tbuckley/cabot-search huggingface dataset:
Cellular sensors of feast and famine
Authors: Eric Ravussin
Journal: Journal of Clinical Investigation (2002)

In response to changes in environmental conditions, animals and humans alike can initiate physiological regulatory mechanisms to assure survival. For example, when food is scarce, the body becomes “thrifty”, and conversely, when it is abundant, physiological “unthrifty” mechanisms are initiated. Recent work has uncovered novel cellular mechanisms of fuel sensing that contribute to these shifts and has established a potential relationship between these responses and the common metabolic phenotype of insulin resistance.
How stress gets under the skin: cortisol and stress reactivity in psoriasis
Authors: A.W.M. Evers, E.W.M. Verhoeven, F.W. Kraaimaat, E.M.G.J. De Jong, S.J.M. De Brouwer, J. Schalkwijk, F.C.G.J. Sweep, P.C.M. Van De Kerkhof
Journal: British Journal of Dermatology (2010)

Psychological stressors might contribute to the severity of chronic inflammatory diseases such as psoriasis by dysregulating hypothalamic-pituitary-adrenal (HPA) axis activity.To evaluate the role of cortisol, a key component of the HPA axis, in reaction to psychological stress in patients with psoriasis.Serum cortisol, clinical indicators of disease severity (Psoriasis Area and Severity Index) and self-report measures of daily stressors were measured monthly for 6 months in 62 patients with psoriasis.In addition to the previous findings in this sample showing that peak levels of daily stressors predicted an increase in disease severity a month later, the peak levels of daily stressors were also significantly associated with a lower cortisol level. Moreover, patients who persistently experienced higher levels of daily stressors had lower mean cortisol levels than patients who experienced lower levels of daily stressors.Results suggest that daily stressors influence disease outcome in patients with psoriasis by affecting cortisol levels at moments of high stress. Furthermore, patients with persistently high levels of stressors seem to have a specific psychophysiological profile of lowered cortisol levels and may be particularly vulnerable to the influence of stressors on their psoriasis.
A Phase I Trial of Humanized Monoclonal Antibody A33 in Patients with Colorectal Carcinoma: Biodistribution, Pharmacokinetics, and Quantitative Tumor Uptake
Authors: Andrew M. Scott, Fook-Thean Lee, Robert Jones, Wendie Hopkins, Duncan MacGregor, Jonathan S. Cebon, Anthony Hannah, Geoffrey Chong, Paul U, Anthony Papenfuss, Angela Rigopoulos, Susan Sturrock, Roger Murphy, Veronika Wirth, Carmel Murone, Fiona E. Smyth, Simon Knight, Sydney Welt, Gerd Ritter, Elizabeth Richards, Edouard C. Nice, Antony W. Burgess, Lloyd J. Old
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To determine the in vivo characteristics of huA33, a CDR-grafted humanized antibody against the A33 antigen, we have conducted an open-label, dose escalation, biopsy-based phase I trial of huA33 in patients with colorectal carcinoma. Experimental Design: Patients with colorectal carcinoma were infused with [131I]huA33 (400 MBq: 10 mCi) and [125I]huA33 (40 MBq: 1 mCi) 1 week before surgery. There were four huA33 dose levels (0.25, 1.0, 5.0, and 10 mg/m2). Adverse events, pharmacokinetics, biodistribution, tumor biopsies, and immune responses to huA33 were evaluated. Results: There were 12 patients entered into the trial (6 males and 6 females; age range, 39-66 years). No dose-limiting toxicity was observed. The biodistribution of huA33 showed excellent uptake of [131I]huA33 in metastatic colorectal carcinoma. Pharmacokinetic analysis showed no significant difference in terminal half-life (T1/2β) between dose levels (mean ± SD, 86.92 ± 22.12 hours). Modeling of colon uptake of huA33 showed a T1/2 of elimination of 32.4 ± 8.1 hours. Quantitative tumor uptake ranged from 2.1 × 10−3 to 11.1 × 10−3 %ID/g, and tumor/normal tissue and tumor/serum ratios reached as high as 16.3:1 and 4.5:1, respectively. Biosensor analysis detected low-level human anti-human antibody responses in four patients following huA33 infusion. Conclusions: huA33 shows selective and rapid localization to colorectal carcinoma in vivo and penetrates to the center of large necrotic tumors, and colon elimination half-life of huA33 is equivalent to basal colonocyte turnover. The excellent targeting characteristics of this humanized antibody indicate potential for the targeted therapy of metastatic colorectal cancer in future trials.
Diverging effects of HLA–DPB1 matching status on outcome following unrelated donor transplantation depending on disease stage and the degree of matching for other HLA alleles
Authors: B E Shaw, N P Mayor, N H Russell, J F Apperley, R E Clark, J Cornish, P Darbyshire, M E Ethell, J M Goldman, A-M Little, S Mackinnon, D I Marks, A Pagliuca, K Thomson, S G E Marsh, J A Madrigal
Journal: Leukemia (2009)
Preconditioning with death ligands FasL and TNF- protects the cirrhotic mouse liver against ischaemic injury
Authors: J-H Jang, W Moritz, R Graf, P-A Clavien
Journal: Gut (2007)

<h3></h3> 1) Context: This audit took place in Glan Clwyd Hospital, a DGH in north Wales. The project involved all patients who were prescribed oxygen in the hospital and was carried out by junior doctors in the respiratory department with senior supervision. 2) Issue: The main purpose of the audit was to develop junior doctors as leaders and bring about a meaningful change in a system that was already saturated with audits that were performed as a tick box exercise for curriculum purposes. Incorrect oxygen prescription was an issue which all of the junior doctors identified during their placement and often had profound effects on patient management. We postulated that by performing this audit, we would bring about a very positive effect on the management of patients on oxygen and would result in a major change in practice, all driven by foundation year one doctors. 3) Assessment of issue and analysis of its causes: Objectives of the audit were: To check compliance there is with oxygen prescription by doctors according to the ALL Wales Drug Chart, whether the oxygen was prescribed correctly, whether the patient was receiving the correct amount of oxygen as stated on the observations chart and whether the target saturations were met– for this, we divided into groups of two and visited wards, identifying patients on oxygen and going through their drug charts manually. To see how many nurses had received formal oxygen training– this was done as individual interviews of the nursing staff by junior doctors. Whether doctors and nurses were correctly able to interpret oxygen flow rate correctly– this was done in real time by asking doctors and nurses to correctly identify the flow meter reading by the bedside.
Specific binding of leukotriene B4 to a receptor on human polymorphonuclear leukocytes.
Authors: R A Kreisle, C W Parker
Journal: The Journal of Experimental Medicine (1983)

In this paper we have described the binding of nanomoler concentrations of [3H]leukotriene B4 (LTB4) to human polymorphonuclear leukocytes. Because up to 80% of the total [3H]LTB4 binding was blocked by excess (greater than 100 times) [14C]LTB4, the majority of binding is specific. Stereospecificity of the LTB4 binding is demonstrated by the diminished relative abilities of the 6-trans-and 12-epi-6-trans- isomers of LTB4 to block [3H]LTB4 binding. With these two isomers 3-10-fold higher than [14C]LTB4 concentrations were needed for equivalent inhibition of [3H]LTB4 binding. This difference is quantitatively less dramatic than the differences between these isomers in many in vitro functional assays such as chemokinesis, chemotaxis, and degranulation. Binding of [3H]FMLP is not blocked at greater than 100-fold excess of LTB4. The binding of [3H]LTB4 to cells appears to be essentially irreversible at 4 degrees C, but not at 37 degrees C where initially bound LTB4 is rapidly converted to metabolites which then enter the medium. These results suggest the presence of a saturable, stereospecific site for LTB4 on PMN. The association of LTB4 binding and the initiation of pharmacological responses to LTB4 will require further studies.
Beyond hepatitis C: The anti-inflammatory role of heme oxygenase-1 in systemic infections
Authors: Shailendra Kapoor
Journal: Hepatology (2008)

The recent article by Zhu et al. was highly enlightening and thought-stimulating.1 The authors have clearly shown that Heme oxygenase-1 suppresses replication of hepatitis C virus and increases resistance of hepatocytes to oxidant injury. The findings of Zhu et al. are highly significant because they further corroborate recent studies that suggest that Heme oxygenase-1 may play a major protective role in other systemic inflammatory conditions besides hepatitis C. For instance, Heme oxygenase-1 increases the synthesis of decay-accelerating factor and thereby attenuates complement-induced endothelial dysfunction in systemic infections.2 Similarly, Heme oxygenase-1 protects tissue such as pulmonary tissue from red blood cell–induced inflammation in lung infections, while increased expression of Heme oxygenase-1 limits systemic damage in septic shock by decreasing endotoxin-induced overexpression of the Type-2 cationic amino acid transporter (CAT-2) enzyme.3 It also inhibits nitric oxide production in endotoxic shock.4 On the other hand, inhibition of Heme oxygenase-1 function has a potent anticarcinogenic influence. For instance, knockdown of Heme oxygenase-1 function by small interfering RNAs has a negative effect on tumor growth in malignancies such as hepatocellular carcinomas.5 Interestingly, a number of factors influence and alter Heme oxygenase-1 levels in the body. For instance, lipopolysaccharide affects the nuclear factor-E2–related factor (nrf2) pathway and thereby accentuates the expression of Heme oxygenase-1 in monocytes, thereby protecting organs such as the liver from damage in severe systemic infections.6 Similarly, hemin arginate induces Heme oxygenase-1 production thereby enhancing hepatic microcirculation and protecting hepatic tissue following septic shock.7 Besides these anti-inflammatory functions, Heme oxygenase-1 also has a major role to play in other hepatic functions. For instance, accentuated Heme oxygenase-1 production decreases ischemia/reperfusion injury in hepatic cells.8 The above examples clearly illustrate the massive therapeutic potential of the anti-inflammatory properties of Heme oxygenase-1. There is a clear and urgent need for further studies to fully elaborate and harness these anti-inflammatory functions of Heme oxygenase-1 for the management of other systemic infections besides hepatitis C. Shailendra Kapoor M.D.*, * Schaumburg, IL.
Pressure Variations in Small Veins in the Hindleg of the Dog
Authors: MARY P. WIEDEMAN
Journal: Circulation Research (1960)

Rhythmical changes in small vein pressure were shown to follow the direction of changes in intra-abdominal pressure. Pressure waves in small veins could be diminished considerably during femoral artery occlusion when the venous cannula was directed away from the vena cava. They were only slightly affected when the venous cannula was directed toward the vena cava. Small vein pressure waves were markedly decreased by opening the abdomen and reducing intra-abdominal pressure. It is concluded that intra-abdominal pressure change is a major factor in varying small vein pressure in the hindleg of an anesthetized dog in a supine position.
Development of Systems of Care for ST-Elevation Myocardial Infarction Patients
Authors: Gray Ellrodt, Lawrence B. Sadwin, Thomas Aversano, Bruce Brodie, Peter K. O’Brien, Richard Gray, Loren F. Hiratzka, David Larson
Journal: Circulation (2007)

D evelopers of systems to improve access to primary percutaneous intervention (PCI) must recognize that most ST-elevation myocardial infarction (STEMI) patients present to hospitals that do not have PCI capability.Indeed, only Ϸ25% of US hospitals are currently capable of delivering this intervention. 1These non-PCI-capable institutions are often located in rural areas and face real challenges related to distance from PCI centers.In addition, these institutions face significant financial challenges 2 in pursuing any of the 3 potential strategies to increase timely access to primary PCI.These 3 strategies include the following 3 : (1) hospitals currently without PCI capability can develop primary PCI services without cardiac surgery on-site (SOS); (2) non-PCIcapable facilities can rapidly diagnose and transfer STEMI patients to primary PCI-capable hospitals and thereby serve as STEMI referral hospitals; or (3) communities can develop systems that bypass non-PCI-capable hospitals.Each of these strategies is addressed in this article.For each, we review the current status, the ideal system, gaps in and barriers to development of the ideal system, and recommendations.
The Challenge of CONTEMPO
Authors: Harriet S. Meyer
Journal: JAMA (1981)

For this, the fourth edition of our annual review issue, CONTEMPO, we challenged our contributors to provide articles of interest both to specialists in the same field and to colleagues in other fields. Our contributors have met the challenge. Now, we challenge our readers—to become aware of the clinical developments, research advances, and philosophies of other fields of medicine. As Drs Harry Jacob and Dale Hammerschmidt will discuss in our July 3 CLINICAL PERSPECTIVES, such awareness can spark ideas for new applications of one's own specialized knowledge. We hope all of our readers will profit from the CONTEMPO articles in other fields as well as their own. If computed tomography was the advance of the decade (see CONTEMPO '80), monoclonal antibodies are the advance of the year. Their promise in cancer detection, disease therapy, and research is cited in this year's articles on "The Drug Year," "Oncology," "Nuclear Medicine," "Immunology,"
EFFECTS ON TITRATIONS OF INEQUALITY OF SENSITIZATION OF CORPUSCLES
Authors: C. H. Bailey
Journal: The Journal of Experimental Medicine (1912)

The absorption of amboceptor by corpuscles is rapid, a considerable amount being absorbed in as short a period as fifteen seconds. In the sensitization of corpuscles, the amount of amboceptor absorbed by the different corpuscles is not uniform, the inequality depending on the time taken in obtaining an even distribution of the corpuscles through the diluted immune serum. Amboceptor absorption is apparently influenced by the concentration of the corpuscles, being more rapid with a 5 per cent. than with a 2 per cent. suspension, and thus the stronger concentration is more susceptible to inequality of sensitization from variations in the method of activation. In experimental work, it is of importance to obtain as equal a sensitization as possible. It is essential that in comparative titrations the same method of activation be employed in the several titrations, and where possible it is advisable that all the cells used be sensitized together in bulk. The results obtained in titrating hemolytic sera and complement depend to a considerable extent upon the evenness of sensitization of the corpuscles.
Interindividual Variability in Inhibition and Induction of Cytochrome P450 Enzymes
Authors: Jiunn H Lin, Anthony YH Lu
Journal: The Annual Review of Pharmacology and Toxicology (2001)

Drug interactions have always been a major concern in medicine for clinicians and patients. Inhibition and induction of cytochrome P450 (CYP) enzymes are probably the most common causes for documented drug interactions. Today, many pharmaceutical companies are predicting potential interactions of new drug candidates. Can in vivo drug interactions be predicted accurately from in vitro metabolic studies? Should the prediction be qualitative or quantitative? Although some scientists believe that quantitative prediction of drug interactions is possible, others are less optimistic and believe that quantitative prediction would be very difficult. There are many factors that contribute to our inability to quantitatively predict drug interactions. One of the major complicating factors is the large interindividual variability in response to enzyme inhibition and induction. This review examines the sources that are responsible for the interindividual variability in inhibition and induction of cytochrome P450 enzymes.
Further Experimental Studies on the Prevention of Rh Haemolytic Disease
Authors: C. A. Clarke, W. T. A. Donohoe, R. B. McConnell, J. C. Woodrow, R. Finn, J. R. Krevans, W. Kulke, D. Lehane, P. M. Sheppard
Journal: BMJ (1963)

In a previous report (Finn et al., 1961) we gave reasons for thinking that the rapid removal of Rh-positive foetal erythrocytes from the circulation of a mother who was Rh-negative would prevent her from becoming immunized and producing Rh antibodies.We have now investigated the matter further, and the present paper describes the completed results of the earlier work (Experiment I) and then gives details of some subsequent observations (Experiments II and III).The reasoning involved and the scope of the investigations are first discussed.Levine (1943) demonstrated the marked degree of protection against Rh haemolytic disease afforded by ABO incompatibility between mother and foetus.We agreed with Race and Sanger (1950) that the probable mechanism lay in the rapid destruction of the incompatible foetal cells in the circulation by the anti-A and anti-B.Experiment I was therefore designed to determine whether immunization resulting from injection of ABO compatible Rh-positive blood into Rh-negative male volunteers could be prevented by the infusion of plasma containing high-titre saline-reacting (complete) anti-D antibodies, simulating the effect of anti-A and anti-B.Some initial results of this experiment have been briefly reported (Finn et al., 1962).It was found that, compared with control subjects, antibody formation was enhanced rather than prevented and we noted that in some cases nearly half the injected cells survived in the circulation for over a week, though at that time free complete anti-D could be detected in the recipients' sera.On the basis of these results a second approach which forms the substance of Experiment II was tried.Stern et al. (1961) had shown that prior in vitro coating of Rh-positive erythrocytes with incomplete anti-D would prevent antibody formation after subsequent injection
The Role of Public Health Institutions in Global Health System Strengthening Efforts: The US CDC's Perspective
Authors: Peter Bloland, Patricia Simone, Brent Burkholder, Laurence Slutsker, Kevin M. De Cock
Journal: PLoS Medicine (2012)

N Health system strengthening has become a recognized priority for achieving major public health goals such as those identified by disease-specific global health initiatives for HIV/AIDs, tuberculosis, malaria, childhood immunizations, and others.N The contribution that strengthening of public health systems makes to strengthening health systems in general has been inadequately described.N To guide its support of public health in low-and middle-income countries around the world, the US Centers for Disease Control and Prevention (CDC) proposes to prioritize its investments on strengthening six key public health functions that would contribute the most towards health systems strengthening efforts as a whole and have the greatest impact on improving the public's health.N In this Policy Forum article, we set out the US CDC's perspective on the role of public health institutions in global health system strengthening efforts.
Nasal histamine challenge in nonallergic and allergic subjects evaluated by acoustic rhinometry
Authors: O. Hilberg, L. F. Grymer, O. F. Pedersen
Journal: Allergy (1995)

Nasal patency shows spontaneous variations but is influenced by a number of factors like exercise and allergic conditions. Nasal histamine challenge has been used to define nasal hypersensitivity. We have applied acoustic rhinometry as a new objective method to study the spontaneous variations of the nasal mucosa and its response to histamine challenge in 12 nonallergic subjects and 12 subjects with nasal allergy to pollen, but out of the pollen season. Measurements of the minimum cross‐sectional area and the volume of the nasal cavities were done every 15 min for 6 h. More pronounced spontaneous variations, defined by the coefficient of variation of the measurements, were encountered in the allergic than in the nonallergic subjects, especially with regard to the minimum cross‐sectional areas in the nasal cavities ( P &lt; 0.02). Allergic subjects showed increased sensitivity to histamine, as compared with nonallergic subjects, during low‐concentration (0.1%) challenge ( P &lt; 0.05) and a prolonged effect of histamine challenge ( P = 0.01). Antihistamine (cetirizine) had a significant effect on the histamine‐induced symptoms and decrease of nasal dimensions during histamine challenge, but no significant effect on pollen‐induced changes. In the allergic group, the decrease in minimum area during allergen provocation correlated with the level of specific IgE ( r = 0.81; P = 0.0015).
An unusual case of biliary pain
Authors: J Boujaoude
Journal: Gut (2005)

Background: In the intestinal tract, the role of sympathetic neurotransmitters has been largely ignored in mucosal neuroimmunology.Aim: Our aim was to investigate the influence of the sympathetic microenvironment on the mucosal interplay of tumour necrosis factor (TNF) and interleukin 6 (IL-6).Methods: Colon strips of normal and colitic BALB/c mice were superfused in vitro.Tissue was electrically stimulated to investigate the influence of endogenous norepinephrine (NE) on secretion of IL-6, with or without anti-TNF antibodies (anti-TNF) and adrenoceptor antagonists.IL-6 was secreted from macrophages.Results: Superfusion with anti-TNF stimulated IL-6 secretion in normal but not in colitic colon (p,0.005).Parallel superfusion with a b-adrenergic antagonist abrogated this phenomenon.Anti-TNF increased release of NE from normal colonic strips (p,0.05), which demonstrates TNF induced inhibition of preterminal NE release.In colitic mice, anti-TNF did not change NE release.In the presence of anti-TNF, exogenous and endogenous NE stimulated colonic IL-6 secretion via b-adrenoceptors in normal (p,0.001)but not in colitic mice.In the absence of anti-TNF, endogenous and exogenous NE inhibited IL-6 secretion via the b-adrenoceptor in normal but not in colitic mice (p,0.01).Colitic mice demonstrated loss of sympathetic nerve fibres.Conclusions: Modulation of mucosal IL-6 is largely dependent on the sympathetic microenvironment and availability of local TNF in normal but not in colitic mice.Anti-TNF strategies may lead to an increase in the proinflammatory cytokine depending on adrenergic tone.This would be relevant with normal sympathetic innervation, which is lost in colitic mice.We present a model of sympathetic regulation of colonic macrophage TNF and IL-6 secretion.