tbuckley/cabot-search huggingface dataset:
New hope for tumor vaccines
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

The way a tumor cell dies determines its immune-stimulating capacity, according to a study by Casares and colleagues on page 1691. Tumor cells that die from exposure to the chemotherapy drug doxorubicin, they show, become highly immunogenic and induce the regression of established tumors when injected into mice.






Figure 

Tumor growth is blunted in mice immunized with doxorubicin-treated cells.




Inactivated tumor cells have long been considered to be attractive vaccine immunogens, in part because whole-cell vaccines would allow each patient to be immunized against his or her own tumor. But this approach has met with limited success, probably because traditional ways of inducing tumor cell death—by irradiation or freeze-thawing—somehow strip the cells of their immunogenicity.

Many vaccine strategists have instead turned to T cell-inducing dendritic cell (DC) vaccines, in which DCs are grown from a patient's blood, pulsed with tumor antigens, and reinjected. But the new data by Casares and colleagues might help revive interest in the simpler whole-cell approach.

Casares et al. show that tumor cells treated with doxorubicin, but not those treated with the chemotherapy drug mitomycin, elicit a tumor-specific T cell response in mice. Although both treatments induced apoptosis of the injected tumor cells, only the doxorubicin-treated cells were taken up by DCs, which then activated specific T cells. The immune-stimulating effect of doxorubicin required the activity of the death-inducing caspase enzymes in the tumor cells, although the relevant caspase targets were not identified.

The authors are now trying to pin down the doxorubicin-induced changes on the dying tumor cells that render them more palatable to DCs. In the meantime, they suggest that this approach—should it work in humans—might provide a more practical alternative to anticancer vaccine strategies that require the labor-intensive cultivation of autologous DCs.
Combined features of pemphigus and pemphigoid induced by penicillamine
Authors: P.J. VELTHUIS, J.C. HENDRIKSE, J.J. NEFKENS
Journal: British Journal of Dermatology (2006)

d-Penicillamine is able to induce a bullous eruption with the clinical, histological and immunological features of pemphigus. We present a case that had all the characteristics of pemphigus, but also in vivo bound IgG against the dermo-epidermal junction, i.e. the immunological features of bullous pemphigoid. Since no subepidermal blistering was observed, it is concluded that the penicillamine-induced auto-antibodies against the basement membrane zone were biologically inactive.
Drug Dependence, a Chronic Medical Illness
Authors: A T McLellan, D C Lewis, C P O'Brien, H D Kleber
Journal: JAMA (2000)

The effects of drug dependence on social systems has helped shape the generally held view that drug dependence is primarily a social problem, not a health problem. In turn, medical approaches to prevention and treatment are lacking. We examined evidence that drug (including alcohol) dependence is a chronic medical illness. A literature review compared the diagnoses, heritability, etiology (genetic and environmental factors), pathophysiology, and response to treatments (adherence and relapse) of drug dependence vs type 2 diabetes mellitus, hypertension, and asthma. Genetic heritability, personal choice, and environmental factors are comparably involved in the etiology and course of all of these disorders. Drug dependence produces significant and lasting changes in brain chemistry and function. Effective medications are available for treating nicotine, alcohol, and opiate dependence but not stimulant or marijuana dependence. Medication adherence and relapse rates are similar across these illnesses. Drug dependence generally has been treated as if it were an acute illness. Review results suggest that long-term care strategies of medication management and continued monitoring produce lasting benefits. Drug dependence should be insured, treated, and evaluated like other chronic illnesses.
The Role of the PGE2–Aromatase Pathway in Obesity-Associated Breast Inflammation
Authors: Dingzhi Wang, Raymond N. DuBois
Journal: Cancer Discovery (2012)

Abstract Subbaramaiah and colleagues present the first evidence indicating that a cyclooxygenase-2–prostaglandin E2–aromatase pathway promotes obesity-associated inflammation in women's breast tissues. Their findings shed new light on obesity-associated inflammation in general and provide a rationale for developing effective chemopreventive and therapeutic strategies targeting this pathway for obese women with breast inflammation and patients with hormone-dependent breast cancer. Cancer Discov; 2(4); 308–10. ©2012 AACR. Commentary on Subbaramaiah et al., p. 356.
The Bactericidal Activity of Moxifloxacin in Patients with Pulmonary Tuberculosis
Authors: Roly D. Gosling, Leonard O. Uiso, Noel E. Sam, Emily Bongard, Esther G. Kanduma, Mramba Nyindo, Richard W. Morris, Stephen H. Gillespie
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Patients in whom acid-fast bacilli smear-positive pulmonary tuberculosis was newly diagnosed were randomized to receive 400 mg moxifloxacin, 300 mg isonaizid, or 600 mg rifampin daily for 5 days. Sixteen-hour overnight sputa collections were made for the 2 days before and for 5 days of monotherapy. Bactericidal activity was estimated by the time taken to kill 50% of viable bacilli (vt50) and the fall in sputum viable count during the first 2 days designated as the early bactericidal activity (EBA). The mean vt50 of moxifloxacin was 0.88 days (95% confidence interval [CI], 0.43-1.33 days) and the mean EBA was 0.53 (95% CI 0.28-0.79). For the isoniazid group, the mean vt50 was 0.46 days (95% CI, 0.31-0.61 days) and the mean EBA was 0.77 (95% CI, 0.54-1.00). For rifampin, the mean vt50 was 0.71 days (95% CI, 0.48-0.95 days) and the mean EBA was 0.28 (95% CI, 0.15-0.41). Using the EBA method, isoniazid was significantly more active than rifampin (p < 0.01) but not moxifloxacin. Using the vt50 method, isoniazid was more active than both rifampin and moxifloxacin (p = 0.03). Moxifloxacin has an activity similar to rifampin in human subjects with pulmonary tuberculosis, suggesting that it should undergo further assessment as part of a short course regimen for the treatment of drug-susceptible tuberculosis.
Scrum injury risk in English professional rugby union
Authors: Aileen E Taylor, Simon Kemp, Grant Trewartha, Keith A Stokes
Journal: British Journal of Sports Medicine (2014)

Objective To assess and evaluate the injury risk associated with the scrum in English professional rugby union in the 2011–2012 season. Design Prospective, cohort. Participants Players at English Premiership rugby union clubs. Outcome measures Frequency of team scrum-events per match; incidence (injuries per 1000 player-hours; propensity (injuries/1000 events); risk (days absence per 1000 player-hours and days absence per 1000 events). Results 31% of scrums in competitive matches resulted in collapse. Injury incidence associated with collapsed scrum-events (incidence: 8.6 injuries/1000 scrum-events) was significantly higher than those scrums that did not collapse (incidence: 4.1/1000 scrum-events). Conclusions The injury risk associated with collapsed scrum supports the continued focus on reducing scrum collapse through changes in, and strict application of, the laws surrounding the scrum.
Dynamic Interactions of Macrophages with T Cells during Antigen Presentation
Authors: David M. Underhill, Michael Bassetti, Alexander Rudensky, Alan Aderem
Journal: The Journal of Experimental Medicine (1999)

We have established a method for real-time video analysis of the interaction of antigen-presenting cells (APCs) with T cells. Green fluorescent protein expression controlled by a nuclear factor of activated T cells (NFAT)-responsive promoter permits the visualization of productive antigen presentation in single T cells. The readout is rapid (within 2 h) and semiquantitative and allows analysis by video microscopy and flow cytometry. Using this approach, we demonstrate that macrophages have the capacity to simultaneously activate multiple T cells. In addition, the interaction of T cells with macrophages is extraordinarily dynamic: after initial stable contact, the T cells migrate continuously on the surface of the macrophage and from APC to APC during productive antigen presentation. Thus, T cells sum up signals from multiple interactions with macrophages during stimulation.
Decongestant-Induced Blepharospasm and Orofacial Dystonia
Authors: J. Michael Powers
Journal: JAMA (1982)

DECONGESTANTS are ubiquitous drugs, frequently obtained without a prescription and often used habitually. Dystonic reactions may rarely result from long-term use of decongestants. Self-medication may go unrecognized, obscuring the diagnosis. A 34-year-old man had blepharospasm and orofacial dystonia. Habitual use of a decongestant spray was eventually acknowledged, and the dyskinesia decreased substantially when use was discontinued. Persons with blepharospasm or orofacial dystonia should be questioned specifically about use of decongestants. <h3>Report of a Case</h3> A 34-year-old man complained of eye irritation and spasms of eye closure of three months' duration, which he attributed to new soft contact lenses. Ocular irritation, tearing, photophobia, and blepharospasm gradually increased in severity until he was unable to read or work. Discontinuation of use of the contact lenses and therapy with a variety of topical medications did not alter the symptoms. Spasms were increased by bright light, reading, and stress. They persisted throughout the day,
Sports medicine, confidentiality and the press
Authors: Bill Ribbans, Hannah Ribbans, Craig Nightingale, Michael McNamee
Journal: British Journal of Sports Medicine (2012)

<h3>Objective</h3> To analyse athletes9 medical information disclosed by English newspapers. <h3>Methods</h3> Ten daily national newspapers, nine Sunday newspapers and one local newspaper were studied during March 2010 for media releases relating to the medical conditions of athletes. <h3>Results</h3> Three hundred and thirty-three newspapers were reviewed revealing 5640 specific bulletins regarding athletes9 health. Daily national newspapers averaged 18.72 daily bulletins, Sunday newspapers 11.86 and one local newspaper reviewed 6.07. The frequency with which various sports had their athletes9 medical details published was analysed. Football accounted for 83.78%. The information source in 77.32% of articles is not clearly stated. The patient was only responsible in 6.10% of cases, where the source of attribution is clear. <h3>Conclusions</h3> English newspapers are replete with athletes9 medical details, with football dominant. A significant risk to clinicians9 professional status exists if they collude to release the un-consented confidential medical information to those with no direct involvement in athletes9 medical care. Athletes9 education as to their rights as patients and to sports medicine professionals as to their obligations are urgently required.
Alterations in Airway Wall Properties in Infants with a History of Wheezing Disorders
Authors: URS FREY, KATRI MAKKONEN, TERRY WELLMAN, CAROLINE BEARDSMORE, MICHAEL SILVERMAN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Airway diameter and airway wall mechanics (compliance) are important determinants of flow limitation and wheezing. We have previously used the high-speed interrupter technique (HIT) to measure input impedance (Zin) in infants at frequencies up to 900 Hz, including antiresonance phenomena, which are known to be related to wave propagation velocity, and have shown that the frequency at which the first antiresonance occurs (far,1) is a function of airway wall compliance. We aimed to determine whether far,1 (and thus airway wall compliance) was different in infants with a history of wheezing disorders. We compared 23 asymptomatic infants (aged 36 to 81 wk) with a history of wheezing with an age-matched group of 19 healthy control infants. We found that far,1 was significantly lower in infants with wheezing disorders than in the control group (p < 0.005), implying differences in airway wall compliance, even when they were clinically asymptomatic. Developmental differences in airway wall mechanics may be important in the pathogenesis of wheezing disorders or, alternatively, alterations in airway wall mechanics might be a consequence of postinflammatory remodeling.
Safety of short-term administration of celecoxib in decompensated cirrhosis
Authors: Mical S. Campbell, George A. Makar
Journal: Hepatology (2005)

We read with interest the paper by Claria et al.1 Twenty-eight patients with cirrhosis, ascites, and high plasma renin activity were randomized to receive a short course of placebo, naproxen, or celecoxib. Renal function, renal response to furosemide, plasma norepinephrine levels and renin activity, and urinary prostaglandin metabolites before and after treatment were compared. This elegant study was performed under tightly controlled conditions, as patients were hospitalized, diuretics were withheld, and a salt-restricted diet was administered. The authors concluded that short-term celecoxib administration did not lead to renal impairment in patients with decompensated cirrhosis. We are concerned about the interpretation of the results. Drug safety cannot be assessed by comparing average values before and after an intervention. Some patients may experience declining renal function because of drug exposure, whereas other patients' renal function may improve as a result of care provided during study hospitalization, continued withholding of diuretics, or other reasons. Reporting only average renal function before and after treatment may mask effects of drug toxicity in some patients. In small studies, such as the current one, lack of power decreases the likelihood of detecting a significant change in average renal function, even if the drug were significantly toxic to some. This problem is highlighted by the only other study examining the effect of renal toxicity from celecoxib in patients with cirrhosis and ascites.2 Guevara et al. showed that mean glomerular filtration rate did not significantly change before and after treatment. However, 4 out of 9 patients showed a decrease greater than 20% in glomerular filtration rate after celecoxib. We are also concerned about exclusion from analysis of the 7 patients with hepatorenal syndrome who completed the study. All seven had serum creatinine <1.5 mg/dL, and were identified as having hepatorenal syndrome only after technetium 99m-diethylenetriaminepentaacetic acid clearance was performed, a test not commonly available in clinical practice. These patients had an increased likelihood of experiencing adverse effects from celecoxib, and they would not have been distinguished in clinical practice from the rest of the study cohort. In conclusion, this is an elegant physiological study on the renal effects of short-term celecoxib and naproxen administration in patients with cirrhosis, ascites, and preserved renal function. However, without patient-level data, we cannot accept the conclusion that short-term celecoxib is safe for patients with decompensated cirrhosis. Mical S. Campbell*, George A. Makar*, * Division of Gastroenterology, University of Pennsylvania Health System, Philadelphia, PA.
Epitope Location in the <i>Cryptococcus neoformans</i> Capsule Is a Determinant of Antibody Efficacy
Authors: Gabriel Nussbaum, Wendy Cleare, Arturo Casadevall, Matthew D. Scharff, Philippe Valadon
Journal: The Journal of Experimental Medicine (1997)

Monoclonal antibodies (mAbs) to the polysaccharide capsule of Cryptococcus neoformans can prolong survival in mice. However, the properties of antibodies that mediate protection are not fully understood. The IgM mAbs 12A1 and 13F1 originated from the same B cell and differ only by somatic mutations in their variable regions; yet mAb 12A1 protects against serotype D infection, while mAb 13F1 does not. Phage peptide display libraries were used to analyze the fine specificity of these two mAbs. The selection of distinct peptide motifs from identical libraries confirmed that mAbs 12A1 and 13F1 bound to two distinct epitopes. Immunofluorescence and immunoelectron microscopy studies revealed differences in antibody localization within the capsule of serotype D strain; mAb 12A1 bound to the outer rim of the capsule resulting in an annular pattern, whereas mAb 13F1 bound throughout the capsule and had a punctate appearance. The difference in the binding pattern of mAb 12A1 and 13F1 was not observed on serotype A organisms, where both mAbs bound to the capsule with an annular fluorescence pattern. The fluorescence pattern of binding correlated with protective efficacy; mAb 13F1 prolonged survival of mice infected with the J11 serotype A strain (annular fluorescence), but not serotype D strains (punctate pattern). Annular binding, but not punctate binding, was associated with increased opsonic efficacy for phagocytosis of C. neoformans by J774.16 macrophage-like cells. The correlation between capsular binding pattern, opsonic activity, and ability to prolong survival suggests that the efficacy of anticryptococcal antibodies is dependent upon where they bind in the polysaccharide capsule.
Detection of Ovarian Cancer Cells: Comparison of a Telomerase Assay and Cytologic Examination
Authors: Bridgette D. Duggan, Lynda D. Roman, Laila I. Muderspach, Minghong Wan, Erika Delgadillo, Wei-Zhi Li, Sue Ellen Martin, Louis Dubeau, Mimi C. Yu
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Telomerase is an enzyme essential for the normal replication of chromosomes. Telomerase activity is absent in most somatic cells in adults, but it is usually expressed in cancer cells, including ovarian carcinoma cells. Our principal goal was to compare the sensitivity of a telomerase assay, i.e., the telomeric repeat amplification protocol (TRAP) assay, with that of cytologic examination in detecting cancer cells in the peritoneal cavity of patients with ovarian carcinoma. Methods: TRAP assays and cytologic examinations were performed on peritoneal washings and ascitic fluids from 42 patients with active ovarian carcinoma. Control specimens included washings from 29 patients with benign ovarian diseases and ascitic fluids from 14 patients with liver failure. We also evaluated the stability of telomerase in ascitic fluids left unprocessed at room temperature as well as the ability of the TRAP assay to detect cancer cells in mixtures containing large numbers of normal cells. Results: Specimens from 37 (88%) of the 42 patients with ovarian carcinoma tested positive for telomerase. Cytologic examination detected cancer cells in only 27 of the telomerase- positive specimens (i.e., in specimens from 64% of the 42 patients). This difference of 24% (95% confidence interval = 17%–30%) in sensitivity between the two tests was statistically significant (two-sided P = .002). Specimens from five of the patients with ovarian carcinoma were cytologically negative and telomerase negative. All 43 control specimens were cytologically negative, but the TRAP assay detected telomerase in two of them. Telomerase activity was detected in unprocessed samples left at room temperature for 5 days and in mixtures containing a small number of cancer cells and a 2000- to 10 000-fold excess of normal cells. Conclusions: Assaying for telomerase is more sensitive than cytologic examination in detecting cancer cells in the peritoneal cavity of patients with ovarian carcinoma.
Pyruvate Kinase M2: Multiple Faces for Conferring Benefits on Cancer Cells
Authors: Mayumi Tamada, Makoto Suematsu, Hideyuki Saya
Journal: Clinical Cancer Research (2012)

The M2 splice isoform of pyruvate kinase (PKM2), an enzyme that catalyzes the later step of glycolysis, is a key regulator of aerobic glycolysis (known as the Warburg effect) in cancer cells. Expression and low enzymatic activity of PKM2 confer on cancer cells the glycolytic phenotype, which promotes rapid energy production and flow of glycolytic intermediates into collateral pathways to synthesize nucleic acids, amino acids, and lipids without the accumulation of reactive oxygen species. PKM2 enzymatic activity has also been shown to be negatively regulated by the interaction with CD44 adhesion molecule, which is a cell surface marker for cancer stem cells. In addition to the glycolytic functions, nonglycolytic functions of PKM2 in cancer cells are of particular interest. PKM2 is induced translocation into the nucleus, where it activates transcription of various genes by interacting with and phosphorylating specific nuclear proteins, endowing cancer cells with a survival and growth advantage. Therefore, inhibitors and activators of PKM2 are well underway to evaluate their anticancer effects and suitability for use as novel therapeutic strategies.
JKTBP (hnRNPDL) is a novel toll7/9 dependent target in humans and animal models of inflammatory rheumatic diseases
Authors: B Marklein, Z Konthur, A Cope, M Shlomchik, G Burmester, K Skriner
Journal: Annals of the Rheumatic Diseases (2010)

Autoimmune diseases are characterised and regularly diagnosed by the presence of autoantibodies to heterogeneous nuclear RNP (hnRNP) autoantigens. These proteins represent a group of autoantigens which are targeted by autoantibodies from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and mixed connective tissue disease. The authors investigated a new member of the hnRNP family targeted by autoantibodies and tested a combination of hnRNPs in humans and …
Colon Cancer Survival Rates With the New American Joint Committee on Cancer Sixth Edition Staging
Authors: J. B. O'Connell, M. A. Maggard, C. Y. Ko
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: The recently revised American Joint Committee on Cancer (AJCC) sixth edition cancer staging system increased the stratification within colon cancer stages II and III defined by the AJCC fifth edition system. Using nationally representative Surveillance, Epidemiology, and End Results (SEER) data, we compared survival rates associated with colon cancer stages defined according to both AJCC systems. Methods: Using SEER data (from January 1, 1991, through December 31, 2000), we identified 119 363 patients with colon adenocarcinoma and included all patients in two analyses by stages defined by AJCC fifth and sixth edition systems. Tumors were stratified by SEER’s “extent of disease” and “number of positive [lymph] nodes” coding schemes. Kaplan–Meier analyses were used to compare overall and stage-specific 5-year survival. All statistical tests were two-sided. Results: Overall 5-year survival was 65.2%. According to stages defined by the AJCC fifth edition system, 5-year stage-specific survivals were 93.2% for stage I, 82.5% for stage II, 59.5% for stage III, and 8.1% for stage IV. According to stages defined by the AJCC sixth edition system, 5-year stage-specific survivals were 93.2% for stage I, 84.7% for stage IIa, 72.2% for stage IIb, 83.4% for stage IIIa, 64.1% for stage IIIb, 44.3% for stage IIIc, and 8.1% for stage IV. Under the sixth edition system, 5-year survival was statistically significantly better for patients with stage IIIa colon cancer (83.4%) than for patients with stage IIb disease (72.2%) (P<.001). Conclusions: The AJCC sixth edition system for colon cancer stratifies survival more distinctly than the fifth edition system by providing more substages. The association of stage IIIa colon cancer with statistically significantly better survival than stage IIb in the new system may reflect current clinical practice, in which stage III patients receive chemotherapy but stage II patients generally do not.