tbuckley/cabot-search huggingface dataset:
Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation.
Authors: H O Steinberg, M Tarshoby, R Monestel, G Hook, J Cronin, A Johnson, B Bayazeed, A D Baron
Journal: Journal of Clinical Investigation (1997)

We have recently shown that insulin-resistant obese subjects exhibit impaired endothelial function. Here, we test the hypothesis that elevation of circulating FFA to levels seen in insulin-resistant subjects can impair endothelial function. We studied leg blood flow responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (Mch) or the endothelium-independent vasodilator sodium nitroprusside during the infusion of saline and after raising systemic circulating FFA levels exogenously via a low- or high-dose infusion of Intralipid plus heparin or endogenously by an infusion of somatostatin (SRIF) to produce insulinopenia in groups of lean healthy humans. After 2 h of infusion of Intralipid plus heparin, FFA levels increased from 562+/-95 to 1,303+/-188 micromol, and from 350+/-35 to 3,850+/-371 micromol (P < 0.001) vs. saline for both low- and high-dose groups, respectively. Mch-induced vasodilation relative to baseline was reduced by approximately 20% in response to the raised FFA levels in both groups (P < 0.05, saline vs. FFA, ANOVA). In contrast, similar FFA elevation did not change leg blood flow responses to sodium nitroprusside. During the 2-h SRIF infusion, insulin levels fell, and FFA levels rose from 474+/-22 to 1,042+/-116 micromol (P < 0.01); Mch-induced vasodilation was reduced by approximately 20% (P < 0.02, saline vs. SRIF, ANOVA). Replacement of basal insulin levels during SRIF resulted in a fall of FFA levels from 545+/-47 to 228+/-61 micromol, and prevented the impairment of Mch-induced vasodilation seen with SRIF alone. In conclusion, (a) elevated circulating FFA levels cause endothelial dysfunction, and (b) impaired endothelial function in insulin-resistant humans may be secondary to the elevated FFA concentrations observed in these patients.
NK cells expressing inhibitory KIR for non–self-ligands remain tolerant in HLA-matched sibling stem cell transplantation
Authors: Andreas T. Björklund, Marie Schaffer, Cyril Fauriat, Olle Ringdén, Mats Remberger, Christina Hammarstedt, A. John Barrett, Per Ljungman, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
Journal: Blood (2010)
Impact of using stated instead of measured height upon screening spirometry.
Authors: J M Parker, T A Dillard, Y Y Phillips
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

This study examined the impact of using stated height instead of measured height on predicted normal values and clinical interpretation of screening spirometry in an outpatient referral population. In a prospective fashion, we evaluated 210 patients, 20 to 89 yr of age, referred for spirometry to our pulmonary function laboratory by obtaining both stated height (HTs) and measured height (HTm). The mean difference between stated and measured height progressively increased with age, from 0.80 cm (20 to 29 yr; p = 0.01) to 5.70 cm (80 to 89 yr; p < 0.001). For men and women, use of HTs instead of HTm produced a mean difference for all ages in computing predicted FEV1 and FVC values of 3.9 and 4.3%, respectively. This effect was more prominent in the older age groups (80 to 89 yr, n = 30); mean differences were 11.0% (211 ml) and 11.7% (303 ml), respectively. Use of HTs instead of HTm altered the detection of restriction by reduced FVC in 17 patients and the detection of obstruction by reduced FEV1/FVC ratio in four patients. Use of HTs altered the clinical assessment of severity by FEV1 in 15 of 108 (13.9%) obstructed patients and altered the assessment of severity by FVC in 11 of 32 (34.4%) restricted patients, with older patients more frequently affected than younger patients. We conclude that the use of stated height instead of measured height in the performance of screening spirometry can have significant impact on the calculation of predicted normal values. These discrepancies can potentially influence the clinical interpretation of screening spirometry, affecting the detection of abnormality and the assessment of severity of disease, particularly among older patients.
Detection of nickel and palladium contact hypersensitivity by a flow cytometric lymphocyte proliferation test
Authors: I. Spoerri, K. Scherer, S. Michel, S. Link, A. J. Bircher, I. A. F. M. Heijnen
Journal: Allergy (2014)

We established a flow cytometric lymphocyte proliferation test (LPT) for the detection of nickel (Ni) and palladium (Pd) sensitization. Eighty-one consecutive patients with an indication for patch test (PT) were tested by LPT with Ni (NiSO4 ) and Pd (Na2 PdCl4 and PdCl2 ) salts. The imprecision of the LPT was low (coefficient of variation 7.2%). Using PT as a diagnostic reference, the sensitivity and specificity of LPT were 74.4% and 80% for NiSO4 , 74.4% and 78.3% for Na2 PdCl4 , and 57.2% and 85.4% for PdCl2 , respectively. For both Ni and Pd, the likelihood ratio for a positive PT markedly increased with increasing LPT value. With medical history as a reference, the sensitivity and specificity were 40.6% and 82.1% for LPT and 59.4% and 89.7% for PT, respectively. Combination of LPT and PT resulted in a higher specificity of 95%, albeit lower sensitivity of 34.4%. In conclusion, flow cytometric LPT represents a reliable and useful method for the detection of Ni and Pd sensitization. LPT values correlate with PT results and, when used in combination with PT, increase test specificity.
Increased endothelin release by cultured human smooth muscle cells from atherosclerotic coronary arteries
Authors: C HAUG, R VOISARD, A LENICH, R BAUR, M HOHER, H OSTERHUES, A HANNEKUM, U VOGEL, T MATTFELDT, V HOMBACH
Journal: Cardiovascular Research (1996)

Endothelin, a 21-amino acid peptide initially purified from the medium of cultured endothelial cells, is a potent vasoconstrictor exerting its effects predominantly in a paracrine or autocrine manner. Recent data indicate that endothelin is also synthesized by cultured vascular smooth muscle cells and that endothelin is an effective stimulator of smooth muscle cell proliferation. This study aimed to investigate the endothelin release of cultured human smooth muscle cells, isolated from coronary plaques and from normal coronary tunica media, and to determine circulating endothelin concentrations in patients with coronary artery disease compared to control subjects.Coronary plaque material was extracted by thrombendarterectomy during aorto-coronary bypass grafting (n = 19). Segments of normal coronary arteries were obtained at autopsy (n = 33). Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells with antibodies against smooth muscle alpha-actin. Venous blood samples were drawn from patients with coronary artery disease undergoing cardiac catheterization (n = 32) and from control subjects (n = 38). Endothelin concentrations in culture medium and in plasma samples were measured by radioimmunoassay after Sep Pak C18 extraction.Cultured smooth muscle cells, isolated from coronary plaques, released a significantly (P < 0.001) higher amount of immunoreactive endothelin into the culture medium (39.2 +/- 3.9 pg/10(4) cells, mean +/- s.e.m., 31 supernatant samples) than smooth muscle cells from normal coronary tunica media (3.9 +/- 0.8 pg/10(4) cells, 28 samples). Circulating endothelin concentrations were slightly elevated (P < 0.01) in patients with coronary artery disease (3.8 +/- 0.2 pg/ml) compared to control subjects (3.0 +/- 0.2 pg/ml).These data suggest that the endothelin production is markedly increased in smooth muscle cells of coronary atherosclerotic plaques. The enhanced endothelin release may stimulate smooth muscle cell proliferation in a paracrine or autocrine manner and thus may contribute to the development or progression of coronary artery disease.
Cow's milk allergy in children
Authors: J. R Apps, R M. Beattie
Journal: BMJ (2009)

#### Case scenarios

##### Case 1

A 3 month old infant, previously breast fed, presented with a urticarial rash, irritability, and vomiting shortly after introduction of cow’s milk formula. He was referred to a paediatric allergy clinic where skin prick testing and specific IgE testing were positive for cow’s milk protein. The mother did not wish to continue breast feeding. The formula was changed to an extensively hydrolysed protein feed, and the symptoms resolved rapidly. Re-challenge with cow’s milk was deferred until 12 months and proceeded uneventfully. 

##### Case 2

An otherwise well and thriving 6 week old breast fed infant presented with frequent stools, irritability, and perianal redness. Because physical examination was otherwise unremarkable and stool virology and culture were negative, he was referred to the paediatric (gastroenterology) outpatients department. Dietary protein induced proctocolitis was suspected. Because cow’s milk is the most common allergen implicated in this condition, the mother was advised to stop taking all dairy products, but to continue breast feeding. The symptoms resolved within 72 hours but reappeared on challenge. The mother therefore continued to avoid dairy products while breast feeding (an extensively hydrolysed feed would be an alternative), and the infant was weaned at 6 months on to dairy free solids. Cow’s milk was reintroduced at 12 months, and the child’s original symptoms did not recur. The mother was referred for dietetic advice and prescribed calcium supplements.

Cow’s milk (protein) allergy is an adverse immunological response to cow’s milk proteins seen mainly in the first few years of life. It can have diverse manifestations. It can be broadly divided into IgE (type I hypersensitivity) mediated disease and non-IgE (usually type IV hypersensitivity) mediated disease, sometimes referred to as cow’s milk (protein) intolerance. These differ in clinical presentation, diagnostic testing, and prognosis; for example, type I hypersensitivity classically presents early, with symptoms such as urticaria, …
947. Effects of Natural Pre-Existing Humoral Immunity to AAV on Administration of AAV2-NTN to the Brain of Non-Human Primates
Authors: Marie A. Printz, Christopher D. Herzog, Alistair Wilson, Dawn Gammon, Richard Lin, Roberto Calcedo, Biplob Dass, Medhi Gasmi, Jeffrey H. Kordower, Raymond T. Bartus
Journal: Molecular Therapy (2005)

The prevalence of antibodies (ab) to wild type AAV2 in humans is estimated to be 50-90%, with 30% developing neutralizing ab (Nab). In an attempt to mimic pre-existing immunity in animal models, many groups have immunized naive animals in order to study its effect on gene transfer. One limitation of this approach is that direct inoculation with high titers of AAV with adjuvant does not mimic the natural course of infection of the wild type virus. Therefore, the nature and intensity of the immune response may differ considerably from that generated by mucosal exposure. In addition, gene transfer is often attempted during the acute phase of the immune response. In contrast, human AAV2 seroconversion typically occurs in childhood, while AAV gene transfer is often performed in adults.
Anti-IgE–induced accumulation of leukocytes, mediators, and albumin in skin chamber fluid from healthy and atopic subjects
Authors: Johan Raud, Gunilla Halldén, Annika Roquet, Marianne van Hage-Hamsten, Ulf Alkner, Jan Hed, Olle Zetterström, Sven-Erik Dahlén, Per Hedqvist, Reidar Grönneberg
Journal: Journal of Allergy and Clinical Immunology (1996)
The exaggerated claims of the mental health industry
Authors: D. A. Summerfield
Journal: BMJ (2012)

Godlee’s comments take the supposed rational technical modernity of the mental health industry at face value.1 Psychiatry has shallow epistemological foundations: neither essence nor cause of any “mental disorder” is understood, except for disorders associated with physical disease. For example, “depression” is not a biologically validated entity, merely a symptom cluster—clustered by us, not nature. The editorial …
ON THE ABSORPTION OF BACTERIAL ENDOTOXIN FROM THE GASTRO-INTESTINAL TRACT OF THE NORMAL AND SHOCKED ANIMAL
Authors: H. A. Ravin, D. Rowley, C. Jenkins, J. Fine
Journal: The Journal of Experimental Medicine (1960)

Coliform-free rabbits fed P32 labeled E. coli 0111B4 prior to the induction of experimental hemorrhagic shock were shown to have a substantial amount of the type-specific 0111B4 antigen in the circulating blood, liver, and spleen, whereas normal rabbits fed the same amount of these bacteria and held under identical conditions, but not exposed to shock, have the antigen within the liver, and occasionally in the kidney, but not in the blood. That the antigen recovered from the blood and tissues was derived from this specific strain of bacteria was demonstrated by the use of the hemagglutination inhibition reaction, by the absence of cross-reacting antigens in appropriate control animals, and by agreement in the amount of antigen as estimated by two different technics. Transport of bacterial endotoxin across the intestinal membrane appears to be achieved primarily by passive diffusion. The accumulation of biologically active endotoxin in the blood and tissues of the shocked animal appears to be due to a reduction in the detoxifying potential of the reticulo-endothelial system, and not to a greater than normal absorption of endotoxin from the intestine. The absence of toxicity in the specific antigen extracted from normal liver demonstrates that the degradation of endotoxic potency can be achieved without altering the chemical integrity of the polysaccharide moiety of the molecule. The implications of the hypothesis that there is a continuous but fluctuating absorption of bacterial endotoxin from the intestine are briefly discussed, and the contribution of free circulating bacterial endotoxin of intestinal origin to the fate of the shocked animal is noted.
Racial discrimination in medicine
Authors: K. J Mckenzie
Journal: BMJ (1995)

thrombolysis the treatment may cause intramyocardial haemorrhage, which may predispose to cardiac rupture. 19urthermore, though thrombolytic treatment has been shown to reduce the size of the infarct and mortality, improvements in left ventricular function have been less striking.The reasons for this discrepancy have been a source of debate, and the traditionally accepted relation between patency of the coronary artery, myocardial salvage, and ventricular function has been questioned.Restoration of the patency of vessels may not in itself be sufficient to restore myocardial contractile function in all patients.These findings imply that there is a trade off between the early problems of thrombolytic treatment and the longer term benefits.They may also represent a previously hidden manifestation of reperfusion injury.The clinical evidence strongly suggests that the components of reperfusion injury identified in the laboratory are of practical importance.Myocardial reperfusion may not benefit all patients and may actually be harmful to some.Components of reperfusion injury may occur not only in isolation but also in combination-when more profound consequences might be expected.The exact mechanisms of reperfusion injury are uncertain, but they probably include cellular overload of calcium, osmotic cell swelling, and myocyte or microvascular damage from cytotoxic free radicals derived from oxygen.The evidence for this last mechanism comes from inter- ventional studies designed to show whether agents targeting the formation offree radicals might protect against reperfusion injury.20 Direct evidence of the presence of free radicals has now been provided by electron paramagnetic resonance spectroscopy and spin trapping techniques in coronary venous effluent blood, before and after primary angioplasty reperfusion.21Nevertheless, confirming the presence of free radicals does not in itself indicate that reperfusion injury has occurred or that free radicals are the only mediators of reperfusion injury.Further clinical studies are needed to examine closely the relation between free radical generation and various components of myocardial reperfusion injury.Only when these data are available can the potential benefits of adjuvant pharmacological agents in modulating the extent oftissue injury be determined by randomised clinical trials.
Dominant Epstein-Barr virus-specific T-cell responses are maintained during moderate and intense immunosuppressive treatment
Authors: T. Daikeler, G. Hoenger, I. Oehri, A. Tyndall, A. Gratwohl, C. Brander, T. Klimkait, O. Gasser, C. Hess
Journal: Annals of the Rheumatic Diseases (2010)

CD8 T cells mediate antiviral immunity but are also implicated in autoimmunity.1,–,2 Responses elicited by immunogenic peptides target only a minute fraction of all potential peptide determinants, a phenomenon termed immunodominance.3–4 Immunodominance can be readily assessed for CD8 T-cell responses targeting Epstein–Barr virus (EBV), a herpes family virus that establishes life-long persistent infection in over 90% of the adult population.5 Here we hypothesised that, largely independent of an individual's medical condition, immunosuppression is inefficient at shifting established immunodominance. To test this hypothesis, we quantitatively assessed CD8 T-cell responses targeting defined EBV-derived peptides in individuals with differing medical histories exposed to immunosuppressive regimens of variable intensity.

The frequency of interferon γ-secreting T cells specific for any of 91 defined EBV-derived major histocompatibility complex I epitopes, optimally restricted by a wide range of human leucocyte antigen class I alleles, was quantified by enzyme-linked immunospot assays (ELISpot).6 In …
Combined occurrence of chyloperitoneum and chylothorax after retroperitoneal surgery
Authors: G Muns, SI Rennard, AA Floreani
Journal: European Respiratory Journal (1995)

Chyloperitoneum is a rare complication of abdominal or retroperitoneal surgery, and the combined occurrence of chylothorax and chyloperitoneum has been reported in only a few cases. We describe a case of this complication, which became clinically apparent 20 days after a Warren shunt operation. The large chylous effusion compromised breathing and required chest tube drainage, pleurodesis, medium chain triglyceride (MCT) diet, and, later, total parenteral nutrition (TPN). The patient made a full recovery on TPN for 5 weeks.
Nonlegacy PCBs: Pigment Manufacturing By-Products Get a Second Look
Authors: Elizabeth Grossman
Journal: Environmental Health Perspectives (2013)

A 87 P olychlorinated biphenyls (PCBs) were commercially manufactured in the United States from about 1930 until 1979, when their production was banned under the Toxic Substances Control Act (TSCA) because of concerns about their extreme environmental persistence, ability to bioaccumulate, and adverse human health effects.PCBs were used in numerous industrial and consumer applications, most notably as insulation fluids in electrical transformers and generators but also in products including fluorescent lamp ballasts, caulk, and carbonless copy paper.These now-discontinued manufactured chemicals have received a great deal of attention in terms of research and environmental remediation.But other, lesser-known PCBs continue to be generated and released into the environment, not from intentionally created commercial products but as unintentional by-products of manufacturing processes including, according to recent studies, those used to make certain pigments used in dyes, inks, and paints.PCBs do not occur naturally, and once in the environment they can last for decades.Until recently, PCBs that were being detected in the environment were thought to come entirely from "legacy" sources.Yet developments in analytical technology have given researchers a better understanding of PCB sources, of the patterns of individual PCBs (or congeners) that are being detected environmentally, and the fate of PCBs in the environment-how they move between soil, sediment, water, and air.These advances have also enabled the detection of individual congeners at very low levels and the identification of many new and ongoing sources of PCBs beyond those resulting from historical commercial mixtures.
Tobacco Hearings: Penetrating the Smoke Screen
Authors: Charles Marwick
Journal: JAMA (1994)

WOULD-BE DIEHARD smokers are facing a new challenge—federal regulation of tobacco products. Concern about the hazards to health of smoking has led in recent years to a ban against the practice in most public buildings and nearly all parts of government and many private office buildings, not to mention the sequestration of smokers in restaurants. Congress is considering a bill that would ban smoking in all public buildings. Smoking, in short, has become an antisocial habit. Now there are moves in Congress that may result in regulating tobacco to reduce its addictive potential. At the same time, no outright prohibition against smoking is contemplated, and Congress is unlikely to pass any new federal legislation regulating tobacco products in the current session. But the opening salvos have been fired. The issue of regulating tobacco has been put on the table and is not going to disappear in a cloud of smoke.
Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse
Authors: Timothy S Gomez, Michael J Hamann, Sean McCarney, Doris N Savoy, Casey M Lubking, Michael P Heldebrant, Christine M Labno, David J McKean, Mark A McNiven, Janis K Burkhardt, Daniel D Billadeau
Journal: Nature Immunology (2005)
Abstract 1207: Opposite effects on proliferation and bone metastasis genes by Estrogen Receptor B1 and Estrogen Receptor B2 in the prostate cancer cell line PC3
Authors: Prasenjit Dey, Philip Jonsson, Johan Hartman, Cecilia Williams, Jan-Åke Gustafsson, Anders Ström
Journal: Cancer Research (2012)

Abstract The estrogen receptor β1 (ERα1) is successively lost during cancer progression while its splice variant estrogen receptor β2 (ERα2) is still expressed in advanced prostate cancer. The latter cancer often metastases to bone. We wanted to investigate, if the loss of ERα1 and/or expression of its splice variant ERα2 affect signaling pathways involved in bone metastasis of prostate cancer. ERα2 is a 495 amino acid long splice variant of estrogen receptor ERα1, which is 530 amino acids long. Using PC3 cells stably expressing ERα1, we found that ERα1 represses expression of the bone metastasis regulator Runx2 and its target gene Slug. On the other hand, using PC3 cells stably expressing ERα2 we found that the same factors are up-regulated. In addition, the expression of Twist1, a factor whose expression strongly correlates with high Gleason grade of prostate carcinoma is increased by ERα2. In agreement with increased Twist1 expression we find increased expression of DKK1, a factor which has been shown to increase the RANKL/OPG ratio and enhance osteoclastogenesis indicating that expression of ERα2 can cause a cancer to be osteolytic. Furthermore, we found that only ERα1 and not ERα2 inhibits proliferation and expression of the proliferation markers ki67, cyclin E, c-Myc and p45Skp2. In addition, nuclear β-catenin and its mRNA levels are reduced by ERα1 expression. In conclusion we find that ERα1 inhibits proliferation and factors known to be involved in bone metastasis while ERα2 increases proliferation and up-regulates factors involved in bone metastasis. Thus, ERα2 has oncogenic abilities in strong contrast to the tumor suppressor effect of ERα1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1207. doi:1538-7445.AM2012-1207