspectives, since it has a unique capacity to synthesize, gauge and emulate other moral perspectives without necessarily replacing them. Questions of spousal fidelity, parental identity, sexual relations, reshaping of family ties, preimplantation diagnosis, discarding of human life, up to the question of what kind of life is generally acknowledged as worth living, and which is not, all these are morally significant topics. As well as providing a description of the techniques used in reproductive medicine, our article presents a rationale for charting potentials for moral problems. This renders it possible to elucidate the moral costs of each of the options offered by reproductive medicine in the light of whatever moral view one identifies with. Keywords: discourse/ethics/reproductive medicine