tbuckley/cabot-search huggingface dataset:
Mechanism for the inflammatory response in primate lungs. Demonstration and partial characterization of an alveolar macrophage-derived chemotactic factor with preferential activity for polymorphonuclear leukocytes.
Authors: J A Kazmierowski, J I Gallin, H Y Reynolds
Journal: Journal of Clinical Investigation (1977)

Approximately 4 h after an initial bronchoalveolar lavage (BAL) of a primate's lung, an appreciable number of polymorphonuclear leukocytes (PMNs) were noted to accumulate in respiratory fluids when lavage was repeated. Whereas, alveolar macrophages (90%) and lymphocytes (7%) were the principal respiratory cells recovered initially from lavage fluid, later samples contained 45-90% PMNs To explain the observed ingress of PMNs into lung fluids, concentrated BAL fluid was tested for chemoattractant activity. Such fluid obtained 4 and 24 h after an initial lavage contained material that produced directed migration (chemotaxis) for PMNs and mononuclear cells isolated from peripheral blood of normal donors. Gel filtration chromatography of BAL disclosed two peaks of chemotactic activity in the effluent fractions. Material from the column with an estimated molecular weight of 15,000 daltons was chemotactic for both PMNs and mononuclear cells. Because it was susceptible to inactivation with antiserum against the fifth component of complement, resistant to heating, and unaffected by antiserum against C3, this factor was considered analogous to the cleavage product of the fifth component of complement. C5a. In addition chemotactic activity for PMNs only was contained in an effluent peak having a molecular weight of about 5,000 daltons. This material was heat labile but unaffected by antisera to complement components. To locate the possible source of these factors in respiratory fluid, in vitro cultures of alveolar macrophages were established. These cells, whether stimulated by phagocytosis of opsonized bacteria or merely by attachment to a glass surface, produced chemotactic material which had physical characteristics similar to the small molecular weight material in BAL. Moreover, it induced preferential chemotaxis for PMNs. Thus, in primate lungs, at least two chemotactic substances may generate an inflammatory response; one which is a fragment of the complement component C5 and another small molecular weight factor which is released from alveolar macrophages.
Blood dyscrasia associated with azapropazone therapy.
Authors: S T Green, H McMillan, L Erwin
Journal: Annals of the Rheumatic Diseases (1985)

containing the D-Ala-D-Ala sequence apparent discrepancy between our result sera is not surprising.Furthermore we failing to note an association between s bacterial PG and RA.Pope et al. have similar observation.'There is, however, one point on wh anti-PG concur; namely, that the hun sponse to bacterial PG in humans is diver for this diversity is more clearly undc tionship of anti-PG to rheumatic disease: and RA, will probably remain a matt(
N-retinoyl-D-glucosamine, a new retinoic acid agonist, mediates topical retinoid efficacy with no irritation on photoaged skin
Authors: H. Kambayashi, Y. Odake, K. Takada, Y. Funasaka, M. Ichihashi, S. Kato
Journal: British Journal of Dermatology (2005)

Chronic ultraviolet (UV) radiation from sunlight induces wrinkle formation. Retinoic acid (RA) can markedly improve wrinkles, although RA does have some side-effects, such as skin irritation. As the efficacy and cytotoxicity of RA has been traced to its free carboxylic acid, we synthesized a new molecule, N-retinoyl-D-glucosamine (GRA), in which a glucosamine has been attached to the polar end group of all-trans retinoic acid.To analyse the effect of topical GRA in wrinkle repair and anti-irritation in photoaged mice compared with topical RA, as well as to determine retinoic acid receptor (RAR) and retinoid X receptor (RXR) transactivation activity in vitro.Hairless mice were irradiated with 60 mJ cm-2 of UVB for 10 weeks, and then topically treated with 0.05% GRA or 0.05% RA for 8 weeks. An in vitro transcriptional assay was performed and the activity of GRA in 293 cells transfected with RAR-alpha or RXR-alpha expression plasmid and luciferase reporter plasmid then determined.Topical GRA and RA brought about almost complete disappearance of the wrinkles caused by UVB irradiation. The two ligands promoted both a wide repair zone histologically, and the expression of type 1 collagen in the skin. In contrast, topical GRA treatment did not produce irritation such as erythema or roughness, or alteration of transepidermal water loss values, compared with RA. In the in vitro luciferase assay, GRA resulted in significant dose-dependent RAR transactivation activity in a 100 times higher concentration range than RA. GRA did not mediate RXR transactivation activity at all.Topical GRA appears to be able to repair photoaged skin damage without any of the irritation caused by topical RA, probably via RAR transactivation activity.
The value of tpmt measurement in the routine clinical management of patients with IBD
Authors: S. West, J. Moore, S. Bharathi, S. Kelly
Journal: Gut (2011)

<h3>Introduction</h3> The measurement of thiopurine methyl transferase (TPMT) can be used to identify patients at risk of marrow suppression from azathioprine. Across the medical specialities, there is no clear consensus or guidelines on the place of routine measurement of TPMT prior to commencing azathioprine. However, this is now widely accepted as standard practice among gastroenterologists in the UK. In this study the authors aimed to assess the value of TPMT level measurement in routine clinical practice in IBD patients commencing azathioprine. <h3>Methods</h3> A retrospective study of all patients with IBD commencing azathioprine in our hospital between 2007 and 2009. The laboratory ranges used in our lab classify patients as TPMT deficient at values less than 10, intermediate 10–26 and normal 26–50. Data was collected on disease type, demographics, TPMT levels, marrow suppression and other adverse effects, including hepatotoxicity, pancreatitis and GI intolerance. <h3>Results</h3> 139 patients were identified; 69 with Crohn9s disease, 62 with ulcerative colitis and 8 with indeterminate colitis. Basic demographic analysis revealed a mean age of 40 years (range 18–84). Patients were followed up for a median 14 weeks, (range 3–48 weeks). Of these patients, 116 (83%) had normal TPMT levels and 23 (17%) intermediate levels. In the group of 23 with intermediate TPMT levels, 15 patients (65%) had to stop azathioprine due to adverse effects. 3 (13%) developed marrow suppression, including 1 who developed neutropenic sepsis, 7 (30%) developed hepatotoxicity or pancreatitis and 5 others (22%) stopped azathioprine due to other GI intolerance. In the group of 116 patients with normal TPMT levels, 53 (46%) developed adverse effects. Of these, 9 patients had bone marrow suppression, 2 continued the drug but with dose reduction and 7 discontinued azathioprine. This equates to 8% of all patients with normal TPMT levels experiencing bone marrow suppression. 16 patients (14%) developed hepatotoxicity or pancreatitis and 27 (23%) other GI intolerance. One patient stopped azathioprine during an acute illness and never restarted it. <h3>Conclusion</h3> Our patients with intermediate levels of TPMT were at increased risk of marrow suppression (13% vs 8%) compared to those with normal TPMT levels. Also a greater proportion of this group stopped azathioprine due to other side effects (52% vs 37%). However, patients with normal TPMT levels were also clearly at risk of side effects, and it does not appear that knowledge of TPMT status really affected an individual patient9s clinical outcome. It is not at all certain that measurement of TPMT really adds anything to routine vigilant clinical and laboratory monitoring in this group of patients.
High Altitude Illness
Authors: Robert P. Younes
Journal: JAMA (1977)

<h3>To the Editor.—</h3> I read Dr Houston's discussion on high altitude sickness (236:2193, 1976) with a great deal of interest. It has always occurred to me whenever reading articles about high altitude sickness that the clue to the origin of this condition lies in its name—altitude (that is, diminished barometric pressure). Human beings living at sea level have their bodies shaped and compressed somewhat by sea level barometric pressure. However, when one ascends, the intracellular and extracellular volume expands slightly because there is less external pressure to maintain their former volumes. The resulting diminished pulse pressure in the renal arteries associated with the relative hypovolemia causes the juxtaglomerular apparatus to activate the renin-angiotensin-aldosterone mechanism, thereby causing fluid retention. Hypoxia-induced pulmonary hypertension and other hypoxic cellular changes in combination with fluid retention may be enough to cause increased vascular permeability, which in turn causes acute mountain sickness, high altitude pulmonary edema,
Medical surveillance of exposed persons after exposure to PCBs, chlorinated dibenzodioxins and dibenzofurans after PCB transformer or capacitor incidents.
Authors: A Schecter
Journal: Environmental Health Perspectives (1985)

The panel discussion from the perspective of occupational medicine regarding appropriate medical surveillance after a PCB transformer or capacitor incident is reviewed. A thorough occupational medicine history and physical examination is stressed for any worker or other patient who may have been exposed. Appropriate laboratory tests, including complete blood count with differential, serum chemistries, serial blood PCB determinations, fat biopsy to estimate furan and dioxin levels, if indicated, pulmonary function tests, chest X-rays, urinalysis including porphyrin measurement, nerve conduction velocity testing and other tests are discussed. No consensus was reached on recommended length of medical followup. Because the field is rapidly changing, yearly updates of medical protocols are warranted. In addition, the need for surveillance to be conducted by specialists with training and experience in the fields of occupational medicine and nursing was emphasized. It was stressed that measuring the chemicals and their levels in soot and air and then comparing these with the patient's blood or fat levels, in the case of PCBs, furans and dioxins, is vital. It was noted that at present no modality of treatment is known to be clinically efficacious in removing PCBs, furans and dioxins from tissues or blood.
History of Parental Allergy and Asthma as Predictors of Allergic Sensitization in their Offspring
Authors: E.L. Anderson, M.D. Evans, D.F.G. DaSilva, T.E. Pappas, L.E. Pleiss, K.A. Roberg, K.T. Sullivan Dillie, C.J. Tisler, R.E. Gangnon, J.E. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2006)
Once Daily Fluticasone Furoate∗ Nasal Spray (FFNS), a Novel Enhanced Affinity Steroid, Provides 24-hour Relief for the Nasal Symptoms of Perennial Allergic Rhinitis (PAR)
Authors: R. Nathan, W. Berger, W. Yang, A. Cheema, M.J. Silvey, W. Wu, M. Faris, E. Philpot
Journal: Journal of Allergy and Clinical Immunology (2007)
The Use of Theological Classics in Teaching Medical Ethics-Reply
Authors: Bernard H. Adelson
Journal: JAMA (1987)

<h3>In Reply.—</h3> Dr Rosner's suggestions that we consider the use of theological classics and that we add a theologian to our teaching team are excellent and pertinent. It is our intent to achieve both of these goals in our use of literary classics in teaching medical ethics to physicians. We agree that the use of theological classics will add important insight into our understanding of the ethical relationships between the patient and the physician.
Work related upper limb disorder: the relationship between pain, cumulative load, disability, and psychological factors.
Authors: P.S Helliwell, D.B Mumford, J.E Smeathers, V Wright
Journal: Annals of the Rheumatic Diseases (1992)

Repetitive strain injury, or work related upper limb disorder, provides an interesting paradigm for the study of the relative contribution of physical and psychological factors to the resulting pain and disability. Sixty three subjects were studied, comprising the work-force of a subsection of a large local industrial company, in whom pain in the arm related to work was known to be common. Ergonomic data were obtained by estimating the cumulative daily load on the wrist joint for each of four identified tasks. Data on the occurrence of pain, treatment sought, and disability were obtained by a structured self administered questionnaire. Psychological data were obtained by administering the Hospital Anxiety and Depression (HAD) scale, a self reported measure of anxiety and depression, and the Bradford Somatic Inventory (BSI), an inventory of somatic symptoms associated with anxiety and depression. The employment specific period prevalence of work related upper limb disorder was 81%, with 30% of the subjects having pain at the time of the study. Domestic disability was minimal in all but two subjects, though the use of devices such as jar openers at home was common (12 of 51 subjects). Medical advice was seldom sought. Twenty per cent of subjects had received anti-inflammatory drugs, 10% had received physiotherapy, and 47% had wrist splints. Pain was related to the tasks with the highest estimated daily loads, but a history of pain and current pain were associated with higher scores on the HAD and BSI scales, suggesting an interaction between physical and psychological factors.
Regulation of Cardiac MicroRNAs by Cardiac MicroRNAs
Authors: Scot J. Matkovich, Yuanxin Hu, Gerald W. Dorn
Journal: Circulation Research (2013)

MicroRNAs modestly suppress their direct mRNA targets, and these direct effects are amplified by modulation of gene transcription pathways. Consequently, indirect mRNA modulatory effects of microRNAs to increase or decrease mRNAs greatly outnumber direct target suppressions. Because microRNAs are products of transcription, the potential exists for microRNAs that regulate transcription to regulate other microRNAs.Determine whether cardiac-expressed microRNAs regulate expression of other cardiac microRNAs, and measure the impact of microRNA-mediated microRNA regulation on indirect regulation of nontarget mRNAs.Transgenic expression of pre-microRNAs was used to generate mouse hearts expressing 6- to 16-fold normal levels of microRNA (miR)-143, miR-378, and miR-499. Genome-wide mRNA and microRNA signatures were established using deep sequencing; expression profiles provoked by each microRNA were defined. miR-143 suppressed its direct cardiac mRNA target hexokinase 2, but exhibited little indirect target regulation and did not regulate other cardiac microRNAs. Both miR-378 and miR-499 indirectly regulated hundreds of cardiac mRNAs and 15 to 30 cardiac microRNAs. MicroRNA overexpression did not alter normal processing of either transgenic or endogenous cardiac microRNAs, and microRNA-mediated regulation of other microRNAs encoded within parent genes occurred in tandem with parent mRNAs. MicroRNA regulation by miR-378 and miR-499 was stimulus specific, and contributed to observed mRNA downregulation.MicroRNAs that modulate cardiac transcription can indirectly regulate other microRNAs. Transcriptional modulation by microRNAs, and microRNA-mediated microRNA regulation, help explain how small direct effects of microRNAs are amplified to generate striking phenotypes.
Clofibrate in Coronary Heart Disease
Authors: Louis R. Krasno
Journal: JAMA (1972)

A series of 1,001 men free of coronary heart disease and 67 with disease with an average age of 47.5 years were divided in two groups pairmatched for risk factors. One group was treated with an antilipemic agent (clofibrate) whereas the other remained untreated for 39 months. The nonfatal myocardial infarction rate was 6.6/1,000/yr and 1.89/1,000/yr for untreated and treated men, respectively. Two younger unmatched treated and untreated groups totaling 2,218 men who had an average age of 37.5 years and were free of coronary heart disease were observed for 32.4 and 22.8 months, respectively. The incidence of nonfatal myocardial infarction was 5.0/1,000/yr in the untreated and 0.64/1,000/yr in the treated individuals. These results were observed notwithstanding the persistence of varying degrees of hyperlipidemia in some treated individuals. There was no significant difference in mortality at this time.
Decreased Cardiovascular Disease and Increasing Cancer
Authors: James C. Maher
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The article by Dr Davis and colleagues<sup>1</sup>is statistically confusing and contains statements that are not borne out by the data presented. For example, in Table 5, the male cohort aged 20 to 25 years in 1973 to 1977 must be the cohort 25 to 29 years from 1978 to 1982 and 30 to 35 years between 1983 and 1987. This cohort increases from 3.6 million to 4.128 million during that period. Despite the 5700 cancer deaths, the population was enlarging. I fail to see how "[m]en born in 1948 through 1957 have developed more than three times more cancer not related to smoking than did those born at the last century's end," when the incidence of nonsmoking cancer in men born in 1898 to 1907 is 2.7%, while the risk for those born from 1948 through 1957 is 0.03%. While these data may show both
Multiple VH gene segments encode murine antistreptococcal antibodies.
Authors: R M Perlmutter, J L Klotz, M W Bond, M Nahm, J M Davie, L Hood
Journal: The Journal of Experimental Medicine (1984)

Most mouse strains are able to mount a diverse antibody response against group A streptococcal carbohydrate (GAC). We have previously reported that murine anti-GAC antibodies are for the most part restricted to IgM and IgG3 subclasses. In addition, despite extensive heterogeneity in their isoelectric focusing patterns, greater than 50% of A/J anti-GAC antibodies share a common light chain defined by spectrotypic and idiotypic (VK1GAC) criteria. We have used protein and DNA sequencing strategies to examine the genetic basis of diversity in murine anti-GAC antibodies. In particular, we report that, (a) multiple, closely homologous VH gene segments contribute to the generation of anti-GAC antibodies, (b) a common framework sequence, related to the VK27 subgroup, probably defines VK1GAC, and (c) the A/J anti-GAC VH regions and BALB/c anti-inulin VH sequences are 95% homologous at the protein level and are likely encoded by overlapping VH gene families. Lastly, we discuss the genetic mechanisms that might permit the evolution of multiple, closely homologous germline VH gene segments in the context of highly divergent flanking region sequences.
Abstract 4296A: Myeloproliferative disease induced by leukemogenic Ptpn11 (Shp-2) phosphatase arises from hematopoietic stem cells
Authors: Dan Xu, Siying Wang, Wen-Mei Yu, Gordon Chan, Toshiyuki Araki, Kevin D. Bunting, Benjamin G. Neel, Cheng-Kui Qu
Journal: Cancer Research (2010)

Abstract Germline and somatic gain-of-function (GOF) mutations in the tyrosine phosphatase PTPN11 (SHP-2) are associated with juvenile myelomonocytic leukemia (JMML), a clonal myeloproliferative disease (MPD) of early childhood. However, the mechanism by which PTPN11 mutations induce this disease is not fully understood. Here we report that the germline mutation Ptpn11D61G increases mouse hematopoietic stem cell (HSC) activity, as evidenced by accelerated cycling, increased stem cell pool, enhanced self-renewal, and elevated short-term and long-term repopulating capabilities. More importantly, the MPD is reproduced in primary and secondary recipient mice transplanted with Ptpn11D61G mutant marrow cells or sorted Lineage- Sca-1+c-Kit+ cells, indicative of the long-term stem cell origin of the disease. The leukemogenic effect of Ptpn11D61G mutation appears to be attributed to enhancing cytokine signaling. Furthermore, HSC homeostasis disrupted by Ptpn11D61G mutation is partially restored by deletion of Gab2, an important interacting protein/target of SHP-2. MPD phenotypes are markedly ameliorated in Ptpn11D61G/+/Gab2−/− double mutant mice. Together, these studies suggest that SHP-2 associated JMML arises from HSCs and that targeting SHP-2/Gab2 mediated signaling in stem cells may be useful for the treatment of this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4296A.
LOCALIZED HEADACHE ASSOCIATED WITH LESION OF MENINGEAL VESSELS
Authors: WINCHELL McKendree Craig
Journal: JAMA (1933)

Generalized headache, or cephalagia, may be a symptom of many different diseases and is of doubtful diagnostic significance unless associated with other symptoms of intracranial changes. Localized headache, however, is frequently of diagnostic significance and may indicate the region of intracranial involvement, as illustrated by the case here to be reported. Intracranial operations under regional anesthesia have demonstrated that the brain is insensitive to pain and that the dura mater is probably the only sensitive tissue encountered; the greatest discomfort is caused by ligation or manipulation of the meningeal vessels. According to Teachenor,<sup>1</sup>the dura has a rich and somewhat complicated nerve supply. It is supplied mainly from the fifth and tenth cranial nerves and the sympathetic system, although some fibers are derived from the fourth and twelfth cranial nerves. A branch of the mandibular division of the fifth nerve, which is given off directly after the exit of
THYROID THERAPY AND THYROID TOLERANCE IN CHRONIC NEPHROSIS
Authors: ALBERT A. EPSTEIN
Journal: JAMA (1926)

My purpose in this communication is to put on record some new observations on the use and effect of thyroid and thyroxin in the treatment of chronic nephrosis. In earlier publications I<sup>1</sup>have drawn attention to certain biochemical features present in chronic nephrosis which also appear in myxedema and other hypothyroid states, chief of which are the hypercholesterolemia and the reduced basal metabolism. Other observers, notably Eppinger,<sup>2</sup>have pointed out clinical resemblances between these two groups of disease, and I have recorded a case of chronic nephrosis which ultimately developed into a genuine myxedema.<sup>3</sup>Moreover, two cases have come under my observation, and I have been informed of a third, in which chronic nephrosis supervened on prolonged irradiation of the neck, involving the chest and thyroid. From these clinical and biochemical studies the conclusion was drawn that the function of the thyroid gland is in some way
Agonistic Autoantibodies and Rejection of Renal Allografts
Authors: Julie R. Ingelfinger
Journal: New England Journal of Medicine (2005)

Allograft rejection remains a major problem in renal transplantation, despite the substantial improvements in post-transplantation management that now result in fewer acute rejection episodes and better overall survival.1 Rejection can be an acute event or a chronic, indolent process in which fibrosis within the graft is prominent and ultimately results in graft loss. Allograft rejection is usually considered to be mediated by T cells, but there is substantial evidence of antibody-mediated injury to the graft outside the now rare context of hyperacute rejection (which occurs when high titers of anti-HLA antibodies are present before transplantation2). Indeed, antibody-mediated rejection (also . . .