tbuckley/cabot-search huggingface dataset:
Different superantigens interact with distinct sites in the Vbeta domain of a single T cell receptor.
Authors: S C Hong, G Waterbury, C A Janeway
Journal: The Journal of Experimental Medicine (1996)

CD4 T cell receptors (TCRs) recognize antigenic peptides presented by self major histocompatibility complex (MHC) class II molecules as well as non-self MHC class II molecules. The TCRs can also recognize endogenous retroviral gene products and bacterial toxins known collectively as superantigens (SAGs) that act mainly on the Vbeta gene segment-encoded portion of the Vbeta domain; most SAGs also require MHC II class for presentation. We have studied the interaction of the TCR from a well-characterized CD4 T cell line with SAGs by mutational analysis of its Vbeta domain. This appears to separate viral (v)SAG from bacterial (b)SAG recognition. T cells having a TCR with glycine to valine mutation in amino acid residue 51 (G51V) in complementarity determining region 2 of the TCR Vbeta domain fail to respond the bSAGs staphylococcal enterotoxin B (SEB), SEC1, SEC2, and SEC3, whereas they retain the ability to respond to non-self MHC class II molecules and to foreign peptides presented by self MHC class II molecules. It is interesting to note that T cells expressing mutations of both G51V and G53D of V beta regain the response to SEB and partially that to SEC1, but do not respond to SEC2, and SEC3, suggesting that different bacterial SAGs are viewed differently by the same TCR. These results are surprising, because it has been generally believed that SAG recognition by T cells is mediated exclusively by hypervariable region 4 on the exposed, lateral face of the TCR Vbeta domain. Response to the vSAG Mtv-7 was generated by mutation in Vbeta residue 24 (N24H), confirming previously published data. These data show that the vSAG Mtv-7 and bSAGs are recognized by different regions of the TCR Vbeta domain. In addition, various bSAGs are recognized differently by the same TCR. Thus, these mutational data, combined with the crystal structure of the TCR beta chain, provide evidence for distinct recognition sites for vSAG and bSAG.
A monoclonal antibody against basal cells of human epidermis. Potential use in the diagnosis of cervical neoplasia.
Authors: V B Morhenn, A B Schreiber, O Soriero, W McMillan, A C Allison
Journal: Journal of Clinical Investigation (1985)

A murine monoclonal antibody was generated against human skin cells obtained from psoriatic plaques. The antibody, called VM-2, recognizes an epitope expressed on the basal cell layer of human skin and other epithelia. VM-2 also binds to cultured cells from a variety of human carcinomas including HeLa cervical carcinoma, A-431 vulvar carcinoma, A-549 lung alveolar carcinoma, and SCL-1 skin squamous cell carcinoma cells. In several primary human cell lines, including fibroblasts, endothelial cells, and cells from the hematopoietic lineage, the antigenic site recognized by VM-2 could not be detected. The cellular antigen when immunoprecipitated by VM-2 from both normal and transformed cells appears to be proteins of approximately 100,000 and 120,000 mol weight. In frozen sections from human tumor-containing tissues, VM-2 labels skin, cervical, and lung squamous carcinoma cells, as well as skin basal carcinoma cells. Malignant cells present in exfoliative smears from epidermoid invasive neoplasias of the cervix are also selectively recognized by VM-2 in distinction to normal squamous cervical cells. VM-2 is thus directed against an antigen associated with neoplastic cells when applied in selected sites of exfoliative cytology. This monoclonal antibody represents a new reagent that should prove useful in the diagnosis of cervical neoplasia.
P50 Pituitary Granulomata - TB or Not TB
Authors: K Khan, WM Drake, S Akker, VLC White
Journal: Thorax (2012)

Granulomatous disease of the pituitary gland is rare and of this pituitary tuberculosis (TB) is the rarest, making its diagnosis or exclusion challenging. We discuss six cases. Patients ages ranged between 25–43; 3 were male. 3 were born in UK, the others in Afghanistan, Bangladesh and Somalia respectively. 5 patients presented with headaches, two of whom had bitemporal haeminopia and one also had diabetes inspidus; one presented with cervical lymphadepothy and diabetes inspidus. 3 had weight loss, pyrexia and night sweats. All had MRI scanning; 4 patients showed thickening of pituitary stalk and intense enhancement of the gland, one had a presumed macro-adenoma and another had a cystic mass. 5 patients had trans-sphenoidal surgery (TSS); 3 for diagnostic biopsy, one for urgent decompression of a pituitary mass, another for the macro-adenoma. One had cervical lymphnode biopsy: histology demonstrated granulomatous inflammation in 4 samples, one also had focal necrosis, another was culture positive for AFB. 4 patients had lumbar puncture: CSF cultures for MTB and PCR were non-diagnostic and CSF-ACE was negative; one sample showed lymphocytosis. One patient had abnormal CXR with cavitating lesions and mediastinal lymphadenopathy. 5 patients had vasculitic screens which were negative. All 5 patients who had TSS were left with hypo-pituitarism and on hydrocortisone replacement. The main differential diagnosis was TB or sarcoidosis. 4 patients were treated with anti-TB therapy (ATT) and high dose steroids for one year. The one who grew MTB was treated with ATT alone. The sixth had ATT for six months as well as high dose steroids. Pituitary TB is very rare and only 50–60 cases are reported in literature where not all patients treated with ATT cultured MTB; Imaging modalities are non-specific and show thickening of pituitary stalk and intense post contrast enhancement of the gland as with our patients but this is commonly described in other infections and neoplasm as well. Diagnosis is therefore difficult and challenging and tissue biopsy or microbiology may even not be conclusive. A multidisciplinary discussion of these patients is crucial. <h3>References</h3> Dastur HM. Tubeculoma. Vinken PJ, Bruyn GW editors. Handbook of clinical Neurology. Colman CC, Richmond VA, Meredith JM, diffuse tuberculosis of pituitary gland simulating tumour. Nissim J. Sarcoidosis and its neurological manifestation.
Miscellanea: Living with a marathon runner
Authors: J. M Crown
Journal: BMJ (1986)

survey was being conducted.This hampered the normal flow ofdata between observer and recorder and may have accounted for the imbalance between east and west.Further distractions included the inconsiderate appearance of an occupant in the middle of a site recording and a large poster requesting information on Tip the cat was nearly mistaken for a shoddy plate.At the high frontier of human endeavour there will always be many more questions raised-.thancan be answered satisfactorily.We hope, however, that this study in its own small way will help to stimulate and encourage further work into this unusual though fascinating field of medical-research.
Combination therapy: the future of management for idiopathic pulmonary fibrosis?
Authors: Wim A Wuyts, Katerina M Antoniou, Keren Borensztajn, Ulrich Costabel, Vincent Cottin, Bruno Crestani, Jan C Grutters, Toby M Maher, Venerino Poletti, Luca Richeldi, Carlo Vancheri, Athol U Wells
Journal: The Lancet Respiratory Medicine (2014)
Out of hours consultations
Authors: K Khayat, M Calnan
Journal: BMJ (1994)

EDITOR, - In her paper on out of hours consultations with general practitioners Lesley Hallam laments the lack of data.1 With regard to the demand for out of hours consultations she states that “studies are generally restricted to individual practices or small areas.” We wish to summarise our data on this issue, which were not available in time for her study.2,4

We combined three surveys of satisfaction. which …
Epstein-Barr virus-induced autoimmune responses. II. Immunoglobulin G autoantibodies to mimicking and nonmimicking epitopes. Presence in autoimmune disease.
Authors: J H Vaughan, M D Nguyen, J R Valbracht, K Patrick, G H Rhodes
Journal: Journal of Clinical Investigation (1995)

During infectious mononucleosis, IgM autoantibodies are generated to a protein, p542, which contains a glycine-rich 28-mer epitope cross-reactive with the Epstein-Barr nuclear antigen-1 through Epstein-Barr nuclear antigen-1's glycine/alanine repeat. In normal individuals it is uncommon to find IgG anti-p542, but among patients with progressive systemic sclerosis, systemic lupus erythematosus, and ulcerative colitis high IgG anti-p542 (> 3 SD above the mean of normal 20-50 yr controls) occurred frequently. Lesser elevations occurred in Sjögren's syndrome, rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease, but none with chronic hepatitis B infection. The reactive epitopes on p542 were mapped with deletion mutants, which indicated that the glycine-rich 28-mer was the major antigenic determinant, with lesser antibody responses to other epitopes. We conclude that normally there is an inability to generate IgG autoantibodies to the cross-reactive (mimicking) epitope of the p542 host protein, but that this inability is overcome in a proportion of patients with autoimmune disease. We conclude also that non-cross-reactive autoepitopes exist on p542 protein, to which IgG autoantibodies can commonly be formed in autoimmune disorders. The mechanisms responsible for the latter must involve different mechanisms than those responsible for autoantibodies to the mimicking epitope.
Appraising doctors and dentists in training
Authors: J. Oxley
Journal: BMJ (1997)

Appraisal is a vital element in improving postgraduate education and training. Here, Jolyon Oxley defines the terms and outlines a checklist for action All doctors are very familiar with assessments - a variety of processes designed to measure knowledge and skills - usually with a view to achieving the next step in a career. Informal day to day feedback is commonplace but increasingly doctors also experience systematic appraisal which has aims that are complementary to, but different from, assessment. Appraisal is now recommended for specialist registrars1 and pre-registration house officers.2 There is little doubt that senior house officers would benefit from it too. Appraisal has been adopted in many fields of employment outside of medicine where it has a wide variety of purposes and applications. It is relatively new in medicine in the NHS, though it has been established in the academic sector for some years. It was obvious at the start of the enquiry into appraisal conducted by the Standing Committee on Postgraduate Medical Education (SCOPME) that little progress could be made until there was greater clarity and agreement about terminology. Appraisal, formative and summative assessment, and individual performance review are all widely used terms that have different meanings to different people, sometimes being used almost interchangeably. Formative (or educational) assessment and summative (or regulatory) assessment are terms well established in general practice where they have been found to be very helpful. #### Criteria for effective appraisal ##### Appraisal will be most effective when
Medical Education Research and Development
Authors: George E. Miller
Journal: JAMA (1966)

Let me begin with a text, drawn from a 16th century work of Niccolo Machiavelli: "There is nothing more difficult to carry out, nor more doubtful of success, nor more dangerous to handle than to initiate a new order of things." Educational research in medicine<i>is</i>a new order of things, formally initiated almost simultaneously by three medical schools in the late 1950's. With the passage of years and the appearance of a hard core of workers in the field, the glamor of the enterprise is fast disappearing, but the mystery of what these workers really do is still widespread. My task is not to restore glamour; it is rather to dispel some of the misunderstanding that abounds among those who occupy more conventional seats in the educational hierarchy of medicine, and who sometimes wonder what all the fuss is about. Historical perspective is often useful in elucidating contemporary issues,
Repair and Convalescence After Herniorrhaphy and Appendectomy
Authors: Robert L. Kerry
Journal: JAMA (1971)

<h3>To the Editor. —</h3> Inguinal hernias, whether symptomatic or not, should be repaired before participation in school athletic programs. The repair, unless there is some contraindication to surgery, should be carried out at the earliest convenient date. This implies one to two months, as herniorrhaphy is an elective and not an emergency procedure. Athletic activity tends to aggravate and enlarge an inguinal hernia. The larger, the more difficult a hernia is to repair. Also, with strenuous activity the possibility of incarceration and strangulation is increased, thereby increasing morbidity and mortality form an emergency operation. The asymptomatic hernia which is incarcerated requires prompt attention with operation within 24 to 48 hours unless it has been present for a long time. Of course, the strangulated hernia requires emergency surgery. The only contraindication to a hernia repair would be some other major health program, which in itself would contraindicate active participation in athletics.
Alcohol-induced rosacea flushing blocked by naloxone
Authors: J.E. BERNSTEIN, K. SOLTANI
Journal: British Journal of Dermatology (1982)

We evaluated the roles of endogenous opioid peptides and histamine in the pathophysiology of alcohol-induced facial flushing in rosacea. Non-diabetic patients with rosacea ingested 360 ml of 6% ethanol after receiving either subcutaneous naloxone hydrochloride or oral chloropheniramine maleate. Only pretreatment with naloxone blocked the alcohol-induced rosacea flushing (AIRF), suggesting an active role of endogenous enkephalin and/or endorphin in this vascular reactivity. In this respect, AIRF is similar to chlorpropamide alcohol flushing and menopausal flushing.
IL-27 and type 2 immunity in asthmatic patients: Association with severity, CXCL9, and signal transducer and activator of transcription signaling
Authors: Min Xie, Anthony T. Mustovich, Yi Jiang, John B. Trudeau, Anuradha Ray, Prabir Ray, Haizhen Hu, Fernando Holguin, Bruce Freeman, Sally E. Wenzel
Journal: Journal of Allergy and Clinical Immunology (2014)
The Etiology of Syncope in Patients With Negative Tilt Table and Electrophysiological Testing
Authors: Andrew D. Krahn, George J. Klein, Caro Norris, Raymond Yee
Journal: Circulation (1995)

Background Patients with syncope of unknown etiology after negative noninvasive and electrophysiological testing may suffer from recurrent disability. Syncopal episodes are often too infrequent and unpredictable for detection by conventional ambulatory monitoring techniques. Methods and Results A long-term subcutaneous monitoring device was implanted in patients with negative ambulatory monitoring, tilt table and electrophysiological testing to establish cardiac rhythm during spontaneous syncope. Sixteen patients aged 57±19 years with a mean of 8.4±4.4 previous episodes of syncope underwent device implantation. Fifteen patients (94%) had recurrent syncope 4.4±4.2 months after implantation. The remaining patient has not had recurrent syncope and continues to be followed. A diagnosis was obtained in every patient who had recurrent episode. Syncope was secondary to sinus arrest in 5, atrioventricular block in 2, ventricular tachycardia in 1, supraventricular tachycardia in 1, and nonarrhythmic in 6. Successful therapy was implemented in all 15 patients, without recurrence of syncope during 13.0±8.4 months of follow-up. Conclusions Unexplained syncope in patients with negative investigations has a broad spectrum of etiologies, the most common of which is bradycardia. An implantable long-term monitoring device is useful for establishing a diagnosis when symptoms are recurrent but too infrequent for conventional monitoring techniques.
Mosaic analysis of insulin receptor function
Authors: Tadahiro Kitamura, Yukari Kitamura, Jun Nakae, Antonio Giordano, Saverio Cinti, C. Ronald Kahn, Argiris Efstratiadis, Domenico Accili
Journal: Journal of Clinical Investigation (2004)

Insulin promotes both metabolism and growth. However, it is unclear whether insulin-dependent growth is merely a result of its metabolic actions. Targeted ablation of insulin receptor (Insr) has not clarified this issue, because of early postnatal lethality. To examine this question, we generated mice with variable cellular mosaicism for null Insr alleles. Insr ablation in approximately 80% of cells caused extreme growth retardation, lipoatrophy, and hypoglycemia, a clinical constellation that resembles the human syndrome of leprechaunism. Insr ablation in 98% of cells, while resulting in similar growth retardation and lipoatrophy, caused diabetes without β-cell hyperplasia. The growth retardation was associated with a greater than 60-fold increase in the expression of hepatic insulin-like growth factor binding protein-1. These findings indicate that insulin regulates growth independently of metabolism and that the number of insulin receptors is an important determinant of the specificity of insulin action.
Injuries: Part 1, Mechanical Injuries; Part 2, Non-Mechanical Injuries
Authors: Albert M. Potts
Journal: JAMA (1972)

This two-part volume is an updating of volume 6 of Duke-Elder's<i>Textbook of Ophthalmology</i>which appeared in 1954. The present publication adheres closely to the format of the previous volume and is a little under 200 pages longer. The updating has been conscientious and the new literature in each category of injury is faithfully recorded. After a short and general introductory section on the nature and incidence of ocular injuries, part 1 of the new volume deals with mechanical injuries, under the major headings of concussions and contusions, incised wounds, retained foreign bodies, explosion and gunshot injuries, and the indirect effects of mechanical injuries. Part 2 takes up the nonmechanical thermal, ultrasonic, radiational, and stress injuries. The effects of chemical substances are expounded in two discrete sections separated by the section on stress injuries. The effects of externally contacting chemicals are presented under the heading of "Chemical Injuries," and all
Controlled trial of speech therapy versus oxprenolol for stammering.
Authors: L Rustin, A Kuhr, P J Cook, I M James
Journal: BMJ (1981)

In a controlled trial of treatment for stammering under stress oxprenolol (40 mg) compared with placebo was assessed in a double-blind manner over two days, six weeks apart, in 31 stammerers before and after speech therapy. The trial design also allowed six weeks of intensive speech therapy, using a slowed-speech and relaxation technique, to be compared with not treatment and assessed single-blind. Oxprenolol produced a significant fall in pulse rate and systolic blood pressure but no overall change in performance either before or after speech therapy. Intensive speech therapy produced a highly significant improvement in the global performance of untrained subjects (p less than 0.001) and a significant reduction in the number (p less than 0.001) and duration (p less than 0.001) of blocks. Maintenance speech therapy tended to produce further improvement in trained subjects. Speech therapy is apparently an effective treatment for stammering, whereas oxprenolol appears to be of no value when given routinely; oxprenolol may be of value, however, in very stressful conditions.
OC-042 Endoscopic Ultrasound Guided Fine Needle Aspiration of Pancreatic Mass Lesions can be Less Accurate with a Metallic Stent in Situ but should not Delay Treatment of Obstructive Jaundice
Authors: A D Hopper, R Vinayagam, A Dube
Journal: Gut (2013)

<h3>Introduction</h3> Endoscopic ultrasound (EUS) examination and fine needle aspiration (FNA)of the pancreas is now a routine method of obtaining diagnositic tissue for suspected pancreatic mass lesions, however if a biliary self expanding metal stent (SEMS) is in situ it can cast an acoustic shadow and cause local inflammation making EUS visualisation and FNA interpretation more challenging. Despite this it is common for a SEMS to be in place at the time of EUS due to the early treatment required for obstructive jaundice. Conflicting results have been published regarding the success of FNA in the presence of a SEMS, our aim was to analyse the accuracy of pancreatic FNA with or without a SEMS in an hepatobiliary-pancreatic cancer network in the United Kingdom. <h3>Methods</h3> A retrospective analysis of all FNAs performed for solid pancreatic lesions in a single centre by 2 endosonographers from August 2010 to December 2012. Patents were identified if they had a biliary SEMS or plastic stent in situ. All FNAs were performed with 22 gauge FNA needle with no on site pathologist and direct expulsion of material into cyto-rich red medium. A standard 3 passes were performed in all lesions. Patient were excluded if they did not have a gold standard comparison for FNA results which was defined as surgical specimen comparison, death resulting from disease or clinical follow up and imaging for a minimum of 6 months. <h3>Results</h3> 831 EUS procedure were performed during the study period of which 129 had FNA of a solid pancreatic lesions. 23 patents had a SEMS in situ at the time of EUS FNA and 5 had a plastic stent. The accuracy of pancreatic FNA with a SEMS was 65% (15/23)(95%CI: 44–81%) a plastic stent was 80%(4/5)(95%CI: 36% to 98%) and with no stent was 84.3% (86/102)(95%CI:76–90%) and overall was 82.2% (106/129)(95%CI: 75–88%). The FNA accuracy for the presence of a metallic stent was significantly lower χ<sup>2</sup> = 4.4 (p = 0.036). All 8 patients with a SEMS had a false negative result of which 5 were felt well enough to undergo a further procedure for consideration of chemotherapy which gave an accuracy of 80%(4/5). All patients were happy to undergo a repeat biopsy. <h3>Conclusion</h3> The accuracy for FNA of solid pancreatic lesions in the presence of a SEMS can be significantly lower than without and should be taken into account when consenting patients and planning treatment. However it should not delay the insertion of a SEMS as if definitive cytology is required a repeat FNA is a feasible option with an acceptable accuracy. <h3>Disclosure of Interest</h3> None Declared
German hospital curtails services because of deficit
Authors: A. Tuffs
Journal: BMJ (2003)

For the first time in Germany a hospital has decided to halt all patient care for a period, apart from emergency services.

The university hospital at Greifswald, in the east German state of Mecklenburg-West Pomerania, announced in December that it was planning to stop all regular treatments until 31 December 2002, because the hospital budget could not cover them.

The budget, granted by …
Hormonal Shock Therapy and Intracellular Enzymes
Authors: Hermann Zondek
Journal: JAMA (1963)

<h3>To the Editor:</h3> —In their interesting paper, "Phosphorylase Enzyme of Brain in Mental Illness" (<i>JAMA</i><b>184</b>:283 [April 27] 1963), Iriye and Simmonds present experimental evidence which suggests that insulin in excessive doses (shock therapy) produces its beneficial effects upon mental illness by increasing phosphorylase activity. This reminds us of another form of hormonal shock therapy ("stosstherapy") which we have used in a completely unrelated disease entity, goitrous cretinism. Further, we had interpreted our surprisingly favorable results in an identical manner, although our conclusions were based on clinical evidence only. Our experience was as follows: Three siblings with frank goitrous cretinism were treated with large amounts of thyroid substances in a<i>short</i>period of time (90 mg of triiodothyroacetic acid [Triac] within 9 days). Thereupon all three became euthyroid and agoitrous and remained so for<i>protracted</i>periods, two of them for 6 to 10 months, and the third for 4