tbuckley/cabot-search huggingface dataset:
Visceral perception: sensory transduction in visceral afferents and nutrients
Authors: H E Raybould
Journal: Gut (2002)

The possible mechanisms that may be involved in nutrient detection in the wall of the gastrointestinal tract are reviewed. There is strong functional and electrophysiological evidence that both intrinsic and extrinsic primary afferent neurones mediate mechano- and chemosensitive responses in the gastrointestinal tract. This review focuses on the extrinsic afferent pathways as these are the ones that convey information to the central nervous system which is clearly necessary for perception to occur.
Streptococcal perianal infection in children
Authors: R. Lehman, S. Pinder
Journal: BMJ (2009)

#### Case scenario 

A 3 year old child is brought by her mother, who says that her daughter has had an itchy bottom and pain on opening her bowels most days for the past two weeks. On examination she has an erythematous and excoriated anus with multiple anal fissures. As these symptoms and findings in a preschool child are highly suggestive of streptococcal proctitis, you undertake a perianal swab, which shows a pure growth of group A streptococcus.

Streptococcal perianal infection in children is caused by group A Streptococcus pyogenes and is usually confined to the immediate perianal area, though it can spread to the perineum and occasionally the genitalia.1 2

The incidence of perianal infection caused by group A S pyogenes is not known, but since the first case descriptions in 19663 it has been reported in children from around the world. In a US general paediatric practice, perianal streptococcal disease was detected in one consultation per 300, and perineal disease (that is, perianal plus vulvovaginal disease) in one per 200.1 A 1996 audit of our own practice (an urban British practice with 7000 patients and four full …
Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells.
Authors: Y Hirata, T Emori, S Eguchi, K Kanno, T Imai, K Ohta, F Marumo
Journal: Journal of Clinical Investigation (1993)

Endothelins (ET) produce endothelium-dependent vasodilation through nitric oxide (NO) synthesis. The present study was designed to elucidate the cellular mechanism by which ET induces synthesis and release of endothelium-derived NO by cultured bovine endothelial cells (EC). Binding studies revealed that bovine EC membrane had the binding sites of a novel agonist (BQ3020) for non-isopeptide-selective receptor subtype (ETB). Affinity labeling studies showed a major labeled band with the apparent molecular mass of 50 kD. Northern blot analysis demonstrated the expression of mRNA for ETB receptor. BQ3020 rapidly and dose dependently induced formation of inositol-1,4,5-triphosphate and increased intracellular Ca2+ concentrations in fura-2-loaded cells. Concomitantly, BQ3020 dose dependently stimulated production of both nitrate/nitrite (NOx) and cyclic GMP; a highly significant correlation existed between NOx and cGMP production. The stimulatory effect on NOx and cGMP production by ETB agonist was inhibited by NO synthase inhibitor monomethyl-L-arginine; this effect was reversed by coaddition of L-arginine, but not D-arginine. NOx and cGMP production stimulated by BQ3020 was inhibited by pretreatment with pertussis toxin. ETB agonist-induced NOx production was blocked by a calmodulin inhibitor and an intracellular Ca2+ chelator, but not by an extracellular Ca2+ chelator or a Ca2+ channel blocker. These data suggest that endothelins stimulate ETB receptor-mediated phosphoinositide breakdown via pertussis toxin-sensitive G-protein(s), which triggers release of intracellular Ca2+, thereby activating Ca2+/calmodulin-dependent NO synthase in EC.
Hyperuricemia in Infectious Mononucleosis
Authors: Stephen C. Cowdrey
Journal: JAMA (1966)

Lymphadenopathy with splenomegaly and abnormal leukocytes are present in both leukemia and infectious mononucleosis. To the author's knowledge, the hyperuricemia that often accompanies the leukemic states has not been documented in infectious mononucleosis. Uricacid levels from 13 male and eight female patients were obtained during the acute stages of the disease. The mean serum-uric-acid levels of both male and female patients were found to be significantly elevated. The elevations were found to be maximal within the first two weeks of the disease and tended to parallel the presence of abnormal lymphocytosis. Recent studies indicating an increased nucleic-acid synthesis by the abnormal mononuclear leukocytes in infectious mononucleosis suggest a possible mechanism for the hyperuricemia recorded in this report.
Prevention of Prednisone-lnduced Negative Nitrogen Balance
Authors: MARTIN G. COGAN
Journal: Annals of Internal Medicine (1981)

To assess whether increasing dietary protein and calorie intake can ameliorate the negative nitrogen balance induced by 70 to 120 mg/d prednisone, we studied nitrogen intake and net urea generation rate in patients undergoing hemodialysis for 10 to 14 days after renal transplantation. Seven patients receiving prednisone with moderately restricted protein (0.73 +/- 0.03 g/kg of body weight per day) and calorie (20 +/- 4 kcal/kg of body weight per day) intake had high urea nitrogen generation rates (199 +/- 18 mg/kg.d) and protein catabolic rates (1.45 +/- 0.12 g/kg.d) and were in marked negative protein balance (-0.72 +/- 0.12 g/kg.d). An increase in protein (1.30 +/- 0.06 g/kg.d) and calorie (33 +/- 3 kcal/kg.d) consumption in another eight prednisone-treated patients resulted in protein balance (-0.02 +/- 0.12 g/kg.d) without further increasing urea generation (174 +/- 9 mg/kg.d). Six control patients undergoing hemodialysis after surgery who were not receiving prednisone had lower urea generation rates (109 +/- 15 mg/kg.d) and were in nitrogen balance. Nitrogen wasting is therefore not an inevitable consequence of high-dose glucocorticoid therapy and can be effectively prevented by simple nutritional modification without increasing hemodialytic requirements.
Stability of murine bradykinin type 2 receptor despite treatment with <scp>NO</scp>, bradykinin, icatibant, or <scp>C</scp>1‐<scp>INH</scp>
Authors: F. Khosravani, T. Suvorava, V. T.‐V. Dao, N. Brockmann, O. Kocgirli, F. F. Herbst, S. Valcaccia, M. U. Kassack, M. Bas, G. Kojda
Journal: Allergy (2014)

Little is known about factors which trigger and/or contribute to hereditary angioedema or ACE-inhibitor-mediated angioedema including variations in bradykinin type 2 receptor (B2R) expression and activity.Protein and mRNA expression of B2R and the increase of intracellular calcium (iCa) in response to bradykinin were monitored in porcine and murine endothelial cells in response to NO donors or bradykinin. B2R protein expression was evaluated in skin, heart, and lung of (i) mice with endothelial-specific overexpression of eNOS (eNOS(tg) ), (ii) in eNOS(-/-) mice and (iii) in C57BL/6 mice treated with the NO donor pentaerythritol tetranitrate (PETN), the NOS inhibitor l-nitroarginine (L-NA), plasma pool C1-INH, and the B2R antagonist icatibant. Aortic reactivity to bradykinin was investigated including eNOS(-/-) mice.B2R protein and mRNA expression remained unchanged in cells subjected to L-NA, NO donors, and bradykinin in a time- and concentration-dependent manner. Likewise, increases of iCa in murine brain endothelial cells remained unchanged. B2R protein levels were similar in eNOS(tg) and eNOS(-/-) as compared to transgene-negative littermates. Likewise, treatment of C57BL/6 mice with PETN, L-NA, C1-INH or icatibant did not change B2R protein expression. In aortic rings of C57BL/6 mice, bradykinin induced B2R-dependent constrictions which were attenuated by endothelial NO and abolished by diclofenac indicating the functional importance of B2R-induced activation of endothelial NO synthase and cyclooxygenase.These data suggest that alterations of B2R protein expression induced by NO, bradykinin, C1-INH, or icatibant unlikely contribute to bradykinin-induced angioedema. This finding does not rule out a role for NO in bradykinin-induced extravasation and/or angioedema.
Role of microglia in ethanol-induced neurodegenerative disease: Pathological and behavioral dysfunction at different developmental stages
Authors: Jing-Yu Yang, Xue Xue, Hua Tian, Xiao-Xiao Wang, Ying-Xu Dong, Fang Wang, Ya-Nan Zhao, Xue-Chun Yao, Wei Cui, Chun-Fu Wu
Journal: Pharmacology & Therapeutics (2014)
Definitions of the phenotypic manifestations of sickle cell disease
Authors: Samir K. Ballas, Susan Lieff, Lennette J. Benjamin, Carlton D. Dampier, Matthew M. Heeney, Carolyn Hoppe, Cage S. Johnson, Zora R. Rogers, Kim Smith‐Whitley, Winfred C. Wang, Marilyn J. Telen
Journal: American Journal of Hematology (2009)

Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multiorgan effects. The low prevalence of SCD ( approximately 100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of SCD gathered to identify and categorize the most common complications. From this group, a formal writing team was formed that further reviewed the literature, sought specialist input, and produced definitions in a standard format. This article provides an overview of the process and describes 12 body system categories and the most prevalent or severe complications within these categories. A detailed Appendix provides standardized definitions for all complications identified within each system. This report proposes use of these definitions for studies of SCD complications, so future studies can be comparably robust and treatment efficacy measured. Use of these definitions will support greater accuracy in genotype-phenotype studies, thereby achieving a better understanding of SCD pathophysiology. This should nevertheless be viewed as a dynamic rather than final document; phenotype descriptions should be reevaluated and revised periodically to provide the most current standard definitions as etiologic factors are better understood, and new diagnostic options are developed.
What can we do to reduce mother to child transmission of HIV?
Authors: J. McIntyre
Journal: BMJ (2002)

<h3>Abstract</h3> The frontal eye field (FEF) is a critical region for the deployment of overt and covert spatial attention. While investigations in the macaque continue to provide insight into the neural underpinnings of the FEF, due to its location within a sulcus the macaque FEF is virtually inaccessible to electrophysiological techniques such as high-density and laminar recordings. With a largely lissencephalic cortex, the common marmoset (<i>Callithrix jacchus</i>) is a promising alternative primate model for studying FEF microcircuitry. Putative homologies have been established with the macaque FEF on the basis of cytoarchitecture and connectivity, however physiological investigation in awake, behaving marmosets is necessary to physiologically locate this area. Here we addressed this gap using intracortical microstimulation in a broad range of frontal cortical areas in marmosets. We implanted marmosets with 96-channel Utah arrays and applied microstimulation trains while they freely viewed video clips. We evoked short-latency fixed vector saccades at low currents (&lt;50 μA) in areas 45, 8aV, 8C and 6DR. We observed a topography of saccade direction and amplitude consistent with findings in macaques and humans; we observed small saccades in ventrolateral FEF and large saccades combined with contralateral neck and shoulder movements encoded in dorsomedial FEF. Our data provide compelling evidence supporting homology between marmoset and macaque FEF and suggest the marmoset is a useful primate model for investigating FEF microcircuitry and its contributions to oculomotor and cognitive functions. <h3>Significance Statement</h3> The frontal eye field (FEF) is a critical cortical region for overt and covert spatial attention. The microcircuitry of this area remains poorly understood, as in the macaque, the most commonly used model, it is embedded within a sulcus and is inaccessible to modern electrophysiological and optical imaging techniques. The common marmoset is a promising alternative primate model due to its lissencephalic cortex and potential for genetic manipulation. However, evidence for homologous cortical areas in this model remains limited and unclear. Here we applied microstimulation in frontal cortical areas in marmosets to physiologically identify the FEF. Our results provide compelling evidence for a frontal eye field in the marmoset, and suggest that the marmoset is a useful model for FEF microcircuitry.
Association of Helicobacter species with hepatitis C cirrhosis with or without hepatocellular carcinoma
Authors: M Rocha
Journal: Gut (2005)

<b>Background and aims:</b> Recent studies have suggested that bacterial coinfection with <i>Helicobacter</i> species in patients already infected with hepatitis C virus (HCV) could be involved in the development of cirrhosis and hepatocellular carcinoma (HCC). A retrospective cross sectional study was performed in order to explore the association between <i>Helicobacter</i> species and HCV associated liver diseases. <b>Methods:</b> The presence of <i>Helicobacter</i> species was tested by polymerase chain reaction on liver samples from four groups of patients. <b>Results:</b><i>Helicobacter</i> 16S rDNA was found in only 4.2% of liver samples from control patients (n = 24) and in 3.5% of liver samples from patients with non-cirrhotic chronic hepatitis C (n = 29) while it was found in 68.0% of liver samples from patients with HCV positive cirrhosis without HCC (n = 25) as well as in 61.3% of cirrhotic liver samples from patients with HCV positive cirrhosis and HCC (n = 31). In addition, when the HCC tumour tissue was tested (n = 21), 90.5% of samples were positive. DNA from <i>Helicobacter pylori</i>- and <i>Helicobacter pullorum</i>-like organisms was found. <b>Conclusions:</b> There is an association between the presence of <i>Helicobacter</i> species DNA in the liver and hepatitis C cirrhosis, with or without HCC. Indeed, the presence of these bacteria could be the result of structural changes in the liver. Alternatively, <i>Helicobacter</i> species could be a co-risk factor in HCV chronic liver diseases. This result warrants prospective studies to determine the possible causal role of these bacteria in the progression of chronic hepatitis C.
The NHS revisited
Authors: C. Ellis
Journal: BMJ (2001)

Iwas one of those doctors who emigrated from Great Britain in the late 1960s, now over 30 years ago. At that time the NHS seemed to have reached its lowest point since its inception in 1948. I have been in practice in Africa for over 25 years.

Since emigrating I have hardly ever returned to England, so recently I decided to do some general practice locums and get the feel and rhythm of the NHS again. I worked in five London general practices and one in Essex. The man from the locum agency, who acted rather like a controller from a John Le Carre spy novel, would ring me up and send me off.

> Practice seemed to have become part time, bitty, sessional, and agency driven 

My first locum was for a singlehanded general practitioner in south London. Over half the practice patients were either on housing or income support. I had forgotten about the sheer drudgery of inner city life. The lonely aged person's ceremonial visit to the doctor. The …
MMA:DMA ratios reversed.
Authors: T Slayton
Journal: Environmental Health Perspectives (1997)

s Focus article, "Measuring Mercury" (1), which appeared in the August 1996 issue of EHP, contained a serious omission.Wheeler concentrated on methyl mercury and, to a lesser extent, ele- mental mercury in dental amalgams.He failed to mention the relatively recently described but extremely significant expo- sures to elemental mercury in ethnically Hispanic and Caribbean homes, conse- quent to its use for a variety of magico-religious and ethnomedical purposes (2-3).Such domestic use and presumed expo- sure has been documented in a number of published papers, as well as by research sponsored by the ATSDR (4-6) and the EPA (7).In fact, an ATSDR monograph specifically alerts clinicians to this exposure pathway: "Metallic mercury has been used by Mexican-Americans and Asian popula- tions in folk remedies for chronic stomach disorders and by Latin-American and Caribbean natives in occult practices" (4).This monograph was edited by Thomas Clarkson, who was interviewed by Wheeler, and who has long been aware of elemental mercury's domestic use.Similarly, the EPA's Kathryn Mahaffey, also interviewed, has been aware of domestic mercury exposure for some years, and the EPA issued a risk assessment document on cultural uses of mercury in 1993 (7).These mercury exposures are especially significant from an environmental health perspective because, in many cases, they are certain to be orders of magnitude greater than (methyl) mercury exposures from eating fish or from the leaching of mercury in amalgam fillings.Additionally, the mercury vapor released from mercury intentionally sprinkled on floors affects all occupants of contaminated homes, from the fetus to the elderly.Andrew Rowland, cited in "The Issue of Amalgams" (1), has been aware of domestic mercury exposure for several years.Rowland makes a call for more research on health effects of amalgam-mercury exposure.I make a similar call for research on magico-religious mercury exposure.If the environmental health research community continues to ignore magico-religious mercury exposure, its health effects will never be ascertained.
Diagnosis of Menetrier??s Disease With Tc-99m Human Serum Albumin Scintigraphy
Authors: ELMER J. PACHECO, ALBERT J. MORENO, AUGUST RAMOS, ROBERT MURRAY, GOTTLIEB L. TURNBULL, ANTONIO BARZEY
Journal: Clinical Nuclear Medicine (1995)

Technetium-99m labeled human serum albumin has been shown to detect protein leakage into the bowel. A case of a young adult is presented with endoscopic and pathological correlation of scintigraphic findings supporting Menètrier's disease.
VASOMERA™, A NOVEL VPAC2-SELECTIVE VASOACTIVE INTESTINAL PEPTIDE AGONIST, ENHANCES CONTRACTILITY AND DECREASES MYOCARDIAL DEMAND IN DOGS WITH BOTH NORMAL HEARTS AND WITH PACING-INDUCED DILATED CARDIOMYOPATHY
Authors: Carlos L. del Rio, Robert George, Pamela Kloepfer, Yukie Ueyama, Bradley Youngblood, Lynne Georgopoulos, Sue Arnold, Robert L. Hamlin
Journal: Journal of the American College of Cardiology (2013)
Oncostatin M induces association of Grb2 with Janus kinase JAK2 in multiple myeloma cells.
Authors: D Chauhan, S M Kharbanda, A Ogata, M Urashima, D Frank, N Malik, D W Kufe, K C Anderson
Journal: The Journal of Experimental Medicine (1995)

Oncostatin M (OSM) is a 28-kD glycoprotein recently identified as a growth factor for human multiple myeloma cells. It belongs to a family of distantly related cytokines that includes interleukin 6, ciliary neurotrophic factor, leukemia-inhibitory factor, and interleukin 11. These cytokines initiate signaling by inducing either homodimerization of gp130 or heterodimerization of gp130 with leukemia-inhibitory factor receptor beta components. Such dimerization in turn activates receptor-associated tyrosine kinases. In the present study using U266B1 human multiple myeloma cells, we show that OSM induces tyrosine phosphorylation and activation of JAK2, but not JAK1 or Tyk2, kinases. The results also demonstrate that OSM induces direct interaction of JAK2 kinase with Grb2, an SH2/SH3 domain containing adaptor protein. The SH2 domain of Grb2 is directly associated with tyrosine-phosphorylated JAK2. Furthermore, the presence of Sos in the JAK2-Grb2 complex suggests a role for Ras in OSM-transduced signaling.
Sarcomas of Soft Tissues
Authors: Robert C. Horn
Journal: JAMA (1963)

Until a definitive cause that can be removed or a magic chemotherapeutic or other "bullet" is found for malignant tumors of the soft tissues, further progress toward the goal of their control must depend upon not only the efforts of individual physicians and investigators but also upon the close cooperation and sympathetic understanding of physicians and scientists representing a variety of disciplines concerned with care of the patient— the family physician, the surgeon, radiotherapist, chemotherapist or "oncologist," pathologist, and every other specialist, generalist, or dentist whom the patient might consult. Two briefly cited case reports will serve to introduce important points for consideration. <h3>Report of Cases</h3><h3>Case 1.</h3> —The parents of a 2-yr-old girl consulted a physician when they noticed a "pea-sized pimple" on her neck. During a 10-week period of observation by two physicians the pimple grew slowly and adjacent glands became swollen. The swelling was associated with clinical
5-Fluorouracil Selectively Kills Tumor-Associated Myeloid-Derived Suppressor Cells Resulting in Enhanced T Cell–Dependent Antitumor Immunity
Authors: Julie Vincent, Grégoire Mignot, Fanny Chalmin, Sylvain Ladoire, Mélanie Bruchard, Angélique Chevriaux, François Martin, Lionel Apetoh, Cédric Rébé, François Ghiringhelli
Journal: Cancer Research (2010)

Abstract Myeloid-derived suppressor cells (MDSC) accumulate in the spleen and tumor bed during tumor growth. They contribute to the immune tolerance of cancer notably by inhibiting the function of CD8(+) T cells. Thus, their elimination may hamper tumor growth by enhancing antitumor T-cell functions. We have previously reported that some anticancer agents relied on T cell–dependent anticancer responses to achieve maximal efficacy. However, the effect of anticancer agents on MDSC has remained largely unexplored. In this study, we observed that gemcitabine and 5-fluorouracil (5FU) were selectively cytotoxic on MDSC. In vivo, the treatment of tumor-bearing mice with 5FU led to a major decrease in the number of MDSC in the spleens and tumor beds of animals whereas no significant effect on T cells, natural killer cells, dendritic cells, or B cells was noted. Interestingly, 5FU showed a stronger efficacy over gemcitabine to deplete MDSC and selectively induced MDSC apoptotic cell death in vitro and in vivo. The elimination of MDSC by 5FU increased IFN-γ production by tumor-specific CD8(+) T cells infiltrating the tumor and promoted T cell–dependent antitumor responses in vivo. Altogether, these findings suggest that the antitumor effect of 5FU is mediated, at least in part, by its selective cytotoxic action on MDSC. Cancer Res; 70(8); 3052–61. ©2010 AACR.