tbuckley/cabot-search huggingface dataset:
Non-HLA-DRB1 RA-associated risk alleles associate with anti-CCP and specific ACPA levels
Authors: O. Snir, D. Gomez-Cabrero, K. U. Klich, M. Seddighzadeh, A. I. Catrina, J. Tegner, L. Klareskog, L. Padyukov, V. Malmstrom
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Anti-citrullinated protein antibodies (ACPA) with different fine specificities are exclusively found in sera and synovial fluid of rheumatoid arthritis (RA) patients. The presence and the levels of all known ACPA are predominantly associated with <i>HLA-DRB1*04</i> alleles. Although commonly controlled by HLA-DRB1 and uniquely identify post-translationally modified citrullinated (cit) epitopes, ACPAs have distinctive fine specificities and display low degree of cross-reactivity. Hence, different pathways may selectively regulate specific anti-citrulline immunity in RA. Here, the authors examined whether non-HLA-DRB1 risk alleles influence the levels of antibodies against cyclic citrullinated peptide (CCP) and four additional citrullinated RA-associated antigens in search for shared and distinctive pathways. <h3>Material and methods</h3> Sera from 384 RA patients with an established disease were analysed for the presence of anti-CCP antibodies and reactivity towards cit-fibrinogen, cit-α-enolase, cit-type-II collagen and cit-vimentin. Genotyping for HLA-DRB1 and 64 additional RA-associated single-nucleotide polymorphisms (SNPs) was preformed. Models of linear regression and contingency tables were used to calculate the association between genes and antibody presence and levels. <h3>Results</h3> Two SNPs in HLA-DQ and HLA-DRA regions (rs6457617 and rs6457620, respectively) influenced both the CCP levels as well as the other ACPAs, whereas HLA-DPB2 (rs2064476) only influenced anti-CCP levels but not other fine specificities. Outside the HLA region, PTPN22 (rs2476601) and TRAF1 (rs3761847) were found to have an effect on anti-CCP levels as well as all other fine specificities. Several other genes selectively governed the titres of two or even one single fine specificity; for example, <i>CIITA</i> (rs4781003) for cit-fibrinogen, <i>CD40</i> for cit-α-enolase (rs4810485), <i>CLEC4A</i> (rs1133104) for cit-collagen and <i>OLIG3</i>, <i>TNFAIP3</i> (rs10499194) for cit-vimentin. These results will be replicated in a bigger cohort of approximately 2000 RA patients. <h3>Conclusions</h3> Genes with close association to the immune system, yet outside the HLA-DRB1 region were found to influence the levels of ACPAs. Interestingly, several SNPs affected the overall antibody levels, that is, both against CCP and all four citrullinated antigens. In contrast, other SNPs specifically influenced the antibody levels towards one or two specificities. This data suggests that both common and unique pathways may control anticitrulline immunity in RA.
Duodenal perforation in primary systemic amyloidosis.
Authors: A G Fraser, G I Nicholson
Journal: Gut (1992)

Spontaneous duodenal perforation in two patients with primary systemic amyloidosis associated with multiple myeloma is described. Bowel perforation is a rare and often fatal complication of amyloidosis, and duodenal perforation has not been previously described. Both patients survived the bowel perforation with conservative management. Bowel perforation should be suspected in patients with amyloidosis presenting with acute abdominal pain, and active non-surgical management can be associated with prolonged survival.
Implications for health and disease in the genetic signature of the Ashkenazi Jewish population
Authors: Saurav Guha, Jeffrey A Rosenfeld, Anil K Malhotra, Annette T Lee, Peter K Gregersen, John M Kane, Itsik Pe'er, Ariel Darvasi, Todd Lencz
Journal: Genome biology (2012)

Relatively small, reproductively isolated populations with reduced genetic diversity may have advantages for genomewide association mapping in disease genetics. The Ashkenazi Jewish population represents a unique population for study based on its recent (< 1,000 year) history of a limited number of founders, population bottlenecks and tradition of marriage within the community. We genotyped more than 1,300 Ashkenazi Jewish healthy volunteers from the Hebrew University Genetic Resource with the Illumina HumanOmni1-Quad platform. Comparison of the genotyping data with that of neighboring European and Asian populations enabled the Ashkenazi Jewish-specific component of the variance to be characterized with respect to disease-relevant alleles and pathways. Using clustering, principal components, and pairwise genetic distance as converging approaches, we identified an Ashkenazi Jewish-specific genetic signature that differentiated these subjects from both European and Middle Eastern samples. Most notably, gene ontology analysis of the Ashkenazi Jewish genetic signature revealed an enrichment of genes functioning in transepithelial chloride transport, such as CFTR, and in equilibrioception, potentially shedding light on cystic fibrosis, Usher syndrome and other diseases over-represented in the Ashkenazi Jewish population. Results also impact risk profiles for autoimmune and metabolic disorders in this population. Finally, residual intra-Ashkenazi population structure was minimal, primarily determined by class 1 MHC alleles, and not related to host country of origin. The Ashkenazi Jewish population is of potential utility in disease-mapping studies due to its relative homogeneity and distinct genomic signature. Results suggest that Ashkenazi-associated disease genes may be components of population-specific genomic differences in key functional pathways.
QUANTITATIVE HISTOCHEMISTRY OF THE NEPHRON. III. LACTIC DEHYDROGENASE ACTIVITY IN MAN AND OTHER SPECIES*
Authors: Sjoerd L. Bonting, Victor E. Pollak, Robert C. Muehrcke, Robert M. Kark
Journal: Journal of Clinical Investigation (1960)

In previous papers (1, 2) we have described observations on the quantitative distribution of alkaline phosphatase in the anatomical units of the nephron in man and other species.This enzyme was selected for study by microdissection of lyophilized sections of kidneys and ultra-microassay because there was considerable information avail- able on its qualitative distribution in the nephron.In particular, the known qualitative differences in its distribution in the proximal and distal convolu- tions of the tubule allowed us to verify the accuracy of the microdissection technique we used (2).Once this was accomplished we were able to study the quantitative distribution of other enzymes for which less information was available.In this paper the results of assay of lactic dehydrogenase (LDH) activity on renal tissues from healthy hu- mans and laboratory animals are reported.LDH was chosen for study because it plays an important role in energy metabolism, namely, in the glycolytic formation of lactic acid and in its mobilization for complete oxidation in the tricarboxylic acid cycle.As far as could be ascertained, no data were avail- able on its distribution or functional significance in the cells of the nephron. METHODSHandling of tissue.In previous communications (1, 2) we have described in detail the techniques used for dis- secting, weighing, and enzyme assay of the individual units of the nephron.LDH assay.Optimal conditions for assay of LDH activity in the human kidney were determined (Table I).Tissue samples with a dry weight ranging from 10 to 100
Abstract 5493: Lethal mutagenesis of cancer cells by nucleoside analogs
Authors: Edward J. Fox, Jiang-Cheng Shen, Lawrence A. Loeb
Journal: Cancer Research (2011)

Abstract The evolution of cancer and RNA viruses is characterized by mutation accumulation facilitating phenotypic plasticity and environmental adaptation. We have demonstrated that serial passage of virus from HIV-infected human lymphoblastoid cells in the presence of mutagenic nucleosides results in mutation accumulation, leading to error catastrophe, and viral extinction. In limited phase II clinical studies, administration of a cytidine analog, KP-1461, to individuals infected with HIV results in increased viral mutations. We hypothesize that cancer cells treated with mutagenic nucleoside analogs will progressively accumulate mutations until the error threshold for viability is exceeded and the tumor ablated. We have serially passaged mismatch repair proficient and deficient colon cancer cells in the presence of 36 different mutagenic deoxynucleoside analogs and established a new protocol for measuring both mis-incorporation and repair during DNA synthesis in cells. DNA templates, purified from phage, are blocked with terminal non-hydrolysable nucleotides to prevent degradation by cellular nucleases. After transfection of double-stranded DNA into human cells, we can recover &amp;gt;50,000 molecules/cell. After transfection of single-stranded DNA molecules hybridized to a 5′-biotin labeled primer, extended primers are recovered on streptavidin beads; the frequency of misincorporation into the newly synthesized DNA varies from 10-3 to 10-6, depending on the genetic background of the tranfected cells. The versatility of this assay will facilitate studies on the efficiency of DNA repair, the role of different human DNA polymerases in DNA synthesis and bypass of DNA damage, and the stratification of individuals with respect to DNA repair capacity and fidelity. Enhancing the mutation frequency of cancer cells represents a new avenue for treatment, particularly for patients with tumors that have accumulated large numbers of mutations and/or who failed extensive chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5493. doi:10.1158/1538-7445.AM2011-5493
Getting letters published in journals is good aim for medical students
Authors: B. Hanratty, D. Lawlor
Journal: BMJ (1999)

EDITOR—The increasing emphasis on evidence based medicine in the NHS means that skills in critical appraisal will soon be as important for doctors as clinical competence. Many habits are established at medical school, so encouragement for students to review and publish work should start there. It is our impression that such motivation and support are patchy. To investigate this, we examined letters to the BMJ over three years and quantified the extent of medical student authorship. Authors often begin their careers by writing …
Full public inquiry gets under way into events at Stafford Hospital
Authors: C. Dyer
Journal: BMJ (2010)

The long awaited full public inquiry into the wider lessons of what went wrong at Stafford Hospital was launched this week with a preliminary procedural hearing to outline how the inquiry will be run.

A 2009 Healthcare Commission report on the hospital, run by Mid-Staffordshire NHS Foundation Trust, found that numbers of deaths were between 27% and 45% higher than normal between 2005 and 2008, meaning that there were between 400 and 1200 excess deaths ( BMJ 2009;338:b1141, doi:10.1136/bmj.b1141 …
Polygalacturonase (pectinase), a new oilseed rape allergen
Authors: H. Chardin, C. Mayer, H. Sénéchal, P. Poncet, G. Clément, J. M. Wal, F. X. Desvaux, G. Peltre
Journal: Allergy (2003)

Background: Type I hypersensitivity to rapeseed pollen allergens was described as the result of a cross‐sensitization with various pollens that could constitute an aggravating factor in birch or grass pollen allergies. Recently, a few rapeseed pollen allergens were described. The aim of the present work was to identify new rapeseed pollen allergens by using two‐dimensional gel analysis, microsequencing, and mass spectrometry. Methods: Water extractable proteins from oilseed rape pollen or stamen were separated by two‐dimensional gel electrophoresis. The proteins were then electroblotted onto a nitrocellulose (NC) sheet. The NC sheets were successively incubated with ( 1 ) individual human sera pre‐selected for their immunoglobulin E (IgE) reactivity to rapeseed pollen proteins, ( 2 ) alkaline phosphatase (AP)‐conjugated goat anti‐human IgE and ( 3 ) AP substrate. The allergens localized by this method were then identified by microsequencing andMALDI‐TOF mass spectrometry analysis. Results: Of the 18 sera studied, five recognized a wide multispot zone with a molecular mass around 43 kD and pIs between 6.5 and 8.5. The results obtained with two representative sera are shown. From this zone, two isoforms of the polygalacturonase enzyme were identified by microsequencing. Confirmation was obtained through MALDI‐TOF mass spectrometry analysis. Conclusion: The present results allow the identification of a new rapeseed allergen that can be the main allergen for some patients.
THE SCHOTT METHOD OF TREATING CHRONIC DISEASES OF THE HEART BY BATHS AND GYMNASTICS.
Authors: ROBERT H. BABCOCK
Journal: JAMA (1893)

<h3>E—eyesight.</h3> The eyes are often affected injuriously by school work carried to excess, or conducted amid unwholesome surroundings. There is a strong tendency to the production of near-sightedness; which can, to a great extent, be remedied by the avoidance of known causes. Among the direct causes of near-sight are— bad light, bad position at work, too protracted work, bad print; and to these must be added, as indirect causes, bad ventilation and heating, poor food, and whatever impairs the vigor of health. Light in schoolrooms should never strike the pupil in the face while at work. Excess of light is less common than deficiency, but is also harmful. No desk can be more than twenty feet from the windows of an ordinary schoolroom (supposing the top of the windows to reach the height of about twelve feet from the floor) without impairing the light. A stooping position, and the wearing
COMPLETE RECOVERY FROM DOUBLE NEURO-RETINITIS, CLINICALLY RESEMBLING ALBUMINURIC RETINITIS, IN A CASE OF PROLONGED HEMATURIA WITH SYMPTOMS OF BRIGHT'S DISEASE.
Authors: C. A. VEASEY
Journal: JAMA (1901)

The notes of the following somewhat unusual case are deemed of sufficient interest to merit their isolated report. Mrs. C. H. P., aged 35 years, was referred to me in May, 1899, by her physician, Dr. Hassell, for the examination of her eyes. The following history was obtained: Eight months previously she had suddenly discovered that she was passing bloody urine. This had occurred without any pain or premonition whatever, so that she was naturally much startled, and at once sought medical advice. From that time, however, until the time of my examination, urine had been passed upon but few occasions that it did not contain considerable blood. The exact amount of blood could not be accurately determined, but it was sufficient to make the urine a dark red, and quite thick. For several months the patient had been losing flesh (about 20 pounds altogether), and when I first saw
Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin
Authors: Eloisa S. Moreira, Tim J. Wiltshire, Georgine Faulkner, Antje Nilforoushan, Mariz Vainzof, Oscar T. Suzuki, Giorgio Valle, Roger Reeves, Mayana Zatz, M. R. Passos-Bueno, Dieter E. Jenne
Journal: Nature Genetics (2000)
A New Approach for Fabricating Collagen/ECM‐Based Bioinks Using Preosteoblasts and Human Adipose Stem Cells
Authors: Hyeong Jin Lee, Yong Bok Kim, Seung Hyun Ahn, Ji‐Seon Lee, Chul Ho Jang, Hyeon Yoon, Wook Chun, Geun Hyung Kim
Journal: Advanced Healthcare Materials (2015)

Cell‐printing methods have been used widely in tissue regeneration because they enable fabricating biomimetic 3D structures laden with various cells. To achieve a cell‐matrix block, various natural hydrogels that are nontoxic, biocompatible, and printable have been combined to obtain “bioinks.” Unfortunately, most bioinks, including those with alginates, show low cell‐activating properties. Here, a strategy for obtaining highly bioactive ink, which consisted of collagen/extracellular matrix (ECM) and alginate, for printing 3D porous cell blocks is developed. An in vitro assessment of the 3D porous structures laden with preosteoblasts and human adipose stem cells (hASCs) demonstrates that the cells in the bioinks are viable. Osteogenic activities with the designed bioinks show much higher levels than with the “conventional” alginate‐based bioink. Furthermore, the hepatogenic differentiation ability of hASCs with the bioink is evaluated using the liver‐specific genes, albumin, and TDO2, under hepatogenic differentiation conditions. The genes are activated within the 3D cell block fabricated using the new bioink. These results demonstrate that the 3D cell‐laden structure fabricated using collagen/ECM‐based bioinks can provide a novel platform for various tissue engineering applications.
Routine Use of the Scribner Shunt for Haemodialysis
Authors: P. B. Clark, F. M. Parsons
Journal: BMJ (1966)

The Scribner shunt (Quinton, Dillard, Cole, and Scribner, 1962) (Fig. 1) is an artificial arteriovenous fistula made of inert plastic tubing which is used for repeated haemodialysis. When dialysis is required the U-tube connecting the arterial and venous limbs of the shunt is removed and the patient is con nected to the dialyser. At the end of dialysis the U-tube is replaced. The use of the Scribner shunt in intermittent haemodialysis for chronic renal failure is well recognized, and Chisholm (1961) has advocated its use in some patients with acute renal failure and especially those who have few available veins, it is our belief that it should be used in all patients with acute renal failure who are likely to require more than one haemo dialysis ; certain patients with acute renal failure may be alternatively managed successfully by peritoneal dialysis. It is the purpose of this paper to show that the routine use of the Scribner shunt, as opposed to repeated cannulation, saves time and trouble in a busy artificial kidney unit and increases the safety of dialysis. Now that all parts of this shunt are manufactured in Great Britain the increase in cost is not significant. Improvements in the technique of insert ing the shunt, the experience of the first year, and the com plications encountered are also outlined.
Evaluation of the Aortic Root by MRI
Authors: Ronald M. Summers, Jonathan Andrasko-Bourgeois, Irwin M. Feuerstein, Suvimol C. Hill, Elizabeth C. Jones, Mary K. Busse, Betty Wise, Karen E. Bove, Beth A. Rishforth, Eben Tucker, Thomas L. Spray, Jeffrey M. Hoeg
Journal: Circulation (1998)

Background —In homozygous familial hypercholesterolemia (HFH), the aortic root is prone to develop atherosclerotic plaque at an early age. However, the aortic wall and plaque have not yet been assessed in this condition by MRI. We evaluated the aortic root by use of MRI in 17 HFH patients and 12 normal control subjects in a prospective, blinded, controlled study. Methods and Results —Morphological assessment of the aortic root was done with spin-echo and gradient-echo MRI scanning. Comparisons were made with a number of measures of disease severity, including cholesterol-year score, calcium score on electron-beam CT (EBCT), and size of Achilles tendon xanthomas. Atherosclerotic plaque, visible on fat-suppressed images but never on water-suppressed images, was present in 9 HFH patients (53%). Supravalvular aortic stenosis was present in 7 patients with HFH (41%). Maximum supravalvular aortic wall thickness was significantly greater and OD and lumen cross-sectional area (CSA) were smaller in patients than in control subjects ( P =0.006, 0.0005, and 0.06, respectively). Maximum wall thickness was associated with a greater calcium score on electron-beam CT ( P =0.02). Although the cumulative exposure of the aortic root to cholesterol (the cholesterol-year score) was significantly correlated with the Achilles tendon CSA and vascular calcification, this score did not correlate with the wall thickness or aortic CSA. Conclusions —This study not only demonstrates the utility of MRI for detecting and characterizing aortic root atherosclerotic plaque and supravalvular aortic stenosis in HFH patients but also suggests that the LDL receptor plays a direct or indirect role in aortic mural development and vascular growth.
Diabetes: Clinical Science in Practice
Authors: M. Edmonds
Journal: BMJ (1995)

Ed R D G Leslie, David C Robbins Cambridge University Press, £75, pp 492 ISBN 0 521 45029 2

Recent progress has clarified our understanding of the causes and consequences of diabetes, and in Diabetes: Clinical Science in Practice distinguished scientists provide an authoritative analysis of their subjects and assess the implications of recent advances.

The admirable theme running through the book is that increased scientific knowledge can lead to a better understanding of diabetes and be translated into an improved outlook for patients. This theme is explored in four main aspects of diabetes: the …
Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: Analysis of 5823 cases as the basis of the first consensus staging system
Authors: Bianca D. Lemos, Barry E. Storer, Jayasri G. Iyer, Jerri Linn Phillips, Christopher K. Bichakjian, L. Christine Fang, Timothy M. Johnson, Nanette J. Liegeois-Kwon, Clark C. Otley, Kelly G. Paulson, Merrick I. Ross, Siegrid S. Yu, Nathalie C. Zeitouni, David R. Byrd, Vernon K. Sondak, Jeffrey E. Gershenwald, Arthur J. Sober, Paul Nghiem
Journal: Journal of the American Academy of Dermatology (2010)
Gastro-oesophageal reflux: does it matter what you eat?
Authors: J P GALMICHE
Journal: Gut (1998)

See article on page 330 

Patients with gastro-oesophageal reflux (GORD) are usually advised to modify their dietary habits.1 Among the most popular beliefs is the recommendation to avoid fatty foods which are thought to be detrimental in GORD for several reasons, including reduced lower oesophageal sphincter tone2 and delayed gastric emptying. This latter effect may, in turn, result in an increase in the number of transient lower oesophageal sphincter relaxations (TLOSRs) elicited through a vago–vagal reflex originating in the mechanoreceptors located in the subcardial area.3TLOSRs are considered to be the main motor mechanism associated with the occurrence of reflux episodes both in asymptomatic subjects and reflux patients with or without oesophagitis.

With regard to the therapeutic benefit of a low fat regimen in GORD, a review of the literature has shown that there is a paucity of data to support …
A NOTE ON THE RELATIONS OF CAPILLARY HAEMANGIECTATIC NAEVUS AND NAEVUS ANAEMICUS TO THE NERVOUS SYSTEM*
Authors: F. PARKES WEBER
Journal: British Journal of Dermatology (1929)

Journal Article A NOTE ON THE RELATIONS OF CAPILLARY HÆMANGIECTATIC NÆVUS AND NÆVUS ANÆMICUS TO THE NERVOUS SYSTEM Get access F. PARKES WEBER, M.A., M.D., F.R.C.P F. PARKES WEBER, M.A., M.D., F.R.C.P Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 41, Issue 6, 1 June 1929, Pages 221–225, https://doi.org/10.1111/j.1365-2133.1929.tb09343.x Published: 01 June 1929