tbuckley/cabot-search huggingface dataset:
Abstract 1293: Familial melanoma by histology and age guiding clinical genetic counseling: joint data from five Nordic countries
Authors: Mahdi Fallah, Eero Pukkala, Kristina Sundquist, Steinar Tretli, Jørgen H. Olsen, Laufey Tryggvadottir
Journal: Cancer Research (2014)

Abstract Background: We aimed to estimate lifetime cumulative risk of melanoma (CRM) in relatives of patients with melanoma by histology and age at diagnosis in patients and relatives. Methods: A population-based cohort of 238,724 first-degree relatives of 46,091 melanoma patients diagnosed in 1955-2010 in Nordic countries was followed for cancer incidence. Findings: The CRM (0-79 years) in first-degree relatives of a patient with superficial spreading (SSM), nodular (NM), or lentigo maligna (LMM) melanoma was quite similar, ranging from 2.5% to 2.9%, which represents about 2-fold increase over the general population risk. When one melanoma patient in the family was diagnosed before age 30, the CRM was 3.2%. When there were ≥2 melanoma patients diagnosed before age 30 in a family, CRM for relatives was 13.8%, 5.8% for diagnoses at age 30-59, and 4.8% for diagnoses at age 60 or older. Depending on age at diagnosis of same-sex twins (not known whether monozygotic or dizygotic), their CRM was 7.4-21.3%. Although no familial case of concordant histological types of acral lentiginous/desmoplastic/compound nevus/spindle cell melanomas or malignant blue nevus (MBN) was found, familial risks of discordant histological types of melanoma were interchangeably high for most of the types, e.g. higher risk of SSM when a first-degree relative had NM [standardized incidence ratios (SIR)=2.6, 95%CI=2.1-3.3, n=72] or ALM (4.0, 95%CI=1.5-8.8, n=6) and vice versa. There was a tendency toward concordant age at diagnosis of melanoma among relatives of melanoma patients. Interpretation: This study provides clinically relevant absolute and relative risk estimates for family members of melanoma patients by age at diagnosis in patients and relatives. Our finding may suggest that the role of genetic or environmental factors in the differentiation of histological types of melanoma is not as strong as its role in the development of melanoma as such. Citation Format: Mahdi Fallah, Eero Pukkala, Kristina Sundquist, Steinar Tretli, Jørgen H. Olsen, Laufey Tryggvadottir. Familial melanoma by histology and age guiding clinical genetic counseling: joint data from five Nordic countries. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1293. doi:10.1158/1538-7445.AM2014-1293
Ephedra and Ephedrine
Authors: Janet M. Torpy, Cassio Lynm, Richard M. Glass
Journal: JAMA (2003)

Ephedra and EphedrineE phedra is a plant-based substance from the herb Ephedra sinica.Ephedra is used in many over-the-counter weight loss products.It is also used by some athletes who believe it can improve their performance.It may be combined with herbs containing caffeine (such as guarana) or with other substances in these supplements.Ephedra, also known as ma huang, has also been used in traditional Chinese medicine to treat asthma or other lung problems.Because ephedra is marketed by companies as a supplement (not a drug to treat a disease), the US Food and Drug Administration (FDA) does not regulate its use.However, many serious adverse (bad) effects related to ephedra use have been reported.Recent research has shown that use of ephedra appears to be more risky than use of other herbal preparations.The March 26, 2003, issue of JAMA includes an article about the efficacy and safety of ephedra and ephedrine.
SOME PHYSIOLOGIC FACTORS INVOLVED IN THE ORIGIN OF SCURVY (SCORBUTUS).
Authors: ROY RAVONE ROGERS
Journal: JAMA (1902)

Scarcely any disease has afforded opportunity for such abundant speculation and investigation as scurvy. Till within the last twenty years its ravages among maritime and military ranks were appalling, and it has been largely due to the work of Lind, Garrod, Buzzard, Chalvet, and particularly that of Ralfe, that our knowledge of its etiology, prevention and treatment has reached a stage where it can be expressed in definite terms. <h3>VARIOUS OPINIONS ON ETIOLOGY.</h3> The causes in which the origin of scurvy have been sought have been indeed, in many cases, in no way related, each theory has had its grains of truth, but has failed to explain all and it is our purpose to correlate these various observations and refer them to simple terms. Lheridon-Cremorne<sup>1</sup>sought its cause in nostalgia, Gueit<sup>2</sup>in mental depression, Murray<sup>3</sup>in despondency and hypochondria, Fabre<sup>4</sup>in a vasomotor disturbance induced by
Abstract 4739: miR-627 and histone demethylase JMJD1A as new therapeutic targets in colon cancer
Authors: Sathish Padi, Bin Guo
Journal: Cancer Research (2012)

Abstract Vitamin D has excellent antitumor activities against various types of cancers, but it cannot be used for cancer therapy due to its side effect of causing hypercalcemia. To understand its mechanism of action in tumor suppression, we investigated the effects of calcitriol (1α,25-dihydroxyvitamin D3, the active form of vitamin D) on microRNA expression in colon cancer cells. We identified miR-627 as the sole microRNA whose expression was stimulated by calcitriol. Furthermore, JMJD1A (jumonji domain containing 1A), the gene encoding a histone demethylase, was identified as the target of miR-627. By downregulating JMJD1A, miR-627 mediated the effects of calcitriol to increase histone H3K9 methylation and to suppress the expression of growth-promoting genes, such as GDF15. Calcitriol also induced miR-627 and downregulated JMJD1A in colon cancer xenografts in nude mice. Overexpression of miR-627 decreased JMJD1A and suppressed colon cancer growth both in vitro and in vivo in the nude mice. In addition, we found that miR-627 expression was decreased in human colon cancer specimens when compared to its levels in the normal colon tissues. Thus, miR-627 plays an important role in the epigenetic action of vitamin D in tumor suppression. miR-627 and JMJD1A may serve as potential targets to exploit the antitumor activity of vitamin D without eliciting its hypercalcemic side effect. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4739. doi:1538-7445.AM2012-4739
Near patient testing in primary care
Authors: R. Hobbs
Journal: BMJ (1996)

Near patient or point of care testing has been documented at least since Thomas Willis (1621-1675) wrote of tasting urine to test for glycosuria. Today, every doctor uses dry reagent laboratory sticks for simple urine analysis or blood sugar estimation, both in clinics or offices and in patients' homes. In the United States near patient testing now comprises 20% of all testing,1 and the past decade has seen increasing interest in the use of dedicated single test devices or desk top chemistry analysers among doctors in Europe, particularly in Britain,2 3 the Netherlands,4 and Scandinavia.5 In all countries it is in primary care that the true potential for near patient testing will be realised.

Near patient testing could improve the accuracy of clinical decision making and the reliability of monitoring chronic diseases, assisted if necessary by expert decision support.6 Primary care physicians are under multiple pressures to …
638. Combined LDL Receptor and ApoA-I Gene Therapy for Advanced Atherosclerosis in a Mouse Model of Familial Hypercholesterolemia
Authors: Hsu Chao, Kerry Ko, Lawrence Chan, Kazuhiro Oka
Journal: Molecular Therapy (2005)

Management of patients with autosomal dominant familial hypercholesterolemia continues to be a major challenge. Somatic gene therapy may offer an alternative treatment for these patients. We have previously reported that helper-dependent adenovirus (HDAd)-mediated LDL receptor (LDLR) gene transfer reversed hypercholesterolemia for over 108 weeks and markedly retarded development of atherosclerosis in LDLR-deficient mice (Gene Ther 11:1540-1548, 2004). We also reported that HDAd expressing apolipoprotein A-I (apoA-I) was effective in inhibition of progression of advanced atherosclerosis. After 24 weeks treatment, the lesions had a more stable-appearing phenotype with a decrease in subendothelial lipid deposits and a reduction in macrophage-derived cells and adhesion molecule expression (Circulation 107:2726-2732, 2003). ApoA-I and LDLR work via different mechanisms. ApoA-I elevates HDL, which has anti-inflammatory and anti-oxidative effects, and also promotes reverse cholesterol transfer. LDL works mainly by lowering atherogenic non-HDL lipoproteins. We, therefore, compared the efficacy of HDAd-mediated hepatic transfer of ApoA-I only, LDLR only, and ApoA-I + LDLR on atherosclerosis development in LDL-/- mice. LDLR-deficient mice (6-8 weeks of age) were fed a high cholesterol diet for 36 weeks and were separated into 5 groups (baseline, HDAd-0 empty vector, HDAd-AI + HDAd-0, HDAd-LDLR + HDAd-0, HDAd-AI + HDAd-LDLR). The baseline group was sacrificed, and the remaining mice were treated with 2 |[times]| 10E11 VP of HDAd vectors. The plasma cholesterol levels in HDAd-0 (n=6) or HDAd-AI + HDAd-0 (n=7) group were around 500 mg/dl throughout the experiment. Plasma cholesterol levels were reduced to 72 mg/dl 2 weeks after treatment in HDAd-LDLR group and gradually increased to 300 mg/dl over the next 28 weeks (n=7). The mice treated with both genes had a cholesterol level of 182 mg/dl at 2 weeks which gradually increased to 297 mg/dl at 28 weeks (n=8). FPLC analysis revealed that the prominent IDL/LDL fraction is reduced in HDAd-LDLR treated groups. Atherosclerotic lesion areas were measured by quantitative morphometry. Mean lesion area was 5.7 mm2 in the baseline group. It was 12.5 mm2 in the HDAd-0 group, 9.5 mm2 in the HDAd-AI group, 3.2 mm2 in the HDAd-LDLR group, and 3.3 mm2 in the HDAd-AI + HDAd-LDLR group. Compared with baseline and HDAd-0 group, HDAd-AI treatment inhibited the lesion progression by 25%, while HDAd-LDLR alone or combined treatment induced lesion regression by 44%. The combined treatment is very effective. However, our data suggest that LDLR gene transfer accounts for most of the effects in the combined treatment. Moreover, these results indicate that HDAd-mediated LDLR gene therapy is highly effective in inhibition of lesion progression as well as in inducing atherosclerotic lesion regression in a mouse model of familial hypercholesterolemia.
Erythropoietin stimulates spleen BMP4-dependent stress erythropoiesis and partially corrects anemia in a mouse model of generalized inflammation
Authors: Sarah Millot, Valérie Andrieu, Philippe Letteron, Saïd Lyoumi, Margarita Hurtado-Nedelec, Zoubida Karim, Olivier Thibaudeau, Samira Bennada, Jean-Luc Charrier, Sigismond Lasocki, Carole Beaumont
Journal: Blood (2010)
Interaction of beta1H globulin with cell-bound C3b: quantitative analysis of binding and influence of alternative pathway components on binding.
Authors: D H Conrad, J R Carlo, S Ruddy
Journal: The Journal of Experimental Medicine (1978)

Purified beta1H globulin (beta1H) was shown to bind to C3b coated cells by both immunofluorescent and radioactive tracer techniques. With EAC43, the amount of beta1H bound was directly proportional to the amount of C3 used to prepare the cells; EA, EAC14 and EAC14oxy2 bound very small amounts of beta1H. The C3b binding site on beta1H was labile in that not all of the purified 125I-beta1H was capable of binding to C3b, even when an excess of cell-bound C3b was present. Scatchard analysis of binding of beta1H to C3b-coated cells indicated an equilibrium constant of 10(9) L/M. Deviations from linearity were regularly found on Scatchard analyses. This was consistent with the hypothesis that the beta1H binding sites exhibit negative cooperativity in that as more sites become occupied, it becomes more difficult to fill the remaining sites. The stoichiometry of the reaction between C3b and beta1H was examined using EAC14oxy23 prepared with 131I-C3 and beta1H labeled with 125I. Between 0.5--0.8 beta1H molecules were bound per C3b molecule. Other alternative pathway components influenced the binding of 125I-beta1H to cell bound C3b. Both C3b and native C3 inhibited binding of labeled beta1H at an efficiency approximately 1/1,000 that of unlabeled beta1H. Factor B inhibited binding with 1/280 the efficiency of unlabeled beta1H. Properdin caused a dose-dependent increase in the binding of beta1H; this enhancement was abrogated if B was also present in the reaction mixture. Scatchard analysis indicated that the enhancement of beta1H binding by P resulted in an increased number of available binding sites rather than an increase in the affinity of binding.
Cardiotonic activity of amrinone--Win 40680 [5-amino-3,4'-bipyridine-6(1H)-one].
Authors: A A Alousi, A E Farah, G Y Lesher, C J Opalka
Journal: Circulation Research (1979)

The cardiotonic activity of a new, noncatechol, nonglycoside agent, amrinone, was investigated in vitro and in anesthestized and unanesthetized dogs. Amrinone (3-100 microgram/ml) caused a dose-dependent increase in papillary muscle developed tension and df/dt without significant changes in duration of the contractile cycle or time-to-peak tension. Amrinone induced slight increases in right atrial rate with no changes in electrophysiological properties of the cat papillary muscle or dog Purkinje fibers. In anesthetized dogs, intravenous bolus injections of amrinone at doses ranging from 1 to 10 mg/kg caused increases in cardiac contractile force and left ventricular dp/dt max with relatively small changes in heart rate and blood pressure. No significant changes in lead II ECG were observed. In unanesthetized dogs, intravenous infusion of amrinone (10-100 microgram/kg per min) caused increases in left ventricular dp/dt max and only small changes in heart rate and blood pressure. Amrinone, tested orally in this model at doses of 2-10 mg/kg, produced a positive inotropic effect with a rapid onset and long duration of action. The inotropic response to amrinone was not blocked by propranolol, dibenzyline, chlorisondamine, atropine, metiamide, or reserpine. Amrinone's inotropic response was not associated with significant alterations in cardiac norepinephrine, phosphodiesterase, cyclic AMP, or Na+, K+-activated ATPase.
Sweat gland disturbances in granuloma annulare and necrobiosis lipoidica
Authors: J. HATZIS, A. VARELZIDIS, A. TOSCA, J. STRATIGOS
Journal: British Journal of Dermatology (1983)

We Studied sweat gland distribution, density and activity in thirteen cases of granuloma annulare and ten cases of necrobiosis lipoidica, using a combination of the plastic impression and starch‐iodine methods. The pattern of sweat gland disturbance in the two diseases was entirely different. In necrobiosis lipoidica an intense and uniform hypohidrosis was detected throughout the lesion, whereas in granuloma annulare the disturbance followed the morphology of the lesion (the papular border showed complete anhidrosis, whereas the flat central part of the lesion showed only moderate hypohidrosis or normal sweating). The method assigns numerical values to the 'relative density' and the 'relative activity' of the functioning sweat glands compared with normal skin, thus permitting statistical evaluation of the results.
FACTORS IN THE ADVANCEMENT OF ORTHOPEDIC SURGERY
Authors: JOHN PRENTISS LORD
Journal: JAMA (1927)

The evolution of orthopedic surgery has been a slow and interesting process. One would not be justified in antedating Hippocrates, the father of medicine, who was so wonderfully well rounded in his wisdom and possessed so many qualifications as a wise surgical counselor, and discoursed so learnedly on fractures, deformities and improvement of function that we recognize he possessed a singularly strong orthopedic bent. Those were the times before specialties were conceived; though it is probable that there were men in those very early periods who became more adept and skilful along special lines of practice. It is doubtless true that there were those who early gave special attention to deformities, more especially congenital ones; hence the necessity for a name to designate this branch of healing. It was about 2,000 years later that Nicholas Andry presented his "Orthopaedia," from which dates the origin of our word to designate the
Infarction of Papillary Muscles and Mitral Insufficiency Associated with Congenital Aortic Stenosis
Authors: JAMES H. MOLLER, AHMAD NAKIB, JESSE E. EDWARDS
Journal: Circulation (1966)

Study of the papillary muscles in 11 infants dying in the first year of life with congenital aortic stenosis and normal coronary arteries demonstrated infarction of the left ventricular papillary muscles in each. Lesions were more extensive in the posteromedial than in the anterolateral papillary muscle. Infarction of papillary muscles is considered the basis for the common occurrence of mitral insufficiency in symptomatic infants with congenital aortic stenosis. Congenital aortic stenosis, infarction of left ventricular papillary muscles, and mitral insufficiency are so interrelated as to constitute a syndrome.
Serum Biomarker Panels for the Detection of Pancreatic Cancer
Authors: Randall E. Brand, Brian M. Nolen, Herbert J. Zeh, Peter J. Allen, Mohamad A. Eloubeidi, Michael Goldberg, Eric Elton, Juan P. Arnoletti, John D. Christein, Selwyn M. Vickers, Christopher J. Langmead, Douglas P. Landsittel, David C. Whitcomb, William E. Grizzle, Anna E. Lokshin
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Serum–biomarker based screening for pancreatic cancer could greatly improve survival in appropriately targeted high-risk populations. Experimental Design: Eighty-three circulating proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC, n = 333), benign pancreatic conditions (n = 144), and healthy control individuals (n = 227). Samples from each group were split randomly into training and blinded validation sets prior to analysis. A Metropolis algorithm with Monte Carlo simulation (MMC) was used to identify discriminatory biomarker panels in the training set. Identified panels were evaluated in the validation set and in patients diagnosed with colon (n = 33), lung (n = 62), and breast (n = 108) cancers. Results: Several robust profiles of protein alterations were present in sera of PDAC patients compared to the Healthy and Benign groups. In the training set (n = 160 PDAC, 74 Benign, 107 Healthy), the panel of CA 19–9, ICAM-1, and OPG discriminated PDAC patients from Healthy controls with a sensitivity/specificity (SN/SP) of 88/90%, while the panel of CA 19–9, CEA, and TIMP-1 discriminated PDAC patients from Benign subjects with an SN/SP of 76/90%. In an independent validation set (n = 173 PDAC, 70 Benign, 120 Healthy), the panel of CA 19–9, ICAM-1 and OPG demonstrated an SN/SP of 78/94% while the panel of CA19–9, CEA, and TIMP-1 demonstrated an SN/SP of 71/89%. The CA19–9, ICAM-1, OPG panel is selective for PDAC and does not recognize breast (SP = 100%), lung (SP = 97%), or colon (SP = 97%) cancer. Conclusions: The PDAC-specific biomarker panels identified in this investigation warrant additional clinical validation to determine their role in screening targeted high-risk populations. Clin Cancer Res; 17(4); 805–16. ©2010 AACR.
Gastrointestinal Microflora in Mammalian Nutrition
Authors: D C Savage
Journal: Annual Review of Nutrition (1986)

A mammal is a complex organism consisting of eukaryotic animal cells and eukaryotic and prokaryotic microbial cells. Most of the microorganisms reside in communities in the gastrointestinal tract. These gastrointestinal microfloras are known to serve nutritional functions in ruminants, pseudoruminants, and monogastric mammals with only modest or no foregut fermentations but with extensive hindgut fermentations in blind cecal pouches. In adult animals, the microflora hydrolyzes exogenous (dietary) and endogenous polymers, and provides the adult with all or at least a significant proportion of its carbon, energy, vitamins, and macromolecular building blocks. The flora also functions as a conservator of nitrogen that would otherwise be excreted as urea. In exchange, the flora competes directly with the host tissues for nutrients ingested in the diet, and also competes indirectly by somewhat repressing the absorptive capacities of the animal tissues. When the synergism is in balance, the animal tissues and the microflora operate in harmony for the health and nutritional welfare of the host as a whole. The system may be unbalanced by antibacterial drugs that destroy the microflora and by diseases of the animal tissues that destroy the controls regulating where indigenous communities localize in the tract, their microbial composition, and their biochemical activities. At such times, the nutrition of the animal tissues can be adversely affected to the extreme. Humans living in developed and developing countries have extensive microfloras in their hindguts. Humans living in developing countries may also have extensive microfloras in their small bowels. Those floras may function in nutrition of the animal tissues of man much the same as do floras in similar locations in the gastrointestinal tracts of mammals other than man. However, animals of some species other than human gain much of the nutritional benefit from their microflora through the practice of coprophagy. Since adult humans do not normally practice coprophagy, any nutritional benefit from the microflora depends upon the capacity of the bowel mucosa, principally that of the large bowel, to absorb bacterial products, e.g. short-chain volatile fatty acids. Such absorption undoubtedly occurs, but is surely not a major source of carbon and energy for the animal tissues of man.
Airway Dilatation after Inhalation of a Beta-Agonist
Authors: Gen Tamura, Yuji Suda
Journal: New England Journal of Medicine (2005)

A woman with a 25-year history of asthma underwent high-resolution multislice helical computed tomographic scanning. Videos before and after the inhalation of albuterol reveal an increase in the airway caliber from a segmental bronchus to an eighth-generation bronchus.
Thyrotoxicosis with painless goiter may recur or develop into hypothyroidism
Authors: William Check
Journal: JAMA (1978)

About five years ago, reports appeared describing a form of thyrotoxicosis with painless goiter and low radioactive iodine uptake (RAIU) that appeared to resolve spontaneously in two to six months. The initial interpretation was that this condition is a variant of subacute thyroiditis, since the only apparent difference between the two was that in the latter condition the goiter is painful. However, biopsy studies subsequently showed that patients with transient painless goiter and thyrotoxicosis always have a lymphocytic inflammation rather than the granulomatous lesion found in subacute thyroiditis (<i>JAMA</i>240:1520-1521, 1978). New data presented at the recent meeting of the American Thyroid Association now show that there is another major difference: The newly described painless form does not resolve completely, as does subacute thyroiditis, but may recur over a period of years. According to Thomas F. Nikolai, MD, staff physician in the endocrinology section of the Marshfield (Wisconsin) Clinic and