tbuckley/cabot-search huggingface dataset:
Protocadherin 7–Associated Membranous Nephropathy
Authors: Sanjeev Sethi, Benjamin Madden, Hanna Debiec, Johann Morelle, M. Cristine Charlesworth, LouAnn Gross, Vivian Negron, David Buob, Sidharth Chaudhry, Michel Jadoul, Fernando C. Fervenza, Pierre Ronco
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Membranous nephropathy (MN) results from antibodies targeting an antigen in the glomerular basement membrane (GBM). The target antigens identified so far include PLA2R, THSD7A, NELL1, SEMA3B, and EXT1/EXT2. Using laser microdissection and mass spectrometry analysis, the authors identified a novel protein, protocadherin 7 (PCDH7), that is present in the GBM of a subset of patients with MN who are negative for all of the known antigens associated with MN. PCDH7 shows granular GBM staining and colocalizes with Ig in the GBM. Furthermore, antibodies to PCDH7 were detected in both the serum and kidney biopsy tissue from individuals with PCDH7-associated MN but not from controls. These findings suggest that PCDH7-associated MN defines a distinct type of MN. Background Membranous nephropathy (MN) results from deposition of antigen-antibody complexes along the glomerular basement membrane (GBM). PLA2R, THSD7A, NELL1, and SEMA3B account for 80%–90% of target antigens in MN. Methods We performed laser microdissection and mass spectrometry (MS/MS) in kidney biopsies from 135 individuals with PLA2R-negative MN, and used immunohistochemistry/immunofluorescence and confocal microscopy to confirm the MS/MS finding, detect additional cases, and localize the novel protein. We also performed MS/MS and immunohistochemistry on 116 controls and used immunofluorescence microscopy to screen biopsy samples from two validation cohorts. Western blot and elution studies were performed to detect antibodies in serum and biopsy tissue. Results MS/MS studies detected a unique protein, protocadherin 7 (PCDH7), in glomeruli of ten (5.7%) PLA2R-negative MN cases, which also were negative for PLA2R, THSD7A, EXT1/EXT2, NELL1, and SEMA3B. Spectral counts ranged from six to 24 (average 13.2 [SD 6.6]). MS/MS did not detect PCDH7 in controls (which included 28 PLA2R-positive cases). In all ten PCDH7-positive cases, immunohistochemistry showed bright granular staining along the GBM, which was absent in the remaining cases of PLA2R-negative MN and control cases. Four of 69 (5.8%) cases in the validation cohorts (all of which were negative for PLA2R, THSD7A, EXT1, NELL1, and SEMA3B) were PCDH7-positive MN. Kidney biopsy showed minimal complement deposition in 12 of the 14 PCDH7-associated cases. Confocal microscopy showed colocalization of PCDH7 and IgG along the GBM. Western blot analysis using sera from six patients showed antibodies to nonreduced PCDH7. Elution of IgG from frozen tissue of PCDH7-associated MN showed reactivity against PCDH7. Conclusions MN associated with the protocadherin PCDH7 appears to be a distinct, previously unidentified type of MN.
Shall The Journal be Removed to Washington?
Authors: H. H. Middelkamp
Journal: JAMA (1891)

<h3>To the Editor:</h3> —Please allow me to record my vote in favor ofThe Journalremaining in Chicago. " Let well enough alone!" A thousand reasons and arguments might be offered why it should remain in Chicago, while as many could be given against its removal. " Westward the star of Empire takes its course." Chicago is certainly a great medical centre, and perhaps the greatest railroad centre in the Union; her future is great, so that there cannot be a doubt of the future success ofThe Journal, for its financial condition is on a sound and enduring basis, while its editorial management has always been of the highest order. Its editorials are learned, progressive, broad and cosmopolitan. While its attitude has been conservative and judicious, it has assumed a high position for the advancement of the whole domain of medicine. The aim ofThe Journalhas been of a high
Echocardiographic evaluation of the Valsalva Maneuver in healthy subjects and patients with and without heart failure.
Authors: A FParisi, J JHarrington, JAskenazi, R CPratt, K MMcIntyre
Journal: Circulation (1976)

The Valsalva maneuver was evaluated by echocardiography in three groups: A) 10 normal volunteers, B) 10 patients with no history of heart failure and normal ejection fractions, and C) 10 patients with heart failure and depressed ejection fractions. Groups A and B had a significant fall in left ventricular internal dimensions and calculated stroke volume by end strain which returned rapidly to baseline in recovery without significant overshoot. Arterial pressure showed a signoidal strain pattern with a normal overshoot in early recovery in all group B patients. In group C ventricular dimensions did not diminish during strain; arterial pressures showed a square wave pressure elevation during strain without an overshoot in recovery. Echocardiography allows a new approach to evaluate further the left ventricular response to the Valsalva maneuver. Patients with severely depressed ejection fractions, unlike those with normal ventricular function, are unable to alter stroke output in response to acutely increa...
Reoxygenation of endothelial cells increases permeability by oxidant-dependent mechanisms.
Authors: HLum, D ABarr, J RShaffer, R JGordon, A MEzrin, A BMalik
Journal: Circulation Research (1992)

We investigated the effects of hypoxia/reoxygenation exposure on the barrier function of endothelial cell monolayers. Bovine pulmonary microvessel endothelial cells were grown to confluence on microporous filters (0.8-microns pore diameter) and exposed to hypoxia (0.1% O2 or PO2 approximately 1 mm Hg) for 2, 4, 12, or 24 hours, followed by reoxygenation with room air for a period ranging from 16 seconds to 2 hours. The transendothelial clearance rate of 125I-albumin was measured to determine the permeability of endothelial monolayers. Permeability increased twofold or fivefold over control values after 1 hour of reoxygenation in monolayers that had been exposed to either 12 or 24 hours of hypoxia. The response occurred within 5 minutes of reoxygenation, increased maximally by 40 minutes, and remained elevated with continuous reoxygenation for up to 2 hours. The increase in permeability was associated with F-actin reorganization, a change to spindlelike cells, and injured mitochondria. Immunoblot analysis ...
Red Blood Cell Hitchhiking: A Novel Approach for Vascular Delivery of Nanocarriers
Authors: Jacob S. Brenner, Samir Mitragotri, Vladimir R. Muzykantov
Journal: Annual Review of Biomedical Engineering (2021)

Red blood cell (RBC) hitchhiking is a method of drug delivery that can increase drug concentration in target organs by orders of magnitude. In RBC hitchhiking, drug-loaded nanoparticles (NPs) are adsorbed onto red blood cells and then injected intravascularly, which causes the NPs to transfer to cells of the capillaries in the downstream organ. RBC hitchhiking has been demonstrated in multiple species and multiple organs. For example, RBC-hitchhiking NPs localized at unprecedented levels in the brain when using intra-arterial catheters, such as those in place immediately after mechanical thrombectomy for acute ischemic stroke. RBC hitchhiking has been successfully employed in numerous preclinical models of disease, ranging from pulmonary embolism to cancer metastasis. In addition to summarizing the versatility of RBC hitchhiking, we also describe studies into the surprisingly complex mechanisms of RBC hitchhiking as well as outline future studies to further improve RBC hitchhiking's clinical utility.
Digital angiographic impulse response analysis of regional myocardial perfusion: linearity, reproducibility, accuracy, and comparison with conventional indicator dilution curve parameters in phantom and canine models.
Authors: N LEigler, J MPfaff, AZeiher, J SWhiting, J SForrester
Journal: Circulation Research (1989)

The system mean transit time (Tsys) of the impulse response function describing contrast material transit through the coronary circulation was determined from serial digital angiographic images. The linearity, reproducibility, and relations with regional myocardial perfusion and conventional time-density curve parameters, time to peak concentration (TPC), and exponential washout rate (k) were assessed in a dynamic flow x-ray phantom (n = 46) and in six open-chest dogs (n = 102) while coronary flow was altered by stenosis and/or hyperemic stimuli. In the phantom studies, the inverse of the system mean transit time (Tsys-1) closely predicted flow/volume (r = 0.99, slope = 0.99). In dogs, Tsys-1 was independent of the shape of the contrast bolus injection (single or double-peaked), class of contrast agent (ionic or nonionic), the type of hyperemic stimulus (dipyridamole, dipyridamole plus norepinephrine, transient total occlusion, or ionic contrast media), and was highly reproducible between adjacent myocard...
Correlation between echocardiographic endocardial surface mapping of abnormal wall motion and pathologic infarct size in autopsied hearts.
Authors: G TWilkins, J FSouthern, C YChoong, J DThomas, J TFallon, D EGuyer, A EWeyman
Journal: Circulation (1988)

We previously developed a cross-sectional echocardiographic technique for quantitatively mapping the endocardial surface of the left ventricle and on which regions of abnormal wall motion can be superimposed in their correct spatial distribution. This endocardial mapping technique (EMT) provides a measure of the left ventricular endocardial surface area (ESA in cm2), the area of abnormal wall motion (AWM in cm2), and the overall percent dysfunction (%AWM) as a measure of the functional  size. To test this approach, we compared the EMT measurements with the actual endocardial surface area (in cm2) and pathologic infarct size (both percent infarct by volume and percent endocardial surface overlying infarct) measured at later autopsy in 20 adults (14 men, six women) ranging in age from 47 to 76 years (mean 64 +/- 9.6 years). The median interval from echocardiographic study to death was 19 days (range 1 to 269 days). Patients were divided into two groups based on the age of their infarcts at the time...
Recurrent Digestive Bleeding: The Essential Is Invisible To The Eyes
Authors: L Martins Figueiredo, F Correia, G Alexandrino, MA Rafael, M Cardoso, J Carvalho e Branco, D Horta, É Coimbra, A Martins
Journal: Endoscopy (2021)

A 58-year-old woman presented with melena and a hemoglobin of 10.6 g/dL. Esophagogastroduodenoscopy (OGD), colonoscopy and capsule endoscopy were unremarkable. Three weeks later, she was readmitted due to hematochezia and lipothymia. Abdominopelvic Angio-CT highlighed an 8 mm hypervascular nodular image in the duodenal bulb, originating from the gastroduodenal artery. Duodenoscopy revealed a protruding lesion with a central erosion, located on the upper wall of the bulb, immediately distal to the pylorus. Attempted hemostasis with hemoclips failed due to unfavourable endoscopic access and resulted in intermittent pulsatile bleeding. The patient underwent sucessful endovascular embolization of the Dieulafoy’s lesion with coils.
Intermittent brief periods of ischemia have a cumulative effect and may cause myocardial necrosis.
Authors: I LGeft, M CFishbein, KNinomiya, JHashida, EChaux, JYano, JY-Rit, TGenov, WShell, WGanz
Journal: Circulation (1982)

We investigated the effects of brief intermittent periods of ischemia on myocardial viability. Brief periodic coronary occlusions were produced up to 18 times by inflating and deflating the balloon of an intracoronary No. 2F catheter for periods of 15, 10 or 5 minutes, followed by 15-minute periods of reperfusion. Creatine kinase (CK) release, triphenyl tetrazolium chloride staining, and light and electron microscopy were used to detect the presence of myocardial necrosis. For the study of CK release, blood was taken from the great cardiac vein and the aorta before and at 5-minute intervals during each left anterior descending coronary occlusion, as well as during and 1, 5, 10 and 15 minutes after balloon deflation. In seven of 24 dogs with 15-minute occlusions, in five of 21 dogs with 10-minute occlusions, and in three of 32 dogs with 5-minute occlusions, small but distinct areas of subendocardial necrosis were present. In all dogs with morphologic proof of necrosis, there was periodic release of CK into...
ACME dissociation: a versatile cell fixation-dissociation method for single-cell transcriptomics
Authors: Helena García-Castro, Nathan J. Kenny, Marta Iglesias, Patricia Álvarez-Campos, Vincent Mason, Anamaria Elek, Anna Schönauer, Victoria A. Sleight, Jakke Neiro, Aziz Aboobaker, Jon Permanyer, Manuel Irimia, Arnau Sebé-Pedrós, Jordi Solana
Journal: Genome biology (2021)

Abstract Single-cell sequencing technologies are revolutionizing biology, but they are limited by the need to dissociate live samples. Here, we present ACME (ACetic-MEthanol), a dissociation approach for single-cell transcriptomics that simultaneously fixes cells. ACME-dissociated cells have high RNA integrity, can be cryopreserved multiple times, and are sortable and permeable. As a proof of principle, we provide single-cell transcriptomic data of different species, using both droplet-based and combinatorial barcoding single-cell methods. ACME uses affordable reagents, can be done in most laboratories and even in the field, and thus will accelerate our knowledge of cell types across the tree of life.
Colon tumors and colonoscopy
Authors: R. Singh, M. Bourke, M. Jayanna, G. Nind
Journal: Endoscopy (2012)

The 2012 Digestive Disease Week (DDW; 19 – 22 May, San Diego, California, USA) received a record number of submissions on colonoscopy and colorectal cancer (CRC). Scientific presentations focused primarily on colonic polyps and can be broadly divided into polyp detection, characterization, and resection. Among the more interesting topics were the novel concept of polypectomy rate, newer-generation optical imaging technology, and advanced endoscopic resection techniques.
Shots in the desert and Gulf war syndrome
Authors: S. Shaheen
Journal: BMJ (2000)

Papers p 1363 

Vaccinations could have long term, non-specific effects on immune responses in children and adults, some undesirable, others beneficial. For example, there has been speculation that vaccines could influence the development of atopy. We have known for years that the pertussis vaccine is an adjuvant for IgE production, and conjecture that vaccinations might have contributed to the rise in atopic disease in children was an inevitable corollary of the “hygiene hypothesis.” 1 This hypothesis proposes that the prevalence of atopy has increased because infections in early life protect against atopy and children have been less exposed to infections over time. The discovery of polarised T helper cell responses, Th1 and Th2, fuelled the debate.2 It led to a theoretical model whereby the development of atopy characterised by Th2-type cytokine responses to allergens and production of IgE might be promoted by vaccines that induce Th2 cytokines or inhibited by those that induce Th1 cytokines.

However, evidence from observational studies that vaccinations increase the risk of atopy is contradictory, and early follow up of a cohort from a trial of pertussis vaccine suggests that this vaccine, at least, is unlikely to be an important cause of atopic disease.3 …
181P Multicenter real-world study (RWS) on efficacy and early discontinuation predictors in non-small cell lung cancer (NSCLC) patients (pts) receiving nivolumab
Authors: G. Pasello, A. Bortolami, S. Tognazzo, G. Crivellaro, A. Torchia, M. Lorenzi, J. Menis, S. Frega, L. Bonanno, V. Guarneri, P.F. Conte
Journal: Journal of Thoracic Oncology (2021)
Spread of contraction in rabbit ear artery preparations in response to stimulation by norepinephrine.
Authors: MVonderlage
Journal: Circulation Research (1981)

To investigate the spread of contraction in the rabbit ear artery, changes in segment diameter were measured after local stimulation. No spread of contraction was produced by direct current or local application of norepinephrine (NE). Repetitive electrical stimulation caused contraction which spread far from the point of excitation. Since 2 x 10(-7) g/ml tetrodotoxin (TTX) or 10(-5) M phentolamine prevented this spread of contraction, we concluded that it depends on normal function of periarterial nerves and of the alpha-adrenergic receptors at the site of the smooth muscle cells. To check this conclusion and exclude the possibility of myogenic propagation, which normally is due to the conduction of action potentials, the relation between membrane potential of smooth muscle cells and the rapid phase of the contractile response after rapid addition of NE was investigated. In both polarized and depolarized tissues NE induces a biphasic contractile response with no difference in latency. Membrane potential d...
The effect of procaine amide on components of excitability in long mammalian cardiac Purkinje fibers.
Authors: M FArnsdorf, J TBigger
Journal: Circulation Research (1976)

The microelectrode technique of intracellular constant current application and intracellular transmembrane voltage recording was used to study the effects of procaine amide (PA) on cardiac excitability. We measured the effect of PA in a concentration equivalent to clinically effective antiarrhythmic plasma levels (5 mug/ml), on nonnormalized and normalized strength-duration and charge-duration curves, membrane characteristics, and cable properties in long sheep Purkinje fibers in normal Tyrode's solution with [K+]0 = 4.0 mM. PA exerted a complex action and influenced passive resistance-capacitance (RC) and active generator properties by decreasing membrane conductance, primarily membrane sodium conductance. Whether PA increased or decreased excitability depended on the relative contribution of the drug-induced alterations in passive and active membrane properties. These findings may explain, in part, the conflicting results of studies on cardiac excitability in the whole animal, as well as the clinical ob...
EUS-Guided Gallbladder Drainage Using A Lumen-Apposing Metal Stent for Acute Cholecystitis: Results of A Multicenter Study
Authors: C Binda, A Anderloni, E Forti, P Fusaroli, R Macchiarelli, M Manno, A Fugazza, A Redaelli, G Aragona, M Lovera, T Togliani, E Armellini, A Amato, ML Brancaccio, R Badas, N Leone, G de Nucci, B Mangiavillano, M Sbrancia, V Pollino, M Maida, E Sinagra, A Repici, C Fabbri, I Tarantino
Journal: Endoscopy (2021)

Aims The aim of the study is the evaluation of the effectiveness and safety of endoscopic ultrasound guided gallbladder drainage (EUS-GBD) using lumen apposing metal stents (LAMS) for acute cholecystitis (AC) in a large cohort of patients at high-risk for cholecystectomy.
Regulation of hypertrophy and atrophy in cultured adult heart cells.
Authors: W AClark, S JRudnick, J JLaPres, L CAndersen, M CLaPointe
Journal: Circulation Research (1993)

Mechanical loading and alpha-adrenergic receptor stimulation have both been shown to induce hypertrophy in isolated neonatal heart cells. The present study examined the effects of adrenergic hormones and contractile activity on the hypertrophic response in isolated adult feline cardiomyocytes maintained for more than 14 days in insulin- and serum-supplemented medium. Measurements of the hypertrophic response included cell size, total protein content, myosin heavy chain content, and the time course of activation of increased protein synthesis. Reactivation of the fetal gene program was evaluated by secretion of atrial natriuretic factor (ANF) into the medium. Significant myocyte hypertrophy was induced in both quiescent myocytes treated with alpha 1-adrenergic agonists and in beating myocytes treated with beta-adrenergic agonists. However, there were both quantitative and qualitative differences in the response to each type of stimulation. alpha-Adrenergic agonists promoted an increase in cell size, prot...
Antiarrhythmic drug therapy in survivors of prehospital cardiac arrest: comparison of effects on chronic ventricular arrhythmias and recurrent cardiac arrest.
Authors: R JMyerburg, CConde, D SSheps, R AAppel, IKiem, R JSung, ACastellanos
Journal: Circulation (1979)

We studied the long-term effects of membrane-active antiarrhythmic agents on chronic ventricular arrhythmias in patients who have survived prehospital cardiac arrest. Among 16 patients treated with a dose-adjusted, plasma level-monitored antiarrhythmic regimen, eight have survived for longer than 12 months and eight have had recurrent cardiac arrests (RCAs). Monthly Holter monitor tapes (HM) recorded during the 4 months before the eight RCAs were compared with monthly HM tapes matched for time of entry and duration of follow-up in the eight patients who did not have RCAs. Transient or persistent complex ventricular ectopic depolarizations (VEDs) have been recorded on 47 of the 63 monthly HM tapes (75%). The difference between VEDs in the RCA patients (mean 153 VEDs/hr, median 19 VEDs/hr) and VEDs in the patients who have not had RCA (mean 122 VEDs/hr, median 8 VEDs/hr) was not significant (p less than 0.2); nor was there a predictable relationship between therapeutic plasma levels of antiarrhythmic agents...
EUS-Cholecystogastrostomy Followed by Cholangioscopy with Spyglass Through the Lumen Of The Lams Stent and Lithotripsy of Gallbladder Stones
Authors: A Raiter, K Kozłowska-Petriczko, J Petriczko, A Wiechowska-Kozłowska, KM Pawlak
Journal: Endoscopy (2021)

An 88-year-old male with cholangitis (bile stone 2x3 cm) and empyema of the gallbladder was disqualified from surgery due to severe comorbidities. The complex endoscopic treatment was planned. Two ERCP procedures with a successful cholangioscopy (Spyglass, Spyscope BS), followed by the electrohydraulic lithotripsy (EHL; Autolith BS) of the CBD stone were performed. Additionally, the EUS guided Hot Axios stent (10x10mm) for cholecystogastrostomy creation was implanted. The last procedure was a cholecystoscopy through the Hot Axios stent lumen, using Spyglass (via the working channel of the colonoscope) with EHL of gallstones. The treatment was successful. Presently, the patient remains without symptoms.
Simulation of action potential propagation in an inhomogeneous sheet of coupled excitable cells.
Authors: R WJoyner, FRamón, J WMorre
Journal: Circulation Research (1975)

Cable theory and active equivalent circuits have been used to simulate the propagation of action potentials along a single nerve or muscle fiber by representing the cell as a unidimensional cable composed of isopotential segments. We extended this method to a two-dimensional sheet of cells which in many ways represents the atrium. Our method consisted of solving for the potential profile of a sheet composed of a large number of isopotential membrane patches, each of which was represented by an active equivalent circuit in which the ionic conductances were functions of voltage and time. The patches were arranged in a rectangular array with resistive interconnections that could be varied over the sheet. We used this model to study the effect of various inhomogeneities on conduction velocity and the resulting wave fronts in a sheet of excitable tissue. Some of these inhomogeneities included different effective internal resistances in the x and y directions, preferential pathways, and discrete regions of chan...