tbuckley/cabot-search huggingface dataset:
Symptomatic Abdominal Mass
Authors: Jan P. Kaminski, Hai Xu, Matthew Hyser
Journal: JAMA Surgery (2015)

Aman in his mid-20swith a history of alcohol abuse presented with abdominalpainafter3daysofdrinking.Hedescribedthepainasasharp, leftupper-quadrantpainmigrating to theepigastric region for24hours. The patient had a history of multiple episodes of hematemesis attributed to alcoholic gastritis; however, at this admission, he indicated he had not experienced vomiting. He admitted to early satietyover thepast fewmonths.Physicalexamination revealedasoftnondistended abdomen, but it was very tender in the epigastric region without rebound or guarding. There was no palpable mass. Elevated results of liver function tests, as well as amylase and lipase levels consistent with alcoholic pancreatitis, were noted. Magnetic resonance imaging, computed tomographic imaging, andupper endoscopy findings are shown inFigure 1. Biopsy results of themasswere reportedas normal gastric mucosa. Quiz at jamasurgery.com Computed tomography and magnetic resonance imaging A Endoscopic image B
A Role for Gab1/SHP2 in Thrombin Activation of PAK1
Authors: Dong Wang, Biman C. Paria, Qiuhua Zhang, Manjula Karpurapu, Quanyi Li, William T. Gerthoffer, Yoshikazu Nakaoka, Gadiparthi N. Rao
Journal: Circulation Research (2009)

To understand the role of epidermal growth factor receptor (EGFR) transactivation in G protein-coupled receptor (GPCR) agonist-induced signaling events, we have studied the capacity of thrombin in the activation of Gab1-SHP2 in vascular smooth muscle cells (VSMCs). Thrombin activated both Gab1 and SHP2 in EGFR-dependent manner. Similarly, thrombin induced Rac1 and Cdc42 activation, and these responses were suppressed when either Gab1 or SHP2 stimulation is blocked. Thrombin also induced PAK1 activation in a time- and EGFR-Gab1-SHP2-Rac1/Cdc42-dependent manner. Inhibition of activation of EGFR, Gab1, SHP2, Rac1, Cdc42, or PAK1 by pharmacological or genetic approaches attenuated thrombin-induced VSMC stress fiber formation and motility. Thrombin activated RhoA in a time-dependent manner in VSMCs. LARG, a RhoA-specific GEF (guanine nucleotide exchange factor), was found to be associated with Gab1 and siRNA-mediated depletion of its levels suppressed RhoA, Rac1 and PAK1 activation. Dominant negative mutant-mediated interference of RhoA activation inhibited thrombin-induced Rac1 and PAK1 stimulation in VSMCs and their stress fiber formation and migration. Balloon injury induced PAK1 activity and interference with its activation led to attenuation of SMC migration from media to intima, resulting in reduced neointima formation and increased lumen size. Inhibition of thrombin signaling by recombinant hirudin also blocked balloon injury-induced EGFR tyrosine phosphorylation and PAK1 activity. These results show that thrombin-mediated PAK1 activation plays a crucial role in vascular wall remodeling and it could be a potential target for drug development against these vascular lesions.
THE THERAPEUTIC VALUE OF GOLD COMPOUNDS (SANOCRYSIN, KRYSOLGAN, ETC.)*
Authors: A. C. ROXBURGH, H. CORSI
Journal: British Journal of Dermatology (1930)

Journal Article THE THERAPEUTIC VALUE OF GOLD COMPOUNDS (SANOCRYSIN, KRYSOLGAN, ETC.) Get access A. C. ROXBURGH, M.D., F.R.C.P., A. C. ROXBURGH, M.D., F.R.C.P. Skin‐Department, St. Bartholomew's Hospital Search for other works by this author on: Oxford Academic Google Scholar H. CORSI, M.B., F.R.C.S. H. CORSI, M.B., F.R.C.S. Skin‐Department, St. Bartholomew's Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 42, Issue 8-9, 1 August 1930, Pages 382–390, https://doi.org/10.1111/j.1365-2133.1930.tb09431.x Published: 01 August 1930
Improved outcome for prehospital cardiopulmonary collapse with resuscitation by bystanders.
Authors: D P Copley, J A Mantle, W J Rogers, R O Russell, C E Rackley
Journal: Circulation (1977)

Despite the development of trained mobile rescue squads, cardiopulmonary collapse outside the hospital continues to carry a poor prognosis. We examined retrospectively the clinical courses of 19 consecutive coronary unit patients who had experienced prehospital cardiopulmonary resuscitation. Seven patients received basic life support from bystanders within five minutes. Cardiopulmonary resuscitation in the other 12 patients was delayed beyond five minutes pending the arrival of rescue personnel. Six of seven early-resuscitated patients survived compared with six of 12 late-resuscitated patients (P less than 0.01). The early-resuscitated patients were more alert on admission and had lower pulmonary pressures and higher cardiac outputs compared to the late-resuscitated patients. The early-resuscitated patients also had less residual central nervous system and myocardial damage on discharge than the late-resuscitated patients. On follow-up, three early-resuscitated patients had returned to full-time work compared with none in the late group. Training laymen to initiate early basic life support can benefit the cardiopulmonary collapse victim.
Plasticity in Fast Synaptic Inhibition of Adult Oxytocin Neurons Caused by Switch in GABAA Receptor Subunit Expression
Authors: A.B Brussaard, K.S Kits, R.E Baker, W.P.A Willems, J.W Leyting-Vermeulen, P Voorn, A.B Smit, R.J Bicknell, A.E Herbison
Journal: Neuron (1997)
Specialised care for early psychosis
Authors: Swaran P Singh
Journal: BMJ (2005)

Monitoring global health Problems are primarily nationalEditor-Murray et al urge for improved global reporting of health data. 1 They also highlight the difficulty of showing national decision makers that good health data can strongly support decision making.Why is this?A reason may be that data are always subject to interpretation.The article by Murray et al is a case in point.They want to establish "an independent monitoring organisation," arguing that the World Health Organization is not fit to undertake the job because of tension between advocacy, monitoring, and evaluation.But evidence that it is this tension that leads to poor monitoring by WHO is weak, at best.In reality, the problems of global health reporting are primarily national (and subnational).The fact that the sum of deaths claimed by different programmes is greater than the actual number of deaths reflects epidemiological methods and the current limitations in global health reporting, more than any WHO failure.The global burden of disease project was limited by these issues, but it was undertaken as effectively in WHO as in any other organisation.Not only are there problems in capacity, understanding the value of surveillance, and coverage of health services.The reporting of health events can be politically sensitive or even economically damaging.It is therefore likely that political interference will continue (whoever collects the data) until governments can be shown that honesty pays.It is perhaps this failure that needs to be dealt with rather than setting up yet another organisation without a proper analysis of the reasons (and locus) for failures in global health reporting.
Relationship of Clinical Symptomatology to Abnormal EEG Findings: A Family Study
Authors: FRANK W. SULLIVAN, KATHLEEN GENTILE, CORNELIUS BOELHOUWER
Journal: American Journal of Psychiatry (1967)

This paper presents the study of a seven-member family, six of whom showed significant EEG abnormalities. An attempt was made to correlate these data with other clinical information gathered, using the standard MMPI and standard psychological tests which were rated under "blind" techniques. The method of psychological testing and rating used in this study would appear to be quite useful in studying a family or small group as it revealed the most significant data, differentiating clearly those members with EEG abnormalities from the member with a normal EEG. None of the methods employed was able to accurately differentiate the four members with 14 and 6/second positive spiking from the two members with other types of EEG abnormalities.
Renal Scintigraphy of En Bloc Transplantation of Pediatric Kidneys
Authors: CHRISTOPHER J. PALESTRO, STANLEY J. GOLDSMITH
Journal: Clinical Nuclear Medicine (1992)

A 27-year-old man with end stage renal disease received a cadaveric renal transplant from a 15-month-old infant. Because one donor kidney was deemed insufficient for adequate renal function in the recipient, both of the infant's kidneys were transplanted, accounting for the unusual renal scan in the following images.
Evidence for Inefficient Selection Against Deleterious Mutations in Cytochrome Oxidase I of Asexual Bdelloid Rotifers
Authors: Timothy G. Barraclough, Diego Fontaneto, Claudia Ricci, Elisabeth A. Herniou
Journal: Molecular Biology and Evolution (2007)

Evolutionary theory predicts that natural selection should be less efficient in asexually than in sexually reproducing organisms. Obligate asexuals are expected to adapt slowly to changing environments and to accumulate mildly deleterious mutations to their genomes, potentially explaining their typically short evolutionary lifespans. One group of animals that appear to challenge these ideas is the bdelloid rotifers, a large and ancient clade of obligate asexuals. Previous work has found no evidence for inefficient selection against deleterious mutations in protein-coding genes of bdelloids. However, these studies relied mostly on between-species comparisons and were therefore unable to detect mildly deleterious mutations that persist within populations but are removed by selection over longer time periods. Here, we test for inefficient purifying selection acting on the cytochrome oxidase I (cox1) mitochondrial gene in 3 clades of bdelloids. Patterns of variation are compared to those of two facultatively sexual clades: a monogonont rotifer (Brachionus) and a branchiopod crustacean (Daphnia). As predicted due to the strict linkage between mitochondrial and nuclear genomes, bdelloids exhibit higher frequencies of putatively deleterious amino acid polymorphism within populations than the two facultatively sexual clades. While the monophyly and age of bdelloids makes it hard to rule out other explanations for the observed differences, several possible confounding factors, such as differences in effective population size or patterns of codon usage, are shown not to explain the observed differences. We therefore conclude that bdelloid mitochondrial DNA variation does display the signature of inefficient selection expected of obligate asexuals.
Temporal effects of thrombolytic agents on platelet function in vivo and their modulation by prostaglandins.
Authors: M A Rudd, D George, P Amarante, D E Vaughan, J Loscalzo
Journal: Circulation Research (1990)

To examine the temporal effects of plasmin generated in vivo on platelet function, we infused tissue-type plasminogen activator (t-PA) in rabbits over 3 hours and measured ex vivo platelet aggregation. We noted an initial increase in the aggregation response to ADP occurring 30 minutes after the start of infusion. This enhanced response was short-lived and by 180 minutes was reduced, compared with pretreatment levels. Baseline aggregation response was restored by 240 minutes. This pattern of aggregation response to t-PA infusion was also seen with thrombin as the agonist. Coinfusion of either prostaglandin I2 or prostaglandin E1 abolished the initial hyperaggregable phase induced by t-PA; the hypoaggregable phase occurred earlier (after 60 minutes) and persisted throughout the 1-hour recovery period. Similarly, streptokinase infused for 1 hour also increased platelet aggregation at early times and then reduced aggregation responses after the first hour. Plasma plasmin activity increased as expected with t-PA infusion alone, peaking at 30 minutes and returning to baseline by the first hour. Interestingly, prostaglandin E1 blunted the rise in plasma plasmin activity. This same dose of prostaglandin E1 or prostaglandin I2 used alone did not appreciably alter platelet function at any time during the experiment. Our data show that therapeutic doses of t-PA or streptokinase produce a biphasic effect on platelet aggregation response in the rabbit. Coinfusion of either of the antiplatelet agents, prostaglandin E1 or prostaglandin I2, abolishes the hyperaggregable phase and prolongs the inhibitory effects on platelet aggregation produced by t-PA. These data suggest that the effects of thrombolytic agents on platelet function are complex and can be modulated by antiplatelet prostaglandins.
Out-of-hours use of clinical pathologists
Authors: T H Flewett
Journal: BMJ (1978)

This situation occurs because points for medical problems contribute little to the points total.Data from six housing authorities in Wales (see table) that use the points system show that the total number of points which can be granted on medical grounds, and therefore the effectiveness of normal medical intervention, varies markedly.'Within these authorities the maximum number of medical points attainable as a percentage of the lowest Vaclue of miiedical points in relati'oni to qucallfing thrXeslhold for rehousislg in six housing authorities in lt"ales* Qualifying Maximum Maximum threshold medical Housinig illedical for points aulthorit!
Effects of fenoterol on ventilatory response to hypercapnia and hypoxia in patients with chronic obstructive pulmonary disease
Authors: S. Suzuki, Y. Watanuki, Y. Yoshiike, T. Okubo
Journal: Thorax (1997)

BACKGROUND: It has previously been shown that fenoterol, a beta 2 adrenergic agonist, increases the ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) in normal subjects. The effects of beta 2 adrenergic agonists on chemoreceptors in patients with chronic obstructive pulmonary disease (COPD) remain controversial. This study was designed to examine whether fenoterol increases the HVR and HCVR in patients with COPD. METHODS: The HCVR was tested in 20 patients using a rebreathing method and the HVR was examined using a progressive isocapnic hypoxic method. The HCVR and HVR were assessed by calculating the slopes of plots of occlusion pressure (P0.1) and ventilation (VE) against end tidal carbon dioxide pressure (PETCO2) and arterial oxygen saturation (SaO2), respectively. Spirometric values, lung volumes, and respiratory muscle strength were also measured. The HCVR and HVR were examined after the oral administration of fenoterol (15 mg/day) or placebo for seven days. RESULTS: Fenoterol treatment increased the forced expiratory volume in one second (FEV1) and inspiratory muscle strength. In the HCVR the slope of P0.1 versus PETCO2 was increased by fenoterol from 0.35 (0.23) to 0.43 (0.24) (p &lt; 0.01). Moreover, the P0.1 at PETCO2 of 8 kPa was higher on fenoterol than on placebo (p &lt; 0.05) and the VE was also greater (p &lt; 0.01). In the HVR fenoterol treatment increased the P0.1 at 80% SaO2 from 0.90 (0.72) to 0.97 (0.55) kPa (p &lt; 0.05) while the slopes of the response of P0.1 and VE were not changed. CONCLUSIONS: Fenoterol increases the ventilatory response to hypercapnia in patients with COPD, presumably by stimulation of the central chemoreceptor. The hypoxic ventilatory response is only slightly affected by fenoterol.
Flotillin-1 is essential for PKC-triggered endocytosis and membrane microdomain localization of DAT
Authors: M Laura Cremona, Heinrich J G Matthies, Kelvin Pau, Erica Bowton, Nicole Speed, Brandon J Lute, Monique Anderson, Namita Sen, Sabrina D Robertson, Roxanne A Vaughan, James E Rothman, Aurelio Galli, Jonathan A Javitch, Ai Yamamoto
Journal: Nature Neuroscience (2011)
The Role of the Activated MAPK Pathway through the Oncogenic BRAFV600E-Mutation in the Immune Escaping Mechanism of Melanoma
Authors: Hidetoshi Sumimoto, Yutaka Kawakami
Journal: Molecular Therapy (2006)

The somatic mutation of BRAF has been found in as much as 66% of human melanoma. In particular, BRAFV600E accounts for 80% of the mutation cases. The BRAFV600E somatic mutation is closely related to the constitutive activation of MAPK pathway in melanoma, and we have demonstrated that the specific inhibition of the BRAFV600E- MAPK pathway by using RNAi suppressed the proliferative and invasive ability of melanoma cells, suggesting the essential role inthe tumorigenesis (Oncogene23: 6031–39, 2004). We also investigated the role of the BRAFV600E-MAPK pathway in the immune escaping mechanism of melanoma. MEK inhibitor, U0126, or HIV lentiviral vector-mediated RNAi for the BRAFV600E, inhibited the production of immune suppressive factors including IL-6, VEGF and IL-10 from melanoma cells with the mutated BRAFV600E at both mRNA and protein levels. We compared the effects of STAT3 and/or BRAFV600E RNAi on the production of the immune suppressive factors from melanoma cells with both the STAT3 activation and the BRAFV600E-mutation. The equivalent suppression of IL-6, VEGF and IL-10 production with either the STAT3 or BRAFV600E RNAi was observed, and no significant additive or synergistic effects were found with the simultaneous RNAi for both the STAT3 and BRAFV600E. Furthermore, the suppressive activity in the culture supernatant of melanoma cells with both the STAT3 activation and the BRAFV600E- mutation for the production of inflammatory cytokines IL-12 and TNF-α by dendritic cells after LPS stimulation was significantly reduced to the equivalent levels with either the STAT3 or BRAFV600E RNAi, and no additive/synergistic effects were observed with both the STAT3 and BRAFV600E RNAi. These results suggest that theMAPK signal along with the STAT3 signal is essential for immune escaping mechanism of melanoma, and that the BRAFV600E-MAPK pathway is a potential molecular target not only for cellular proliferation/invasive ability, but also for overcoming melanoma escaping from immune surveillance.
Metastatic Pulmonary Calcification in Renal Failure Mimicking Pulmonary Embolism on Lung Scan
Authors: Shiou-Chi Cherng, Cheng-Yi Cheng, Ching-Yuan Chen, Hsian-He Hsu, Pauling Chu
Journal: Clinical Nuclear Medicine (2005)

Metastatic pulmonary calcification (MPC) characterized by diffuse calcium deposition in the lungs is known to occur in patients with chronic renal failure. However, MPC with pulmonary artery calcification is uncommon and has only been detected in a few patients with severe disorders. A 48-year-old man with chronic renal failure had cough and progressive dyspnea. Ventilation-perfusion (V/Q) lung scans showed multiple large-sized mismatched V/Q defects in the left middle and lower zones of lungs, which was consistent with a high probability of pulmonary embolism (PE). The findings of pulmonary scintigraphy resulted from MPC with pulmonary artery calcification, revealed by simultaneous technetium-99m MDP scintigraphy, low-dose computed tomography, and high-resolution computed tomography (HRCT) of the chest.
Physicians' Guide to Rare Diseases
Authors: Alan R. Aronson
Journal: JAMA (1992)

<i>Physicians' Guide to Rare Diseases</i>is a requisite for everyone's library. The book is an authorative reference to diseases the average physician does not see commonly. It is an excellent source text for the physician who is faced with a strange symptom or sign and needs to know the diagnosis, treatment, and where to obtain help. The book is not an in-depth treatise on any disease but, rather, gives the reader a general idea of the cause of the symptom complex that a patient presents with in the office. The definition of a rare disease is that fewer than 200 000 Americans have the disorder. The text does not completely stay within this limit, as certain illnesses described, for instance, the acquired immunodeficiency syndrome, are more prevalent. This is a minor deficiency, and these more common diseases are described in greater detail. The introductory sections are mandatory reading to derive
Primary hepatocyte culture: Is it home away from home?
Authors: Jacquelyn J. Maher
Journal: Hepatology (1988)

Primary Hepatocyte Culture: Is It Home Away from Home?Primary hepatocyte culture is one of many techniques which simplify the analysis of liver function.The advantage of a culture approach over alternative methods such as isolated liver perfusion is that it permits evaluation of hepatocytes as pure isolates in a controlled environment.Cultures have proven applicable to a variety of experiments, including studies of protein synthesis, intermediary metabolism and enzyme function [reviewed in Ref.(l)], and, more recently, membrane potential and electrical coupling (2, 3).The utility of cultures for intermediate-and long-term studies has been limited, however, by morphologic and functional alteration of cells during the first few days after plating and ultimately the deterioration and death of hepatocytes within 1 to 2 weeks (4-6).Loss of liver-specific characteristics reflects the absence in culture of elements that are present and support hepatocellular function in uiuo.Research directed at this problem has involved manipulation of the cell culture environment in an effort to define the appropriate conditions under which hepatocytes will maintain a differentiated phenotype for extended periods.Initial studies demonstrated that medium supplements such as nutrients (7,8) and hormones (9-12) promote increased protein synthesis and secretion by hepatocyte monolayers.Similarly, introduction of an organic substratum, such as Type I collagen, in place of plain tissue culture plastic, enhanced viability and cell attachment (13).In general, though, simple culture additions have resulted only in improvements which are quantitatively minor or transient.Currently under development are more sophisticated culture methods which introduce factors that may play a role in hepatocellular differentiation in uiuo (14) (Table 1).Those which rely on medium supplements alone fail to support liver-specific functions for more than 1 to 2 weeks (15-17).On the other hand, cultures that make use of complex extracellular matrix substrata (18-20) or incorporate cell-cell interactions in the form of coculture (24-29) have provided dramatic results.In this issue of Hepatology, Goulet and colleagues (30) demonstrate that liver-specific morphology and function can be successfully maintained by hepatocytes for up to 4 weeks when established in coculture with a variety of epithelial or mesenchymal cell lines.The following discussion will review the rationale for a coculture technique and assess its benefits in relation to alternative methods.