tbuckley/cabot-search huggingface dataset:
Maximizing Antigen Targeting to the Proteasome for Gene-Based Vaccines
Authors: Helen A. Andersson, Michael A. Barry
Journal: Molecular Therapy (2004)

Wild-type or immunoevasive antigens can drive weak CD8+ T-cell responses against both dominant and subdominant epitopes during gene-based vaccination. For many antigens, fusion to ubiquitin (Ub) to target them to the proteasome circumvents this problem. Although this procedure works in most cases, for one subset of antigens, Ub fusion does not improve immune responses. To determine why these failures occur, we have evaluated in detail the 'rules' for proteasome targeting that have been applied in mammalian vaccine studies, but that were actually defined in yeast systems. To do this, we fused a series of engineered Ub genes to green fluorescent protein (GFP) and tested their ability to target GFP to the proteasome for enhanced antigen processing and CD8+ T-cell responses. Here we demonstrate that Ub fusion mediates enhanced CD8+ responses by proteasome targeting rather than by enhancing protein translation. We also show that several of the yeast-defined Ub constructs failed to target the proteasome in mammalian cells and likewise failed to enhance transgene-specific CD8+ T-cell responses in mice. In contrast, when mammalian-optimized constructs were applied to target the influenza virus nucleoprotein, CD8+ responses were enhanced against its refractory subdominant epitope in mice. This work demonstrates that Ub fusion has efficacy to enhance CD8+ responses, especially against subdominant antigen epitopes, provided constructs are optimized for mammalian use.
A8.8 Hydrogen Sulphide Inhibits IL-1β Stimulation of Fibroblast-Like Synoviocytes from Osteoarthritis Patients in a 3-D Model
Authors: D Sieghart, HP Kiener, G Steiner, B Kloesch
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> Osteoarthritis (OA) is a degenerative and most common joint disease which shows characteristic features like loss of cartilage, formation of osteophytes and alteration of subchondral bone leading to joint impairment and pain. The pathogenesis of OA is still not fully understood. Fibroblast-like synoviocytes (FLS), occurring in the intimal lining layer of the synovial membrane, were shown to promote secondary synovitis by the release of pro-inflammatory cytokines and matrix-metalloproteinases (MMPs). The objective of this study was to analyse the possible anti-inflammatory potential of hydrogen sulphide (H<sub>2</sub>S) on activated FLS cultured in three-dimensional micromass culture. <h3>Methods</h3> Primary cell lines based on FLS derived from patients with OA were cultivated in spherical extracellular matrix micromasses. Micromass cultures were stimulated for 1 h with IL-1β (10 ng/ml) only or with IL-1β plus either 0.125 mM or 1 mM of sodium hydrogen sulphide (NaHS). As a control, cultures were treated with PBS only. Treatments were applied on day three, five, seven, nine, 12, 14, 16 and 19. Micromasses were cultured for 21 days, fixed with paraformaldehyde, sectioned and stained for hematoxylin and eosin (H&amp;E), IL-6 or MMP-3. Secretion of IL-6 was analysed by enzyme-linked immunosorbent assay (ELISA). <h3>Results</h3> We observed the spontaneous formation of a compacted, lining layer-like architecture by OA-FLS, already described for rheumatoid arthritis (RA)-FLS. Untreated cultures, in addition, showed clusters of elongated cells underneath the condensed cell layer. A cellular response, which included increased formation of synovial lining as well as changes in cell morphology, could be seen after stimulation with the pro-inflammatory cytokine IL-1β. Treatment with 1 mM of NaHS had the potential to inhibit structural changes caused by cell activation induced by IL-1β. Furthermore, H<sub>2</sub>S treatment reduced the IL-1β stimulation-related elevated levels of IL-6 secretion. <h3>Conclusions</h3> The ability of NaHS to inhibit the development of cellular responses to pro-inflammatory IL-1β could be considered a cartilage protective effect and has to be elucidated in more detail.
Controlling the resurgent tuberculosis epidemic. A 50-state survey of TB statutes and proposals for reform
Authors: L. O. Gostin
Journal: JAMA (1993)

A LONG-STANDING annual decline in the number of cases of tuberculosis (TB) in the United States led the Department of Health and Human Services to establish an Advisory Council for the Elimination of Tuberculosis (ACET) in 1987.<sup>1</sup>Yet, even before the Council was established, the decline in tuberculosis had ended, and from 1985 through 1991 there were some 39 000 more cases than would have been expected had the downward trend continued.<sup>2,3</sup> More worrisome still is the serious increase in the rate of multidrug-resistant (MDR) tuberculosis, which is much more difficult, and more costly, to treat than nonresistant strains. The course of treatment of MDR-TB increases from approximately 6 months to 18 to 24 months or longer, and the cure rate decreases from nearly 100% to 60% or less.<sup>4,5</sup>A 1992 survey in New York City (NY) found that 33% of patients were infected with organisms resistant
Misquotations of Dr. Sajous.
Authors: C. E. de M. Sajous
Journal: JAMA (1906)

Philadelphia, Nov. 3, 1906. <h3>To the Editor:</h3> —Two letters received from New York, one from San Francisco, and a clipping from a newspaper, the New York<i>Journal</i>, sent by a friend, indicate that an article I read by invitation before the Medical Association of the Greater City of New York, Oct. 15, 1906, has formed the basis of sensational articles in the lay press. The gross misstatements the clipping I hold contains, e. g., that I have discovered "adrenalin" (sic); that I kept "life in the body of a dog for ten hours after its head had been removed"—a distorted reference to Dr. Crile's experiments which I quote—; the use of adrenalin to "keep life" until "water can be expelled from the lungs,"— a fact "absolutely established by experiments," but to which I do not even refer, etc.,—were such, I thought, as to protect me against imputations on the part
THE PHYSIOLOGY OF ESTROGENIC PRINCIPLES
Authors: EDGAR ALLEN
Journal: JAMA (1935)

Note.  —This article and the articles in the previous issues ofThe Journalare part of a series published under the auspices of the Council on Pharmacy and Chemistry. Other articles will appear in succeeding issues. When completed, the series will be published in book from.—Ed.  The term estrus, as used by Heape, designated the restricted period of mating activity of female mammals.1 The outstanding criterion of estrus was the female's intense sex urge or drive. Since sexual activity in women and other female primates is not restricted to such brief intense periods, the term has not been used in connection with the menstrual cycle.  Recent experimental work with ovarian hormones has emphasized another aspect of estrus; namely, the rapid growth of the accessory genital organs, which ushers in the estrous period proper. This growth was first induced experimentally by the overian follicular hormone. This hormone is therefore primarily a
GENERALIZED BLASTOMYCOSIS.REPORT OF A CASE WITH RECOVERY.
Authors: JAMES B. HERRICK
Journal: JAMA (1907)

The following case is reported because it is, I believe, the first instance recorded of recovery from generalized blastomycosis. It is worthy of note also that the patient was a woman and of the better class. Blastomycosis in women is apparently a rarity. The patient was under the care of Dr. A. C. Garvy, with whom I saw her many times. This preliminary report is made with the kind consent of Dr. Garvy, who will later present a more detailed history of the case. It should encourage one in the persistent treatment of blastomycosis even of the generalized type, as it shows that a certain percentage, probably a small one, may terminate in healing. <h3>History.</h3> —The patient was Mrs. O., 24 years of age, for at least 15 years a resident of Chicago, of healthy, well-to-do parents, and with no severe preceding illness except the usual diseases of childhood, and nervous
Renal Vein Thrombosis and Nephrotic Syndrome
Authors: FRANCISCO LLACH
Journal: Annals of Internal Medicine (1975)

During 2 years we studied 36 of 41 consecutive patients with nephrotic syndrome. Twelve (Group 1) had renal vein thrombosis; the renal pathology was membranous glomerulonephritis in 10 and membranoproliferative glomerulonephritis in 2. Eighteen without renal vein thrombosis (Group 2) had either membranous (10 patients) or membranoproliferative (8 patients) glomerulonephritis. Clinical presentation, laboratory data, renal function, renal histology, and immunopathology were similar in both groups; thromboembolic phenomena were frequent. Ten of 12 patients with renal vein thrombosis were given oral anticoagulants and followed for 4 to 24 months. None died or had thromboembolic episodes. The results show that one third of the patients with nephrotic syndrome associated with either membranous or membranoproliferative glomerulonephritis had renal vein thrombosis, and there were no clinical, laboratory, histological, or immunopathological finding(s) diagnostic of renal vein thrombosis. Our data indicate that renal vein thrombosis is a frequent complication in nephrotic syndrome and membranous or membranoproliferative glomerulonephritis.
Chronic Recurrent Multifocal Osteomyelitis Demonstrated by Tc-99m Methylene Diphosphonate Bone Scan
Authors: Lise Hobolth, Michel Nemery, Jens Albrectsen, Philip Hasbak
Journal: Clinical Nuclear Medicine (2008)

A 12-year-old Middle Eastern girl presented with abdominal pain, weight loss, and intermittent pain in both thighs. She was initially suspected of Crohn disease, but this diagnosis was excluded after extensive gastromedical evaluation. Plain x-rays of the femora were normal, whereas the initial Tc-99m methylene diphosphonate (MDP) bone scan showed several foci with increased activity in both femurs. MR scan showed excessive periostal inflammatory and mild intramedullary changes in both femurs. A percutaneous bone biopsy demonstrated changes consistent with chronic recurrent multifocal osteomyelitis (CRMO). The patient's symptoms disappeared spontaneously, but reappeared 1.5 years later, which led to a new MDP bone scan that showed normal findings.
Points from Letters: Alcohol and Road Accidents
Authors: M. Goldman
Journal: BMJ (1964)

BRITSWhile Dr. Stephen does not quote the volume of water in his sink and bottle, it is obvious that the elusive 280 nm. of CO2 has been absorbed by the large quantity of liquid con- tained therein.In order to measure the actual C02 evolved from a beogex suppository it is necesary to collect the gas over a fluid in which it is insoluble, such as mercury or brine previously saturated with CO2.It is the latter fluid which we use for our assay purposes, and when calculating the total volume of gas evolved by this procedure one should also allow for the C02 which will dissolve in the small quantity of water used to promote the reaction.-Weare, etc.,
Serum Formate Concentrations in Methanol Intoxication as a Criterion for Hemodialysis
Authors: JOHN D. OSTERLOH
Journal: Annals of Internal Medicine (1986)

To evaluate the utility of serum formate concentrations, four patients were studied after ingestion of a methanolic copying fluid. All patients were initially intoxicated. Twelve to twenty-four hours later, signs and symptoms included nausea, abdominal pain, hypokalemia, acidosis (three patients), and pathologic ocular findings (two patients). All patients were treated with ethanol and folate. The two patients with ocular signs and acidosis had high serum formate concentrations (75 and 55 mg/dL, respectively). One of the two patients had a high methanol concentration (222 mg/dL) and required hemodialysis; the other patient did not (methanol concentration, 24 mg/dL). In the other two patients without ocular signs, initial formate concentrations were undetectable (limit of detection, 0.5 mg/dL); however, one patient required hemodialysis because the methanol concentration was 72 mg/dL. Formate is the mediator of ocular injury and acidosis. In these patients formate concentrations correlated with the clinical condition but methanol concentrations did not.
1304 TH2 CYTOKINE-MEDIATED BILIARY EPITHELIAL CELL (BEC) BARRIER DYSFUNCTION MAY CONTRIBUTE TO IMMUNOGLOBULIN G4 (IGG4) ASSOCIATED SCLEROSING CHOLANGITIS (IAC)
Authors: T. Müller, C. Beutler, A. Hurtado Pico, E. Schott, A. Fischer, A. Pascher, P. Neuhaus, B. Wiedenmann, T. Berg
Journal: Journal of Hepatology (2011)
Familial Osteosarcoma Fifth Reported Occurrence
Authors: Robert Robbins
Journal: JAMA (1967)

To the Editor:—  In the course of preparing a review on familial tumors,1many reports of unusual familial occurrence of tumors were found, including myelomas, chondrosarcomas, fibromas, lipomas, and other tumors of bone and soft tissues.' -6Four previous instances of familial occurrence of osteosarcoma were found.7-10It is the purpose of this paper to present what is believed to be the fifth such report.  Case 1:—  This 22-year-old man was first seen in May 1963 with a lump on the back of his head (Fig 1). In July a craniotomy and partial resection of a mass was done. It was 8×8 cm in dimensions and very vascular. It involved the flat bones of the posterior portion of the skull, the dura mater, and the sagittal sinus. Histologic examination revealed osteosarcoma. Brain scan revealed a large space-taking component intracerebrally. Radiation therapy to 6,000 rads in six weeks was administered.
C1-04: A phase II study of RAD001 (everolimus) monotherapy in patients with advanced non-small cell lung cancer (NSCLC) failing prior platinum-based chemotherapy (C) or prior C and EGFR inhibitors (EGFR-I)
Authors: Vassiliki Papadimitrakopoulou, Jean-Charles Soria, Jean-Yves Douillard, Giuseppe Giaccone, Jürgen Wolf, Lucio Crino, Federico Cappuzzo, Sunil Sharma, Stefan H. Gross, Frances A. Shepherd
Journal: Journal of Thoracic Oncology (2007)
Relation of Left Ventricular Hypertrophy to Inflammation and Albuminuria in Adults With Type 2 Diabetes
Authors: Vittorio Palmieri, Russell P. Tracy, Mary J. Roman, Jennifer E. Liu, Lyle G. Best, Jonathan N. Bella, David C. Robbins, Barbara V. Howard, Richard B. Devereux
Journal: Diabetes Care (2003)

OBJECTIVE—To evaluate in adults with type 2 diabetes the extent to which the relation of left ventricular hypertrophy (LVH) to markers of systemic inflammation (fibrinogen and high-sensitivity C-reactive protein [hsCRP]) are affected by microangiopathy. RESEARCH DESIGN AND METHODS—We selected adults with type 2 diabetes using American Diabetes Association criteria from a population-based cohort, excluding those with medical history or electrocardiographic evidence of coronary heart disease or dialysis-dependent renal failure. LVH was assessed by echocardiogram. RESULTS—Of the 1,299 eligible participants, 384 (29.6%) had LVH, which was associated with higher BMI, hsCRP, fibrinogen, and albuminuria in univariate analyses. After controlling for significant confounders, fibrinogen and albuminuria were higher in the presence of LVH (both P &amp;lt; 0.01), whereas hsCRP was not (P = 0.2), mostly because of the confounding effect of BMI. Adjustment for albuminuria abolished the relation of LVH to higher fibrinogen (P = 0.2). However, fibrinogen was significantly higher in participants with LVH among those without pathologic levels of albuminuria (&amp;lt;30 mg/g creatinuria), but not independent of BMI. Although hsCRP and fibrinogen were moderately correlated, fibrinogen, but not CRP, showed a significant relation with albuminuria. CONCLUSIONS—In adults with type 2 diabetes, echocardiographic LVH is associated with susceptibility to atherothrombosis and increased albuminuria, which is a marker of microangiopathy and endothelial dysfunction that appears in turn to be a relevant pathogenetic link between LVH and inflammation. However, in the absence of significant microalbuminuria, elevated BMI is a relevant pathogenetic factor in the relation of LVH to increased levels of markers of inflammation, potentially preceding development of significant albuminuria. In the presence of microangiopathy, we found that the atherothrombotic risk profile associated with LVH was independent of BMI and possibly reflected the association of LVH with a higher degree of endothelial dysfunction.
Retroviral transduction of IL2RG into CD34+ cells from X-linked severe combined immunodeficiency patients permits human T- and B-cell development in sheep chimeras
Authors: Emily J. Tsai, Harry L. Malech, Martha R. Kirby, Amy P. Hsu, Nancy E. Seidel, Christopher D. Porada, Esmail D. Zanjani, David M. Bodine, Jennifer M. Puck
Journal: Blood (2002)
High Blood Pressure: Do We Really Know Whom to Treat and How?
Authors: Michael H. Alderman
Journal: New England Journal of Medicine (1977)

Despite the fact that neither the national Health and Nutrition Examination Survey (HANES),1 the Framingham Studies2 , 3 nor the Veterans Administration Cooperative Study of Antihypertensive Therapy4 , 5 were designed to determine the role of hypotensive therapy in a general population, the current approach to the management of high blood pressure in the community rests largely on their conclusions. In fact, proponents of vigorous therapeutic intervention make their case by mobilizing these independent strains of epidemiologic evidence, one related to prevalence and the other to the impact of hypotensive therapy. Unfortunately, important qualifying methodologic features of the relevant studies are often over-looked, and . . .
Anuria Following Phenylbutazone Therapy
Authors: Jacob I. Weisman, Bernard Bloom
Journal: New England Journal of Medicine (1955)

IN recent years there has been an increased use of phenylbutazone (3,5-dioxo-1,2-diphenyl-4-n-butyl pyrazolidine) as a general antiarthritic. Because of possibly indiscriminate administration and subsequent harmful effects, it is considered timely to review some of the more important toxic side reactions, and to include a case report of an undesirable sequela.In a review of the literature, many complications and toxic reactions have been listed, including the following: granulocytopenia; thrombocytopenia; temporary and mild secondary anemia; hepatotoxicity and jaundice; Stevens-Johnson syndrome and other cutaneous manifestations; sensitivity reactions resembling polyarteritis nodosa; reactivation of peptic ulcer, with perforation and hemorrhage; retention of water, sodium . . .
One in four GPs remains reluctant to initiate end of life discussions with patients
Authors: I. Torjesen
Journal: BMJ (2014)

Discussing death with a patient is still a taboo subject for one in four general practitioners, a survey has found.

The survey of 1003 UK GPs was conducted by ComRes for the Dying Matters coalition, a group led by the National Council for Palliative Care. It found that one in four GPs had not initiated any discussion with patients about their end of life wishes, even though GPs can on average expect around 20 of their patients to die each year.

Although the results showed a persistent reluctance among some GPs to broach the subject of death, they were a marked improvement on attitudes studied two years ago. In 2012 more than a third (35%) of 1000 GPs …
Letter: Side effects of practolol.
Authors: P M Garylarde, I Sarkany
Journal: BMJ (1975)

Vomiting with Clonidine Withdrawal SIR,-We would like to report a case of persistent vomiting in a patient after rapid withdrawal of clonidine (Catapres).The dangers of paroxysmal hypertension asso- ciated with raised catecholamine levels following rapid withdrawal of clonidine are well documented.'We have found no previous report of persistent vomiting occur- ring in this situation.
Death after complete detachment of a Bjork-Shiley prosthetic mitral valve.
Authors: D J Gawkrodger, A K Deiraniya
Journal: BMJ (1979)

paras), and to attend a clinic or return the questionnaire after three months.Fifty-two patients (87 %) (15 primiparas and 37 multiparas) completed questionnaires.They were matched with a control group of 52 vaccinated patients who received no hormonal treatment.The mean (i SD) number of days of postpartum bleeding was 58-5 i 18-5 in the treated patients and 20-8 1-1 in the controls.This difference was significant (P <0-001).Patients still bleeding at three months were treated with low-dose oestrogen/ progestogen pills) which invariably stopped bleeding.Only one patient was so treated before three months.Thirty-three treated patients, but only two controls, had continuous bleeding for three months.In no case was the loss heavy and no patients developed anaemia (haemoglobin less than 10-0 g/dl).Six patients (five treated and one control) had a curettage.None had retained placental tissue.None of the 15 treated patients who had cyclical bleeding considered the loss heavy, compared with six controls.Three non-lactating patients in each group had amenorrhoea.Patients with continuous bleeding for the three months found it inconvenient and worrying.It usually made intercourse unacceptable.
NICE says doctors could help 165 000 more smokers to quit
Authors: Balaji Ravichandran
Journal: BMJ (2006)

If GPs encouraged more of their patients to stop smoking by opportunistic advice and referring some patients to intensive support clinics, the number of smokers quitting each year in England would increase by 165 000, the National Institute for Health and Clinical Excellence (NICE) said last week.

NICE calculates that if doctors took such measures the proportion of England's 10 million smokers giving up for more than a year would increase from 2.7% to 4.3%.

The institute published the figures when it launched …
Hemoglobin Evanston (alpha 14 Trp----Arg). An unstable alpha-chain variant expressed as alpha-thalassemia.
Authors: G R Honig, M Shamsuddin, L N Vida, M Mompoint, E Valcourt, L J Bowie, E C Jones, P A Powers, R A Spritz, M Guis
Journal: Journal of Clinical Investigation (1984)

A new hematologic syndrome with phenotypic features of mild Hb H disease was identified in three children from two unrelated black American families. Erythrocytes from each of these children contained Hb H (beta 4) and Hb Barts (gamma 4), as well as a slowly migrating hemoglobin fraction that made up 7-10% of the total hemoglobin. The parents of the affected children all showed mild thalassemia-like changes, with one of the parents in each family also expressing the variant hemoglobin; in the latter individuals the mutant alpha-chains made up less than 2% of the total, and were present mainly or exclusively in combination with delta-chains in the form of a slowly migrating Hb A2. Purified Hb Evanston showed an increased oxygen affinity, but its Bohr effect, cooperativity, and 2,3-diphosphoglycerate effect were normal. The mutant hemoglobin appeared to have normal stability to heat and to isopropanol, and the stability of its alpha-chain in an extended time course synthesis study also appeared to be similar to that of alpha A. However, the results from short-term globin synthesis studies, and from mRNA translation in vitro, suggest that the two types of alpha-chains were synthesized at relatively equal rates, with a major fraction of the newly synthesized variant alpha-chains undergoing rapid catabolism. The hematologic data taken in combination with DNA hybridization and globin synthesis findings indicate that the proposita in each of these families has the genotype--, alpha A/--, alpha Ev. These observations suggest that two separate mechanisms are contributing to the alpha-thalassemia-like expression of Hb Evanston : the newly synthesized alpha EV-chains are unstable and are subject to early proteolytic destruction; and the mutant alpha-allele is linked to an alpha-globin gene deletion.