tbuckley/cabot-search huggingface dataset:
Mesenchymal Stem Cells and Idiopathic Pulmonary Fibrosis. Potential for Clinical Testing
Authors: Rebecca L. Toonkel, Joshua M. Hare, Michael A. Matthay, Marilyn K. Glassberg
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating, and fatal lung disease characterized by interstitial fibrosis with decreasing lung volumes and hypoxemic respiratory failure. The prognosis for patients with IPF is poor and the quest to find effective therapies has been unsuccessful. Despite several clinical trials over the past decade, there are no U.S. Food and Drug Administration-approved treatments for patients with IPF and thus no standard of care. In terms of pathogenesis, IPF is characterized by alveolar epithelial cell injury and activation with interstitial inflammation, fibroblast proliferation with extracellular matrix collagen deposition, and loss of lung function. Because mesenchymal stem cells (MSCs) home to sites of injury, inhibit inflammation, and contribute to epithelial tissue repair, their use has been suggested as a therapy for the treatment of IPF. MSCs have potential as a novel therapeutic agent in multiple diseases and they have been safely administered in a number of clinical trials. Some, but not all, preclinical studies in animal models of lung fibrosis suggest that MSCs might be effective in the treatment of IPF. Given the safety and ease of MSC administration in other patient populations, the results in preclinical animal models of IPF, and the major need for novel therapeutic options in this devastating disease, we propose that carefully designed clinical trials of MSCs for the treatment of patients with IPF are appropriate. Establishing safety in the setting of IPF is the first priority in early clinical trials followed by clinical and biological measures of efficacy.
Abstract 4772: Novel drug discovery approach targeting STAT3 for breast cancer therapy using MLSD and drug repositioning
Authors: Li Lin, Huameng Li, Minghao Xu, Zhenjiang Zhao, Veronica Olson, Yufang Xu, Chenglong Li, Jiayuh Lin
Journal: Cancer Research (2012)

Abstract Constitutive activation of Signal Transducers and Activators of Transcription 3 (STAT3) signaling is frequently detected in human cancer, including breast cancer, and has emerged as a viable molecular target for breast cancer treatment. Novel therapeutic approaches are needed for breast cancer if significant improvements in survival are to occur. To date, few STAT3 inhibitors are available for the therapy of breast cancer. Conventional high throughput screening and virtual docking drug discovery approaches identified many hits, but only a few of them may be developed into drugs. To accelerate STAT3 drug development, we used a novel drug discovery approach with multiple ligand simultaneous docking (MLSD) which we have developed and drug repositioning to search against FDA approved drug and experimental drug database in DrugBank. Using this new method, we identified the FDA-approved drug celecoxib (a COX-2 inhibitor) with a novel function to target STAT3 [Predictive STAT3 binding dissociation constant (Kd)= 8.6 μM]. In addition, a novel celecoxib analog (8A) was developed exhibiting stronger STAT3 binding (Predicted Kd= 0.12 μM, 71-fold stronger than celecoxib). Although 8A has stronger STAT3 binding, it has weaker COX-2 binding (521-fold weaker than celecoxib), suggesting its selectivity on STAT3 versus COX-2. Minimal COX-2 inhibition by 8A may reduce cardiovascular and gastrointestinal risks associated with COX-2 inhibitors. The ability of 8A to inhibit STAT3 was tested through a combination of Western Blot, MTT cell viability assay, and Immunofluorescence Standing. 8A inhibited the P-STAT3 stimulated by IL-6 but not the induction of STAT1, STAT2, STAT4, STAT5, and STAT6 phosphorylation stimulated by IFN-γ, IFN-γ, and IL-4. 8A also inhibited the induction of STAT3 nuclear localization by IL-6, which could prevent STAT3 function as a transcription factor. 8A inhibited STAT3 phosphorylation and resulted in the induction apoptosis on breast cancer cells as evidenced by caspase-3 cleavage. Further, 8A has a lower IC50 than celecoxib and was more potent than celecoxib to inhibit STAT3 phosphorylation and induce apoptosis in breast cancer cells, which confirmed the stronger STAT3 binding energy than celecoxib. In summary, our study is the first report using MLSD and drug repositioning to develop drug-like STAT3 inhibitors. This novel method has a potential to significantly speed up the STAT3 drug development for the therapy of breast cancer and possibly other types of human cancer which express constitutive STAT3 signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4772. doi:1538-7445.AM2012-4772
Nuclear Power and the Public
Authors: E. James Potchen
Journal: JAMA (1971)

Power! Where will it come from, how safe will it be? The concern of the ecologists and the finite limit of natural resources have forced our power-hungry society to thoughtfully consider answers to these questions. This book is the outgrowth of a local meeting to appraise the Minnesota state law which requires more stringent controls for nuclear power plants than those set by the federal government. Although local issues are the raison d'être for this symposium, the stature of the contributors and national importance of the problems make for wide appeal. Many of the major figures in the environment - radiation controversy have the opportunity to present their arguments in clear incisive terms so that the unbiased reader can formulate a legitimate opinion based on the available evidence. The contributors range from Arthur Tamplin and Barry Commoner to Commissioner James T. Ramey and Congressman Craig Hosmer. Of particular interest is the
Extracellular processing of peptide antigens that bind class I major histocompatibility molecules.
Authors: L A Sherman, T A Burke, J A Biggs
Journal: The Journal of Experimental Medicine (1992)

One problem associated with the use of synthetic peptides as antigens in vivo is their susceptibility to inactivation by proteolytic degradation. A situation is described in which a serum protease, angiotensin-converting enzyme (ACE), is actually responsible for the class I binding activity of a commonly used influenza antigen, nucleoprotein (NP)(147-158R-). This peptide has been reported to be a highly efficient class I antigen. Evidence is presented that demonstrates that the peptide is inactive until cleaved by ACE, which is a normal constituent of serum. The enzyme removes a COOH-terminal dipeptide resulting in the sequence NP(147-155), which is identical to the naturally processed peptide. Such extracellular processing of peptides and proteins may occur for a variety of antigens both in vitro and in vivo, and could have important implications for the design of proteolytically resistant vaccines.
Abstract 17083: Progress and Paradox in the Real World Penetration of Percutaneous Coronary Intervention for Treatment of ST-Elevation Myocardial Infarction
Authors: Elizabeth B Pathak, Colin J Forsyth, Joel A Strom
Journal: Circulation (2011)

Background: Much of the surveillance data on the use of percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) comes from patient registries with voluntary hospital participation or from Medicare data. Non-PCI capable hospitals are significantly underrepresented in registry data, and large hospitals are over-represented; consequently registry data is likely to signficantly overestimate the use of PCI in STEMI on a true population basis. Medicare data are more comprehensive, but include only the elderly population. In this study, we used an unselected population-based hospital surveillance system to investigate temporal trends in the use of PCI for STEMI in Florida from 2001-2009. Florida is the 4th largest state with over 18 million persons. Methods: We used statewide hospital discharge data, including detailed diagnosis and procedure codes to identify STEMI patients who did vs. did not receive same-day PCI. We created county maps for 2001, 2003, 2005, 2007, and 2009 to observe geographic disparities in the use of primary PCI. Data for over 100,000 STEMI patients were analyzed. Results: Statewide, same-day PCI for STEMI increased from 23.4% in 2001 to 63.5% in 2009. County-level maps revealed marked and persistent geographic disparities. In 2009, some major metropolitan areas fell below the state average, while some small rural counties had &gt;80% of STEMI patients receiving PCI. Small urban counties with one non-PCI providing hospital had lower rates than many rural counties with no hospital. Counties with only one high-volume PCI center had the highest rates of primary PCI. Conclusions: Few studies have reported population-based rates of primary PCI usage. We found significant progress in the use of same-day PCI from 2001 to 2009 in Florida, but also paradox with some major metropolitan areas lagging behind smaller urban and rural areas. Rural counties adjacent to major metro areas with high-volume PCI centers had high rates of PCI usage. In contrast, major metro areas with many hospitals had average or below average usage rates. Our results suggest that excessive hospital competition creates barriers for STEMI patients to receive primary PCI.
Patatin-Like Phospholipase Domain-Containing Protein 3 rs738409-G in Recipients of Liver Transplants Is a Risk Factor for Graft Steatosis
Authors: Armin Finkenstedt, Claudia Auer, Bernhard Glodny, Ursula Posch, Hansjoerg Steitzer, Gerhard Lanzer, Johann Pratschke, Matthias Biebl, Michael Steurer, Ivo Graziadei, Wolfgang Vogel, Heinz Zoller
Journal: Clinical Gastroenterology and Hepatology (2013)
Expression of the human PAC1 receptor leads to dose-dependent hydrocephalus-related abnormalities in mice
Authors: Bing Lang, Bing Song, Wendy Davidson, Alastair MacKenzie, Norman Smith, Colin D. McCaig, Anthony J. Harmar, Sanbing Shen
Journal: Journal of Clinical Investigation (2006)

Hydrocephalus is a common and potentially devastating birth defect affecting the CNS, and its relationship with G protein–coupled receptors (GPCRs) is unknown. We have expressed 2, 4, or 6 copies of a GPCR — the human PAC1 receptor with a 130-kb transgene in the mouse nervous system in a pattern closely resembling that of the endogenous gene. Consistent with PAC1 actions, PKA and PKC activity were elevated in the brains of Tg mice. Remarkably, Tg mice developed dose-dependent hydrocephalus-like characteristics, including enlarged third and lateral ventricles and reduced cerebral cortex, corpus callosum, and subcommissural organ (SCO). Neuronal proliferation and apoptosis were implicated in hydrocephalus, and we observed significantly reduced neuronal proliferation and massively increased neuronal apoptosis in the developing cortex and SCO of Tg embryos, while neurite outgrowth and neuronal migration in vitro remain uncompromised. Ventricular ependymal cilia are crucial for directing cerebrospinal fluid flow, and ependyma of Tg mice exhibited disrupted cilia with increased phospho-CREB immunoreactivity. These data demonstrate that altered neuronal proliferation/apoptosis and disrupted ependymal cilia are the main factors contributing to hydrocephalus in PAC1-overexpressing mice. This is the first report to our knowledge demonstrating that misregulation of GPCRs can be involved in hydrocephalus-related neurodevelopmental disorders.
A Manual of Electrotherapy
Authors: Sedgwick Mead
Journal: JAMA (1969)

This third edition is a reissue of a volume already familiar to the reviewer. Since it covers the physics of heat, radiant energy, ultraviolet radiation, elementary electricity, and even ultrasound, it is evident that a title such as "Elementary Physics for Students of Physical Therapy" would be a preferable title. Doctor Watkins' writing is clear, if not distinguished; his presentation is easy to follow. There are abundant illustrations. References are skimpy, but perhaps for physical therapy students they should be. This edition deserved a much more complete revision than it received. For example, on page 176, there is an illustration of a static apparatus of a sort which could be found only in a medical museum. The implication that such treatment methods are still in use is unfortunate and gives the book an old-fashioned air which it scarcely deserves. The treatment of electromyography is extremely brief. In the ten years
Effects of diltiazem on left ventricular diastolic behavior in patients with hypertrophic cardiomyopathy: Evaluation with exercise pulsed Doppler echocardiography
Authors: Masatsugu Iwase, Iwao Sotobata, Shigehito Takagi, Kazuhiko Miyaguchi, Hu Xiao Jing, Mitsuhiro Yokota
Journal: Journal of the American College of Cardiology (1987)
GP commissioners are advised "if in doubt, disclose" when managing conflicts of interest
Authors: Z. Kmietowicz
Journal: BMJ (2014)

<b>Background:</b> Because of its non-electrostatic properties the metal Nebuchamber (NC) valved holding chamber (VHC) delivers a greater mass of aerosol to the mouth than the polypropylene Aerochamber (AC) VHC. Delivery of more aerosol to the lungs may also increase systemic absorption of inhaled corticosteroids (ICS) and hypothalamo-pituitary-adrenal (HPA) suppression. <b>Methods:</b> Thirty children (mean 4.3 (SD 0.3) years) received 200 μg budesonide twice daily by NC or AC, both with the mask provided, in a randomised, two month crossover trial. Twenty four hour urinary free cortisol (UFC) was determined as a measure of HPA suppression. <b>Results:</b> UFC decreased from 42.3 (7.8) nmol UFC/nmol creatinine control to 26.2 (2.4) (p = 0.06 <i>v</i> control) after AC, and to 24.5 (2.5) (p = 0.04 <i>v</i> control) after NC (p = 0.4 AC <i>v</i> NC). <b>Conclusions:</b> Despite a greater total dose delivered to the mouth, NC is not associated with greater HPA suppression when using 400 μg/day budesonide under real life conditions in young children.
Hepatic involvement in mastocytosis: Clinicopathologic correlations in 41 cases*1
Authors: J MICAN
Journal: Hepatology (1995)

Mastocytosis is a disease of mast cell hyperplasia that may involve several organ systems, including liver. Between 1988 and 1991, we conducted a retrospective-prospective study of 41 patients with mastocytosis and found 61% had evidence of liver disease. Hepatomegaly was detected in 24%, splenomegaly in 41%, and elevated serum alkaline phosphatase, serum aminotransaminases, 5'nucleotidase, or gamma-glutamyltranspeptidase (GGTP) in 54% of the patients. Alkaline phosphatase levels directly correlated with GGTP levels, hepatomegaly, splenomegaly, and liver mast cell infiltration and fibrosis. Elevated alkaline phosphatase levels and splenomegaly were observed more frequently in patients with categories II and III mastocytosis. Five patients in combined disease categories II or III developed ascites or portal hypertension and died of complications of mastocytosis; three had hypoprothrombinemia at the time of death. Thirty-five liver biopsy specimens from 25 patients were examined. Mast cell infiltration was commonly observed in the biopsy specimens, more severe in those patients with either category II or III disease, and correlated with hepatomegaly, splenomegaly, alkaline phosphatase levels, and GGTP levels. Mast cells were often only detected by using special stains (toluidine blue and chloracetate esterase). Increased portal fibrosis was seen in 68% of the biopsy specimens and correlated with mast cell infiltration and portal inflammation. Cirrhosis was not observed. Nodular regenerative hyperplasia, portal venopathy, and venoocclusive disease was observed in eight biopsy specimens and may have been the cause of the portal hypertension or ascites in four patients. These findings demonstrate that liver disease with mast cell infiltration is a common finding in patients with mastocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Pathological investigation of maternal deaths: a cause for concern.
Authors: J Tomkinson, A C Turnbull
Journal: BMJ (1980)

recently taken drugs that are known to induce liver enyzmes, and at present this must include recent exposure to enflurane.8If for repeated anaesthesia one substitutes enflurane for halothane one may be replacing the rare case of hepatic disease with the perhaps more common case of renal failure.
Abstract P1-17-02: Male breast carcinoma: A clinicopathological and immunohistochemical characterization study
Authors: R Zhou, L Yu, B Yu, S Zhou, R Bi, R Shui, H Lu, X Cai, W Yang
Journal: Cancer Research (2013)

Abstract AIM Male breast carcinoma is a relatively rare disease. This study retrospectively investigated the clinicopathological features of male breast carcinoma in Chinese population, and classified the molecular subtype based on surrogate immunohistochemical definitions. The expression of GCDFP15, MGB, AR and FOXP1 were also evaluated. METHODS Clinical and pathological data on 73 cases of male breast carcinoma were collected and microscopic pathological features were examined. Immunostaining for ER, PR, HER2, Ki-67, CK5/6, EGFR, GCDFP15, MGB, AR and FOXP1 was performed and the molecular subtype was classified. RESULTS Invasive carcinoma of no special type was the major histological type in our study group (71.2%, 52/73). Except for 4 cases of carcinoma in situ, forty-two male invasive carcinomas (42/69, 60.9%) were classified as luminal A subtype while 24 cases (24/69, 34.8%) were classified as luminal B subtype. Only 2 cases of basal-like subtype and 1 case of HER2 positive subtype were identified in this group. Nuclear immunostaining of AR and FOXP1 could be observed in 82.4% (48/57) and 71.9% (41/57) of the cases respectively. Cases of luminal A subtype expressed GCDFP15 (73.5%, 25/34) and MGB (58.8%, 20/34) more frequently than those of luminal B subtype (34.8%, 8/23 and 43.5%, 10/23, respectively). CONCLUSIONS Invasive carcinoma of no special type was the most common histological type in male breast carcinoma. Our study revealed that luminal A and B subtypes were the major types of male breast carcinoma. AR and FOXP1 were highly expressed in male breast cancer. Luminal A subtype tends to express GCDFP15 and MGB more frequently than luminal B subtype. KEYWORDS: breast carcinoma, male, molecular subtype, immunohistochemistry. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-17-02.
Hypersensitivity to local anaesthetics: a direct challenge test with lignocaine for definitive diagnosis.
Authors: M R Barer, M K McAllen
Journal: BMJ (1982)

benoxaprofen damage was reduced; this may be due to a subclinical photosensitivity reaction, as occurs with onycholysis, which may not be associated with obvious sun sensitivity.It is not yet clear whether the hypertrichosis is simply secondary to the photosensitivity, as is seen in porphyria4 and when alopecia areata is treated with ultraviolet B or psoralen-ultraviolet A, or whether a different mechanism is entailed, as in hypertrichosis associated with minoxidil.5
Medical and surgical vagotomy and intrinsic factor secretion
Authors: P. M. Christiansen, P. Rodbro
Journal: BMJ (1967)

Pyloric Stenosis in Turner's Syndrome SIR,-The prevalence of congenital hyper- trophic stenosis in the general population is estimated to be about 2 to 5 per 1,000 live births,'`and Carter was able to demonstrate that the sex ratio for this malformation amounted to 5:1, boys being more affected than girls.'Benson and King have drawn attention to a possibly high prevalence of this condition in patients with Turner's syn- drome.'We have investigated a series of 43 patients with Turner's syndrome and found two patients with congenital pyloric stenosis.'The diagnosis of Turner's syndrome in Case 1 was established at the age of 19 years on the following criteria:(1) Sexual infantilism with primary amenor- rhoea, infantile external and internal genitalia, and absence of breast development.
Prostaglandin-induced abortion and outcome of subsequent pregnancies: a prospective controlled study
Authors: I Z Mackenzie, K. Hillier
Journal: BMJ (1977)

We analysed a prospective series of 204 pregnancies occurring in 168 women after a prostaglandin-induced abortion. The mean (±standard error of mean) interval between abortion and first subsequent conception was 10·4 ± 0·6 months; no patient reported secondary subfertility. Fifty-five of the subsequent pregnancies were terminated, 23 during the second trimester, again using prostaglandins. Of the 149 pregnancies not terminated, 127 were delivered at term, and 19 spontaneously aborted, seven during the second trimester; there was one missed abortion and two ectopic pregnancies. Morbidity in the 127 term pregnancies was infrequent; spontaneous preterm labour occurred in three patients, and four singleton infants weighed less than 2500 g at birth. There was no apparent association between morbidity in the subsequent pregnancies and the period of gestation at the time of the previous abortion, route of prostaglandin administration, or need for post-abortion curettage. The results obtained overall were very similar to a control group of 612 women consecutively admitted for delivery or abortion to the Oxford obstetrical and gynaecological units. There was, however, an increased incidence of spontaneous abortion and placenta praevia after prostaglandin-induced abortion, and the multigravidae in that group had a longer average duration of labour than the control group. Sixty-five per cent of the post-abortion pregnancies were unplanned compared with 36% of the control group.
Frequency, clinical features and prognosis of cutaneous manifestations in adult patients with reactive haemophagocytic syndrome
Authors: L. Fardet, L. Galicier, M.-D. Vignon-Pennamen, S. Regnier, M.E. Noguera, A. De Labarthe, E. Raffoux, V. Martinez, S. Buyse, M. Viguier, A. Osio, C. Lebbé, P. Morel, A. Dupuy, M. Rybojad
Journal: British Journal of Dermatology (2009)

Cutaneous involvement has been reported in 30-40% of children with the familial form of haemophagocytic syndrome. However, few studies have focused on cutaneous manifestations in patients with reactive haemophagocytic syndrome (RHS).To describe the frequency, clinical features and prognosis of skin involvement in adult patients with RHS.We conducted a retrospective study in a French university-based tertiary centre. The medical records of all adult patients with a suspected or confirmed diagnosis of RHS during a 2-year period were reviewed. Demographic, clinical, biological and histological data of patients were compared using nonparametric tests.The medical charts of 151 patients were reviewed, 69 of whom had a definite diagnosis of RHS (35% women; mean +/- SD age 49 +/- 17 years). The aetiology of RHS was mainly B-cell or T-cell lymphoma (n = 33) or herpesvirus infection (n = 19). Cutaneous manifestations were observed in 32 (46%) patients and were of three types: (i) specific to the underlying malignancy (Kaposi sarcoma n = 8, cutaneous lymphoma n = 4), (ii) reflecting the biological consequences of RHS (thrombopenic purpura n = 10, conjunctival jaundice n = 7), and (iii) a generalized, transient, nonpruriginous maculopapular rash (n = 18). None presented with erythroderma, or with eczematiform, ichthyosiform, psoriasiform or bullous lesions. One patient had cytophagic histiocytic panniculitis. Histological features of maculopapular rash biopsies were usually nonspecific. The rate of in-hospital death was not significantly associated with cutaneous involvement.A generalized, nonpruriginous, transient, maculopapular rash is frequently observed in patients with RHS. Although nonspecific, awareness of this cutaneous involvement may assist physicians in the initial diagnosis of RHS.