tbuckley/cabot-search huggingface dataset:
Blood pressure and vascular resistance in genetically hypertensive rats treated at birth with 6-hydroxydopamine.
Authors: D W Clark, D R Jones, E L Phelan, C E Devine
Journal: Circulation Research (1978)

Genetically hypertensive (GH) rats of the New Zealand strain and normotensive (N) rats were sympathectomized from birth with 6-hydroxydopamine (100 mg/kg,s.c, on alternate days, seven treatments). In adult treated rats from each strain (GHTr and NTr), blood pressure was lower than normal. Functional tests and electron microscopy showed that denervation was virtually complete in mesenteric and hindlimb arteries; the innervation of the renal artery was little affected. Ganglionic blockade still caused a large fall in blood pressure in treated rats. Vascular resistance was higher in blood-perfused hindlimbs and tails of GH rats than in those of N rats; in contrast, resistance was similar in limbs and tails of GHTr and NTr rats and was greater than that found in untreated N rats. Saline-perfused limb vessels had neither neurogenic nor myogenic tone and resistance was higher in GH limbs (whether these were from treated rats or not) than in untreated N limbs. In saline-perfused NTr limbs, there was a paradoxical structural adaptation (probably luminal narrowing) of the hindlimb blood vessels and resistance was higher than in untreated N rats. The resistance of saline-perfused GH and GHTr limbs was similar. A high peripheral resistance appears to be the main mechanism sustaining genetic hypertension, and the integrity of the vasomotor sympathetic nerves is necessary for the development of this form of experimental hypertension.
REPORT CII. UPON THE BACTERIOLOGY OF THE SUMMER DIARRHOEA OF INFANTS: [Second Communication]
Authors: H. D. R. Morgan
Journal: BMJ (1907)

ANEuRYSM of the vessels of the foot is of such rare occurrence (Chauvel; quoted by von Bergmann, could only collect the rccords of twenty such), and, when it does occur, is nearly always to be traced to definite trauma, that I have thought tLe history of the following case of spontaneous ar eurysm occurring in my hospital practice worth recording.The patient, a woman aged 53, had noticed a small swelling on the dorsrum of her left foot for over two years.It had until the last four or five weeks given her very little inconvenience, but of late had been enlarging and had given her a good deal of pain.There had never been any ir jury of the foot, and no history of Fyphilis was to be obtained.:~~~Õ n the dorsum of the foot was a puleating, expansile .swelling.about the size of a small walnut, over which the skin was slightly redd ned and thinned.It presented all ,the typical and usual bigns of aneurysm, and was situated towards ihe point of termination uf the dorsa'is pedis artery.The patient's arteries generally were slightly thickened, the puale tension increaEed, and tle second sound over.the aortic valves accentuated.Nothing else abnormal was to te made out in her physical condition.The ti ealment adopted was excision of the aneurysm, and the patient made a good ; ecovery.Well-marked endartnritis of the resected portions of the artery was preseLt, with very considerable 1hiLkpning of its walls.
Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma
Authors: Samuel A. Jensen, Emily S. Day, Caroline H. Ko, Lisa A. Hurley, Janina P. Luciano, Fotini M. Kouri, Timothy J. Merkel, Andrea J. Luthi, Pinal C. Patel, Joshua I. Cutler, Weston L. Daniel, Alexander W. Scott, Matthew W. Rotz, Thomas J. Meade, David A. Giljohann, Chad A. Mirkin, Alexander H. Stegh
Journal: Science Translational Medicine (2013)

Glioblastoma multiforme (GBM) is a neurologically debilitating disease that culminates in death 14 to 16 months after diagnosis. An incomplete understanding of how cataloged genetic aberrations promote therapy resistance, combined with ineffective drug delivery to the central nervous system, has rendered GBM incurable. Functional genomics efforts have implicated several oncogenes in GBM pathogenesis but have rarely led to the implementation of targeted therapies. This is partly because many "undruggable" oncogenes cannot be targeted by small molecules or antibodies. We preclinically evaluate an RNA interference (RNAi)-based nanomedicine platform, based on spherical nucleic acid (SNA) nanoparticle conjugates, to neutralize oncogene expression in GBM. SNAs consist of gold nanoparticles covalently functionalized with densely packed, highly oriented small interfering RNA duplexes. In the absence of auxiliary transfection strategies or chemical modifications, SNAs efficiently entered primary and transformed glial cells in vitro. In vivo, the SNAs penetrated the blood-brain barrier and blood-tumor barrier to disseminate throughout xenogeneic glioma explants. SNAs targeting the oncoprotein Bcl2Like12 (Bcl2L12)--an effector caspase and p53 inhibitor overexpressed in GBM relative to normal brain and low-grade astrocytomas--were effective in knocking down endogenous Bcl2L12 mRNA and protein levels, and sensitized glioma cells toward therapy-induced apoptosis by enhancing effector caspase and p53 activity. Further, systemically delivered SNAs reduced Bcl2L12 expression in intracerebral GBM, increased intratumoral apoptosis, and reduced tumor burden and progression in xenografted mice, without adverse side effects. Thus, silencing antiapoptotic signaling using SNAs represents a new approach for systemic RNAi therapy for GBM and possibly other lethal malignancies.
Migraine and Breast Cancer Risk: A Prospective Cohort Study and Meta-Analysis
Authors: Anke C. Winter, Megan S. Rice, Renée T. Fortner, A. Heather Eliassen, Tobias Kurth, Rulla M. Tamimi
Journal: JNCI Journal of the National Cancer Institute (2014)

Background:The evidence for an association between migraine and breast cancer risk is inconclusive. While female sex hormones have been proposed as one underlying mechanism, data on sex hormone levels in migraineurs are sparse.
The Salford Psoriasis Index: an holistic measure of psoriasis severity
Authors: B. Kirby, D.G. Fortune, M. Bhushan, R.J.G. Chalmers, C.E.M. Griffiths
Journal: British Journal of Dermatology (2000)

Journal Article The Salford Psoriasis Index: an holistic measure of psoriasis severity Get access B. Kirby, B. Kirby Dermatology Centre and Search for other works by this author on: Oxford Academic Google Scholar D.G. Fortune, D.G. Fortune Dermatology Centre andDepartment of Behavioural Medicine, University of Manchester, Hope Hospital, Salford M6 8HD, U.K. Search for other works by this author on: Oxford Academic Google Scholar M. Bhushan, M. Bhushan Dermatology Centre and Search for other works by this author on: Oxford Academic Google Scholar R.J.G. Chalmers, R.J.G. Chalmers Dermatology Centre and Search for other works by this author on: Oxford Academic Google Scholar C.E.M. Griffiths C.E.M. Griffiths Dermatology Centre and Professor C.E.M.Griffiths.E‐mail: cgriffiths@fs1.ho.man.ac.ukThis paper was presented in part at the Annual Meeting of the British Association of Dermatologists, Edinburgh, U.K., 2 July 1999. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 4, 1 April 2000, Pages 728–732, https://doi.org/10.1046/j.1365-2133.2000.03418.x Published: 01 April 2000
Re: HER2 Status and Efficacy of Adjuvant Anthracyclines in Early Breast Cancer: A Pooled Analysis of Randomized Trials
Authors: R. S. Mehta, T. Schubbert
Journal: JNCI Journal of the National Cancer Institute (2008)

Gennari et al. ( 1 ) report an interaction between HER2 status and anthracycline chemosensitivity, but they do not mention tumor grade. Multivariable analysis has revealed that Scarff – Bloom – Richardson grade III tumors respond better to neoadjuvant treatment than Scarff – Bloom – Richardson grade I tumors ( P < .0001) ( 2 ). A recent study suggests that an interaction between HER2 and estrogen receptor pathways may lead to higher proliferation rate and thus a higher tumor grade ( 3 ). Therefore, inclusion of tumor grade might have increased the relative predictive value of HER2 status and grade in predicting anthracycline chemosensitivity ( 2 ). Moreover, among patients who have HER2negative, estrogen receptor – positive breast cancer, those with higher tumor grades may benefit from anthracycline ( 2 ). Furthermore, among patients who have HER2-negative, estrogen receptor – negative, and progesterone receptor – negative breast cancer, we have demonstrated a high rate of pathological complete response ( 4 ), which is an accepted surrogate of improved survival ( 5 , 6 ). Of the 15 patients who re ceived four cycles of dose-dense anthracycline (doxorubicin) and cyclophosphamide followed by three cycles of paclitaxel (cremophor or albumin-bound paclitaxel) plus or minus carboplatin (both at 3 weeks on, 1 week off for one cycle) plus or minus six doses of bevacizumab every 2 weeks, 9 (60%; 95% confidence interval = 32% to 84%) achieved pathological complete response ( 4 ). Specifically, with anthracyclines given biweekly compared with every 3 weeks, there is a higher pathological complete response and, as a result, improved survival ( 7 ). Therefore, the pooled analysis needs to be replicated or refuted in the biweekly anthracycline setting, specifically in estrogen receptor – negative breast cancer.
Metastasis-Associated Protein 1 and Its Short Form Variant Stimulates <i>Wnt1</i> Transcription through Promoting Its Derepression from <i>Six3</i> Corepressor
Authors: Rakesh Kumar, Seetharaman Balasenthil, Bramanandam Manavathi, Suresh K. Rayala, Suresh B. Pakala
Journal: Cancer Research (2010)

Although Wnt1 downstream signaling components have been well studied and activated in human cancer, the pathways that regulate Wnt1 itself have not been explored in depth. Here, we provide gain-of-function, loss-of function, and molecular evidence supporting functional interactions between metastasis-associated protein 1 short-form (MTA1s), metastasis-associated protein 1 (MTA1), and Wnt1 signaling components during mammary gland development and tumorigenesis. Using multiple model systems involving overexpression or knockdown of MTA1s or MTA1, we discovered that MTA1s and MTA1 hyperactivate the Wnt1 pathway due to increased expression of Wnt1 transcription. MTA1s and MTA1 physically interact with Six3 chromatin, a protein product of which is a direct histone deacetylase inhibitor-dependent repressor of Wnt1 transcription. Deletion of the MTA1s and MTA1 allele in murine embryonic fibroblasts resulted in the upregulation of Six3 and downregulation of Wnt signaling. In addition, mammary glands from the MTA1s/MTA1(-/-) mice exhibited increased recruitment of Six3 corepressor complex to the Wnt1 promoter and inhibition of Wnt1 pathway in mammary glands. These findings identify MTA1s and MTA1 as important upstream modifiers of the Wnt1 transcription, and consequently its functions, by directly inhibiting the transcription of Six3, allowing derepression of Wnt1 transcription.
Peripheral ulcerative keratitis associated with erythema elevatum diutinum and a positive rheumatoid factor: a report of three cases
Authors: None Takiwaki, None Kubo, None Tsuda, None Arase, None Shiota
Journal: British Journal of Dermatology (1998)

Peripheral ulcerative keratitis (PUK) is a complication of collagen-vascular diseases such as rheumatoid arthritis (RA) and other systemic vasculitides. We report three cases of erythema elevatum diutinum with PUK. These patients presented with nodules and plaques consistent with erythema elevatum diutinum on the extremities and crusted or ulcerated purpuric lesions on the soles. Histopathological examination of these lesions revealed a dense neutrophilic infiltrate with nuclear dust and fibrin around blood vessels. All the patients developed PUK concomitant with the development of the skin lesions. The rheumatoid factor was positive at high titre in all three patients; this was associated with probable RA in one. Cutaneous lesions were dramatically improved by administration of dapsone in all cases. Dapsone was also effective in treating the ocular lesions in two patients.
Group 2 Innate Lymphoid Cells Are Critical for the Initiation of Adaptive T Helper 2 Cell-Mediated Allergic Lung Inflammation
Authors: Timotheus Y.F. Halim, Catherine A. Steer, Laura Mathä, Matthew J. Gold, Itziar Martinez-Gonzalez, Kelly M. McNagny, Andrew N.J. McKenzie, Fumio Takei
Journal: Immunity (2014)

Naive CD4+ T cell differentiation into distinct subsets of T helper (Th) cells is a pivotal process in the initiation of the adaptive immune response. Allergens predominantly stimulate Th2 cells, causing allergic inflammation. However, why allergens induce Th2 cell differentiation is not well understood. Here we show that group 2 innate lymphoid cells (ILC2s) are required to mount a robust Th2 cell response to the protease-allergen papain. Intranasal administration of papain stimulated ILC2s and Th2 cells, causing allergic lung inflammation and elevated immunoglobulin E titers. This process was severely impaired in ILC2-deficient mice. Whereas interleukin-4 (IL-4) was dispensable for papain-induced Th2 cell differentiation, ILC2-derived IL-13 was critical as it promoted migration of activated lung dendritic cells into the draining lymph node where they primed naive T cells to differentiate into Th2 cells. Papain-induced ILC2 activation and Th2 cell differentiation was IL-33-dependent, suggesting a common pathway in the initiation of Th2 cell responses to allergen.
Healthy gums, healthy heart?
Authors: C. A. Yeung
Journal: BMJ (2010)

It is hard to know from de Oliveira and colleagues’ national survey whether lack of toothbrushing causes cardiovascular disease.1 Brushing regularly may reduce the inflammation caused by periodontal disease, or people who do not brush their teeth take less care of themselves in other ways.

Although a 70% increased risk sounds quite …
Müller's conclusions and linguistic research
Authors: Frederick J. Newmeyer
Journal: Behavioral and Brain Sciences (1996)

Abstract Because Müiller fails to distinguish between two senses of the term “autonomy,” there is a danger that his results will be misinterpreted by both linguists and neuroscientists. Although he may very well have been successful in refuting one sense of autonomy, he may actually have helped to provide an explanation for the correctness of autonomy in its other sense.
Frequent Aberrant Methylation of the <b> <i>CDH4</i> </b> Gene Promoter in Human Colorectal and Gastric Cancer
Authors: Elena Miotto, Silvia Sabbioni, Angelo Veronese, George A. Calin, Sergio Gullini, Alberto Liboni, Laura Gramantieri, Luigi Bolondi, Eros Ferrazzi, Roberta Gafà, Giovanni Lanza, Massimo Negrini
Journal: Cancer Research (2004)

Abstract Gene promoter methylation causes loss of tumor suppressor genes function in human cancer. Here, we show that the CDH4 gene, a member of the cadherin family encoding for R-cadherin, contains a CpG island located at the 5′ of the first exon, which functions as a promoter element and is frequently affected by methylation in human cancer. By using methylation-specific PCR and reverse transcription-PCR in human cancer cell lines, promoter methylation could be directly linked to loss of gene expression. After treatment with the demethylating agent 5-aza-2-deoxycytidine, expression could be restored. Analysis of human primary tumors revealed that the CDH4 gene is methylated in 78% (38 of 49) of colorectal and 95% (20 of 21) of gastric carcinomas. CDH4 methylation was not detected in nonneoplastic colonic (0 of 10) and stomach (0 of 10) tissues or in peripheral blood (0 of 17). CDH4 methylation was detected in histologically normal tissues located in proximity of the neoplasms, indicating that CDH4 methylation is an early event in gastrointestinal tumor progression. We also proved that CDH4 methylation can be revealed in the peripheral blood of cancer patients. Our results indicate that CDH4 may act as a tumor suppressor gene in human gastrointestinal tumors and can potentially be used as an early diagnostic marker for gastrointestinal tumorigenesis.
Oral Disposition Index Predicts the Development of Future Diabetes Above and Beyond Fasting and 2-h Glucose Levels
Authors: Kristina M. Utzschneider, Ronald L. Prigeon, Mirjam V. Faulenbach, Jenny Tong, Darcy B. Carr, Edward J. Boyko, Donna L. Leonetti, Marguerite J. McNeely, Wilfred Y. Fujimoto, Steven E. Kahn
Journal: Diabetes Care (2008)

We sought to determine whether an oral disposition index (DI(O)) predicts the development of diabetes over a 10-year period. First, we assessed the validity of the DI(O) by demonstrating that a hyperbolic relationship exists between oral indexes of insulin sensitivity and beta-cell function.A total of 613 Japanese-American subjects (322 men and 291 women) underwent a 75-g oral glucose tolerance test (OGTT) at baseline, 5 years, and 10 years. Insulin sensitivity was estimated as 1/fasting insulin or homeostasis model assessment of insulin sensitivity (HOMA-S). Insulin response was estimated as the change in insulin divided by change in glucose from 0 to 30 min (DeltaI(0-30)/DeltaG(0-30)).DeltaI(0-30)/DeltaG(0-30) demonstrated a curvilinear relationship with 1/fasting insulin and HOMA-S with a left and downward shift as glucose tolerance deteriorated. The confidence limits for the slope of the log(e)-transformed estimates included -1 for DeltaI(0-30)/DeltaG(0-30) versus 1/fasting insulin for all glucose tolerance groups, consistent with a hyperbolic relationship. When HOMA-S was used as the insulin sensitivity measure, the confidence limits for the slope included -1 only for subjects with normal glucose tolerance (NGT) or impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) but not diabetes. On the basis of this hyperbolic relationship, the product of DeltaI(0-30)/DeltaG(0-30) and 1/fasting insulin was calculated (DI(O)) and decreased from NGT to IFG/IGT to diabetes (P < 0.001). Among nondiabetic subjects at baseline, baseline DI(O) predicted cumulative diabetes at 10 years (P < 0.001) independent of age, sex, BMI, family history of diabetes, and baseline fasting and 2-h glucose concentrations.The DI(O) provides a measure of beta-cell function adjusted for insulin sensitivity and is predictive of development of diabetes over 10 years.
Does prophylactic thyroxine treatment after operation for non-toxic goitre influence thyroid size?
Authors: L Hegedus, J M Hansen, D Veiergang, S Karstrup
Journal: BMJ (1987)

In order to evaluate the influence of thyroxine treatment on thyroid volume after thyroidectomy for non-toxic goitre 110 consecutive patients were randomised to receive thyroxine (150 micrograms daily) or no treatment three months after operation. Thyroid volume determined by ultrasonography did not differ significantly between the two groups one year after operation. Nevertheless, a similar decrease in volume was seen from three to 12 months postoperatively in the thyroxine treated and no treatment groups (median 18 (range 8-70) ml to 16 (range 7-57) ml, and median 20 (range 9-72) ml to 17 (range 8-58) ml, respectively). Three patients (two given thyroxine) had recurrence of goitre within the observation period of one year. In this series thyroid volume decreased during the first postoperative year independently of thyroxine treatment. Hence it seems questionable whether postoperative thyroid function studies can identify patients at risk of recurrence of goitre after operation for non-toxic goitre and whether routine postoperative treatment with thyroxine is justifiable.
Pneumococcal capsular serotypes and lung infection
Authors: Jeremy Stuart Brown
Journal: Thorax (2012)

Streptococcus pneumoniae is second only to Mycobacterium tuberculosis as a bacterial cause of worldwide mortality. Unlike M tuberculosis , S pneumoniae remains a major cause of death in the developed world, with a standardised mortality rate of 25 per 100 000 in the UK. S pneumoniae is the commonest pathogen causing community acquired pneumonia (CAP),1 and the majority of serious S pneumoniae infections are cases of CAP in infants and older people. S pneumoniae is also an important cause of septicaemia, meningitis and infective exacerbations of chronic obstructive pulmonary disease and bronchiectasis. S pneumoniae is surrounded by an extracellular layer of polysaccharide called the capsule which promotes immune evasion and is an essential virulence factor.2 The structure of the capsule differs between S pneumoniae strains, with 93 variants identifiable by serotyping. Serotype prevalence is unequal, with the majority of disease caused by around 20 common serotypes. Which serotypes are predominant varies with age, geography and site of infection (eg, the nasopharynx, pleural space or the blood). In the paper by Bewick et al , technical advances in microbiology have been used to identify which S pneumoniae capsular serotypes are the commonest causes of CAP in a UK centre.3 Why do these rather technical data matter to a clinician, and how could they affect future developments in the management of S pneumoniae lung infection?

First, the ability to identify which serotypes are causing CAP is in itself a major advance. Previously, capsular serotyping required cultured bacteria and was therefore biased towards serotypes that cause septicaemia as respiratory cultures have such low sensitivity in CAP. For example, in Bewick et al 's paper only 58 of 366 cases of S pneumoniae CAP had positive cultures, mainly from blood.3 By using urine samples for a …
Jnk1 in murine hepatic stellate cells is a crucial mediator of liver fibrogenesis
Authors: Gang Zhao, Maximilian Hatting, Yulia A. Nevzorova, Jin Peng, Wei Hu, Mark V Boekschoten, Tania Roskams, Michael Muller, Nikolaus Gassler, Christian Liedtke, Roger J Davis, Francisco Javier Cubero, Christian Trautwein
Journal: Gut (2013)

<h3>Objective</h3> The c-Jun N-terminal kinase-1 (Jnk1) gene has been shown to be involved in liver fibrosis. Here, we aimed to investigate the molecular mechanism and define the cell type involved in mediating the Jnk1-dependent effect on liver fibrogenesis. <h3>Design</h3> Jnk1<sup>f/f</sup> wildtype (WT), Jnk1<sup>−/−</sup> and Jnk1<sup>Δhepa</sup> (hepatocyte-specific deletion of Jnk1) mice were subjected to (i) bile duct ligation (BDL) and (ii) CCl<sub>4</sub>-induced liver fibrosis. Additionally, we performed bone marrow transplantations (BMT), isolated primary hepatic stellate cells (HSCs), studied their activation in vitro and investigated human diseased liver samples. <h3>Results</h3> Phosphorylated Jnk was expressed in myofibroblasts, epithelial and inflammatory cells during the progression of fibrogenesis in humans and mice. In mice, liver transaminases, alkaline phosphatase, bilirubin and liver histology revealed reduced injury in Jnk1<sup>−/−</sup> compared with WT and Jnk1<sup>Δhepa</sup> mice correlating with lower hepatocyte cell death and proliferation. Consequently, parameters of liver fibrosis such as Sirius red staining and collagen IA1 and α-smooth muscle actin expression were downregulated in Jnk1<sup>−/−</sup> compared with WT and Jnk1<sup>Δhepa</sup> livers, 4 weeks after CCl<sub>4</sub> or BDL. BMT experiments excluded bone marrow–derived cells from having a major impact on the Jnk1-dependent effect on fibrogenesis, while primary HSCs from Jnk1<sup>−/−</sup> livers showed reduced transdifferentiation and extracellular matrix production. Moreover, Jnk1 ablation caused a reduced lifespan and poor differentiation of HSCs into matrix-producing myofibroblasts. <h3>Conclusions</h3> Jnk1 in HSCs, but not in hepatocytes, significantly contribute to liver fibrosis development, identifying Jnk1 in HSCs as a profibrotic kinase and a promising cell-directed target for liver fibrosis.