tbuckley/cabot-search huggingface dataset:
Insulin stimulates the L-type Ca2+ current in rat cardiac myocytes
Authors: F Aulbach
Journal: Cardiovascular Research (1999)

Objective: The aim was to study the L-type calcium current (ICa,L) in cardiac myocytes as a possible target of insulin in the regulation of cardiac function. Method: Using the whole-cell configuration of the patch–clamp technique, we investigated the stimulation of ICa,L by insulin in isolated rat ventricular myocytes. Results: The stimulation of ICa,L by insulin was dose-dependent (EC50=33 nM) and reversible. Maximum stimulation of ICa,L over basal ICa,L was 86±11% (n=25) at 1 μM insulin. Insulin (1 μM) shifted the current–voltage relationship and potential-dependent availability of ICa,L to more negative potentials by about 3.5 and 1.5 mV, respectively. The maximum conductance of ICa,L was increased by 1 μM insulin, from 26±4 to 39±5 nS (n=11). Isoproterenol (100 nM), which stimulated ICa,L by 156±23% (n=10) over basal ICa,L, acted faster than insulin. The half-maximum stimulation of ICa,L by isoproterenol and insulin was reached after 44±5 and 80±9 s, respectively. Insulin and isoproterenol responses were not additive. Insulin (1 μM) and isoproterenol (100 nM) stimulation of ICa,L was inhibited by Rp-cAMPS (1 mM) to 12±3 and 32±4%, respectively. Insulin (1 μM) increased cAMP content in rat cardiomyocytes by about two-fold. Insulin-like growth factor-1 (IGF-1; 5 μM) increased ICa,L by only 5.9±0.9% (n=6). Conclusions: Our data show that insulin stimulates the L-type calcium current in isolated rat ventricular myocytes in a dose-dependent and reversible manner and suggest that this effect is mediated by insulin receptors and the cAMP-dependent protein kinase.
Protease-Activated Receptor 2–Mediated Vasodilatation in Humans In Vivo
Authors: Jonathan Robin, Rajesh Kharbanda, Peter Mclean, Richard Campbell, Patrick Vallance
Journal: Circulation (2003)

Systemic hypotension as a consequence of vascular dysfunction is a well-recognized and important feature of critical illness. Although serine protease activation has been implicated as a cause of vascular dysfunction in systemic inflammation, the mechanism is unknown. Recently, a class of receptors with an entirely novel mechanism of action, protease-activated receptors (PARs), has been identified that would explain the link between protease activation and systemic hypotension. Our aim was to test the hypothesis that in vivo activation of protease-activated receptor 2 (PAR-2) in humans would mediate vasodilatation.For these first-in-human studies, an activating peptide for the human PAR-2 receptor was synthesized and administered to healthy volunteers. Using both the dorsal hand vein technique and forearm plethysmography, we studied the effects of PAR-2 activation in human blood vessels and investigated the mechanism of vasodilation. Activation of PAR-2 receptors in vivo dilated human blood vessels in a dose-dependent manner, and the effects were reduced by inhibition of both nitric oxide and prostanoid synthesisThese findings demonstrate that serine protease activity can cause human vasodilation and provide a possible explanation of why serine protease activation in critical illness is associated with vascular dysfunction.
Samuel Prescott and His Midnight Ride
Authors: Henry R. Viets
Journal: New England Journal of Medicine (1956)

DR. Samuel Prescott, son and grandson of Concord physicians, had ridden, during the evening of April 18, 1775, to call on Lydia Mulliken, daughter of a Lexington clockmaker. On the way home, early in the morning of April 19, he learned that Paul Revere and William Dawes had brought the news that the British were on the march from Boston.Spurring his horse, he overtook the midnight couriers on a road that ran through the northern part of Lincoln. While Dawes was stopping to arouse a family of sleeping farmers Revere rode ahead and at a bend of the road . . .
A PLEA FOR THE EARLY TREATMENT OF SQUINT.
Authors: NELSON MILES BLACK
Journal: JAMA (1902)

The majority of laymen and a great many of our professional brethren regard squint with a great deal of indifference. This arises largely from the prevalent idea that the child will outgrow it, is too young to be treated or, if treated, will have to always wear glasses. Yet when children grow up with this horrible deformity, they and their parents often seek for relief without success. What I wish to try to make clear is the fallacy of the above reasons, why the squinting eyes of children should be attended to as soon as the first appearance of even a tendency to squint is noticed. In rare instances in some cases the squint disappears as the patient grows older, but nearly always with vision much impaired in the deviating eye and binocular vision very imperfectly developed. The earlier one can get a case after he has commenced
Hormonal control of the renal immune response and antibacterial host defense by arginine vasopressin
Authors: Cécilia Chassin, Mathias W. Hornef, Marcelle Bens, Michael Lotz, Jean-Michel Goujon, Sophie Vimont, Guillaume Arlet, Alexandre Hertig, Eric Rondeau, Alain Vandewalle
Journal: The Journal of Experimental Medicine (2007)

Ascending urinary tract infection (UTI) and pyelonephritis caused by uropathogenic Escherichia coli (UPEC) are very common infections that can cause severe kidney damage. Collecting duct cells, the site of hormonally regulated ion transport and water absorption controlled by vasopressin, are the preferential intrarenal site of bacterial adhesion and initiation of inflammatory response. We investigated the effect of the potent V2 receptor (V2R) agonist deamino-8-D-arginine vasopressin (dDAVP) on the activation of the innate immune response using established and primary cultured collecting duct cells and an experimental model of ascending UTI. dDAVP inhibited Toll-like receptor 4-mediated nuclear factor kappaB activation and chemokine secretion in a V2R-specific manner. The dDAVP-mediated suppression involved activation of protein phosphatase 2A and required an intact cystic fibrosis transmembrane conductance regulator Cl- channel. In vivo infusion of dDAVP induced a marked fall in proinflammatory mediators and neutrophil recruitment, and a dramatic rise in the renal bacterial burden in mice inoculated with UPECs. Conversely, administration of the V2R antagonist SR121463B to UPEC-infected mice stimulated both the local innate response and the antibacterial host defense. These findings evidenced a novel hormonal regulation of innate immune cellular activation and demonstrate that dDAVP is a potent modulator of microbial-induced inflammation in the kidney.
CTLA-4 blockade decreases TGF-beta, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques
Authors: A. Hryniewicz, A. Boasso, Y. Edghill-Smith, M. Vaccari, D. Fuchs, D. Venzon, J. Nacsa, M. R. Betts, W.-P. Tsai, J.-M. Heraud, B. Beer, D. Blanset, C. Chougnet, I. Lowy, G. M. Shearer, G. Franchini
Journal: Blood (2006)
Pulmonary toxicity and carcinogenicity of trichloroethylene: species differences and modes of action.
Authors: T Green
Journal: Environmental Health Perspectives (2000)

Trichloroethylene (TCE) is both acutely toxic and carcinogenic to the mouse lung following exposure by inhalation. In contrast, it is not carcinogenic in the rat lung and is markedly less toxic following acute exposure. Toxicity to the mouse lung is confined almost exclusively to the nonciliated Clara cell and is characterized by vacuolation and increases in cell replication. Chloral, a metabolite of TCE that accumulates in Clara cells and has been shown to be the cause of the toxicity, also causes aneuploidy in some test systems. Cytotoxicity, increased cell division, and aneuploidy are known risk factors in the development of cancer and provide a plausible mode of action for TCE as a mouse lung carcinogen. All acute and chronic effects of TCE on the mouse lung are believed to be a direct consequence of high cytochrome P450 activity and impaired metabolism of chloral in Clara cells. Comparisons between species suggest that the ability of the human lung to metabolize TCE is approximately 600-fold less than that in the mouse. In addition, the human lung differs markedly from the mouse lung in the number and morphology of its Clara cells. Thus, the large quantitative differences between the metabolic capacity of the mouse lung and the human lung, together with the species differences in the number and morphology of lung Clara cells, suggest that the risks to humans are minimal and that other tumor sites should take precedent over the lung when assessing the potential risks to humans exposed to TCE.
Organic Transdermal Iontophoresis Patch with Built‐in Biofuel Cell
Authors: Yudai Ogawa, Koichiro Kato, Takeo Miyake, Kuniaki Nagamine, Takuya Ofuji, Syuhei Yoshino, Matsuhiko Nishizawa
Journal: Advanced Healthcare Materials (2014)

A completely organic iontophoresis patch is reported. A built-in biofuel cell is mounted on the patch that generates transdermal iontophoretic administration of compounds into the skin. The amplitude of transdermal current is tuned by integrating a conducting polymer-based stretchable resistor of predetermined resistance. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Which component of sulphasalazine is active in rheumatoid arthritis?
Authors: T Pullar, J A Hunter, H A Capell
Journal: BMJ (1985)

Sulphasalazine is known to be effective as a second line agent in the treatment of rheumatoid arthritis. The two chemical constituents of sulphasalazine (sulphapyridine and 5-aminosalicylic acid) were assessed separately in the treatment of rheumatoid arthritis. Over 24 weeks sulphapyridine showed a pronounced second line effect comparable with sulphasalazine and with a similar toxicity profile, whereas 5-aminosalicylic acid showed only a weak first line effect. Thus sulphapyridine appears to be the active moiety responsible for the second line effect of sulphasalazine in rheumatoid arthritis. The efficacy of the antibacterial component of sulphasalazine yet again permits speculation about the role of a bacterial pathogen in the aetiopathogenesis of rheumatoid disease.
MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations
Authors: Yannick Ladeiro, Gabrielle Couchy, Charles Balabaud, Paulette Bioulac-Sage, Laura Pelletier, Sandra Rebouissou, Jessica Zucman-Rossi
Journal: Hepatology (2008)

Molecular classifications defining new tumor subtypes have been recently refined with genetic and transcriptomic analyses of benign and malignant hepatocellular tumors. Here, we performed microRNA (miRNA) profiling in two series of fully annotated liver tumors to uncover associations between oncogene/tumor suppressor mutations and clinical and pathological features. Expression levels of 250 miRNAs in 46 benign and malignant hepatocellular tumors were compared to those of 4 normal liver samples with quantitative reverse-transcriptase polymerase chain reaction. miRNAs associated with genetic and clinical characteristics were validated in a second series of 43 liver tumor samples and 16 nontumor samples. miRNA profiling unsupervised analysis classified samples in unique clusters characterized by histological features (tumor/nontumor, P < 0.001; benign/malignant tumors, P < 0.01; inflammatory adenoma and focal nodular hyperplasia, P < 0.01), clinical characteristics [hepatitis B virus (HBV) infection, P < 0.001; alcohol consumption, P < 0.05], and oncogene/tumor suppressor gene mutations [beta-catenin, P < 0.01; hepatocyte nuclear factor 1alpha (HNF1alpha), P < 0.01]. Our study identified and validated miR-224 overexpression in all tumors and miR-200c, miR-200, miR-21, miR-224, miR-10b, and miR-222 specific deregulation in benign or malignant tumors. Moreover, miR-96 was overexpressed in HBV tumors, and miR-126* was down-regulated in alcohol-related hepatocellular carcinoma. Down-regulations of miR-107 and miR-375 were specifically associated with HNF1alpha and beta-catenin gene mutations, respectively. miR-375 expression was highly correlated to that of beta-catenin-targeted genes as miR-107 expression was correlated to that of HNF1alpha in a small interfering RNA cell line model. Thus, this strongly suggests that beta-catenin and HNF1alpha could regulate miR-375 and miR-107 expression levels, respectively.Hepatocellular tumors may have a distinct miRNA expression fingerprint according to malignancy, risk factors, and oncogene/tumor suppressor gene alterations. Dissecting these relationships provides a new hypothesis to understand the functional impact of miRNA deregulation in liver tumorigenesis and the promising use of miRNAs as diagnostic markers.
Managing spontaneous first trimester miscarriage
Authors: D. J Cahill
Journal: BMJ (2001)

Clinical review p 1343 

Spontaneous miscarriage (inevitable or incomplete) and early fetal demise (previously called missed abortion)1 are components of pregnancy loss in the first trimester. For most of the 20th century spontaneous miscarriage was managed by evacuation of retained products of conception. Traditionally carried out with ovum forceps and curettage, this method changed to vacuum aspiration after advances were made in the equipment to deal with surgical termination of pregnancy. The belief that retained products always needed to be evacuated after spontaneous miscarriage developed because of the two major complications of inappropriately managed miscarriage, bleeding, and infection. However, changes in public health and medical practice have led to questioning of this dogma. Do all women really need evacuation of retained products? And if not, how can we decide who does require it? How likely are complications to arise if evacuation is undertaken—or if it is not?

In their review article in this week's BMJ Ankum et al describe the results of a literature search on managing spontaneous miscarriage.2 They propose …
Imaging of Infected Total Arthroplasty With Tc-99m-labeled Antigranulocyte Antibody Fab′ Fragments
Authors: Thomas von Rothenburg, Martin Schoellhammer, Josef Schaffstein, Odo Koester, Gebhard Schmid
Journal: Clinical Nuclear Medicine (2004)

The objective of this study was to evaluate the diagnostic accuracy of Tc-99m-labeled antigranulocyte antibody Fab' fragments in infected total arthroplasty.A total of 38 immunoscintigrams were evaluated retrospectively with 15 to 25 mCi Tc-99m-labeled antigranulocyte antibody-Fab' fragments. The final diagnosis was assessed by articular puncture or intraoperative sampling.In the total hip replacement group the authors found 10 true positives, 7 true negatives, 8 false positives, and 1 false negative; and in the total knee replacement group they found 4 true positives, 8 true negatives, and no false positives or false negatives. They also found a sensitivity of 93%, a specificity of 65%, and a positive predictive accuracy of 63%. There was a negative predictive accuracy of 94%.The high negative predictive accuracy in the whole group suggests that the scan can be used to exclude infection in most cases. Negative results with a high clinical suspicion merits further investigation. A positive result will require further correlative imaging, especially for total knee replacement.
Quality Assessment Moving From Theory to Practice
Authors: Dennis S. O'Leary
Journal: JAMA (1988)

Throughout the era of modern medicine, physicians have constantly risen to the challenge of resolving difficult problems. The process of resolution has provided both intellectual stimulation and the fundamental satisfaction of improving the human condition. Today, medicine faces a more complex challenge, the challenge to engage in meaningful selfexamination. In this issue of<i>JAMA</i>, Avedis Donabedian,<sup>1</sup>widely recognized for his formulation of quality assessment, sets forth in lucid detail the formidable task now facing clinical medicine. Despite exhortations for self-examination from the physician community since early in this century, what we know and have done about quality assessment to date is remarkably little. Students of quality assessment will find the Donabedian construct to be both provocative and useful. So too should practicing physicians, as we all begin to grapple with the convolutions of a different kind of science. This, of course, is not simply a scientific puzzle. The quality
Household Air Pollution from Coal and Biomass Fuels in China: Measurements, Health Impacts, and Interventions
Authors: Junfeng (Jim) Zhang, Kirk R. Smith
Journal: Environmental Health Perspectives (2007)

ObjectiveNearly all China’s rural residents and a shrinking fraction of urban residents use solid fuels (biomass and coal) for household cooking and/or heating. Consequently, global meta-analyses of epidemiologic studies indicate that indoor air pollution from solid fuel use in China is responsible for approximately 420,000 premature deaths annually, more than the approximately 300,000 attributed to urban outdoor air pollution in the country. Our objective in this review was to help elucidate the extent of this indoor air pollution health hazard.Data sourcesWe reviewed approximately 200 publications in both Chinese- and English-language journals that reported health effects, exposure characteristics, and fuel/stove intervention options.ConclusionsObserved health effects include respiratory illnesses, lung cancer, chronic obstructive pulmonary disease, weakening of the immune system, and reduction in lung function. Arsenic poisoning and fluorosis resulting from the use of “poisonous” coal have been observed in certain regions of China. Although attempts have been made in a few studies to identify specific coal smoke constituents responsible for specific adverse health effects, the majority of indoor air measurements include those of only particulate matter, carbon monoxide, sulfur dioxide, and/or nitrogen dioxide. These measurements indicate that pollution levels in households using solid fuel generally exceed China’s indoor air quality standards. Intervention technologies ranging from simply adding a chimney to the more complex modernized bioenergy program are available, but they can be viable only with coordinated support from the government and the commercial sector.
Quantitation of major allergens in dust samples from urban populations collected in different seasons in two climatic areas of the Basque region (Spain)
Authors: S. Echechipia, P. Ventas, M. Audicana, I. Urrutia, G. Gastaminza, F. Polo, L. Fernández de Corres
Journal: Allergy (1995)

We present the results of allergen content evaluation in 80 dust samples from 31 homes of atopic patients from two climatic areas (humid and subhumid), collected in two seasons of the year (autumn and winter). Monoclonal antibody‐based immunoassays were used to quantify Der p 1, Der f 1, Der 2, Lep d 1, and Pel d 1. The results were compared according to climate, season, and the type of sensitization (Pyroglyphidae mites, storage mites, or grass pollens). We underline the predominance of Dermatophagoides pteronyssinus (89% of samples) over D. farinae (16% of samples) in our environment. Der p 1 rates were higher in the humid area (Mann‐Whitney P &lt;0.001), especially in the autumn (Wilcoxon P &lt;0.05). Lep d 1 was detected in 23 % of samples and Lep d 1 levels were higher in the homes of patients sensitized to storage mites (Mann‐Whitney P &lt;0.05), whereas this allergen was not detected in the homes of pollen‐allergic patients. Pel d 1 was detected in nine of the 31 homes (16% of samples) although there was a cat in only one home.
Over-inclusive referral guidance contributes to overdiagnosis
Authors: K. Barraclough
Journal: BMJ (2012)

Over-inclusive guidelines may also contribute to overdiagnosis.1 The threefold increase in the diagnosis of malignant melanoma since 1975 may be due to rising incidence, or it may be that guidance requires urgent referral on the basis of a clinical prediction rule with a 30-37% specificity.2 General practitioners following this National Institute for Health and …
Acute liver failure associated with antiretroviral treatment for HIV - is there a role for liver transplantation?
Authors: C. Salmon, L. Hennessy, C. Oza, H. McGann, R. Jones
Journal: Gut (2011)

<h3>Introduction</h3> Combination antiretroviral medication has dramatically improved the prognosis of HIV infected individuals. Hepatotoxicity is an adverse event that can lead to interruption of therapy, clinical hepatitis and death. HIV was previously a contraindication to liver transplantation but it has now been shown that HIV+ve patients, without HCV co-infection, do equally well following transplantation for chronic liver failure. The authors report on the management, complications and outcome of 6 patients that presented with acute liver failure secondary to antiretroviral therapy. <h3>Methods</h3> All patients presenting to a single site hospital with acute liver failure secondary to antiretroviral therapy from June 2007 to June 2010 were included. Data collected included demographics, blood results, morbidity, mortality and outcome. <h3>Results</h3> 6 HIV+ve patients, on antiretroviral medication for a median 29 months (range 1–70), were admitted. The median age was 38 years (range 35–43). 4 were female. All patients were encephalopathic, had a raised bilirubin (range 160–585 μmol/l, median 404), raised ALT (range 298–1645 IU/l, median 642) and prolonged PT (range 25–265 s, median 46.5). All 6 patients had necrosis on biopsy or explanted liver. All patients were on NNRTI based HAART, 4 on nevirapine and 2 on efavirenz. The antiretroviral regime was discontinued in each case. Of the 6 patients, 4 had a liver transplant. All transplanted patients had postoperative complications. 3 had episodes of acute rejection requiring pulsed methylprednisolone, 1 developed an anastomotic bile leak requiring ERCP and stenting, 2 developed post-transplant diabetes requiring insulin and 1 had a significant drug interaction with tacrolimus and Kaletra resulting in seizures. 1 transplanted patient had graft dysfunction, recurrent breakthrough HIV activity and died from complications of a liver biopsy. The other 3 patients are well with well-controlled HIV at a median follow-up of 21 months (range 5–40). Of the two patients not transplanted, one patient was treated with high dose steroids and recovered and one patient died. <h3>Conclusion</h3> HIV+ve patients with acute liver failure can be successfully transplanted. Complications in the postoperative period are similar to those of HIV−ve patients although drug interactions can complicate post-transplant immunosuppressive management. In this series giving pulsed methylprednisolone does not appear to have a deleterious effect on their HIV. Liver transplantation can be a life saving treatment that should be considered in this group of patients.
DNMT3a mutations in high-risk myelodysplastic syndrome parallel those found in acute myeloid leukemia
Authors: M Ewalt, N G Galili, M Mumtaz, M Churchill, S Rivera, F Borot, A Raza, S Mukherjee
Journal: Blood Cancer Journal (2011)

DNMT3a mutations in high-risk myelodysplastic syndrome parallel those found in acute myeloid leukemia