tbuckley/cabot-search huggingface dataset:
Signaling by Antibodies: Recent Progress
Authors: Stylianos Bournazos, Taia T. Wang, Rony Dahan, Jad Maamary, Jeffrey V. Ravetch
Journal: Annual Review of Immunology (2017)

IgG antibodies mediate a diversity of immune functions by coupling of antigen specificity through the Fab domain to signal transduction via Fc-Fc receptor interactions. Indeed, balanced IgG signaling through type I and type II Fc receptors is required for the control of proinflammatory, anti-inflammatory, and immunomodulatory processes. In this review, we discuss the mechanisms that govern IgG–Fc receptor interactions, highlighting the diversity of Fc receptor–mediated effector functions that regulate immunity and inflammation as well as determine susceptibility to infection and autoimmunity and responsiveness to antibody-based therapeutics and vaccines.
Oral Contraceptives and Congenital Limb-Reduction Defects
Authors: C R Kay
Journal: New England Journal of Medicine (1975)

The author belives that the congenital limb defects observed and reported in a previous paper by Janerich and others were due to a secondary relation and not causally related to the use of oral contraceptives. In 6 reported cases mothers of affected infants became pregnant while still using oral contraceptives in the prescribed manner. This is in conflict with the writer's experience. In 149 unplanned pregnancies he found that 95 (64%) were due to an incorrect use of the pill. Limb defect due to use of the pill in early pregnancy should also be caused by instance of improver use of the pill with resulting pregnancy. This has not been observed. Reduction in the pills' expected antifertility effect because of the mothers' unusually fertile condition was considered the cause of the limb defects. In the writer's opinion a more likely explanation is that the action of the oral contraceptives in these cases has been inhibited by the concurrent use of their drugs. Suspicion of teratogenicity must therefore be associated with the other drugs.
Incidental recognition of left subclavian vein obstruction on renal scintigraphy.
Authors: MIJIN YUN, CHUN KIM, BORYS KRYNYCKYI, JOSEF MACHAC
Journal: Clinical Nuclear Medicine (2001)

In a renal transplant recipient with persistently poor graft function, the flow phase of a renal scan incidentally revealed multiple venous collaterals with focally increased vascular activity near the left lobe of the liver (quadrate lobe). This was initially assumed to represent superior vena cava (SVC) obstruction. A renal biopsy was contemplated to exclude acute rejection because of a nondiagnostic flow phase (loss of a bolus effect). However, because the possibility of venous obstruction at the level of the subclavian and/or brachiocephalic veins (without involving the SVC) also existed, another renal scan was performed, with injection of radiotracer into the contralateral arm. This showed a patent SVC and reasonably preserved renal perfusion consistent with acute tubular necrosis. Subsequently, left subclavian vein obstruction was identified. The graft function improved with conservative management for acute tubular necrosis. These findings illustrate the danger of considering only SVC obstruction when collateral flow patterns and focal hot spots in the liver are present.
Platelet Function
Authors: Aaron J. Marcus
Journal: New England Journal of Medicine (1969)

Platelet MetabolismIn common with other cells, platelets require a constant supply of ATP for their metabolic activities.1,40 The principal energy source is glucose, which can be metabolized aerobically or anaerobically.1,40, 146 Enzymes of the glycolytic pathway are more active than those of the Krebs cycle, since far more glucose is metabolized to lactate and pyruvate than to carbon dioxide and water. However, oxidative phosphorylation yields 19 times more ATP from each mole of glucose than glycolysis does.1,40 These biochemical findings may be roughly correlated with morphologic observations of the platelet by electron microscopy. Platelet mitochondria are smaller and have fewer . . .
Experience with cetuximab plus paclitaxel/carboplatinum in primary platinum-resistant recurrent head and neck cancer
Authors: J. Buentzel, A. de Vries, O. Micke
Journal: Journal of Clinical Oncology (2007)

6077 Background: In patients with platinum-resistant recurrent head and neck cancer the Anti-EGF-receptor antibody cetuximab could be used as a treatment option. Little is known about results of this therapeutic option. The objective of this study was to evaluate therapeutic benefit of this indication. Methods: 23 patients with histological confirmed recurrent head and neck cancer (18 male, 3 female, median age was 57 years) were included in this exploratory study. All recurrences had occurred after chemotherapy with platinum- derivates. 19 patients received radiation therapy during primary treatment. No surgical or radiotherapeutic option in recurrent disease was possible. Two patients were diagnosed with lung metastasis. The 2 nd -line therapy consisted of carboplatinum (200 mg/m 2 ) + paclitaxel (200 mg/m 2 ) every three weeks (week 1, 4, and 7) and additionally cetuximab, which was given with 400 mg/m 2 as loading dose in week 1 and 250 mg/m 2 in week 2–6. Results: A significant tumor response was observed in 13/23 patients (56%). 7 partial, 5 minor and one complete remission were registered. The median survival time was 8 month (range 3–10), 4 patients are still alive. Median time to progression was 5 month (range 2–8). Side effects were rash (16/22), fever (9/22) and typical chemotherapy induced toxicities as neuropathy (7/22) and cytopenia (4/22). All side effects were moderate and easy to handle. Conclusions: The described combined chemoimmuntherapy with cetuximab and paclitaxel + carboplatinum seems to offer new strategies in 2 nd and 3 rd line chemotherapy for patients with platinum-resistant head and neck cancer, potentially overcoming primary platinum resistance. No significant financial relationships to disclose.
Abstract P4-02-09: Can MRI be used to determine pathological complete response following neo-adjuvant chemotherapy for breast cancer?
Authors: N Sharma, R Dave, R Millican-slater, D Dodwell, K Horgan
Journal: Cancer Research (2016)

Abstract Intro Neo-adjuvant chemotherapy (NACT) is increasingly offered to patients with breast cancer, and it understood that patients with pathological complete response (PCR) have improved survival. It has been suggested that patients with radiological complete response may be spared surgery. We aimed to determine whether MRI findings can predict PCR following NACT. Methods This was a retrospective analysis of a prospectively maintained database. Most patients had NACT with 6 cycles of EC/DC+/-Traztuzumab and response was monitored using MRI. For univariate analysis χ2 and Fisher's exact test was used for categorical data. Log rank test by Kaplan Meier method was used for survival analysis. Results 310 patients had NACT from December 2007 to December 2014. Baseline MRI prior to embarking on NACT was achieved in 251 patients. MRI concorded with size on mammography/USS in the majority of cases (83%) and upgraded the overall size of the lesion in 16% (50% of unifocal lesions on USS upgraded to multifocal). In the 247 patients who had baseline MRI, a radiological response seen on the 2nd MRI (early responders, n=138), was predictive of eventual PCR (p=0.000, sensitivity = 77%). Patients with Her2+ve non-luminal (65%), triple negative (TNBC) (64%) and Luminal B Her2-ve (65%) tumours were more likely to be early responders on MRI. The non-early responders with Her2+ve tumours all had late radiological response, however, the TNBC tumours had low rates of late radiological response. Complete radiological response on the final MRI correlated strongly with PCR; p=0.000, specificity=98%. Tumour vascularity correlated positively and significantly with PCR. There was no difference in survival between those with early and late radiological response (median survival 66.2 months and 66.9 months), but those with no radiological response had significantly poorer survival 53.2 months, p=0.012). Conclusion Response on MRI is predictive of PCR, particularly within the non-luminal Her2+ve and TNBC molecular subtypes. Early response has high sensitivity, and complete response on final MRI has high specificity. Further work on larger data-sets is required before we confidently spare patient from surgery in the event of complete response on MRI. Citation Format: Sharma N, Dave R, Millican-slater R, Dodwell D, Horgan K. Can MRI be used to determine pathological complete response following neo-adjuvant chemotherapy for breast cancer?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-02-09.
Systemic Reaction to the Anti–T-Cell Monoclonal Antibody OKT3 in Relation to Serum Levels of Tumor Necrosis Factor and Interferon-α
Authors: L Chatenoud, C Ferran, A Reuter, C Legendre, Y Gevaert, H Kreis, P Franchimont, J F Bach
Journal: New England Journal of Medicine (1989)
Abstract A41: A single let-7 microRNA bypasses LIN28-mediated repression
Authors: Robinson Triboulet, Mehdi Pirouz, Richard I. Gregory
Journal: Cancer Research (2016)

Abstract The let-7 miRNA family members are small non-coding RNAs that function as tumor suppressors and are frequently down-regulated in many different types of cancers upon reactivation of LIN28 oncogenes. Mammalian genomes contain twelve let-7 isoforms that suppress expression of a common set of target mRNAs comprising key oncogenes and mitotic regulators. LIN28 proteins selectively block let-7 biogenesis postranscriptionally. The current model for coordinate let-7 repression involves the LIN28 cold shock domain (CSD) binding the terminal loop and the two CCHC-type zinc fingers recognizing a GGAG sequence motif in precursor let-7 (pre-let-7) RNAs. Here we perform a systematic analysis of all let-7 miRNAs and find that a single let-7 family member, human let-7a-3 (and its murine ortholog let-7c-2), escapes LIN28-mediated regulation. Mechanistically, we find that the pre-let-7c-2 loop precludes LIN28A binding and regulation. These findings refine the current model of let-7 regulation by LIN28 proteins and have important implications for understanding the LIN28/let-7 axis in cancer. Citation Format: Robinson Triboulet, Mehdi Pirouz, Richard I. Gregory. A single let-7 microRNA bypasses LIN28-mediated repression. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A41.
Genome-based study of a spatio-temporal cluster of invasive meningococcal disease due to Neisseria meningitidis serogroup C, clonal complex 11
Authors: P. Stefanelli, C. Fazio, A. Neri, A. Ciammaruconi, E. Balocchini, A. Anselmo, C. Azzari, G.M. Rossolini, P. Vacca, A. Fortunato, A. Palozzi, S. Fillo, F. Lista, M. Moriondo, F. Nieddu, G. Rezza
Journal: Journal of Infection (2016)

ObjectivesTo describe a spatio-temporal cluster of invasive meningococcal disease (IMD) due to serogroup C meningococci, occurred in a restricted area of Tuscany between January and October 2015, and the results of whole genome sequencing (WGS).MethodsSurveillance activities and public health measures were implemented in the Region. Bacterial isolates from IMD cases were characterized by the National Reference Laboratory of the Istituto Superiore di Sanità (ISS), and WGS was performed on available strains. The kSNP software was used to identify core genome SNPs.ResultsOverall, 28 IMD cases due to meningococcus C were identified up to 31st October, 2015. Of them, 26 were due to meningococcus C:P1.5-1,10-8: F3-6:ST-11 (cc11) and 2 to C:P1.5-1,10-8: F3-6:ST-2780 (cc11). WGS of 13 meningococci isolated during the outbreak occurred in Tuscany in 2015 showed higher similarity when compared with those of 47 C: P1.5-1,10-8: F3-6:ST-11 (cc11) invasive strains from sporadic cases previously detected in Italy.ConclusionsA highly aggressive meningococcal C strain was involved in the cluster of severe IMD occurred in Tuscany, a Region with high vaccine coverage among children. Whether this was due to low herd immunity related to the short duration of vaccine protection needs further investigation.
Abstract A14: Checkpoinblockade enhances oncolytic herpes virotherapy in immunosuppressive sarcoma models
Authors: Chun-yu Chun, Pin-Yi Wang, Brian Hutzen, Kellie Haworth, Joe Conner, Timothy Cripe
Journal: Cancer Research (2016)

Abstract Most solid tumors are characterized by an immunosuppressive microenvironment, limiting the effectiveness of antitumor immunotherapeutics. Programmed cell death protein (PD)-1-mediated T cell suppression via engagement of its ligand, PD-L1, is of particular interest due to recent successes in selected adult cancers. The utility of PD1-directed therapy for pediatric cancers is unknown, especially given the paucity of mutations and thus infrequent neoantigens in many types of childhood tumors. Oncolytic virotherapy induces tumor shrinkage via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines, and induction of anti-tumor T cell responses. We recently demonstrated that intratumoral injection of an oncolytic herpes virus induced growth delays and in some cases durable remissions in several mouse models of rhabdomyosarcoma. The effects were T cell mediated, rendering surviving mice resistant to tumor rechallenge and being absent in athymic nude hosts (Leddon et al., Mol Ther-Oncolytics 1, Article number: 14010, 2015). We found these tumor models express PD-L1, suggesting that T cell checkpoints may in part limit virus-induced antitumor immunity. Here we show the implantable C57Bl/6 rhabdomyosarcoma model, M3-9-M, showed a moderate response to single-agent Seprehvir (HSV1716), a virus currently in pediatric clinical trials (NCT00931931, NCT02031965). Single-agent PD-1 blockade also showed moderate but significant tumor growth delay with no complete responses. Strikingly, combining these two therapies together substantially prolonged overall survival with several complete responses post 40 days treatment. We hypothesize that virotherapy-induced chemokine secretion increases the recruitment of antitumor T cells, while PD-1 blockade increases their effectiveness. Overall, our data suggest the combination of PD-1 and oncolytic herpes virotherapy may be an effective treatment strategy for some cancers. Citation Format: Chun-yu Chun, Pin-Yi Wang, Brian Hutzen, Kellie Haworth, Joe Conner, Timothy Cripe. Checkpoinblockade enhances oncolytic herpes virotherapy in immunosuppressive sarcoma models. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr A14.
Echocardiographic evaluation of pericardial disease
Authors: P. A. Chandraratna
Journal: JAMA (1983)

VARIOUS forms of pericardial disease are commonly encountered in clinical practice. Echocardiography is an effective noninvasive method of assessing many different cardiac conditions; this article explores the uses and limitations of echocardiography in evaluating pericardial disease, with a special emphasis on two-dimensional echocardiography. <h3>Pericardial Effusion</h3> One of the first applications of echocardiography was its use in diagnosing pericardial effusion.<sup>1</sup>The appearance of an echo-free space posterior to the heart, with disappearance or marked reduction of the space at the junction of the left ventricle and left atrium, and absence of motion of the pericardium are the echocardiographic hallmarks of pericardial effusion. The volume of pericardial fluid can be roughly quantitated using M-mode echocardiography. A small, posterior echo-free space denotes a small pericardial effusion, and as the amount of pericardial fluid increases, the posterior space becomes larger. With a large pericardial effusion, a large posterior as well as an anterior
Soundings: A day in the country
Authors: Colin Douglas
Journal: BMJ (2004)

A picture window faces north east. Through the morning, skyscapes come and go: dark rain-clouds, uncertain cumulus, sudden clear blue. Far from the bustle of the city, we sit at ease. When I was a houseman, my colleague for today was our senior student: a diffident, kindly young man. I ask after his father: “A bit sore from running for a bus. Probably shouldn't have. Of course he's 92.” And now we too talk of retirement.

Outside, seagulls, starlings, and sparrows appear and disappear. But we are not here for bird watching. We are examining: in the Practical Assessment of Clinical Examination Skills for the Membership of the Royal College of Physicians. The candidates appear and disappear. This morning we have history taking skills, which in some cases we have not got.

We observe, take notes, take turns to cross examine a little, and come to judgment. In some cases we disagree. Outside, seagulls, starlings, and sparrows, and the occasional blackbird, come and go. Inside, there are hawks and doves.

And this afternoon we are assessing cardiological and neurological skills, which clearly also in some cases we have not got. Clever, pleasant young doctors who have worked and studied hard forget themselves and miss things, or parade obscurities we are not interested in. We are not impressed.

The game has rules but they are not much required. When a clumsy toiler is revealed in the first minute and spends the other nine getting things wrong we do not need them. When an intuitive, informed intellect succeeds in charming both us and the patient with her skill, knowledge, and kindliness, again there is no need for rules.

The devil is in the middle. A sudden access of common sense rescues a decent doctor from the follies of the smallest print; we feel relief, but wonder if that is enough. And we may disagree again when a hitherto coherent train of clinical logic is derailed by the frankly surreal. Good and bad starts, good and bad endings: in exams or in life, which count for more?

Long ago, before I sat the exam, I learned all about Quincke's capillary pulsation, an obscure manifestation of aortic valve disease. That day in the country, I think for the first time ever, I saw it. It was—and remains—quite unimportant. But the exam is fair. Half the candidates fail.
Social skills training compared with pharmacotherapy and psychotherapy in the treatment of unipolar depression
Authors: A S Bellack, M Hersen, J Himmelhoch
Journal: American Journal of Psychiatry (1981)

The authors contrasted four treatments for unipolar (nonpsychotic) depression: 1) amitriptyline, 2) social skills training plus amitriptyline, 3) social skills training plus placebo, and 4) psychotherapy plus placebo. They studied 72 female outpatients, 52 of whom completed the 12 weeks of treatment. The four treatments, conducted by experienced clinicians, were not substantially different from one another. Each treatment produced significant and clinically meaningful changes in symptomatology and social functioning. However, the authors identified several notable differences across groups: a significant difference in dropout rates (from a high of 55.6% for the amitriptyline group to a low of 15% for the social skills plus placebo group) and a significant difference in the proportion of patients who were substantially improved. The social skills plus placebo treatment was the most effective treatment on this dimension.
Evaluation of immunochromatography tests for detection of novel GII.17 norovirus in stool samples
Authors: P Khamrin, A Thongprachum, S Takanashi, S Okitsu, N Maneekarn, S Hayakawa, H Ushijima
Journal: Eurosurveillance (2015)

A novel GII.17 norovirus has emerged as a major cause of epidemic and endemic acute gastroenteritis in several countries in Asia. We used a small panel of stool samples in which GII.17 virus had been quantified by real-time RT-PCR to evaluate four commercially available norovirus immunochromatography (IC) kits. At least 10(8) copies/mL of GII.17 virus were required by each IC kit for a positive result, which is 1,000-fold more than that reported for these assays for GII.4 viruses.
Mechanisms of behaviorally induced arrhythmias.
Authors: Verrier Rl
Journal: Circulation (1987)

Significant progress has been made in the past few years in defining the role of behavioral stress in the precipitation of cardiac arrhythmias. This is largely attributable to the development of relevant biobehavioral models and the advent of quantitative methods for assessing myocardial electrical stability in conscious animals. Classic and instrumental aversive conditioning has been shown to decrease electrical stability even in the normal heart. During evolving myocardial ischemia or infarction, the stress states can precipitate major arrhythmias, including ventricular fibrillation. Natural emotions have also been shown to be capable of altering the propensity to fibrillation. Notably, provocation of an angerlike state has been shown to decrease the vulnerable period threshold by 40% to 50%. The poststress phase can be particularly hazardous, as suggested by the profound myocardial perfusion abnormalities that have been observed within 1 to 3 min after cessation of anger. Cryogenic blockade of the thalamic gating system or its output from the frontal cortex to the brainstem blunts significantly the profibrillatory influence of stress. This indicates that discrete pathways within the central nervous system mediate the deleterious influence of aversive states on heart rhythm. Adrenergic factors appear to constitute the major effector component. This is supported by the observation that pharmacologic or surgical sympathectomy is capable of annulling the arrhythmogenic influence of diverse types of stress. The generally deleterious influence of the adrenergic system appears to be counteracted by vagal activity. The underlying mechanism is a muscarinically mediated inhibition of norepinephrine release from sympathetic nerve endings and a blunting of the actions of the adrenergic transmitters at the receptor level.(ABSTRACT TRUNCATED AT 250 WORDS)
Re: time to question the NHS diabetes prevention programme
Authors: James A. Dunbar, Edward D. Janus, Erkki Vartiainen, Tiina Laatikainen, Vin Versace, John Reynolds, James D. Best, Timothy Skinner, Sharleen O'Reilly, Kevin Mc Namara, Elizabeth Stewart, Michael Coates, Catherine Bennett, Rob Carter
Journal: BMJ (2015)
Results of Radical Prostatectomy in Men with Locally Advanced Prostate Cancer: Multi-Institutional Pooled Analysis
Authors: G S Gerber, R A Thisted, G W Chodak, F H Schroder, H G Frohmuller, P T Scardino, D F Paulson, A W Middleton, D B Rukstalis, J A Smith, M Ohori, M Theiss, P F Schellhammer
Journal: European Urology (1997)