tbuckley/cabot-search huggingface dataset:
Sorting out the roles of PPAR in energy metabolism and vascular homeostasis
Authors: P. Lefebvre
Journal: Journal of Clinical Investigation (2006)

PPARα is a nuclear receptor that regulates liver and skeletal muscle lipid metabolism as well as glucose homeostasis. Acting as a molecular sensor of endogenous fatty acids (FAs) and their derivatives, this ligand-activated transcription factor regulates the expression of genes encoding enzymes and transport proteins controlling lipid homeostasis, thereby stimulating FA oxidation and improving lipoprotein metabolism. PPARα also exerts pleiotropic antiinflammatory and antiproliferative effects and prevents the proatherogenic effects of cholesterol accumulation in macrophages by stimulating cholesterol efflux. Cellular and animal models of PPARα help explain the clinical actions of fibrates, synthetic PPARα agonists used to treat dyslipidemia and reduce cardiovascular disease and its complications in patients with the metabolic syndrome. Although these preclinical studies cannot predict all of the effects of PPARα in humans, recent findings have revealed potential adverse effects of PPARα action, underlining the need for further study. This Review will focus on the mechanisms of action of PPARα in metabolic diseases and their associated vascular pathologies.
Chew on This: Persistent Organic Pollutants May Promote Insulin Resistance Syndrome
Authors: Tanya Tillett
Journal: Environmental Health Perspectives (2010)

Animal studies indicate some persistent organic pollutants (POPs) may be endocrine disruptors and suggest similar health risks for humans. Recent studies have further suggested an association between exposure to POPs and the prevalence of type 2 diabetes. Now an experimental animal study reports evidence of a causal link between POP exposure and insulin resistance syndrome, a cluster of metabolic disorders—including type 2 diabetes—that are marked by sustained high blood sugar [EHP 118:465–471; Ruzzin et al.].

POPs accumulate in fatty tissue, where they can remain for years because they are not easily broken down. Fatty fish are a potential source of POP exposure in many human populations. However, n-3 polyunsaturated fatty acids in fish oil may have beneficial health effects, possibly including protective effects on insulin resistance, that could counterbalance any adverse effects of POPs in fatty fish.

In the current study, rats were exposed for 28 days to high-fat diets that contained either crude fish oil (from farmed Atlantic salmon) or fish oil that was refined to remove POPs. As expected, the crude fish oil contained much higher levels of POPs than the refined oil. Gene expression profile comparisons of the livers of the 2 treatment groups showed that POP exposure disrupted lipid homeostasis.

Rats on the unrefined fish oil diet gained more weight overall and had increased triacylglycerol, diacylglycerol, and total cholesterol levels compared with rats fed refined fish oil. They also showed impaired insulin action in response to the high-fat diet, whereas the high-fat diet did not seem to cause insulin resistance in the rats fed refined fish oil. Further analysis revealed a reduction in the ability of insulin to stimulate glucose uptake in adipocytes treated with a mixture of POPs that was comparable to the mixture of chemicals in crude fish oil. Adipocyte responses to insulin varied with exposures to different mixtures of individual POPs.

The authors conclude that dietary exposure to POPs may be a risk factor for insulin resistance and associated metabolic disorders. Furthermore, the metabolic effects of POP exposures exacerbated deleterious effects of a high-fat diet on rats and appeared to negate protective effects of n-3 polyunsaturated fatty acids on insulin resistance.
AIDS-associated Kaposi's sarcoma (KS) cells express oncostatin M (OM)-specific receptor but not leukemia inhibitory factor/OM receptor or interleukin-6 receptor. Complete block of OM-induced KS cell growth and OM binding by anti-gp130 antibodies.
Authors: K Murakami-Mori, T Taga, T Kishimoto, S Nakamura
Journal: Journal of Clinical Investigation (1995)

Oncostatin M (OM), which shares functional similarity and structural homology to leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), functions as a potent growth factor for AIDS-associated Kaposi's sarcoma-derived cells (AIDS-KS cells). OM was also suggested to bind to the LIF receptor (LIF/OM receptor), which consists of a signal transducing subunit for LIF and IL-6 (gp130) and a LIF receptor alpha-subunit. Recent studies indicate that IL-6 has growth-stimulating activity for AIDS-KS cells. However, we find that AIDS-KS cell growth is exclusively induced by OM and not by LIF or IL-6. We also observed the lack of binding properties of AIDS-KS cells for LIF and IL-6. Scatchard plots revealed the existence of two affinity classes of OM receptor sites on AIDS-KS cells, with Kd values of 6-12 pM (high affinity) and 521-815 pM (low affinity). In competition binding studies, we find that the OM-specific receptor, but not the LIF/OM receptor, contributes to the OM-specific growth stimulation of AIDS-KS cells. We also noted that anti-gp130 antibodies can completely abolish OM-induced growth stimulation of AIDS-KS cells as well as OM binding to AIDS-KS cells. PCR amplification clearly revealed high levels of gp130 expression in AIDS-KS cells, while the transcript of LIF receptor alpha-subunit or IL-6 receptor alpha-subunit was not observed. Therefore, we conclude that (a) AIDS-KS cells express the OM-specific receptor with high and low affinity, but not the LIF/OM receptor; (b) gp130 on AIDS-KS cells plays a key role in OM binding and signaling on the OM-specific receptor; and (c) the lack of biological response of AIDS-KS cells to IL-6 and LIF can be explained by the absence of the IL-6 and LIF/OM receptors. All this evidence shows the correlation of OM-specific biological activity with expression of the OM-specific receptor and the involvement of gp130 on this receptor, as based on findings in in vitro growth assays and binding experiments for AIDS-KS cells.
Serial Blood Gas Studies During Cardiopulmonary Resuscitation
Authors: SIDNEY J. FILLMORE
Journal: Annals of Internal Medicine (1970)

The present study documents by serial blood gas measurements that temporary support of the arrested circulation is more likely to be effective when prompt ventilation and endotracheal intubation are performed. Intubation is associated with lower arterial PCO2 and higher oxyhemoglobin saturation. When arterial PCO2 is near normal, bicarbonate is more effective in normalizing blood pH. Even when normal blood pH is achieved, extremely high blood lactate values may be present. Unsatisfactory blood gas values occurring in intubated, vigorously breathed patients probably reflect impairment of gas exchange due to fluid-filled lungs. Serial blood gas studies have proved useful in understanding and testing the physiologic consequences of cardiopulmonary arrest.
Case 23-1982
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely
Journal: New England Journal of Medicine (1982)

Presentation of Case A 37-year-old woman was admitted to the hospital because of headaches and memory loss. She was well until seven months earlier, when she began to experience nausea and vomiting. Two days later a brief syncopal episode occurred, and a few days thereafter she became transiently disoriented, anxious, and agitated. She did not recognize her friends. She was taken to a local hospital, where examination showed that the blood pressure was 170 mm Hg systolic; no other abnormality was found. A tranquilizer was prescribed, with apparent improvement. She soon began to complain of diffuse headaches that were present . . .
A Comprehensive Vertebrate Phylogeny Using Vector Representations of Protein Sequences from Whole Genomes
Authors: Gary W. Stuart, Karen Moffett, Jeffery J. Leader
Journal: Molecular Biology and Evolution (2002)

We recently developed a method for producing comprehensive gene and species phylogenies from unaligned whole genome data using singular value decomposition (SVD) to analyze character string frequencies. This work provides an integrated gene and species phylogeny for 64 vertebrate mitochondrial genomes composed of 832 total proteins. In addition, to provide a theoretical basis for the method, we present a graphical interpretation of both the original frequency matrix and the SVD-derived matrix. These large matrices describe high-dimensional Euclidean spaces within which biomolecular sequences can be uniquely represented as vectors. In particular, the SVD-derived vector space describes each protein relative to a restricted set of newly defined, independent axes, each of which represents a novel form of conserved motif, termed a correlated peptide motif. A quantitative comparison of the relative orientations of protein vectors in this space provides accurate and straightforward estimates of sequence similarity, which can in turn be used to produce comprehensive gene trees. Alternatively, the vector representations of genes from individual species can be summed, allowing species trees to be produced.
Drug-mediated inhibition of Fli-1 for the treatment of leukemia
Authors: Li Yj, Zhao X, Vecchiarelli-Federico Lm, Li Y, Datti A, Cheng Y, Ben-David Y
Journal: Blood Cancer Journal (2012)

The Ets transcription factor, Fli-1 is activated in murine erythroleukemia and overexpressed in various human malignancies including Ewing's sarcoma, induced by the oncogenic fusion protein EWS/Fli-1. Recent studies by our group and others have demonstrated that Fli-1 plays a key role in tumorigenesis, and disrupting its oncogenic function may serve as a potential treatment option for malignancies associated with its overexpression. Herein, we describe the discovery of 30 anti-Fli-1 compounds, characterized into six functional groups. Treatment of murine and human leukemic cell lines with select compounds inhibits Fli-1 protein or mRNA expression, resulting in proliferation arrest and apoptosis. This anti-cancer effect was mediated, at least in part through direct inhibition of Fli-1 function, as anti-Fli-1 drug treatment inhibited Fli-1 DNA binding to target genes, such as SHIP-1 and gata-1, governing hematopoietic differentiation and proliferation. Furthermore, treatment with select Fli-1 inhibitors revealed a positive relationship between the loss of DNA-binding activity and Fli-1 phosphorylation. Accordingly, anti-Fli-1 drug treatment significantly inhibited leukemogenesis in a murine erythroleukemia model overexpressing Fli-1. This study demonstrates the ability of this drug-screening strategy to isolate effective anti-Fli-1 inhibitors and highlights their potential use for the treatment of malignancies overexpressing this oncogene.
Advancement of Men and Women in Medical Academia-Reply
Authors: Marlys H. Witte
Journal: JAMA (1982)

<h3>In Reply.—</h3> The letters of Drs Ruane and Barton focusing on specific variables such as "having a 'wife' " or the morbidity of "promotion with loss of tenure-track" indicate that they too recognize the differential survival of men and women in medicine as an epidemiologic problem worthy of pursuit. After computing the more basic survival curves suggested originally, these and other lines of inquiry can be more productively examined and placed in proper perspective.
TWO OUTBREAKS OF MILD DYSENTERY: SCHMITZ BACILLUS (B. AMBIGUUS ANDREWES)
Authors: W. Broughton-Alcock
Journal: BMJ (1919)

TWO OUTBREAKS OF MILD DYSENSTERY rMAt it 1 ME61!DICAL J6tlUNAlJrivjt-t not pass the pores of this filter, at least in suLfficient quantity to induce infection.A sheep which had its nostrils swabbed with an emulsion of the brain and spinal cord from an infected monkey showed no after-effects.C. Other Animals.We failed to convey the disease to four dogs, two kittens, three rabbits, two gtiinea-pigs, and one fowl.SUMMARY.
The Effects of the DRG-Based Prospective Payment System on Quality of Care for Hospitalized Medicare Patients
Authors: Katherine L. Kahn
Journal: JAMA (1990)

In 1985, we began a 4-year evaluation of the effects of the diagnosis related groups-based prospective payment system on quality of care for hospitalized Medicare patients. This article provides an overview of the study's background, aims, design, and methods. We used a clinically detailed review of the medical record supplemented by data on postdischarge outcomes drawn from the files of the Health Care Financing Administration and fiscal intermediaries to (1) compare outcomes of care after adjustment for sickness at admission, (2) assess the process of in-hospital care and relationships between processes and outcomes, and (3) assess status at discharge for a nationally representative sample of patients hospitalized before and after prospective payment was implemented.
Excess mortality in osteoarthritis
Authors: C. Cooper, N. K. Arden
Journal: BMJ (2011)

<h3>Abstract</h3> The gravitational biological pump is not large enough to account for microbial heterotrophic activity in the mesopelagic ocean. Migrating zooplankton may be a key source of organic matter transport to depth. Here we show signatures of zooplankton in the suspended organic matter at the zooplankton vertical migration depth in the Eastern Tropical North Pacific Oxygen Deficient Zone (ETNP ODZ). We examine the mesozooplankton community in metagenomic depth profiles using the mitochondrial cytochrome c oxidase (COI) gene as a marker in the ETNP and Eastern Tropical South Pacific (ETSP) ODZs and at the oxic Hawaii Ocean Timeseries (HOT). Additionally, eukaryotic transcripts (polyA-selected) were examined for zooplankton in the ETNP. While zooplankton eDNA increased in the ODZ, zooplankton eRNA decreased in the ODZ, similar to previous net-based data, implying that eDNA is better preserved under anoxia. At all stations, Cnidaria, often missed in net-based data, contributed greatly to the zooplankton eDNA/eRNA. SAR11 abundance, determined from the single-copy core gene (<i>rpoB</i>), significantly correlated with zooplankton eDNA, with R<sup>2</sup> values &gt;0.8 at all stations. Strong correlations between SAR11 and zooplankton have not been previously reported, but are logical as SAR11 bacteria consume and zooplankton excrete simple dissolved organic compounds. SAR11 bacteria possessed genes to utilize urea and taurine in the ODZ, both compounds known to be excreted by zooplankton. In ODZs, SAR11 bacteria preferentially used the taurine degradation pathway leading to C and N assimilation, not the pathway for organic S assimilation, probably due to additional sources of organic S in ODZs.
Effects of diphenylhydantoin on coronary and systemic haemodynamics in awake dogs
Authors: H. J. ZEFT, J. C. REMBERT, C. L. CURRY, J. C. GREENFIELD
Journal: Cardiovascular Research (1973)

Journal Article Effects of diphenylhydantoin on coronary and systemic haemodynamics in awake dogs Get access HOWARD J. ZEFT, HOWARD J. ZEFT 2 From the Department of Medicine (Division of Cardiology), The Veterans Administration Hospital (27705) and Duke University Medical Center, Durham, North Carolina 27710, U.S.A. 2Present address: Suite 210, Professional Arts Building, 7635 West Oklahoma Avenue, Milwaukee, Wisconsin 53219. Search for other works by this author on: Oxford Academic PubMed Google Scholar JUDITH C. REMBERT, JUDITH C. REMBERT From the Department of Medicine (Division of Cardiology), The Veterans Administration Hospital (27705) and Duke University Medical Center, Durham, North Carolina 27710, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar CHARLES L. CURRY, CHARLES L. CURRY From the Department of Medicine (Division of Cardiology), The Veterans Administration Hospital (27705) and Duke University Medical Center, Durham, North Carolina 27710, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar JOSEPH C. GREENFIELD, JR. JOSEPH C. GREENFIELD, JR. From the Department of Medicine (Division of Cardiology), The Veterans Administration Hospital (27705) and Duke University Medical Center, Durham, North Carolina 27710, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 7, Issue 3, May 1973, Pages 331–335, https://doi.org/10.1093/cvr/7.3.331 Published: 01 May 1973
Stenosis of the colon in acute pancreatitis.
Authors: W S Mair, M J McMahon, J C Goligher
Journal: Gut (1976)

A case is described demonstrating a stricture of the colon associated with acute pancreatitis and 20 similar cases found in the literature are reviewed. The colonic stenosis may be of short duration and largely due to oedema or more chronic with deposition of fibrous tissue. Many cases have been confused with a carcinoma both radiologically and at laparotomy. It is suggested that a conservative approach be adopted initially, resection being carried out if follow-up barium examination fails to show resolution of the stenosis.
A CASE TO THE DISCREDIT OF ETHER.
Authors: EVAN O'NEIL KANE
Journal: JAMA (1904)

The occurrence of pregnancy complicated by an ovarian tumor while not unique is not of very frequent occurrence.A pregnancy with hydramnios is probably of slightly greater frequency but a pregnancy with hydramnios and a large der- moid cyst of the ovary developing downward so as to com- pletely fill the true pelvis and lift the pregnant uterus entirely above the pelvic brim is, so far as I have been able to learn, unique.In all the literature at my disposal I can find no such case recorded.
Diminution and Closure of Large Ventricular Septal Defects After Pulmonary Artery Banding
Authors: ZOLTAN G. MESKO, JIMMY E. JONES, ALEXANDER S. NADAS
Journal: Circulation (1973)

In a period of 15 years (1957-1972), 114 infants (51 males, 63 females) with the diagnosis of ventricular septal defect and congestive heart failure underwent pulmonary artery banding at The Children's Hospital Medical Center in Boston. A second study performed in 55 of these revealed the left-to-right shunt through the ventricular septal defect to be greatly diminished in seven and completely closed in three. Pulmonary artery banding proved clinically beneficial to all patients restudied. Important hemodynamic changes, documented at the second study in all ten patients, included a significant decrease in left-to-right shunt and a drop in pulmonary arteriolar resistance to normal range. The right ventricular pressure, post banding, ranged from suprasystemic levels in those with muscular defects to half systemic levels in the majority of those with membranous defect. The muscular ventricular septal defects closed by muscular tissue, the membranous defects by aneurysm formation at the "exit" of the left-to-right shunt on the right ventricular septal surface. There is a surprisingly high closure rate (19%) in these large ventricular septal defects after pulmonary artery banding noted. Hemodynamic mechanisms to account for closure are proposed.
Randomised trial comparing propranolol with atenolol in immediate treatment of suspected myocardial infarction.
Authors: R G Wilcox, J M Roland, D C Banks, J R Hampton, J R Mitchell
Journal: BMJ (1980)

The value of beta-blockade for suspected acute myocardial infarction was assessed by determining the six-week and one-year mortality rates in patients started on propranolol, atenolol, or placebo immediately on entry to a coronary care unit. A total of 388 patients entered this double-blind, randomised study, and when analysed on the basis of the initial, intention-to-treat categories there was no significant difference between the three groups in respect of the mortality rate at one year. There was, however, a high withdrawal rate from the trial; the reasons for this illustrate problems of physician compliance and interpretation of data, which are common to all early-entry trials of haemodynamically active agents in acute myocardial infarction.
Causes of Chronic Diarrhea
Authors: Henry J. Binder
Journal: New England Journal of Medicine (2006)

Diarrhea can be classified in several ways. It is both a symptom and a sign. As a symptom, it is whatever the patient says it is: a decrease in consistency, an increase in the number or volume of bowel movements, or any combination thereof. As a sign, diarrhea is an increase in stool weight (or volume) of more than 200 g (or ml) per 24 hours in a person on a Western diet. The distinction between chronic and acute diarrhea is arbitrary: it is determined by duration. Diarrhea is generally considered acute when it lasts less than two or three . . .
THE IMPENDING REVOLUTION IN MILITARY SURGERY CAUSED BY THE NEW INFANTRY RIFLE.
Authors: EDMUND ANDREWS
Journal: JAMA (1893)

Some nineteen-twentieths of all the wounds received in any modern battle are from infantry rifles, and from the machine guns. England, France, Germany, Austria, the United States, and some other nations, have recently adopted magazine guns for their infantry which can be fired sixty times in a minute, while the Gatling machine gun can throw 1,000 bullets in the same time. A new powder is used which doubles the velocity of the bullets and is smokeless, and sends the missile over two miles; while the cartridge is less than half the weight of the old one, enabling the soldier to carry more than double the former number of cartridges. These weapons change the conditions of warfare, so that all open ground can be swept with a storm of bullets, before which men can neither charge nor stand still. The only exception is where the country is rough enough to admit
Ten-Year Results of a Randomized Clinical Trial Comparing Radical Mastectomy and Total Mastectomy with or without Radiation
Authors: Bernard Fisher, Carol Redmond, Edwin R. Fisher, Madeline Bauer, Norman Wolmark, D. Lawrence Wickerham, Melvin Deutsch, Eleanor Montague, Richard Margolese, Roger Foster
Journal: New England Journal of Medicine (1985)

In 1971 we began a randomized trial to compare alternative local and regional treatments of breast cancer, all of which employ breast removal. Life-table estimates were obtained for 1665 women enrolled in the study for a mean of 126 months. There were no significant differences among three groups of patients with clinically negative axillary nodes, with respect to disease-free survival, distant-disease–free survival, or overall survival (about 57 per cent) at 10 years. The patients were treated by radical mastectomy, total ("simple") mastectomy without axillary dissection but with regional irradiation, or total mastectomy without irradiation plus axillary dissection only if nodes were subsequently positive. Similarly, no differences were observed between patients with clinically positive nodes treated by radical mastectomy or by total mastectomy without axillary dissection but with regional irradiation. Survival at 10 years was about 38 per cent in both groups. Our findings indicate that the location of a breast tumor does not influence the prognosis and that irradiation of internal mammary nodes in patients with inner-quadrant lesions does not improve survival. The data also demonstrate that the results obtained at five years accurately predict the outcome at 10 years. We conclude that the variations of local and regional treatment used in this study are not important in determining survival of patients with breast cancer. (N Engl J Med 1985; 312:674–81.)