tbuckley/cabot-search huggingface dataset:
Characterisation of nucleolar proteins as autoantigens using human autoimmune sera.
Authors: J Pfeifle, F A Anderer, M Franke
Journal: Annals of the Rheumatic Diseases (1986)

Sera from 271 patients with systemic rheumatic diseases were screened for antinucleolar antibodies using immunofluorescence. Antinucleolar antibodies were found in the sera of 73% of patients with progressive systemic sclerosis, 4% of patients positive for autoantibodies with rheumatoid arthritis, and 8% of patients with rheumatoid arthritis associated with sicca complex, but not in patients with systemic lupus erythematosus, Sjögren's syndrome, undifferentiated connective tissue disease, or in healthy donors. The antinucleolar sera (n = 20) were analysed by immunoblotting techniques. In four sera antibodies against nucleolar proteins with molecular weights of 35 kD, 37 kD, 69 kD, 92-93 kD, and 93 kD could be immunodetected. The nucleolar autoantigens were extractable from the nucleoli together with the preribosomal particle fraction and could be solubilised by ribonuclease (RNAse) treatment. Their presence in the nucleolus was sensitive to actinomycin D treatment of cells. The 37 kD autoantigen could be identified as nucleolar phosphoprotein B23.
Thinking and Feeling
Authors: George Ehni
Journal: JAMA (1964)

<h3>To the Editor:—</h3> One measure of a physician's competence is his ability to make effective use of language to communicate to others precisely and clearly what he has observed and the conclusions he has drawn. Vagueness and turbidity of thought and expression conceal such competence and knowledge regarding a subject as may exist when the speaker or writer chooses, through ignorance or in mimicry of current fashion, language elements that are soft and indirect rather than forceful and direct. Inappropriate use of the verb feel adulterates and fogs much medical speaking and writing nowdays, and misguided users of this word, especially residents and other trainees who should be sharpening their facility with language whilst perfecting their scientific skills, would profit by avoidance of it. The physician presenting a case in conference or in writing should not say, "we felt that the patient was suffering from so-and-so" but rather "I thought"
Abdominal Pain Resembling Acute Appendicitis in Rocky Mountain Spotted Fever
Authors: Arthur E. Davis
Journal: JAMA (1982)

ROCKY Mountain spotted fever (RMSF) is an acute, febrile, exanthematous illness caused by<i>Rickettsia rickettsii</i>and transmitted by the bite of a tick. This infectious disease is endemic in the South Atlantic states, and the case-fatality rate is increasing. Reduction of mortality requires early diagnosis with recognition of the cardinal features of the illness, such as fever, characteristic rash, history of tick contact, and myalgias. Unfortunately, lack of documented tick exposure, late onset of rash, and gastrointestinal complaints are more frequently associated with fatal cases.<sup>1</sup>Rocky Mountain spotted fever may present in unusual and unfavorable forms, such as fulminant fatal disease and a viscerotrophic variety in which cutaneous manifestations are delayed or absent entirely.<sup>2</sup>It should be recognized that rickettsial vasculitis may involve the abdominal wall and abdominal viscera, and mimic acute appendicitis. Significant abdominal pain leading to laparotomy was present in the cases reported here. These cases
Electron Microscopy of Mucosa of Small Intestine
Authors: Jerry S. Trier, Patricia C. Phelps, Cyrus E. Rubin
Journal: JAMA (1963)

SEVERAL PERORAL BIOPSY techniques are now available which make it possible to repeatedly take samples from the small bowel. Sick individuals or normal volunteers can undergo this procedure with safety on an outpatient ambulatory basis. These so-called suction biopsies can be delivered from the biopsy site and fixed within seconds after excision, virtually eliminating autolysis, and thus providing tissue which is suitable for the most meticulous morphologic study by light or electron microscopy. This is a report of our experience in using the electron microscope for clinical investigation of the small bowel in man.  The intestinal biopsies were obtained by peroral intubation with either our multipurpose biopsy tube, 1 which is activated by a pull-wire, or with our hydraulically activated biopsy tube. 2 Tissue samples so obtained were immediately fixed in osmic acid fixative, 3,4 dehydrated in graded strengths of alcohol or acetone and then embedded in methylbutyl methacrylate mixtures
Endothelin-1 could be one of the targets of psoriasis therapy
Authors: P. SIMEONE, M. TESON, A. LATINI, M. CARDUCCI, A. VENUTI
Journal: British Journal of Dermatology (2004)

Journal Article Endothelin‐1 could be one of the targets of psoriasis therapy Get access P. SIMEONE, P. SIMEONE Laboratory of Virology, Regina Elena Cancer Institute, Rome, Italy Laboratory of Molecular and Cell Biology, IDI‐IRCCS, Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar M. TESON, M. TESON Laboratory of Virology, Regina Elena Cancer Institute, Rome, Italy Laboratory of Molecular and Cell Biology, IDI‐IRCCS, Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar A. LATINI, A. LATINI Department of Allergology and Inflammatory Dermatology, San Gallicano Institute, Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar M. CARDUCCI, M. CARDUCCI Department of Allergology and Inflammatory Dermatology, San Gallicano Institute, Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar A. VENUTI A. VENUTI Laboratory of Virology, Regina Elena Cancer Institute, Rome, Italy Laboratory of Molecular and Cell Biology, IDI‐IRCCS, Rome, Italy A. Venuti, E‐mail: venuti@ifo.it; venutie4@yahoo.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 6, 1 December 2004, Pages 1273–1275, https://doi.org/10.1111/j.1365-2133.2004.06277.x Published: 01 December 2004
Cardiopulmonary resuscitation can be futile and sometimes worse in dying patients
Authors: C. Mawer
Journal: BMJ (2014)

McCartney raises important points about the futility of cardiopulmonary resuscitation (CPR) in some dying patients.1 The judges in the judgment she refers to emphasised the possibility of success after CPR, repeatedly referring to its potentially life saving nature.2

Although CPR is certainly a valuable intervention in many patients, a 2013 systematic review provides good evidence that cardiopulmonary resuscitation will be unsuccessful in palliative care patients …
World Medical Association Meets in Helsinki
Authors: S. Gilder
Journal: BMJ (1964)

What you feel about the World Medical Association probably depends on the standards you apply to it.If you judge it in terms of a successful national medical association, you are bound to be disappointed, because the world has scarcely.got beyond thinking in terms of nations.If, however, you com- pare it with other non-governmental international bodies you may find that it has considerable merit.At least it has con- trived to survive and not to split up into linguistic or political or confessional groups.Furthermore, at times when its dis- integration has been prophesied by the pessimists it has managed to find new sources of energy and inspire its supporters with hope.In the words of its recent chairman of council, Dr. Felix Worre, its motto could well be that of tne City of Paris, " Fluctuat nec mergitur," which may be freely and inaccurately translated as "It has its ups and downs but it does not sink."The XVIII World Medical Assembly, held in Helsinki in June, was by common consent one of the best for years; and once more the optimists found cause for satisfaction.The business sessions were conducted efficiently and expeditiously; there was less irrelevant debate than usual ; and there was a general air of hope and good will among the delegates.For this happy state of affairs our Finnish hosts were largely responsible.They had contrived to organize the meeting with a minimum of fuss and a maximum of efficiency.They had even contrived to ensure perfect summer weather, and their unobtrusive hospitality and friendliness were a model for international gatherings.The Assembly got under way at the rather odd hour of 1 p.m. on Sunday, 14 June, when the Opening Ceremony was graced by the President of the Republic of Finland, Urho Kekkonen, a tall and somewhat austere figure, and the Mayor of the City of Helsinki, Lauri Aho, a somewhat shorter and considerably less austere figure.There were the usual exchanges of greetings, and the Finns performed well, from the President of the Republic downwards, in giving short and sensible addresses of welcome.
S-palmitoylation regulates AMPA receptors trafficking and function: a novel insight into synaptic regulation and therapeutics
Authors: Jun Han, Pengfei Wu, Fang Wang, Jianguo Chen
Journal: Acta Pharmaceutica Sinica B (2014)

Glutamate acting on AMPA-type ionotropic glutamate receptor (AMPAR) mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system. Dynamic regulation of AMPAR by post-translational modifications is one of the key elements that allow the nervous system to adapt to environment stimulations. S-palmitoylation, an important lipid modification by post-translational addition of a long-chain fatty acid to a cysteine residue, regulates AMPA receptor trafficking, which dynamically affects multiple fundamental brain functions, such as learning and memory. In vivo, S-palmitoylation is controlled by palmitoyl acyl transferases and palmitoyl thioesterases. In this review, we highlight advances in the mechanisms for dynamic AMPA receptors palmitoylation, and discuss how palmitoylation affects AMPA receptors function at synapses in recent years. Pharmacological regulation of S-palmitoylation may serve as a novel therapeutic strategy for neurobiological diseases.
Animal Models of Inflammatory Bowel Disease at the Dawn of the New Genetics Era
Authors: Ludvig M Sollid, Finn-Eirik Johansen
Journal: PLoS Medicine (2008)

Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory intestinal diseases with multifactorial etiologies. CD and UC are distinguished both by the location and by the nature of the inflammation. CD displays a transmural discontinuous inflammation, often with granulomas, in any part of the digestive system (most often ileum and/or colon). UC is almost exclusively restricted to the colon with a continuous superficial mucosal and submucosal inflammation. Both CD and UC can be further subphenotyped, suggesting that there is heterogeneity within each disorder. Despite many clinical and pathological features that distinguish CD and UC, the collective term inflammatory bowel disease (IBD) is often used for the two diseases. Clustering of IBD in families without specificity for a given form of IBD supports the notion of common genetic factors in the etiologies of the two conditions. In addition, higher concordance rates in monozygotic twins than dizygotic twins, particularly in CD, points to the importance of genes [1]. Recent advances in genetics have proven that both CD and UC are truly polygenic, but there are also strong environmental influences on IBD. This notion is first and foremost supported by the rapid increase in incidence of IBD during the past 50 years.

Understanding the complex interplay between genetic and environmental factors that lead to IBD is a formidable challenge. Animal models have been very helpful in this respect, providing fundamental insight into the importance of immunologic dysregulation and intestinal microbiota [2,3]. Animal models are continuing to give new insights into the pathogenesis of IBD, as shown by two recent papers in PLoS Medicine [4,5]. Simultaneously, there have been remarkable advances in the understanding of the genetics of human IBD, and the mapping of IBD genes is continuously progressing [6–8]. The new genetic findings bear promise for new and better therapies. This translation of basic science into the clinic will be much facilitated by relevant and good animal models. We can thus expect that the new genetic findings will set the stage for future development of animal models in IBD.
When doctors learned to speak carbon
Authors: Ian Roberts
Journal: BMJ (2006)

T o start with health professionals paid little attention. After all, it was an environmental issue and their core business was health. But the burning of fossil fuels was increasing the concentration of carbon dioxide in the atmosphere to alarming levels. This was rapidly changing the earth's climate, threatening the balance of the biosphere with serious implications for human health ( Lancet (2002);360: 1347-60 and BMJ 1999;318: 1682-5).

The stakes could not have been higher. Reducing carbon dioxide emissions required global, national, and personal commitments to reduce fossil fuel energy use. Governments would not implement the necessary measures without public support, but personal carbon rationing required a carbon literate society and radical changes in lifestyles.

Societal changes of this magnitude required …
Late results of a prospective randomised study comparing forceful dilatation and oesophagomyotomy in patients with achalasia.
Authors: A Csendes, I Braghetto, A Henriquez, C Cortes
Journal: Gut (1989)

Late results in 81 patients with achalasia treated in a prospective randomised study comparing forceful pneumatic dilatation with the Mosher bag and surgical anterior oesophagomyotomy by abdominal route, are reported. There were no deaths from either of the treatments. Two patients (5.6%) had a perforation of the abdominal oesophagus after pneumatic dilatation and were excluded from late follow up. In patients having surgery at radiological evaluation there was gullet diameter significantly increased at the oesophagogastric junction and decreased at the middle third of the oesophagus. One patient was lost from follow up and one died of an oesophageal carcinoma, leaving 95% of excellent results at the late follow up (median 62 months). Resting gastro-oesophageal sphincter pressure decreased significantly to approximately 10 mmHg; this was maintained five years after surgery. By contrast, in patients having pneumatic dilatation, there were good results in only 65% (follow up median 58 months), with 30% failures. One patient was lost from follow up and one developed oesophageal carcinoma. Measurement of resting gastro-oesophageal sphincter pressure after dilatation was highly predictive of the outcome. The study shows that surgical treatment offers a better final clinical result than pneumatic dilatation with the Mosher bag.
Leishmania promastigotes are recognized by the macrophage receptor for advanced glycosylation endproducts.
Authors: D M Mosser, H Vlassara, P J Edelson, A Cerami
Journal: The Journal of Experimental Medicine (1987)

In this paper we demonstrate the involvement of the macrophage receptor for advanced glycosylation endproducts (AGE) in the phagocytosis of Leishmania major promastigotes. Blocking of this receptor with the ligand, AGE-BSA, leads to a 50% decrease in phagocytosis relative to controls, and a comparable decrease in the respiratory burst. The inhibition of phagocytosis by AGE-BSA was specific to leishmania. The binding of zymosan or C3bi-RBC and the phagocytosis of IgG-RBC or latex beads was not affected by the presence of AGE-BSA. Blocking of both the AGE receptor and CR3 decreases leishmania binding by nearly 90%, and reduces the respiratory burst by 80%, indicating that the two receptors account for the bulk of L. tropica promastigote recognition and uptake by the macrophage.
Rethinking the Psoriasis Area and Severity Index: the impact of area should be increased
Authors: C.C. Jacobson, A.B. Kimball
Journal: British Journal of Dermatology (2004)

The Psoriasis Area and Severity Index (PASI) is the most frequently used clinical severity scale in clinical trials. Drug approval often depends on a 75% improvement in the baseline PASI score, also known as a PASI 75 or Delta PASI 75. This benchmark may be an overly stringent way to determine the success of psoriasis treatments as Delta PASIs appear to under-represent true clinical improvement. This discrepancy may relate to the way numerical values are assigned to the degree of body surface area (BSA) involvement.To assess whether altering the BSA component of the PASI formula so that it is weighted more heavily will result in a calculated change in psoriasis severity that more closely reflects patient assessment of improvement. Models developed included the Psoriasis Log-based Area and Severity Index (PLASI), which assigns values to the BSA score based on a linear scale using logarithms to define the intervals, and the Psoriasis Exact Area and Severity Index (PEASI), which uses the actual BSA as the multiplicative factor in the area score.Data were abstracted retrospectively from two clinical trials involving psoriasis treatments that used the PASI. The same trained psoriasis graders were involved in both trials. In these trials, baseline and end-point PASI worksheets were completed that included the actual clinician-estimated BSA involvement (0-100%) for each of the four areas (head, upper extremities, trunk and lower extremities). In one of the trials, patients were asked to assess the percentage improvement in their psoriasis at the end of the treatment window. PASIs and Delta PASIs were recalculated based on the new models and all scoring systems were validated by analysing their relationship to patients' self-assessments.Clinical improvements under the new grading systems translated into greater percentage changes than calculated using the Delta PASI formula. Specifically, the Delta PASI 50 translated to a Delta PLASI 57.2 and Delta PEASI 61.1; Delta PASI 75 was equivalent to Delta PLASI 85.7 and Delta PEASI 91.7. Importantly, Delta PASI tended to be systematically lower than patients' self-assessment, while Delta PLASI and Delta PEASI better matched patients' self-assessments using a best-fit model.These results suggest that the Delta PASI underestimates percentage improvement when compared with measures of patient's self-assessment, while Delta PLASI and Delta PEASI correlate better. Prospective studies will have to be performed to confirm these relationships, but weighting BSA more heavily in the severity score may result in a more accurate reflection of clinical status.
Lentiviral Gene Transfer of Rpe65 Rescues Survival and Function of Cones in a Mouse Model of Leber Congenital Amaurosis
Authors: Alexis-Pierre Bemelmans, Corinne Kostic, Sylvain V Crippa, William W Hauswirth, Janis Lem, Francis L Munier, Mathias W Seeliger, Andreas Wenzel, Yvan Arsenijevic
Journal: PLoS Medicine (2006)

Background RPE65 is specifically expressed in the retinal pigment epithelium and is essential for the recycling of 11-cis-retinal, the chromophore of rod and cone opsins. In humans, mutations in RPE65 lead to Leber congenital amaurosis or early-onset retinal dystrophy, a severe form of retinitis pigmentosa. The proof of feasibility of gene therapy for RPE65 deficiency has already been established in a dog model of Leber congenital amaurosis, but rescue of the cone function, although crucial for human high-acuity vision, has never been strictly proven. In Rpe65 knockout mice, photoreceptors show a drastically reduced light sensitivity and are subject to degeneration, the cone photoreceptors being lost at early stages of the disease. In the present study, we address the question of whether application of a lentiviral vector expressing the Rpe65 mouse cDNA prevents cone degeneration and restores cone function in Rpe65 knockout mice. Methods and Findings Subretinal injection of the vector in Rpe65-deficient mice led to sustained expression of Rpe65 in the retinal pigment epithelium. Electroretinogram recordings showed that Rpe65 gene transfer restored retinal function to a near-normal pattern. We performed histological analyses using cone-specific markers and demonstrated that Rpe65 gene transfer completely prevented cone degeneration until at least four months, an age at which almost all cones have degenerated in the untreated Rpe65-deficient mouse. We established an algorithm that allows prediction of the cone-rescue area as a function of transgene expression, which should be a useful tool for future clinical trials. Finally, in mice deficient for both RPE65 and rod transducin, Rpe65 gene transfer restored cone function when applied at an early stage of the disease. Conclusions By demonstrating that lentivirus-mediated Rpe65 gene transfer protects and restores the function of cones in the Rpe65−/− mouse, this study reinforces the therapeutic value of gene therapy for RPE65 deficiencies, suggests a cone-preserving treatment for the retina, and evaluates a potentially effective viral vector for this purpose.
MicroRNA profiles in graft preservation solution are predictive of ischemic-type biliary lesions after liver transplantation
Authors: Cornelia J. Verhoeven, Waqar R.R. Farid, Petra E. de Ruiter, Bettina E. Hansen, Henk P. Roest, Jeroen de Jonge, Jaap Kwekkeboom, Herold J. Metselaar, Hugo W. Tilanus, Geert Kazemier, Luc J.W. van der Laan
Journal: Journal of Hepatology (2013)
Unusual Cause for Baldness Inspires the Muse
Authors: Christopher M. Papa
Journal: JAMA (1993)

<h3>To the Editor</h3> —It appears that one of the effects of direct consumer advertising of prescription drugs is the intemperate demand for therapy by a presold and pressing patient. A 29-year-old man was annoyed that I actually wished to examine him and order laboratory tests. Responding to the Rogaine (minoxidil) television advertisements, he simply wanted a prescription so he could get along with growing hair. Clinically, there was diffuse thinning, with many long hairs with depigmented bulbs (telogen hairs) easily dislodged with gentle traction. The remainder of the physical examination was unremarkable. He denied recent illness, sores, or rashes. His serological test for syphilis was reactive at a 1:320 dilution. The hair loss was his only clinical manifestation of secondary syphilis. The limerick muse inspires the following cautionary rhyme: A young man on Rogaine rub bent, Desired to Docs circumvent, His hairs, tho' they're willin', Really need penicillin, So instead
Red wine polyphenols prevent angiotensin II-induced hypertension and endothelial dysfunction in rats: Role of NADPH oxidase
Authors: M SARR, M CHATAIGNEAU, S MARTINS, C SCHOTT, J ELBEDOUI, M OAK, B MULLER, T CHATAIGNEAU, V SCHINIKERTH
Journal: Cardiovascular Research (2006)

Chronic administration of moderate amounts of red wine has been associated with a protective effect on the cardiovascular system. This study examined whether red wine polyphenols prevent the angiotensin II (Ang II)-induced hypertension and endothelial dysfunction in rats, and, if so, to elucidate the underlying mechanism.Hypertensive rats were obtained by a 14-day infusion of Ang II. Red wine polyphenols were administered in the drinking water one week before and during the Ang II infusion. Arterial pressure was measured in conscious rats. Ex vivo vascular relaxation was assessed in organ chambers, vascular superoxide anion production by dihydroethidine and vascular NADPH oxidase expression by immunohistochemistry.Ang II-induced hypertension was associated with decreased relaxation to acetylcholine but not to red wine polyphenols. The Ang II treatment also increased vascular superoxide anion production and expression of nox1 and p22phox NADPH oxidase subunits. Intake of red wine polyphenols prevented the Ang II-induced hypertension and endothelial dysfunction and normalized vascular superoxide anion production and NADPH oxidase subunit expression. Red wine polyphenol treatment alone did not affect blood pressure.Intake of red wine polyphenols prevents Ang II-induced hypertension and endothelial dysfunction. Prevention of vascular NADPH oxidase induction and preservation of arterial nitric oxide availability during Ang II administration likely contribute to this effect.