tbuckley/cabot-search huggingface dataset:
A CASE OF MOLLUSCUM FIBROSUM: (VON RECKLINGHAUSEN'S DISEASE)
Authors: A. W. Gill
Journal: BMJ (1915)

THE case described below illustrates the usual features of mnolluscum-i fibrosuni, and little is to be added to the ori,ginal description of tlle disease publishted by von Reckliughlausen in 1882.Several cases lhave been de- scribed and investigated since that date, and lhave all corroborated hiis discovery that tlle multiple growtlls occurring, in tlle sliiii are of thenature of fibromnata growing from the connective tissue of the terminal filaments of the cutaneous nerves.Tlle standard work on the subject in this country is the exhauistive monograph by Alexis Thomson,2 On Neuroma, and Netroflbrornatosis, publislhed in 1900.Therein will be found a fuLll description of tlle two cases recorded by von Recklinglhausen, a complete account of symiptoms, diagnosis, prognosis, etc., and a list of all the recorded cases of neurofibromatosis up to that dlate.Rolleston anid Macilaughlton 2 in 1912, in their paper on lhereditary and famililial types of tlle disease, aive a furtlher list of familial and lhereditary cases publislhed after 1900.
Some implications from language development for merge
Authors: Peter W. Jusczyk, Elizabeth K. Johnson
Journal: Behavioral and Brain Sciences (2000)

Recent investigations indicate that, around 7-months-of-age, infants begin to show some ability to recognize words in fluent speech. In segmenting and recognizing words, infants rely on information available in the speech signal. We consider what implications these findings have for adult word recognition models in general, and for Merge, in particular.
Traditional Chinese medicine and sports drug testing: identification of natural steroid administration in doping control urine samples resulting from musk (pod) extracts
Authors: Mario Thevis, Wilhelm Schänzer, Hans Geyer, Detlef Thieme, Joachim Grosse, Claudia Rautenberg, Ulrich Flenker, Simon Beuck, Andreas Thomas, Ruben Holland, Jiri Dvorak
Journal: British Journal of Sports Medicine (2012)

The administration of musk extract, that is, ingredients obtained by extraction of the liquid secreted from the preputial gland or resulting grains of the male musk deer (eg, Moschus moschiferus ), has been recommended in Traditional Chinese Medicine (TCM) applications and was listed in the Japanese pharmacopoeia for various indications requiring cardiovascular stimulation, anti-inflammatory medication or androgenic hormone therapy. Numerous steroidal components including cholesterol, 5α-androstane-3,17-dione, 5β-androstane-3,17-dione, androsterone, etiocholanolone, epiandrosterone, 3β-hydroxy-androst-5-en-17-one, androst-4-ene-3,17-dione and the corresponding urea adduct 3α-ureido-androst-4-en-17-one were characterised as natural ingredients of musk over several decades, implicating an issue concerning doping controls if used for the treatment of elite athletes. In the present study, the impact of musk extract administration on sports drug testing results of five females competing in an international sporting event is reported. In the course of routine doping controls, adverse analytical findings concerning the athletes' steroid profile, corroborated by isotope-ratio mass spectrometry (IRMS) data, were obtained. The athletes' medical advisors admitted the prescription of TCM-based musk pod preparations and provided musk pod samples for comparison purposes to clarify the antidoping rule violation. Steroid profiles, IRMS results, literature data and a musk sample obtained from a living musk deer of a local zoo conclusively demonstrated the use of musk pod extracts in all cases which, however, represented a doping offence as prohibited anabolic–androgenic steroids were administered.
Estimating Incidence from Prevalence in Generalised HIV Epidemics: Methods and Validation
Authors: Timothy B Hallett, Basia Zaba, Jim Todd, Ben Lopman, Wambura Mwita, Sam Biraro, Simon Gregson, J. Ties Boerma
Journal: PLoS Medicine (2008)

Background HIV surveillance of generalised epidemics in Africa primarily relies on prevalence at antenatal clinics, but estimates of incidence in the general population would be more useful. Repeated cross-sectional measures of HIV prevalence are now becoming available for general populations in many countries, and we aim to develop and validate methods that use these data to estimate HIV incidence. Methods and Findings Two methods were developed that decompose observed changes in prevalence between two serosurveys into the contributions of new infections and mortality. Method 1 uses cohort mortality rates, and method 2 uses information on survival after infection. The performance of these two methods was assessed using simulated data from a mathematical model and actual data from three community-based cohort studies in Africa. Comparison with simulated data indicated that these methods can accurately estimates incidence rates and changes in incidence in a variety of epidemic conditions. Method 1 is simple to implement but relies on locally appropriate mortality data, whilst method 2 can make use of the same survival distribution in a wide range of scenarios. The estimates from both methods are within the 95% confidence intervals of almost all actual measurements of HIV incidence in adults and young people, and the patterns of incidence over age are correctly captured. Conclusions It is possible to estimate incidence from cross-sectional prevalence data with sufficient accuracy to monitor the HIV epidemic. Although these methods will theoretically work in any context, we have able to test them only in southern and eastern Africa, where HIV epidemics are mature and generalised. The choice of method will depend on the local availability of HIV mortality data.
A guinea-pig model of ultrasonically nebulized distilled water-induced bronchoconstriction
Authors: M Fujimura, M Amemiya, S Myou, M Mizuguchi, T Matsuda
Journal: European Respiratory Journal (1997)

Ultrasonically nebulized distilled water-induced bronchoconstriction (UNDW-IB) is specific to asthma. The mechanisms underlying UNDW-IB are not fully understood, and no reproducible animal model has been reported. The purpose of this study was to develop a guinea-pig model of UNDW-IB. Ultrasonically nebulized distilled water (UNDW) was inhaled 20 min after an aerosolized antigen challenge in passively sensitized and artificially ventilated guinea-pigs. UNDW was also inhaled 5 and 20 min after 0.1 mg x mL(-1) methacholine inhalation in nonsensitized animals. In addition, 0.1 mg x kg(-1) S-1452, a thromboxane A2 antagonist, or saline was given intravenously 5 min before UNDW inhalation in sensitized animals. The inhalation of UNDW caused bronchoconstriction, when inhaled 20 min after an antigen challenge in sensitized guinea-pigs. UNDW inhalation did not produce bronchoconstriction after saline inhalation in nonsensitized or sensitized guinea-pigs, or after antigen inhalation in nonsensitized animals. Methacholine-induced bronchoconstriction did not evoke UNDW-IB. Neither did S-1452 reduce the UNDW-IB. In conclusion, the guinea-pig model of ultrasonically nebulized distilled water-induced bronchoconstriction developed in this study suggests that allergic reaction, but not bronchoconstriction, can induce bronchial hyperresponsiveness to ultrasonically nebulized distilled water, and that thromboxane A2 is not involved in ultrasonically nebulized distilled water-induced bronchoconstriction.
Human Tuberculosis of Bovine Origin in Staffordshire
Authors: A. S. Griffith
Journal: BMJ (1936)

ConclusionsNon-spirochaetal infectious jaundice is to be regarded as a general infection in which symptoms of disorganized liver functioh predominate.These symptoms are due to two main causes: first a maladjustment between the metabolisms of fat and carbohydrate causing acidosis and secondly an escape of bile into the blood stream causing jaundice, bilirubinuria, a tendency to haemorrhages, etc. Jaundice of skin and conjunctiva is not invariable, and was not present in about 8 per cent. of the present series.Enlargement of the liver is common, occurring in 63 per cent. of cases, and is probably due to a deposit of fat in the liver cells.The spleen was enlarged in 15 per cent. of cases, and 17 per cent.showed albuminuria.The causative organism or virus is unknown.Guineapigs do not appear to be susceptible to the disease.The evidence is in favour of a primary nasopharyngeal in- fection in some cases.Second attacks &re rare, but do occur.The symptomatology differs from that of Weil's disease in degree only.In epidemics, Weil's disease should be excluded as soon as possibl3.Every case of " catarrhal " jaundice in children should be isolated for a period of at least four weeks.Any case may be the starting-point of an epidemic.In institutions observation of contacts (particularly with reference to the urine) and quarantine for a similar period should be enforced.Treatment should be directed principally against the acidosis.I am indebted to Mrs.
RASA1 functions in EPHB4 signaling pathway to suppress endothelial mTORC1 activity
Authors: Jun Kawasaki, Sandrine Aegerter, R. Dawn Fevurly, Akiko Mammoto, Tadanori Mammoto, Mustafa Sahin, John D. Mably, Steven J. Fishman, Joanne Chan
Journal: Journal of Clinical Investigation (2014)

Vascular malformations are linked to mutations in RAS p21 protein activator 1 (RASA1, also known as p120RasGAP); however, due to the global expression of this gene, it is unclear how these mutations specifically affect the vasculature. Here, we tested the hypothesis that RASA1 performs a critical effector function downstream of the endothelial receptor EPHB4. In zebrafish models, we found that either RASA1 or EPHB4 deficiency induced strikingly similar abnormalities in blood vessel formation and function. Expression of WT EPHB4 receptor or engineered receptors with altered RASA1 binding revealed that the ability of EPHB4 to recruit RASA1 is required to restore blood flow in EPHB4-deficient animals. Analysis of EPHB4-deficient zebrafish tissue lysates revealed that mTORC1 is robustly overactivated, and pharmacological inhibition of mTORC1 in these animals rescued both vessel structure and function. Furthermore, overexpression of mTORC1 in endothelial cells exacerbated vascular phenotypes in animals with reduced EPHB4 or RASA1, suggesting a functional EPHB4/RASA1/mTORC1 signaling axis in endothelial cells. Tissue samples from patients with arteriovenous malformations displayed strong endothelial phospho-S6 staining, indicating increased mTORC1 activity. These results indicate that deregulation of EPHB4/RASA1/mTORC1 signaling in endothelial cells promotes vascular malformation and suggest that mTORC1 inhibitors, many of which are approved for the treatment of certain cancers, should be further explored as a potential strategy to treat patients with vascular malformations.
Modulation of Tumor-host Interactions, Angiogenesis, and Tumor Growth by Tissue Inhibitor of Metalloproteinase 2 via a Novel Mechanism
Authors: Andrew L. Feldman, William G. Stetler-Stevenson, Nick G. Costouros, Vladimir Knezevic, Galina Baibakov, H. Richard Alexander, Dominique Lorang, Stephen M. Hewitt, Dong-Wan Seo, Marshall S. Miller, Sarah O’Connor, Steven K. Libutti
Journal: Cancer Research (2004)

Abstract Solid tumors depend on angiogenesis for sustained growth. Tissue inhibitor of metalloproteinase 2 (TIMP-2) is an angiogenesis inhibitor initially characterized for its ability to block matrix metalloproteinases; however, recent data suggest that the antiangiogenic action of TIMP-2 may rely on matrix metalloproteinase-independent mechanisms. The aim of this study was to identify molecular pathways involved in the effects of TIMP-2 on processes dependent on tumor-host interactions such as angiogenesis. Using in vitro cell culture and a syngeneic murine tumor model, we compared the effects of TIMP-2 overexpression on gene expression profiles in vitro to those observed in vivo. Validating these findings by real-time quantitative PCR and layered protein scanning, we identified up-regulation of mitogen-activated protein kinase phosphatase 1 as an effector of the antiangiogenic function of TIMP-2. Up-regulation of mitogen-activated protein kinase phosphatase 1 in tumors overexpressing TIMP-2 leads to dephosphorylation of p38 mitogen-activated protein kinase and inhibition of tumor growth and angiogenesis. Phosphatase activity appears important in regulating tumor angiogenesis, offering a promising direction for the identification of novel molecular targets and antiangiogenic compounds for the treatment of cancer.
Adrenergic Blocking Agents in the Treatment of Shock
Authors: J H Bloch, C H Pierce, R C Lillehei
Journal: Annual Review of Medicine (1966)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Kinetics and Dynamics of Prednisolone*
Authors: F. J. FREY
Journal: Endocrine Reviews (1987)

THE PHARMACOLOGICAL response (dynamics) to corticosteroids is determined by the affinity of these steroids to specific receptors at the target organ and by the availability and duration of time spent at receptor sites (1). The latter is determined by kinetic factors such as systemic availability, protein binding, distribution, metabolism, and excretion. Two comprehensive reviews of the pharmacokinetics of prednisolone have been published by Pickup in 1979 (2) and Jusko and Rose in 1980 (3). This review examines factors which modulate the kinetics and dynamics of prednisone/prednisolone, the most commonly prescribed synthetic glucocorticosteroids in clinical practice. In the past, investigations of prednisone and prednisolone metabolism were performed by analyzing the plasma disappearance of [3H]prednisolone (4,5). In those studies chromatography was mandatory before radioactive counting in order to distinguish between prednisolone or prednisone and labeled metabolites (5–7). GLC and spectrophotometric techniques which do not require the administration of radioactive steroid enable one to estimate prednisone and/or prednisolone concentrations in plasma, but these methods lack the sensitivity required for measuring plasma concentrations after usual therapeutic doses (8–11).
Numb and Numbl are required for maintenance of cadherin-based adhesion and polarity of neural progenitors
Authors: Mladen-Roko Rašin, Valeswara-Rao Gazula, Joshua J Breunig, Kenneth Y Kwan, Matthew B Johnson, Susan Liu-Chen, Hua-Shun Li, Lily Yeh Jan, Yuh-Nung Jan, Pasko Rakic, Nenad Šestan
Journal: Nature Neuroscience (2007)
Genetic variation and gastric cancer risk: a field synopsis and meta-analysis
Authors: Simone Mocellin, Daunia Verdi, Karen A Pooley, Donato Nitti
Journal: Gut (2015)

<h3>Background</h3> Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pace, but to date no comprehensive overview and quantitative summary has been available. <h3>Methods</h3> We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing stomach cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Meta-analysis was also conducted for subgroups, which were defined by ethnicity (Asian vs Caucasian), tumour histology (intestinal vs diffuse), tumour site (cardia vs non-cardia) and <i>Helicobacter pylori</i> infection status (positive vs negative). <h3>Results</h3> Literature search identified 824 eligible studies comprising 2 530 706 subjects (cases: 261 386 (10.3%)) and investigating 2841 polymorphisms involving 952 distinct genes. Overall, we performed 456 primary and subgroup meta-analyses on 156 variants involving 101 genes. We identified 11 variants significantly associated with disease risk and assessed to have a high level of summary evidence: MUC1 rs2070803 at 1q22 (diffuse carcinoma subgroup), MTX1 rs2075570 at 1q22 (diffuse), PSCA rs2294008 at 8q24.2 (non-cardia), PRKAA1 rs13361707 5p13 (non-cardia), PLCE1 rs2274223 10q23 (cardia), TGFBR2 rs3087465 3p22 (Asian), PKLR rs3762272 1q22 (diffuse), PSCA rs2976392 (intestinal), GSTP1 rs1695 11q13 (Asian), CASP8 rs3834129 2q33 (mixed) and TNF rs1799724 6p21.3 (mixed), with the first nine variants characterised by a low FPRP. We also identified polymorphisms with lower quality significant associations (n=110). <h3>Conclusions</h3> We have identified several high-quality biomarkers of gastric cancer susceptibility. These data will form the backbone of an annually updated online resource that will be integral to the study of gastric carcinoma genetics and may inform future screening programmes.
Activity of Bruton's tyrosine-kinase inhibitor ibrutinib in patients with CD117-positive acute myeloid leukaemia: a mechanistic study using patient-derived blast cells
Authors: Stuart A Rushworth, Genevra Pillinger, Amina Abdul-Aziz, Rachel Piddock, Manar S Shafat, Megan Y Murray, Lyubov Zaitseva, Matthew J Lawes, David J MacEwan, Kristian M Bowles
Journal: The Lancet Haematology (2015)
Resistance to 1,25-dihydroxyvitamin D. Association with heterogeneous defects in cultured skin fibroblasts.
Authors: U A Liberman, C Eil, S J Marx
Journal: Journal of Clinical Investigation (1983)

We evaluated the interaction of [3H]1,25(OH)2D3 with skin fibroblasts cultured from normal subjects or from affected members of six kindreds with rickets and resistance to 1-alpha, 25(OH)2D [1,25(OH)2D]. We analyzed two aspects of the radioligand interaction; nuclear uptake with dispersed, intact cells at 37 degrees C and binding at 0 degrees C with soluble extract ("cytosol") prepared from cells disrupted in buffer containing 300 mM KCl and 10 mM sodium molybdate. With normal fibroblasts the affinity and capacity of nuclear uptake of [3H]1,25(OH)2D3 were 0.5 nM and 10,300 sites per cell, respectively; for binding with cytosol these were 0.13 nM and 8,900 sites per cell, respectively. The following four patterns of interaction with [3H]1,25(OH)2D3 were observed with cells cultured from affected patients: (a) two kindreds; cytosol binding and whole-cell nuclear uptake both unmeasurable; (b) one kindred, decreased capacity and normal affinity both for binding in cytosol and for nuclear uptake in whole cells; (c) two kindreds, normal or nearly normal capacity and affinity of binding in cytosol but unmeasurable whole-cell nuclear uptake; and (d) one kindred, normal capacity and affinity of both cytosol binding and whole-cell nuclear uptake. In all cases where the radioligand bound with high affinity in nucleus or cytosol, the nucleus- or cytosol-associated radioligand exhibited normal sedimentation velocity on sucrose density gradients. When two kindreds exhibited similar patterns (i.e. pattern a or c) with the analyses of cultured fibroblasts, clinical features in affected members suggested that the underlying genetic defects were not identical. In conclusion: (a) Fibroblasts cultured from human skin manifest nuclear uptake and cytosol binding of [3H]1,25(OH)2D3 that is an expression of the genes determining these processes in target tissues. (b) Based upon data from clinical evaluations and from analyses of cultured fibroblasts, severe resistance to 1,25(OH)2D resulted from five or six distinct genetic mutations in six kindreds.
Intracellular Protein Degradation and Its Therapeutic Implications
Authors: Teru Hideshima, James E. Bradner, Dharminder Chauhan, Kenneth C. Anderson
Journal: Clinical Cancer Research (2005)

Lysosomal and ubiquitin (Ub)-mediated protein degradation are two mechanisms for intracellular protein catabolism. The latter is further divided into Ub-proteasome and Ub-aggresome pathways. Recent advances have both defined the mechanisms of protein degradation and identified opportunities for
Asbestos, Asbestosis, Smoking, and Lung Cancer. New Findings from the North American Insulator Cohort
Authors: Steven B. Markowitz, Stephen M. Levin, Albert Miller, Alfredo Morabia
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Asbestos, smoking, and asbestosis increase lung cancer risk in incompletely elucidated ways. Smoking cessation among asbestos-exposed cohorts has been little studied.Objectives: To measure the contributions of asbestos exposure, asbestosis, smoking, and their interactions to lung cancer risk in an asbestos-exposed cohort and to describe their reduction in lung cancer risk when they stop smoking.Methods: We examined lung cancer mortality obtained through the National Death Index for 1981 to 2008 for 2,377 male North American insulators for whom chest X-ray, spirometric, occupational, and smoking data were collected in 1981 to 1983 and for 54,243 non–asbestos-exposed blue collar male workers from Cancer Prevention Study II for whom occupational and smoking data were collected in 1982.Measurements and Main Results: Lung cancer caused 339 (19%) insulator deaths. Lung cancer mortality was increased by asbestos exposure alone among nonsmokers (rate ratio = 3.6 [95% confidence interval (CI), 1.7–7.6]), by asbestosis among nonsmokers (rate ratio = 7.40 [95% CI, 4.0–13.7]), and by smoking without asbestos exposure (rate ratio = 10.3 [95% CI, 8.8–12.2]). The joint effect of smoking and asbestos alone was additive (rate ratio = 14.4 [95% CI, 10.7–19.4]) and with asbestosis, supra-additive (rate ratio = 36.8 [95% CI, 30.1–45.0]). Insulator lung cancer mortality halved within 10 years of smoking cessation and converged with that of never-smokers 30 years after smoking cessation.Conclusions: Asbestos increases lung cancer mortality among nonsmokers. Asbestosis further increases the lung cancer risk and, considered jointly with smoking, has a supra-additive effect. Insulators benefit greatly by quitting smoking.
Disruption of Endothelial-Cell Caveolin-1α/Raft Scaffolding During Development of Monocrotaline-Induced Pulmonary Hypertension
Authors: Rajamma Mathew, Jing Huang, Mehul Shah, Kirit Patel, Michael Gewitz, Pravin B. Sehgal
Journal: Circulation (2004)

In the monocrotaline (MCT)-treated rat, there is marked stimulation of DNA synthesis and megalocytosis of pulmonary arterial endothelial cells (PAECs) within 3 to 4 days, followed by pulmonary hypertension (PH) 10 to 14 days later. Growing evidence implicates caveolin-1 (cav-1) in plasma membrane rafts as a negative regulator of promitogenic signaling. We have investigated the integrity and function of endothelial cell-selective cav-1alpha/raft signaling in MCT-induced PH.Although PH and right ventricular hypertrophy developed by 2 weeks after MCT, a reduction in cav-1alpha levels in the lung was apparent within 48 hours, declining to approximately 30% by 2 weeks, accompanied by an increase in activation of the promitogenic transcription factor STAT3 (PY-STAT3). Immunofluorescence studies showed a selective loss of cav-1alpha and platelet endothelial cell adhesion molecule-1 in the PAEC layer within 48 hours after MCT but an increase in PY-STAT3. PAECs with cav-1alpha loss displayed high PY-STAT3 and nuclear immunostaining for proliferating cell nuclear antigen (PCNA). Biochemical studies showed a loss of cav-1alpha from the detergent-resistant lipid raft fraction concomitant with hyperactivation of STAT3. Moreover, cultured PAECs treated with MCT-pyrrole for 48 hours developed megalocytosis associated with hypo-oligomerization and reduction of cav-1alpha, hyperactivation of STAT3 and ERK1/2 signaling, and stimulation of DNA synthesis.MCT-induced disruption of cav-1alpha chaperone and scaffolding function in PAECs likely accounts for diverse alterations in endothelial cell signaling in this model of PH.