tbuckley/cabot-search huggingface dataset:
Letter: Interaction of nalidixic acid and warfarin.
Authors: B I Hoffbrand
Journal: BMJ (1974)

and transient swelling of face, body, and limbs (1); hypopyon of left eye (1); acute monarticular arthritis (1); and sulphonamide crystalluria (1).Of the 12 meningococcal isolates obtained so far only one has shown sulphonamide resistance employing standard disc diffusion methods.Three of the four most recent strains have been found to be groupo I meningococci, the fourth belonging to group C. The minimum inhibitory concentration of the group B strains to sodium sulpha- diazine was 16 Mg/ml, and in two of them it was 0 4 ,ug/ml to benzylpenicillin.Follow- up studies on six patients (including four infants less than 1 year of age) 4-10 weeks after discharge showed no evidence of residual damage.-Weare, etc.,
Paxillin Predicts Survival and Relapse in Non–Small Cell Lung Cancer by MicroRNA-218 Targeting
Authors: De-Wei Wu, Ya-Wen Cheng, John Wang, Chih-Yi Chen, Huei Lee
Journal: Cancer Research (2010)

Abstract Paxillin (PXN) gene mutations are associated with lung adenocarcinoma progression and PXN is known to be a target gene of microRNA-218 (miR-218). On this basis, we hypothesized that PXN overexpression via miR-218 suppression may promote tumor progression and metastasis and that PXN may predict survival and relapse in non–small cell lung cancer (NSCLC). Expression of miR-218 and PXN in 124 surgically resected lung tumors were evaluated by real-time PCR and immunohistochemical analysis. The prognostic value of miR-218 and PXN expression on overall survival (OS) and relapse-free survival (RFS) was analyzed by the Kaplan–Meier test and Cox regression analysis. miR-218 expression in lung tumors was negatively associated with PXN expression. Multivariate analyses showed that PXN and miR-218 might independently predict OS and RFS, respectively, in NSCLC. Moreover, patients with low miR-218 combined with PXN-positive had the worst OS and RFS among the 4 combinations. In a cell model, PXN was negatively regulated by miR-218 and cell proliferation, invasion, and soft agar colony formation were enhanced by PXN overexpression induced by miR-218 suppression. Taken together, our findings suggest that PXN overexpression induced by miR-218 suppression is an independent predictor of survival and relapse in NSCLC, highlighting PXN as a potential therapeutic target to improve clinical outcomes in this disease. Cancer Res; 70(24); 10392–401. ©2010 AACR.
Possible Host-Defense Mechanisms in Toxic Shock Syndrome
Authors: JEFFREY P. DAVIS
Journal: Annals of Internal Medicine (1982)

Future research activity in toxic shock syndrome should provide further understanding of the ways different host-defense mechanisms are involved in toxic shock syndrome; such efforts must consider toxic shock syndrome as a toxin-mediated disease. Topics that require further research include Staphylococcus aureus acquisition in relation to toxic shock syndrome; bacterial colonization factors including bacterial adherence, vaginal mucosal alteration, secretory IgA, and indigenous flora; conditions that affect organism growth and toxin production including the presence of iron, the availability of calcium, potential defects in opsonization and neutrophil function, and potential defects in lymphocyte function; and the development of natural antibodies against a suspected toxin associated with toxic shock syndrome.
iPS Programmed Without c-MYC Yield Proficient Cardiogenesis for Functional Heart Chimerism
Authors: Almudena Martinez-Fernandez, Timothy J. Nelson, Satsuki Yamada, Santiago Reyes, Alexey E. Alekseev, Carmen Perez-Terzic, Yasuhiro Ikeda, Andre Terzic
Journal: Circulation Research (2009)

Induced pluripotent stem cells (iPS) allow derivation of pluripotent progenitors from somatic sources. Originally, iPS were induced by a stemness-related gene set that included the c-MYC oncogene.Here, we determined from embryo to adult the cardiogenic proficiency of iPS programmed without c-MYC, a cardiogenicity-associated transcription factor.Transgenic expression of 3 human stemness factors SOX2, OCT4, and KLF4 here reset murine fibroblasts to the pluripotent ground state. Transduction without c-MYC reversed cellular ultrastructure into a primitive archetype and induced stem cell markers generating 3-germ layers, all qualifiers of acquired pluripotency. Three-factor induced iPS (3F-iPS) clones reproducibly demonstrated cardiac differentiation properties characterized by vigorous beating activity of embryoid bodies and robust expression of cardiac Mef2c, alpha-actinin, connexin43, MLC2a, and troponin I. In vitro isolated iPS-derived cardiomyocytes demonstrated functional excitation-contraction coupling. Chimerism with 3F-iPS derived by morula-stage diploid aggregation was sustained during prenatal heart organogenesis and contributed in vivo to normal cardiac structure and overall performance in adult tumor-free offspring.Thus, 3F-iPS bioengineered without c-MYC achieve highest stringency criteria for bona fide cardiogenesis enabling reprogrammed fibroblasts to yield de novo heart tissue compatible with native counterpart throughout embryological development and into adulthood.
Authors' response to Hasan
Authors: Manoj Ramachandran, Jeffrey K Aronson
Journal: Journal of the Royal Society of Medicine (2011)

Dr Hasan's helpful observation highlights the problems of diagnosing ailments from ancient texts written in languages that may provide difficulties with translation.


The Arabic text by Muhammed ibn Zakariya′ al-Rāzī (commonly known as Rhazes) to which Dr Hasan refers was originally published in Persia in around 865 AD; versions in Arabic1 and German2 are available in modern sources. Meyerhof has also given an English translation of one of Rhazes' cases, labelled ‘Hay-fever (?), followed by Rheumatic Polyarthritis’, as follows:3

The son of Al-Hasan Ibn ‘Abdawaih suffered from attacks of coryza so heavy and severe that I have never witnessed a similar case before. Even the slighter form of it used to remain with the sufferer a month and more and to descend to the chest, causing coughing and expectoration. This patient showed an improvement about the middle of the day so that he did not feel any discomfort, but this caused him pain in the articulations.


In 1565 Leonardus Botallus from Pavia also published an account of a case that might have been hayfever.4,5

However, in neither case does it seem to have been clear that the condition described was the same as that which Bostock described, which is clearly recognizable as hayfever; Bostock's paper is regarded as the first clear description.5
Molecular Pathways: Linking Tumor Microenvironment to Epithelial–Mesenchymal Transition in Metastasis
Authors: Hae-Yun Jung, Laurent Fattet, Jing Yang
Journal: Clinical Cancer Research (2014)

Abstract During tumor development, tumor cells constantly communicate with the surrounding microenvironment through both biochemical and biophysical cues. In particular, the tumor microenvironment can instruct carcinoma cells to undergo a morphogenesis program termed epithelial-to-mesenchymal transition (EMT) to facilitate local invasion and metastatic dissemination. Growing evidence uncovered a plethora of microenvironmental factors in promoting EMT, including proinflammatory cytokines secreted by locally activated stromal cells, hypoxia conditions, extracellular matrix components, and mechanical properties. Here, we review various biochemical and biophysical factors in the tumor microenvironment that directly impinge upon the EMT program. Specifically, cytokines such as TGFβ, TNFα, and IL6 and hypoxia are capable of inducing EMT in various tumors. Several extracellular matrix (ECM) proteins, including collagen-I, fibronectin, and hyaluronan, and ECM remodeling via extracellular lysyl oxidase are also implicated in regulating EMT. In preclinical studies and ongoing clinical trials, targeting these tumor microenvironmental signals has shown promises in halting tumor progression in various human cancers. Clin Cancer Res; 21(5); 962–8. ©2014 AACR.
Mechano growth factor (MGF) and transforming growth factor (TGF)-β3 functionalized silk scaffolds enhance articular hyaline cartilage regeneration in rabbit model
Authors: Ziwei Luo, Li Jiang, Yan Xu, Haibin Li, Wei Xu, Shuangchi Wu, Yuanliang Wang, Zhenyu Tang, Yonggang Lv, Li Yang
Journal: Biomaterials (2015)
INCREMENTAL PROGNOSTIC VALUE OF LEFT VENTRICULAR EJECTION FRACTION RESERVE IN GATED RB-82 POSITRON EMISSION TOMOGRAPHY OVER CLINICAL VARIABLES IN PATIENTS WITH RESTING LEFT VENTRICULAR DYSFUNCTION
Authors: B. Tamarappoo, Lee Fong Ling, Venu Menon, Wael Jaber, Richard Brunken, Manuel Cerqueira, Thomas Marwick, Marcelo Di Carli, Rory Hachamovitch
Journal: Journal of the American College of Cardiology (2013)
Vancomycin encapsulation in biodegradable poly(ε-caprolactone) microparticles for bone implantation. Influence of the formulation process on size, drug loading, in vitro release and cytocompatibility
Authors: A.-M Le Ray, S Chiffoleau, P Iooss, G Grimandi, A Gouyette, G Daculsi, C Merle
Journal: Biomaterials (2002)
Acute upper gastrointestinal haemorrhage in west of Scotland: case ascertainment study
Authors: O. Blatchford, L. A Davidson, W. R Murray, M. Blatchford, J. Pell
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objectives:</b> To determine the incidence and case fatality of acute upper gastrointestinal haemorrhage in the west of Scotland and to identify associated factors. <b>Design:</b> Case ascertainment study. <b>Setting:</b> All hospitals treating adults with acute upper gastrointestinal haemorrhage in the west of Scotland. <b>Subjects:</b> 1882 patients aged 15 years and over treated in hospitals for acute upper gastrointestinal haemorrhage during a six month period. <b>Main outcome measures:</b> Incidence of acute upper gastrointestinal haemorrhage per 100 000 population per year, and case fatality. <b>Results:</b> The annual incidence was 172 per 100 000 people aged 15 and over. The annual population mortality was 14.0 per 100 000. Both were higher among elderly people, men, and patients resident in areas of greater social deprivation. Overall case fatality was 8.2%. This was higher among those who bled as inpatients after admission for other reasons (42%) and those admitted as tertiary referrals (16%). Factors associated with increased case fatality were age, uraemia, pre-existing malignancy, hepatic failure, hypotension, cardiac failure, and frank haematemesis or a history of syncope at presentation. Social deprivation, sex, and anaemia were not associated with increased case fatality after adjustment for other factors. <b>Conclusions:</b> The incidence of acute upper gastrointestinal haemorrhage was 67% greater than the highest previously reported incidence in the United Kingdom, which may be partially attributable to the greater social deprivation in the west of Scotland and may be related to the increased prevalence of <i>Helicobacter pylori</i>. Fatality after acute upper gastrointestinal haemorrhage was associated with age, comorbidity, hypotension, and raised blood urea concentrations on admission. Although deprivation was associated with increased incidence, it was not related to the risk of fatality. <h3>Key messages</h3> The incidence of upper gastrointestinal haemorrhage in the west of Scotland was 67% higher than the highest incidence previously reported in the United Kingdom A substantial part of this excess incidence may be attributable to socioeconomic deprivation The overall population mortality from upper gastrointestinal haemorrhage may increase as the elderly population increases because both incidence and case fatality rise steeply with age A reduction in the overall case fatality from acute upper gastrointestinal haemorrhage will be best achieved by reducing case fatality among elderly patients
721 SCREENING FOR HEPATOCELLULAR CARCINOMA (HCC) IN HCV-MONOINFECTED PATIENTS: IMPACT ON STAGING, THERAPY, AND SURVIVAL AFTER ADJUSTMENT FOR LEAD-TIME BIAS
Authors: R. Fox, P. Xiao, Z. Naqvi, A. Trikha, M. Sherman, E.J. Bini, N. Bräu
Journal: Journal of Hepatology (2008)
CD271 is expressed in melanomas with more aggressive behaviour, with correlation of characteristic morphology by<i>in vivo</i>reflectance confocal microscopy
Authors: F. Beretti, P. Manni, C. Longo, G. Argenziano, F. Farnetani, A.M. Cesinaro, A.M. Witkowski, A. De Pol, G. Pellacani
Journal: British Journal of Dermatology (2014)

Melanoma is the most highly aggressive type of skin cancer. Its resistance to existing treatments and the rapid rise in incidence underscore the importance of acquiring a better understanding of melanomagenesis.To assess the impact of reflectance confocal microscopy (RCM) on the description of cell morphology, which may influence the growth pattern and changes with increasing tumour severity, correlating with biological aspects.A retrospective analysis of 30 primary melanomas in vivo, evaluated by RCM, to correlate cell morphology and cellular arrangement with a marker of melanoma progression (CD271) using immunohistochemical evaluations.Typical cells organized in dermal nests with peculiar in vivo confocal morphology result in melanoma with high malignancy and positivity to CD271. This architecture might be due to the presence of a type of cells, intrinsically predisposed to invasion, as a result of dedifferentiation programming, revealed by expression of the neural crest marker CD271.With the hypothesis that dedifferentiated cells would be strongly responsible for initiation of tumour development and progression, we propose that CD271 detection could be associated with RCM evaluation in order to detect more aggressive melanoma subtypes.
Chemotherapy with or without Radiation Therapy in Limited Small-Cell Carcinoma of the Lung
Authors: Michael C. Perry, Walter L. Eaton, Kathleen J. Propert, James H. Ware, Bonnie Zimmer, A. Philippe Chahinian, Arthur Skarin, Robert W. Carey, Harvey Kreisman, Charles Faulkner, Robert Comis, Mark R. Green
Journal: New England Journal of Medicine (1987)

We conducted a prospective, randomized study to clarify the role of radiotherapy of the primary tumor in limited small-cell cancer of the lung. After stratification for sex and for performance score based on the ability to ambulate, patients were randomly assigned to receive initial radiotherapy plus chemotherapy, delayed radiotherapy plus chemotherapy, or chemotherapy alone. The chemotherapy consisted of cyclophosphamide, etoposide (VP-16-213), and vincristine, with doxorubicin subsequently replacing etoposide in alternate cycles 7 through 18. Chemotherapy was given every three weeks for 18 months. The radiotherapy comprised 4000 rad in four weeks, followed by a 1000-rad "boost" directed against residual disease. All patients received prophylactic whole-brain radiation. The patients enrolled totaled 426, and 399 were evaluable. There was a statistically significant difference in the frequency of complete responses in favor of the two radiotherapy regimens (P = 0.0013). Failure-free survival was also longer with these two regimens (P less than 0.001), as was the interval before treatment failure in the chest (P less than 0.001) and overall survival (P = 0.0099). As expected, toxic effects--chiefly neutropenia--were also increased. The addition of radiotherapy of the primary tumor to combination chemotherapy improved both complete-response rates and survival, with increased but acceptable toxicity.
Tc-99m Sestamibi Before and During Treatment in a Patient With Sarcoidosis and Persistent Hyperparathyroidism
Authors: ALIDA C. FRÖBERG, WOUTER W. DE HERDER, H. JAAP BONJER, ERIC P. KRENNING, H. YOE OEI, DIK J. KWEKKEBOOM
Journal: Clinical Nuclear Medicine (2000)

Purpose: Tc-99m sestamibi (MIBI) uptake in pulmonary sarcoidosis has been reported, but it has never been studied before and during treatment with glucocorticoids. Methods: The authors performed MIBI scintigraphy and somatostatin receptor scintigraphy in a patient with sarcoidosis of the mediastinum, lungs, and liver and who had persistent hyperparathyroidism after unsuccessful neck exploration. Results: Somatostatin receptor scintigraphy showed high mediastinal and pulmonary uptake in a pattern characteristic of sarcoidosis. Sustained MIBI uptake occurred in the same, although smaller, region. After the diagnosis was confirmed by liver biopsy, the patient was treated with glucocorticoids. Repeated MIBI scintigraphy showed that the uptake in the mediastinum had clearly decreased. Conclusions: This decrease of MIBI uptake in the mediastinal lymph nodes with therapy may imply that MIBI can be used to assess the response to treatment in sarcoidosis. Perhaps a relation exists between MIBI uptake at the moment of diagnosis and prognosis. Further studies in more patients are needed to evaluate the role of MIBI in the management of sarcoidosis.
Hepatic lobar differences in progression of chronic liver disease: Correlation of asialoglycoprotein scintigraphy and hepatic functional reserve
Authors: S Matsuzaki, M Onda, T Tajiri, D Y Kim
Journal: Hepatology (1997)

We studied the hepatic functional reserve in the lobes of the liver in 28 patients with chronic liver disease and 13 controls using single photon emission computed tomography (SPECT) imaging with a radiolabeled asialoglycoprotein analog, Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (Tc-99m GSA). Counts of Tc-99m GSA radioactivity in the liver on SPECT images significantly correlated (P < .0001) with the serum albumin level (r = .612), log (serum cholinesterase activity) (r = .618), serum bilirubin level (r = .628), prothrombin time (r = .715), hepaplastin test (r = .637), and indocyanine green retention rate at 15 minutes (r = .771), making it possible to estimate the distribution of functional reserve in the liver based on counts. Using the intact hepatocyte theory, we estimated the number of viable hepatocytes based on the counts. With progression of hepatic functional degeneration, counts per unit hepatic volume decreased (rho = .779, P < .0001), and left lobe to right lobe ratio of this parameter increased (rho = .491, P = .0019) significantly. These findings suggest that the reduction of hepatic functional reserve per unit hepatic volume and numerical density of the hepatocytes, and the proliferation of fibrosis in patients with chronic liver disease is slower in the left lobe than in the right. We discuss a possible biological basis for these apparent lobar differences and for hepatic morphological changes seen in cirrhosis.
Antitumor activity of EGFR targeted pH-sensitive immunoliposomes encapsulating gemcitabine in A549 xenograft nude mice
Authors: In-Young Kim, Young-Sook Kang, Doo Sung Lee, Heon-Joo Park, Eun-Kyung Choi, Yu-Kyoung Oh, Hye-Jung Son, Jin-Seok Kim
Journal: Journal of Controlled Release (2009)
Abstract P6-15-08: KGFR Tyrosine Kinase Inhibitors for the Treatment of Breast Cancer
Authors: T Pento, MM Meghna, JW Kesinger, RW Brueggemeier, J Hackett, Z Xiao, MR Lerner, DJ Brackett, V Awasthi, P-K. Li
Journal: Cancer Research (2010)

Abstract Background: Keratinocyte growth factor (KGF) produces a rapid increase in the proliferation and motility of estrogen receptor (ER)-positive breast cancer cells (Zang, XP and Pento, JT, Clin. &amp; Exptl. Metastasis 18: 573-80, 2001). It has been demonstrated that the KGF receptor (KGFR) is up-regulated in breast cancer; thus, KGF/KGFR signaling appears to be an early event in breast cancer progression (Zang, XP, Lerner, ML, Bahr, SJ, Brackett, DJ and Pento, JT, Cancer Genomics &amp; Proteomics, 3: 369-72, 2006). Molecular modeling was used to create group of KGFR selective tyrosine kinase inhibitors (TKI) (Pento, JT and Li, PK, Drugs of the Future, 32: 965-72, 2007). The present study examined the effect of a group of these compounds on KGF-mediated proliferation and Erk signaling in MCF-7 breast cancer cells. In addition, the oncolytic potential of compound L-27, a potent KGFR TKI, was examined in an orthotopic xenograft model of human breast cancer. Methods: A group of high affinity KGFR TKI were tested for their ability to inhibit KGF-mediated proliferation and Erk phosphorylation in MCF-7 cells using MTS and ELISA assays. In addition, immuno-cytochemistry was used to examine the influence of the 5 most potent inhibitor compounds on the density of cell membrane KGFR. The effects of a KGFR TKI on breast cancer growth and progression in vivo was examined using an orthotopic xenograft model, with clones of MCF-7 cells which were transfected with a KGF-producing plasmid to enhance cell growth and metastasis and a GFP reporter to quantify tumor growth and metastasis. PET imaging was also used to identify metastatic development. Results: From the initial group of 53 compounds, 5 compounds were observed to produce greater than 50% inhibition of KGF-mediated cancer cell proliferation, reduce Erk phosphorylation and the density of the KGFR on the membrane surface of the cancer cells. Compound L-27, one of the most potent KGFR inhibitors, reduced the growth of MCF-7 tumors and metastatic development in the xenograft model in a dose-related fashion at doses of 4, 10 and 25 mg/kg. Animal weights in the treatment groups remained the same as the control group; indicating a lack of toxicity at the doses employed. Discussion: The novel compounds tested in this project reduce or abolish KGF-mediated proliferation, Erk signaling and KGFR membrane density in vitro. In addition, compound L-27, a potent KGFR inhibitor in vitro, was found to reduce the progression of MCF-7 tumor xenografts in vivo. In conclusion, the KGFR TKI represent a novel class of anticancer agents for the prevention of metastatic progression and may provide a new therapeutic approach for the treatment of breast and other cancers. Acknowledgement: This work was supported by the grants from DoD (DAMD17-01-1-0591) and the NCI (CA-89740) and (CA-125493). Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-15-08.
Characterization of rat hepatic acetyltransferase.
Authors: S J Land, C M King
Journal: Environmental Health Perspectives (1994)

Rat liver cytosol is capable of N-acetylation (NAT) of arylamines, O-acetylation (OAT) of arylhydroxylamines, and N,O-acetyltransfer (AHAT) of arylhydroxamic acids. Physical, enzymatic, and immunochemical techniques now support the conclusion that a single 32 kDa protein accounts for all of these activities. Of the five immunoglobulin (IgG1) mouse monoclonal antibodies (mAb) produced against this protein, each affected one or more of these acetylation activities. When mixed with rat hepatic cytosol and then chromatographed on a gel filtration column, mAbs 1F2 and 5F8 increased the apparent size of all enzymes capable of acetylation from 32 kDa to the exclusion volume. Each of the mAbs reacted with only a single 32 kDa protein on SDS-PAGE/Western blots, regardless of the state of purity of the enzyme. This enzyme is unstable in low salt solutions, as reflected by a relative loss in NAT versus AHAT activity, but it does not result in changes in either molecular weight or isoelectric point (pl). A second form of instability is shown by the formation of more basic peptides with pls as high as 6, again without change in molecular weight. Although NAT activity is retained in acetyltransferase (AT) that has a minimally modified pl, further increases in pl result in total loss of enzyme activity. The differential effects of the mAbs on AT suggest that the ratios of NAT, OAT, and AHAT may be highly dependent on the conformation of the enzyme and, consequently, provide insight as to why the abilities of ATs from different species exhibit such dissimilar potentials for the activation of aromatic amines by OAT and AHAT.