tbuckley/cabot-search huggingface dataset:
The glycosyl phosphatidylinositol-linked FcγRIII(PMN) mediates transmembrane signaling events distinct from FcγRII
Authors: RP Kimberly, JW Ahlstrom, ME Click, JC Edberg
Journal: The Journal of Experimental Medicine (1990)

To investigate the ability of FcγRIII(PMN), the GPI-anchored isoform of FcγRIII (CD16) in polymorphonuclear leukocytes (PMN), to mediate transmembrane signaling events, we measured changes in membrane potential with DiOC(5) and in intracellular calcium with indo-1. FcγR were ligated by anti-FcγRIII mAb 3G8 (IgG and Fab), anti-FcγRII mAb IV.3 (IgG and Fab), and human IgG aggregates. Cell bound mAbs were also crosslinked by goat F(ab')(2) anti-mouse IgG. 3G8 IgG elicited a rapid change in [Ca(2+)](i), which was unaffected by EGTA, Vibrio cholerae toxin (CT), or Bordetella pertussis toxin (PT), and was abolished by BAPTA . Univalent receptor binding with 3G8 Fab gave no response but crosslinking with F(aV)2 GAM gave a rapid [Ca2,](i) response. Neither IV.3 Fab, IV.3 IgG, nor crosslinking of IV.3 Fab elicited a calcium signal. PI-PLC-treated PMN with the density of FcγRIII(PMN) reduced to that of FcγRII showed an unattenuated change in [Ca(2+)](i), with a 3G8 stimulus. The effects of IgG aggregates paralleled those of 3G8 mAb. These data indicate that multivalent ligation of FcγRIII(PMN) initiates an increase in [Ca(2+)];, derived from intracellular stores, that is distinct from both the FMLP- and FcγRII-induced responses. Ligand-dependent interaction with FcγRII is not required. Since FcγRIII(PMN) can internalize the FcγRIII-specific probe Con A-opsonized E and lyse anti-FcγRIII heteroantibody-opsonized chick E, this GPI-anchored molecule mediates both signal transduction and integrated cell responses.
Is there an ideal prognostic model for hepatocellular carcinoma?
Authors: Huo Ti, Huang Yh, Lee Sd, Wu Jc
Journal: Gut (2005)

We read with interest the paper by Grieco et al ( Gut 2005; 54 :411–8). It is an elegant study that retrospectively compared the prognostic power among the Okuda, Cancer of the Liver Italian Program (CLIP), and Barcelona Clinic Liver Cancer (BCLC) staging systems for patients with hepatocellular carcinoma (HCC). The authors concluded that BCLC and CLIP were good models for non-surgical HCC, and BCLC had better predictive value compared with the others for patients with early stage HCC. As the CLIP system has been prospectively validated and proposed as the primary staging system for HCC,1 it would be interesting to examine how these commonly …
Starting to develop self-help for social anxiety associated with vitiligo: using clinical significance to measure the potential effectiveness of enhanced psychological self-help
Authors: R. Shah, J. Hunt, T.L. Webb, A.R. Thompson
Journal: British Journal of Dermatology (2014)

Vitiligo can be associated with high levels of distress, yet there are currently no self-help interventions available.To describe the initial development of a psychosocial self-help intervention designed to reduce social anxiety associated with vitiligo. Also to examine whether including a planning exercise, aimed at increasing use of the intervention (termed implementation intentions), has the potential to achieve a clinically significant reduction in distress.Participants (n = 75) were randomized to one of three groups: cognitive behavioural self-help (CBSH), CBSH augmented with implementation intentions (CBSH+), or no intervention. Participants were assessed at baseline and after 8 weeks on measures of social anxiety, anxiety and depression, and appearance-related concern. The two intervention groups also completed a questionnaire evaluating their use of, and satisfaction with, the intervention.High levels of social anxiety and concern over appearance were reported. Twenty-four per cent of participants in the CBSH+ group experienced clinically significant change on the measure of social anxiety compared with 8% in the CBSH group and 0% in the control group. In addition, 58% of the control group deteriorated during the study period. There were no significant differences between the conditions on the other outcome measures. Participants reported that the self-help leaflets were helpful.The findings demonstrate that augmented CBSH provides a relatively simple and accessible intervention that can result in a clinically significant reduction in social anxiety. The augmented intervention has potential and might be further developed and evaluated in subsequent trials.
Different surgical techniques to reduce post-operative adhesion formation: a systematic review and meta-analysis
Authors: R.P.G. ten Broek, N. Kok- Krant, E.A. Bakkum, R.P. Bleichrodt, H. van Goor
Journal: Human Reproduction Update (2012)

Adhesion formation is the most common complication following peritoneal surgery and the leading cause of small bowel obstruction, acquired infertility and inadvertent organ injury at reoperation. Using a ‘good surgical technique’ is advocated as a first step in preventing adhesions. However, the evidence for different surgical techniques to reduce adhesion formation needs confirmation. Pubmed, Embase and CENTRAL were searched to identify randomized controlled trials that investigated the effect of various aspects of surgical technique on adhesion-related outcomes. Clinical outcomes and incidence of adhesions were the primary endpoints. Identification of papers and data extraction were performed by two independent researchers. There were 28 papers with 27 studies included for a systematic review. Of these, 17 studies were eligible for meta-analysis and 11 for qualitative assessment only. None of the techniques that were compared significantly reduced the incidence of adhesive small bowel obstruction. In a small low-quality trial, the pregnancy rate increased after subserous fixation of suture knots. However, the incidence of adhesions was lower after laparoscopic compared with open surgery [relative risk (RR) 0.14; 95% confidence interval (CI): 0.03–0.61] and when the peritoneum was not closed (RR 0.36; 95% CI: 0.21–0.63). None of the specific techniques that were compared reduced the two main adhesion-related clinical outcomes, small bowel obstruction and infertility. The meta-analysis provides little evidence for the surgical principle that using less invasive techniques, introducing less foreign bodies or causing less ischaemia reduces the extent and severity of adhesions.
Deep brain stimulation in Parkinson’s disease
Authors: Raja Mehanna, Eugene C Lai
Journal: Translational Neurodegeneration (2013)

For the last 50 years, levodopa has been the cornerstone of Parkinson's disease management. However, a majority of patients develop motor complications a few years after therapy onset. Deep brain stimulation has been approved by the FDA as an adjunctive treatment in Parkinson disease, especially aimed at controlling these complications. However, the exact mechanism of action of deep brain stimulation, the best nucleus to target as well as the best timing for surgery are still debatable. We here provide an in-depth and critical review of the current literature on this topic.
Phyllis Marjorie Mortimer, nee Spreadbury
Authors: A. Elliman
Journal: BMJ (2002)

Emergency Ward 10 was the Casualty or ER of its day. It was a huge hit, drawing in 16 million viewers a week and 24 million at its peak. Produced by Associated Television, Emergency Ward 10 , which was broadcast live in black and white, ran from 1957 to 1967, spawning a spin-off feature length film, a board game, and children's annuals. Phyllis was medical adviser and a writer for the series from 1960 to 1963. At Elstree studios, she worked closely with television writers and actors, much improving the accuracy of medicine and medical storylines. Emergency Ward 10 was a series of much integrity and public health value, and, effectively, the origin of all medical “soaps.” Phyllis maintained …
Identifying Eosinophilic Esophagitis through Evaluation of Plasma Biomarkers
Authors: J. Joh, J. Huang, T. Nguyen, N. Vishwaanath, A. Patel, J. Fuentebella, V. Saper, J. Kerner, K. Cox, W. Berquist
Journal: Journal of Allergy and Clinical Immunology (2009)
Treatment of Rheumatoid Arthritis by a Sanatorium Regime: The Black Notley Experiment
Authors: R. M. Mason, W. G. Wenley
Journal: Annals of the Rheumatic Diseases (1959)

In 1954, as a direct result of the recommendations of the Royal College of Physicians Committee on Chronic Rheumatic Diseases (1951), the North-East Metropolitan Regional Hospital Board initiated a regional scheme for the treatment of this group of diseases.This involved a Central Regional Rheumatism Centre at the London Hospital with peri- pheral centres elsewhere in the Region.One of
Effect of acute ammonia intoxication on cerebral metabolism in rats with portacaval shunts.
Authors: B Hindfelt, F Plum, T E Duffy
Journal: Journal of Clinical Investigation (1977)

Rats were made chronically hyperammonemic by portal-systemic shunting and, 8 wk later, were subjected to acute ammonia intoxication by the intraperitoneal injection of 5.2 mmol/kg of ammonium acetate. In free-ranging animals, ammonia treatment induced a brief period of precoma (10-15 min) that progressed into deep, anesthetic coma lasting for several hours and was associated with a high mortality. In paralyzed, artificially ventilated animals that were lightly anesthetized with nitrous oxide, acute ammonia intoxication caused major disturbances of cerebral carbohydrate, amino acid, and energy metabolism that correlated in time with the change in functional state. At 10 min after injection (precoma), the concentrations of most glycolytic intermediates were increased, as was the lactate/pyruvate ratio. Citrate declined, despite a twofold rise in pyruvate, suggesting that the conversion of pyruvate to citrate had been impaired. Concentrations of phosphocreatine, and of the putative neurotransmitters, glutamate and aspartate, declined during precoma, but the concentrations of the adenine nucleotides in the cerebral hemispheres, cerebellum, and brain stem remained within normal limits. At 60 min after injection (coma), ATP declined in all regions of brain; the reduction in total high-energy phosphates was most notable in the brain stem. The findings indicate that cerebral dysfunction in chronic, relapsing ammonia intoxication is not due to primary energy failure. Rather, it is suggested that ammonia-induced depletion of glutamic and aspartic acids, and inhibition of the malate-asparate hydrogen shuttle are the dominant neurochemical lesions.
Validated or Not Validated? That Is the Question
Authors: J. M. S. Bartlett, K. I. Pritchard, M. Spears
Journal: JNCI Journal of the National Cancer Institute (2014)

deviation estimates were … acceptable as they are <5% of the … reportable range” (page 24 of Supplementary Data). Although this suggests the assay has potential for technical validation, data on assay reproducibility, particularly with respect to diagnosis of patients with “borderline” results is not presented, making it difficult to be confident that the assay robustly stratifies patients, either at central or peripheral hospital laboratories. Experience with single markers [eg, HER2 (6,7)] suggests these are critical components of technical validation, and in our opinion this is as important for multiparameter tests as it is for “simple” single marker assays. Accuracy is more challenging to demonstrate, particularly when a broad phenotypic assay is applied, but evidence shows this challenge can be addressed with appropriately designed studies (8–10). EGAPP (5) guidelines state that “convincing” evidence for analytical validity requires “studies that provide confident estimates of analytic sensitivity and specificity” using representative samples, particularly addressing challenging cases. Such data may be available, and, if so, should be published to demonstrate technical validity of the DNA-damage response deficiency (DDRD) assay. The authors present several analyses supporting utility of the DDRD signature to predict outcome after chemotherapy in both neoadjuvant and adjuvant settings, They show convincingly that the DDRD signature is associated with either pathological complete response or relapse after chemotherapy but not in patients who did not receive chemotherapy. They used publically available and institutional cohorts, including three neoadjuvant cohorts (n = 51, 66, and 86 patients, respectively) treated with fluorouracil, epirubicin, and cyclophosphamide (FEC)/fluorouracil, doxorubicin, and cyclophosphamide (FAC), and four adjuvant cohorts, of which three were untreated and one (n = 191 patients) was treated “historically” with FAC. The data support a role for the DDRD signature in prediction of residual risk after chemotherapy, but do they clinically validate the formalin-fixed paraffin-embedded DDRD assay for anthracycline/cyclophosphamide chemotherapy response as claimed? We argue that, although these data are interesting and part of a pathway leading to clinical validation, they rep
Activation of Tumor-Specific CD8+ T Cells after Intratumoral Ad5-TRAIL/CpG Oligodeoxynucleotide Combination Therapy
Authors: Rebecca L. VanOosten, Thomas S. Griffith
Journal: Cancer Research (2007)

Abstract CD8+ T-cell activation via cross-presentation of antigens from apoptotic tumor cells is controversial. Dendritic cells capture naturally shed tumor antigens and cross-present them to CD8+ T cells; unfortunately, the frequency of activated CD8+ T cells is often too low to mount an effective response against the tumor. By increasing the amount of antigen for presentation, a larger T-cell response can be theoretically elicited. We used a recombinant adenovirus encoding full-length murine tumor necrosis factor–related apoptosis-inducing ligand (Ad5-mTRAIL) to induce tumor cell apoptosis, and when given intratumorally to mice bearing experimental renal cell carcinoma (Renca) tumors, Ad5-mTRAIL minimally prolonged survival and induced a low level of CTL activity. To enhance dendritic cell efficiency, an immunostimulatory CpG oligodeoxynucleotide (CpG ODN) was combined with Ad5-mTRAIL. This combination therapy significantly augmented in vivo antigen-specific T-cell proliferation and CTL activity, as well as prolonged survival of Renca tumor-bearing mice. Interestingly, depletion of CD4+ or CD25+ cells before therapy further enhanced survival and in vivo CTL activity. In addition, tumor-free mice depleted of CD4+ cells were also able to reject a subsequent challenge of Renca cells, but not MHC-matched RM-11 prostate tumor cells, demonstrating the existence of immunologic memory. These results collectively show that local treatment with Ad5-mTRAIL and CpG ODN can augment tumor antigen cross-presentation resulting in T-cell proliferation, enhanced CTL activity, and increased animal survival. [Cancer Res 2007;67(24):11980–90]
Issues in the Registration of Clinical Trials
Authors: Deborah A. Zarin, Nicholas C. Ide, Tony Tse, William R. Harlan, Joyce C. West, Donald A. B. Lindberg
Journal: JAMA (2007)

Public concerns about the perils associated with incomplete or delayed reporting of results from clinical trials has heightened interest in trial registries and results databases. Here we review the current status of trial registration efforts and the challenges in developing a comprehensive system of trial registration and reporting of results. ClinicalTrials.gov, the largest trial registry with 36 249 trials from approximately 140 countries, has procedures in place to help ensure that records are valid and informative. Key challenges include the need to minimize inadvertent duplicate registrations, to ensure that interventions have unambiguous names, and to have a search engine that identifies all trials that meet a user's specifications. Recent policy initiatives have called for the development of a database of trial results. Several issues confound the implementation of such a database, including the lack of an accepted format or process for providing summaries of trial results to the public and concerns about disseminating data in the absence of independent scientific review.
Papillary Neoplasms of the Bronchus of Low-grade Malignancy
Authors: J. F. Smith, D. Dexter
Journal: Thorax (1963)

In this paper we describe eight examples of papillary neoplasms of the bronchus in which atypical cytological features were present.In seven the lesion was localized and invasion was not pre- sent, in one extensive spread within the bronchial tree of a lobe had occurred but invasion into the lung parenchyma was doubtful.Lesions of this type receive little comment in the literature although they can be perplexing in diagnosis and management.Typical benign papillomas of the bronchus are also rare, and one is briefly described for comparison.CASE REPORTS CASE I This man was a physician, aged 50. a non- smoker except for occasional cigars.Although a mild diabetic, he had been in good health until June, 1959, when a febrile illness occurred.At this time a radio- graph of the chest showed a shadow in the right lower lobe which was thought to be a collapse in the posterior basal segment.At bronchoscopy on 4 July 1959 the larynx.trachea.
Improvement of Alveolar–Capillary Membrane Diffusing Capacity With Enalapril in Chronic Heart Failure and Counteracting Effect of Aspirin
Authors: Marco Guazzi, Giancarlo Marenzi, Marina Alimento, Mauro Contini, Piergiuseppe Agostoni
Journal: Circulation (1997)

Background KII ACE, the enzyme that converts angiotensin I and inactivates bradykinin, is highly concentrated in the lungs; its blockade reduces exposure to angiotensin II and enhances exposure to prostaglandins generated by local kinin hyperconcentration. Our hypothesis is that ACE inhibitors improve pulmonary function in chronic heart failure (CHF) by readjusting lung vessel tone and permeability or alveolar–capillary membrane diffusion. Methods and Results In 16 CHF patients and 16 normal volunteers or mild untreated hypertensives, pulmonary function and exercise tests with respiratory gas analysis were assessed on placebo, enalapril (10 mg BID), enalapril plus aspirin (325 mg/d), or aspirin, in random order and double blind, for 15 days each. In CHF, enalapril increased pulmonary carbon monoxide diffusion (DLCO), oxygen consumption (V̇ o 2 ), and exercise tolerance and reduced the ratio of dead space to tidal volume (V d /V t ) and the ventilatory equivalent for carbon dioxide production V̇ e /V̇ co 2 ). On enalapril, V̇ o 2 ( r =.80, P &lt;.0001) and V d /V t ( r =−.69, P =.003) changes from placebo correlated with those in DLCO. These effects were inhibited by aspirin and were absent in control subjects. In 8 additional patients, hydralazine–isosorbide dinitrate, as an alternative treatment for reducing pulmonary capillary wedge pressure (PCWP) and increasing exercise capacity, were more effective than enalapril for the PCWP but did not affect DLCO and V̇ e /V̇ co 2 ; amelioration in V̇ o 2 and V d /V t was unrelated to DLCO and was not modified by aspirin. Conclusions ACE inhibition improved pulmonary diffusion in CHF. Hydralazine–isosorbide dinitrate failed to provide this result. Counteraction by aspirin, a prostaglandin inhibitor, bespeaks prostaglandin participation while on enalapril that might readjust capillary permeability or alveolar–capillary membrane diffusion.
Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations
Authors: T. Kinno, K. Tsuta, K. Shiraishi, T. Mizukami, M. Suzuki, A. Yoshida, K. Suzuki, H. Asamura, K. Furuta, T. Kohno, R. Kushima
Journal: Annals of Oncology (2013)
Percutaneous Versus Surgical Revascularization in Patients With Ischemic Mitral Regurgitation
Authors: Duk-Hyun Kang, Byung Joo Sun, Dae-Hee Kim, Sung-Cheol Yun, Jong-Min Song, Suk Jung Choo, Cheol Hyun Chung, Jae-Kwan Song, Jae-Won Lee, Seong-Wook Park, Seung-Jung Park
Journal: Circulation (2011)

The proper way of revascularization remains controversial in patients with ischemic mitral regurgitation (IMR). We sought to compare the long-term results of percutaneous coronary intervention (PCI) and surgical revascularization in IMR.From 1996 to 2008, 185 consecutive patients (132 men; age, 63 ± 9 years) with significant IMR underwent PCI (PCI group) (n=66) or coronary artery bypass graft surgery (OP group) (n=119). In the OP group, 68 (57%) patients also underwent concomitant mitral annuloplasty. Significant IMR was defined as functional MR occurring >1 week after myocardial infarction with an effective regurgitant orifice area ≥ 0.2 cm(2). During a median follow-up of 54 months, there were 2 operative mortalities, 26 cardiac deaths, and 11 heart failure hospitalizations in the OP group and 22 cardiac deaths and 10 heart failure hospitalizations in the PCI group. The survival and cardiac mortality rates were not significantly different between the 2 groups, but event-free survival rates were significantly higher in the OP group. For the 45 propensity score-matched pairs, the risk of cardiac events was significantly lower in the OP group than in the PCI group (hazard ratio, 0.499; 95% CI, 0.251 to 0.990; P=0.043). Compared with patients who underwent coronary artery bypass graft surgery alone, event-free survival rates were significantly higher in those who underwent additional mitral annuloplasty.Compared with PCI, surgical revascularization is associated with an improved long-term event-free survival, and concomitant mitral annuloplasty should be considered in patients with significant IMR.
Endometrial stem/progenitor cells: the first 10 years
Authors: Caroline E. Gargett, Kjiana E. Schwab, James A. Deane
Journal: Human Reproduction Update (2015)

BACKGROUNDThe existence of stem/progenitor cells in the endometrium was postulated many years ago, but the first functional evidence was only published in 2004. The identification of rare epithelial and stromal populations of clonogenic cells in human endometrium has opened an active area of research on endometrial stem/progenitor cells in the subsequent 10 years.
Primary Sclerosing Cholangitis and Celiac Disease
Authors: J. Eileen Hay
Journal: Annals of Internal Medicine (1988)

The association of primary sclerosing cholangitis and celiac disease was observed in three patients, an association not previously reported. All three patients were men who presented with chronic cholestatic liver disease at ages 32, 46, and 62 years, respectively. In each patient, endoscopic retrograde cholangiography showed the typical findings of primary sclerosing cholangitis. Histologic features of liver biopsy were compatible with the diagnosis. Two patients had associated chronic ulcerative colitis. All three patients complained of frequent loose stools and weight loss; subsequent testing showed severe steatorrhea (204 to 323 mmol/d of fecal fat on a 100 g fat diet). Total villous atrophy was found in all three patients on histologic examination of the small bowel. Celiac disease was diagnosed at the time of presentation in two patients who had primary sclerosing cholangitis and was diagnosed three years after the onset of primary sclerosing cholangitis in the third patient. The celiac disease responded to a gluten-free diet in each patient whereas the primary sclerosing cholangitis was not affected by dietary treatment. The possibility of a chance association of primary sclerosing cholangitis and celiac disease cannot be accurately assessed but seems unlikely given the rarity of both diseases. The relationship between the two diseases remains unknown, although an immunologic connection is suspected. Celiac disease should be considered in the differential diagnosis of severe steatorrhea in patients with primary sclerosing cholangitis.