tbuckley/cabot-search huggingface dataset:
The Lumleian Lectures on the Digestive Ferments, and the Preparation and Use of Artificially Digested Food
Authors: W. Roberts
Journal: BMJ (1880)

TIIE suggestion to administer to invalids artificially digested food ap- pears at first sight a somewhat startlingproposal.So great an interfer- ence with the order of nature woul(d seemi to go beyond the legitimate province of art.But when we reflect hoow largely art already interferes in the preparation of our food, the taking of this further step will appear less surprising.The practice of cooking is in reality as complete a de- parture from the ways of untutored nature as artificial digestion would be.Among the almost countless species of animals, not one of them, except man alone, cooks his food; insomuch that man has, not inaptly, been defined as the cooking animal.E9ects of Cookizg.-The process of cooking ful-fils far more important ends than that of improving the savour of food-far more important even than the nmechanical disintegration which generally attends the process.It produces certain chemical changes in several of the most important alimentary principles, which render them incomparably more susceptible to the action of the digestive ferments than in the uncooked state.The discovery of the use of fire-heat in the preparation of his food must, indeed, have constituted one of the earliest and most im-
Coffee Drinking and Risk of Bladder Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Patricia Hartge, Robert Hoover, Dee W. West, Joseph L. Lyon
Journal: JNCI Journal of the National Cancer Institute (1983)

The relationship between coffee drinking and risk of bladder cancer was assessed with the use of data from a case-control study of bladder cancer. Incident cases (2,982) and general population controls (5,782) were interviewed. Overall, the relative risk (RR) of bladder cancer for subjects who had ever drunk coffee was estimated as 1.4 (95% confidence interval = 1 .1 -1 .8). There was no consistent relation between the RR estimate and the current consumption level. Among men who drank coffee, those who drank more than 49 cupfuls of coffee per week had an apparent excess in risk, but women who drank that much had an apparent deficit in risk.
ABSENCE OF A PROSTHETIC GROUP IN A TYPE-SPECIFIC POLYSACCHARIDE OF PNEUMOCOCCUS
Authors: Michael Heidelberger, Colin M. MacLeod, Harold Markowitz, Marie M. DiLapi
Journal: The Journal of Experimental Medicine (1951)

The specific polysaccharide of Type III pneumococcus, with only 0.05 per cent of N and 0.01 per cent of P, still shows almost maximal precipitation of a Type III antipneumococcus rabbit serum and the expected antigenicity in man. There is therefore no evidence that a prosthetic group is involved in these characteristic activities.
Doubling Times and CT Screen–Detected Lung Cancers in the Pittsburgh Lung Screening Study
Authors: David O. Wilson, Adam Ryan, Carl Fuhrman, Matthew Schuchert, Steven Shapiro, Jill M. Siegfried, Joel Weissfeld
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

As computed tomography (CT) screening for lung cancer becomes more widespread, volumetric analyses, including doubling times, of CT-screen detected lung nodules and lung cancers may provide useful information in the follow-up and management of CT-detected lung nodules and cancers.To analyze doubling times in CT screen detected lung cancers and compare prevalent and nonprevalent cancers and different cell types on non small cell lung cancer.We performed volumetric and doubling time analysis on 63 non–small cell lung cancers detected as part of the Pittsburgh Lung Screening Study using a commercially available VITREA 2 workstation and VITREA VITAL nodule segmentation software.Doubling times (DT) were divided into three groups: rapid (DT<183 d), typical (DT 183–365 d), and slow (DT>365 d). Adenocarcinoma/bronchioloalveolar carcinoma comprised 86.7% of the slow DT group compared with 20% of the rapid DT group. Conversely, squamous cell cancer comprised 60% of the rapid DT group compared with 3.3% of the slow DT group. Twenty-eight of 42 (67%) prevalent and 2 of 21 (10%) nonprevalent cancers were in the slow DT group (P<0.0001; Fisher's exact test). Twenty-four of 32 (75%) prevalent and 1 of 11 (9%) nonprevalent adenocarcinomas were in the slow DT group (P<0.0002; Fisher's exact test).Volumetric analysis of CT-detected lung cancers is particularly useful in AC/BAC. Prevalent cancers have a significantly slower DT than nonprevalent cancers and a higher percentage of adenocarcinoma/bronchioloalveolar carcinoma. These results should affect the management of indeterminant lung nodules detected on screening CT scans.
Structural Organization of the Synaptic Exocytosis Core Complex
Authors: Richard C Lin, Richard H Scheller
Journal: Neuron (1997)

Syntaxin, vesicle-associated membrane protein (VAMP), and synaptosome-associated protein of 25 kDa (SNAP-25) form a ternary "core complex" central to the process of synaptic vesicle docking and fusion. Several lines of evidence support the hypothesis that the proteins assemble in a coiled-coil structure, but the alignment of α helices in this coil and the overall conformation of the coil are unknown. We employ the technique of fluorescence resonance energy transfer (FRET) to investigate the alignment between syntaxin and VAMP. With the acceptor probe coupled to the amino-terminal end of the VAMP coiled-coil domain, the donor probe fluorescence is quenched to a greater extent when it is on the amino-terminal end of the syntaxin H3 domain than when it is on the carboxy-terminal end. The data indicate that syntaxin and VAMP bind primarily in a parallel arrangement and suggest a coiled-coil structure that is bent rather than fully extended. We propose a model in which binding of SNAP receptor (SNARE) protein coiled-coil domains helps drive vesicle fusion.
A translational approach to myocardial remodelling
Authors: J. Diez, G. Ertl
Journal: Cardiovascular Research (2008)

The concept of cardiac remodelling was initially created to describe the changes in the anatomy of the left ventricle that occur following myocardial infarction. 1 Today myocardial remodelling is used to qualify a variety of changes in the biophysiology of the cardiomyocyte, the volume and composition of cardiomyocyte, and non-cardiomyocyte compartments, and the geometry and architecture of the left ventricular chamber that occur in response to myocardial infarction, pressure or volume overload, cardiomyopathic states, and exposure to infectious or cardiotoxic agents. 2 Myocardial remodelling results from modifications that are not necessarily adaptive to the initial insult, but pathological and potentially self-perpetuating in a progressive vicious circle.In addition, the effects of the insult on the final phenotype are modulated by several interfering factors, including senescence, obesity, diabetes, a number of cardiac and systemic humoral factors and, probably, genetics. 3Myocardial remodelling may result in alterations of cardiac energetics, deterioration of both diastolic and systolic function, and propensity for arrhythmias. 2Therefore, myocardial remodelling is a key determinant of the clinical course and outcome of a number of cardiac diseases.This Spotlight Issue is committed to a review of information provided by the intensive research performed in the past few years on mechanisms involved in the development, consequences, detection, and treatment of myocardial remodelling.An early feature of the maladapted heart is a loss of metabolic flexibility.Metabolic signals regulate fluxes through enzyme-catalyzed reactions in metabolic pathways and regulate transcriptional, translational, and posttranslational signalling in the heart.The paradigm is emerging that metabolic remodelling precedes, triggers, and sustains functional and structural remodelling. 4ngwall 5 reviews in this Spotlight Issue the energetic phenotype of remodelled myocardium and discuss in depth the interrelations between a lower metabolic reserve and an impaired contractile reserve.Van Bilsen et al. 6 focus their article on the analysis of metabolic interventions that
Prostaglandin E2 Promotes Tumor Progression by Inducing Myeloid-Derived Suppressor Cells
Authors: Pratima Sinha, Virginia K. Clements, Amy M. Fulton, Suzanne Ostrand-Rosenberg
Journal: Cancer Research (2007)

Abstract A causative relationship between chronic inflammation and cancer has been postulated for many years, and clinical observations and laboratory experiments support the hypothesis that inflammation contributes to tumor onset and progression. However, the precise mechanisms underlying the relationship are not known. We recently reported that the proinflammatory cytokine, interleukin-1β, induces the accumulation and retention of myeloid-derived suppressor cells (MDSC), which are commonly found in many patients and experimental animals with cancer and are potent suppressors of adaptive and innate immunity. This finding led us to hypothesize that inflammation leads to cancer through the induction of MDSC, which inhibit immunosurveillance and thereby allow the unchecked persistence and proliferation of premalignant and malignant cells. We now report that host MDSC have receptors for prostaglandin E2 (PGE2) and that E-prostanoid receptor agonists, including PGE2, induce the differentiation of Gr1+CD11b+ MDSC from bone marrow stem cells, whereas receptor antagonists block differentiation. BALB/c EP2 knockout mice inoculated with the spontaneously metastatic BALB/c-derived 4T1 mammary carcinoma have delayed tumor growth and reduced numbers of MDSC relative to wild-type mice, suggesting that PGE2 partially mediates MDSC induction through the EP2 receptor. Treatment of 4T1-tumor–bearing wild-type mice with the cyclooxygenase 2 inhibitor, SC58236, delays primary tumor growth and reduces MDSC accumulation, further showing that PGE2 induces MDSC and providing a therapeutic approach for reducing this tumor-promoting cell population. [Cancer Res 2007;67(9):4507–13]
Is HIF-1 a Valid Therapeutic Target?
Authors: R. Pili, R. C. Donehower
Journal: JNCI Journal of the National Cancer Institute (2003)

Hypoxia, a reduction in the normal level of tissue oxygen tension, occurs during several pathophysiological processes including tumorigenesis. It may occur during the initial avascular phase or develop in established tumors as a result of new blood vessel formation which is ineffective and provides poor blood flow. Although hypoxia generates a situation unfavorable for cell growth, cancer cells may undergo a series of genetic and metabolic changes that allow them to survive and even proliferate. Tumor hypoxia plays a major role in the induction of the “angiogenic switch” during tumor development. Targeting the critical steps in tumor angiogenesis, including hypoxia-induced pathways, has become a focus for many basic research scientists and clinical investigators. Hypoxia is associated with poor treatment outcome regardless of the modality, suggesting that it should be considered in the development of optimum treatment strategies. One mechanism through which tumor cells respond to reduced oxygen levels is via activation of hypoxia-inducible transcription factors (HIF) (1). HIF-1 is a heterodimer consisting of the hypoxic response factor HIF-1 and the constitutively expressed receptor nuclear activator ARNT or HIF-1 (2) .I n the presence of oxygen, HIF-1 is bound to the tumor suppressor von Hippel–Lindau (VHL) protein that determines the ubiquitination and consequent proteosomal degradation of the transcription factor (3). In the absence of oxygen, HIF-1 degradation is impaired with consequent binding to hypoxia-response genes, such as the proangiogenic vascular endothelial growth factor (VEGF) (4). To date, three members of the HIF family have been cloned: HIF-1 HIF-2 and HIF-3. Whether these components are redundant with overlapping functions or whether they have distinct biological properties remains to be revealed. Of the HIF subunits, the function of HIF-1 has been the most extensively characterized. A growing body of evidence suggests that HIF-1 is an important contributor to tumor progression and metastasis. Remaining questions related to the role of HIFs in general, and HIF-1 in particular, is whether they are in all cases a positive regulator of tumor growth (5,6) and whether HIF-1 is the only member of the HIF family capable of promoting
Effects of Corticosteroids and Splenectomy on the Immune Clearance and Destruction of Erythrocytes
Authors: John P. Atkinson, Alan D. Schreiber, Michael M. Frank
Journal: Journal of Clinical Investigation (1973)

Corticosteroids and splenectomy constitute two important therapeutic modalities in the treatment of autoimmune hemolytic anemia. Each of these may affect both the rate of synthesis of autoantibody and the clearance of antibody sensitized cells. The latter possibility has been examined in an experimental model which allows evaluation of the role of antibody and complement in the immune clearance of erythrocytes in molecular terms. The in vivo clearance of (51)Cr-labeled guinea pig erythrocytes sensitized with purified rabbit IgG or IgM antibody to produce a known number of complement-fixing sites per cell was studied. Corticosteroid therapy increased the survival of both IgG and IgM sensitized erythrocytes by decreasing sequestration in the reticuloendothelial system (RES). 5 days of therapy prior to injection of antibody coated cells were required for a maximal effect. It appeared that the RES of cortisone-treated animals had a lowered sensitivity to erythrocytes coated with antibody and complement and the cells were removed as though they were coated with fewer complement sites/cell. The general pattern and kinetics of clearance and the localization of sequestered cells were not modified by corticosteroids. As the number of IgG C1-fixing sites was increased, the difference betwen cortisone treated and control animals was less marked. Splenectomy led to an increased survival of IgG-coated cells and a sixfold increase in IgG C1-fixing sites was necessary in order to obtain similar rates of clearance in splenectomized and control animals. The liver was responsible for this much less efficient clearance of cells in splenectomized animals: the clearance pattern was typical of that noted for IgG. No effect at all was noted on the clearance of IgM sensitized cells in splenectomized animals. These experiments clearly demonstrate that both corticosteroid therapy and splenectomy act to decrease the in vivo clearance of IgG-sensitized cells: only corticosteroids alter the clearance of IgM-sensitized erythrocytes. This effect may be of major importance in explaining the efficacy of these therapeutic modalities in autoimune hemolytic anemia.
Interleukin-10 inhibits apoptotic cell death in infectious mononucleosis T cells.
Authors: K Taga, J Chretien, B Cherney, L Diaz, M Brown, G Tosato
Journal: Journal of Clinical Investigation (1994)

T lymphocytes from patients with acute EBV-induced infectious mononucleosis rapidly die by apoptosis in vitro. Because human and viral IL-10 are likely to be induced during acute EBV infection and display a variety of functions on human T cells, we examined IL-10 effects on infectious mononucleosis T cell death. After 12 h of incubation in medium alone, only 35.6 (+/- 8.2%) of the originally seeded infectious mononucleosis T cells were viable. Addition of human IL-10 (100 U/ml) to T cell cultures significantly improved recovery of viable cells (71.3 +/- 6.2%, P = 0.0156). Viral IL-10 had comparable effects to human IL-10 in this system. Protection from death by human and viral IL-10 (100 U/ml) was dose dependent and continued over a 6-d culture period. The human IL-10 effect was neutralized by the anti-human IL-10 mAb 19F1. Morphology and analysis of DNA after separation on agarose gels showed that IL-10 inhibits loss of cell volume, chromatin condensation, and DNA fragmentation, characteristics of death by apoptosis. As assessed by [3H]thymidine incorporation, the T cells were not induced to proliferate by IL-10 above the level exhibited when first removed from blood. T cells protected from death by IL-10 proliferated to IL-2 and spontaneously killed sensitive targets as effectively as medium-precultured T cells. Thus, IL-10 promotes the survival of infectious mononucleosis T cells otherwise destined to die by apoptosis and may be critical for the establishment of immunologic memory after resolution of the illness.
Serum eosinophil cationic protein measurements in the management of perennial and periodic asthma: a prospective study
Authors: F de Blay, A Purohit, R Stenger, P Gries, C Hamberger, B David, N Frossard, G Pauli
Journal: European Respiratory Journal (1998)

We performed a prospective study in order: 1) to determine whether a correlation could be found between serum eosinophil cationic protein (ECP) levels and clinical and functional status in perennial asthmatics during a 5 month prospective study; and 2) to evaluate the relationship between allergic exposure and ECP levels in periodic asthmatics. Two groups of asthmatic patients were selected: a group of acutely ill perennial asthmatics and a group of periodic asthmatics. The acutely ill perennial asthmatics (n=22, mean age=39.4 yrs) were included on the basis of hospitalization for acute asthma. At the end of the hospitalization, there was a 5 month follow-up of clinical, functional and medication scores, as well as eosinophil counts and ECP levels. The periodic asthmatic group was composed of asthmatics sensitized to birch and tree pollens (n=10, mean age=33.8 yrs). The same measurement were performed on this group, before, during and after the pollen season. Under corticosteroid treatment in the acutely ill patients, there was a significant decrease in serum ECP levels between the first day of hospitalization and the day of discharge (mean: 23.2 microg x L(-1) and 9.5 microg x L(-1), respectively; p=0.006). No correlation was found between the clinical status, functional status and serum ECP levels during the 5 month follow-up. A significant increase in ECP levels was found in periodic asthmatics during the pollen season. Our results suggest that serum eosinophil cationic protein is a useful marker of allergen exposure and of acute asthma treatment. This could be of importance in the prevention and follow-up of allergic asthma; the value of serum eosinophil cationic protein measurements in the day-to-day management of adult asthmatics needs to be further clarified.
Patients With Familial Hypertrophic Cardiomyopathy Caused by a Phe110Ile Missense Mutation in the Cardiac Troponin T Gene Have Variable Cardiac Morphologies and a Favorable Prognosis
Authors: Ryuichiro Anan, Hirohisa Shono, Akira Kisanuki, Shinichi Arima, Shoichiro Nakao, Hiromitsu Tanaka
Journal: Circulation (1998)

Background —Mutations that cause familial hypertrophic cardiomyopathy have been identified in several genes that encode contractile proteins. Patients with mutations in the cardiac troponin T (cTnT) gene have particularly poor prognosis but only mild hypertrophy. To date, no benign mutation in the cTnT gene has been reported. The clinical characteristics and prognosis of patients with the Phe110Ile mutation in the cTnT gene is unclear because few affected individuals have been identified. Methods and Results —Forty-six probands with familial hypertrophic cardiomyopathy were screened for mutations in the cTnT gene. The Phe110Ile missense mutation was found in 6 probands. Individuals in the 6 families were analyzed genetically and clinically. Haplotype analysis was performed with markers encompassing the cTnT gene. Left ventricular hypertrophy was classified as type I, II, III, or IV according to the criteria of Maron et al. The Phe110Ile mutation in the cTnT gene was identified in 16 individuals. Two of the 6 families shared the same flanking haplotype, and 4 were different from each other. Affected individuals exhibited different cardiac morphologies: 4 had type II, 6 had type III, and 3 had type IV hypertrophy with apical involvement. Three individuals with the disease-causing mutation did not fulfill clinical criteria for the disease. The product-limit survival curve analysis demonstrated a favorable prognosis. Conclusions —Multiple independent mutations of residue 340 in the cTnT gene have been described, suggesting that this may be a “hot spot” for such events. The Phe110Ile substitution causes hypertrophic cardiomyopathy with variable cardiac morphologies and a favorable prognosis.
Lower Total Adipocyte Number but No Evidence for Small Adipocyte Depletion in Patients With Type 2 Diabetes
Authors: Magdalena Pasarica, Hui Xie, David Hymel, George Bray, Frank Greenway, Eric Ravussin, Steven R. Smith
Journal: Diabetes Care (2009)

OBJECTIVE We hypothesized that, compared with obese subjects, patients with type 2 diabetes have a lower total adipocyte number with fewer small adipocytes. RESEARCH DESIGN AND METHODS Abdominal subcutaneous adipose tissue was obtained from lean and obese subjects with or without type 2 diabetes matched for BMI. Adipocyte size was measured by osmium fixation and sizing/counting in a Coulter counter. Adipocyte size and number subdistributions (small, medium, large, and very large) were determined. RESULTS Compared with obese subjects, type 2 diabetic patients had larger mean adipocyte size and 67% bigger very large adipocytes; the total adipocyte number was lower, but the fraction of small adipocytes was increased by 27%. CONCLUSIONS Total adipocyte cellularity is lower in type 2 diabetic subjects than in obese subjects. We found no evidence for depletion of small adipocytes in patients with type 2 diabetes. This suggests the presence of a defect in early maturation of adipocytes in patients with type 2 diabetes.
Distinct murine macrophage receptor pathway for human triglyceride-rich lipoproteins.
Authors: S H Gianturco, A H Lin, S L Hwang, J Young, S A Brown, D P Via, W A Bradley
Journal: Journal of Clinical Investigation (1988)

Murine P388D1 macrophages have a receptor pathway that binds human hypertriglyceridemic very low density lipoproteins (HTG-VLDL) that is fundamentally distinct from the LDL receptor pathway. Trypsin-treated HTG-VLDL (tryp-VLDL), devoid of apolipoprotein (apo)-E, fail to bind to the LDL receptor, yet tryp-VLDL and HTG-VLDL cross-compete for binding to P388D1 macrophage receptors, indicating that these lipoproteins bind to the same sites. The specific, high affinity binding of tryp-VLDL and HTG-VLDL to macrophages at 4 degrees C is equivalent and at 37 degrees C both produce rapid, massive, curvilinear (receptor-mediated) triglyceride accumulation in macrophages. Ligand blots show that P388D1 macrophages express a membrane protein of approximately 190 kD (MBP190) that binds both tryp-VLDL and HTG-VLDL; this binding is competed by HTG-VLDL, trypsinized HTG-VLDL, and trypsinized normal VLDL but not by normal VLDL or LDL. The macrophage LDL receptor (approximately 130 kD) and cellular uptake of beta-VLDL, but not MBP 190 nor uptake of tryp-VLDL, are induced when cells are exposed to lipoprotein-deficient medium and decreased when cells are cholesterol loaded. Unlike the macrophage LDL receptor, MBP 190 partitions into the aqueous phase after phase separation of Triton X-114 extracts. An anti-LDL receptor polyclonal antibody blocks binding of HTG-VLDL to the LDL receptor and blocks receptor-mediated uptake of beta-VLDL by P388D1 cells but fails to inhibit specific cellular uptake of tryp-VLDL or to block binding of tryp-VLDL to MBP 190. Human monocytes, but not human fibroblasts, also express a binding protein for HTG-VLDL and tryp-VLDL similar to MBP 190. We conclude that macrophages possess receptors for abnormal human triglyceride-rich lipoproteins that are distinct from LDL receptors in ligand specificity, regulation, immunological characteristics, and cellular distribution. MBP 190 shares these properties and is a likely receptor candidate for the high affinity uptake of TG-rich lipoproteins by macrophages.