tbuckley/cabot-search huggingface dataset:
Abstract 12226: Left Atrial Structure and Function and Cardiovascular Events in Patients With Diabetes Mellitus: Results From Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Timothy M Markman, Mohammadali Habibi, Bharath Ambale-Venkatesh, Mytra Zareian, Colin Wu, Susan R Heckbert, David A Bluemke, João A Lima
Journal: Circulation (2014)

Introduction: Diabetes mellitus (DM) is associated with the development of cardiovascular disease (CVD). Morphological changes in the LA may appear before symptoms. We aimed to investigate the association between cardiac magnetic resonance imaging (CMR) measured LA structure and function and incident CVD in asymptomatic individuals with DM. Methods: Tissue tracking CMR was used to measure LA size and phasic emptying fraction (EF) on all 574 MESA participants with DM and available baseline CMR, which was performed between 2000 and 2002. MESA is a population based, multi-center cohort study of 6814 healthy individuals. CVD was defined as MI, resuscitated cardiac arrest, angina, stroke, heart failure, atrial fibrillation, and any mortality secondary to CVD. Cox regression was used to assess the association of LA parameters with incident CVD adjusted for traditional risk factors, LV mass assessed by CMR, NT Pro-BNP and maximum LA volume. Adjusted Kaplan-Meier curves are based on 25th percentile cut-offs. Results: After a mean follow up of 7 years, 96 individuals developed CVD (mean age 64, 53%male, 79% treated). Individuals with incident CVD (mean age 66 years, 66% male vs. mean age 4 years, 50% male) had larger maximum and minimum LA volume index (LAVI) (32±13 mm3/m2 vs. 27±10 mm3/m2; 20±10mm3/m2 vs. 14 ±6 mm3/m2), and lower total and active EF than those without CVD (42±11% vs. 48±9%; 29±11% vs. 32±11%). p&lt;0.01 for all. In the final model, there was a significant association of minimum LAVI, LA total EF, and LA active EF with incident CVD. Conclusions: CMR measured LA structure and function are predictive of CVD in a diabetic multi-ethnic population free of any symptomatic CVD at baseline.
Book: What to do in a general practice emergency
Authors: T. Usherwood
Journal: BMJ (1998)

Rosaleen Gregg, Ed Peile BMJ Books, £12.95, pp 112 SBN 0 7279 1183 X Rating: ![Graphic][1]</img>![Graphic][2]</img> Emergencies can be scary. In order to respond effectively a doctor needs the right drugs and equipment, the right skills, and up to date knowledge. All this for a problem that she or he may have never, or only rarely, met before. Any book that provides clear and practical advice on what to carry in the car and what to do when you arrive at the scene must be … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
Efficient and Rapid Induction of a Chronic Myelogenous Leukemia-Like Myeloproliferative Disease in Mice Receiving P210 bcr/abl-Transduced Bone Marrow
Authors: Warren S. Pear, Juli P. Miller, Lanwei Xu, John C. Pui, Benny Soffer, Robert C. Quackenbush, Ann Marie Pendergast, Roderick Bronson, Jon C. Aster, Martin L. Scott, David Baltimore
Journal: Blood (1998)
Abstract 374: A novel sequencing method for genome-wide profiling of 5-hydroxymethylcytosine with single-base resolution
Authors: Xueguang Sun, Tzu-Hung Chung, Yap Ching Chew, Darany Tan, Xi-Yu Jia
Journal: Cancer Research (2014)

Abstract 5-hydroxymethylcytosine (5hmC) is an epigenetic mark abundant in embryo stem cells and brain tissues. The exact biological functions of 5hmC are still under close investigation although several lines of evidence have indicated it could be involved in active DNA demethylation. Meanwhile, extensive studies have been carried out to determine its genomic distribution. A number of approaches have been developed using either affinity based enrichment, such as hMeDIP, that rely on antibody and other specific binding proteins to target 5hmC, or modified bisulfite sequencing, namely oxidative bisulfite sequencing (OxBS) and TET assisted bisulfite sequencing (TAB-sequencing). However, all those methods have limitations which hamper their application. For example, affinity based methods lack single base resolution while modified bisulfite sequencing methods require efficient chemical or enzymatic oxidation which cannot be easily achieved or guaranteed. As an alternative, we have developed a novel genome-wide sequencing method that utilizes an enzyme based modification approach coupled with bisulfite-sequencing for detecting 5hmC. This methodology allows quantification of 5hmC levels with single CpG resolution and can also be employed for locus-specific assays. Using this method, we were able to map and quantify 5hmC sites at the genomic scale for several different biological samples. This novel method can determine the exact location and abundance of 5hmC, which will facilitate our understanding of 5hmC in regulating gene expression in different biological contexts. Citation Format: Xueguang Sun, Tzu-Hung Chung, Yap Ching Chew, Darany Tan, Xi-Yu Jia. A novel sequencing method for genome-wide profiling of 5-hydroxymethylcytosine with single-base resolution. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 374. doi:10.1158/1538-7445.AM2014-374
Development of a polymerase chain reaction dot-blotting system for detecting cutaneous tuberculosis
Authors: S.K. Arora, B. Kumar, S. Sehgal
Journal: British Journal of Dermatology (2000)

For a definitive diagnosis of cutaneous tuberculosis the demonstration of mycobacteria is essential, but this is generally not possible in skin lesions. Routinely available techniques have poor sensitivity and are time consuming, therefore, delaying the institution of timely therapy. The high sensitivity and speed of polymerase chain reaction (PCR) for the detection of infectious agents has prompted investigators to use this technique for the detection of Mycobacterium tuberculosis in body fluids such as cerebrospinal fluid or pleural fluid. In the present study, PCR was used to examine punch biopsy specimens from the affected skin of 10 patients with clinical diagnoses of tuberculosis verrucosa cutis, lupus vulgaris, scrofuloderma, papulonecrotic tuberculide and erythema induratum. A control group of 20 patients included individuals having skin manifestations with definite clinical diagnoses other than cutaneous tuberculosis, such as leprosy, fungal mycetoma, chronic bullous disease of childhood and pemphigus vulgaris. The PCR amplified products were dot hybridized with a probe which was random prime labelled with 32P. The results were compared with routine microbiological and histological findings. Among the test group, six of 10 (60%) were positive for M. tuberculosis by PCR, although their histopathology showed non-specific chronic inflammation with no definite diagnosis. Microbiological investigations, including acid-fast bacillus smear and culture, were positive in a single case of scrofuloderma. All patients in the control group were negative by PCR for M. tuberculosis. The data indicate that the combination of dot hybridization with PCR markedly increased the sensitivity and specificity of PCR. This may be a useful tool in the diagnosis of tuberculosis when conventional methods fail.
Harnessing endogenous stem/progenitor cells for tendon regeneration
Authors: Chang H. Lee, Francis Y. Lee, Solaiman Tarafder, Kristy Kao, Yena Jun, Guodong Yang, Jeremy J. Mao
Journal: Journal of Clinical Investigation (2015)

Current stem cell-based strategies for tissue regeneration involve ex vivo manipulation of these cells to confer features of the desired progenitor population. Recently, the concept that endogenous stem/progenitor cells could be used for regenerating tissues has emerged as a promising approach that potentially overcomes the obstacles related to cell transplantation. Here we applied this strategy for the regeneration of injured tendons in a rat model. First, we identified a rare fraction of tendon cells that was positive for the known tendon stem cell marker CD146 and exhibited clonogenic capacity, as well as multilineage differentiation ability. These tendon-resident CD146+ stem/progenitor cells were selectively enriched by connective tissue growth factor delivery (CTGF delivery) in the early phase of tendon healing, followed by tenogenic differentiation in the later phase. The time-controlled proliferation and differentiation of CD146+ stem/progenitor cells by CTGF delivery successfully led to tendon regeneration with densely aligned collagen fibers, normal level of cellularity, and functional restoration. Using siRNA knockdown to evaluate factors involved in tendon generation, we demonstrated that the FAK/ERK1/2 signaling pathway regulates CTGF-induced proliferation and differentiation of CD146+ stem/progenitor cells. Together, our findings support the use of endogenous stem/progenitor cells as a strategy for tendon regeneration without cell transplantation and suggest this approach warrants exploration in other tissues.
Repression of transcription via cyclin-dependent kinase-9 inhibition is associated with flavopiridol - induced enhancement of radiosensitivity of human esophageal adenocarcinoma cells
Authors: Uma Raju, Masashi Koto, Jessica Pickett, Walter Hittelman, Jaffer A. Ajani, Luka Milas
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4389 

Current treatment strategies for the esophageal malignancies have been developed and tested based on downstream parameters such as local/regional tumor response, progression-free survival, and overall survival. While this approach has led to modest improvements in outcome through combined modality approaches, major improvements have been slow to emerge. A better understanding of the molecular determinants of cancer pathophysiology and the factors that underlie cellular sensitivity and resistance to standard treatments provide the opportunity to explore new targeted approaches to the long-term management of this disease. Our working hypothesis is that cyclin dependent kinase inhibitors (such as flavopiridol(FP)) may provide synergy when combined with chemoradiotherapy by impacting several radioresistance mechanisms. First, FP may slow the rate of accelerated repopulation. Second, it may enhance the effects of sensitivity of the tumor cell clonogens to chemoradiotherapy through inhibition of DNA repair, cell cycle redistribution, and induction of apoptosis. Third, through transcriptional inhibition of expression of critical genes and their products, it may enhance the chemoradiosensitivity of the cells. To investigate this approach in preclinical settings, we have explored the ability of FP, a wide spectrum cyclin-dependent kinase (cdks) inhibitor, to enhance in vitro sensitivity of SEG-1, an esophageal adenocarcinoma cell line, to radiation and docetaxel. FP enhanced radiosensitivity of these cells in a dose dependent manner; the enhancement factor (EF) ranged from 1.20 to 1.86. Flow cytometry analysis of SEG-1 cells showed that FP increased the percent of G1 phase cells a radiosensitive phase of the cell cycle. In addition, FP induced apoptosis in these cells and also enhanced the radiation-induced apoptosis. At molecular level, FP down regulated the levels of phosphorylated forms of cdk-1 and cdk-2, Rb protein and cyclin D1 protein consistent with the cell cycle redistribution. FP also abolished the phosphorylation of the RNA polymerase II at its carboxyl terminus domain that was induced by radiation implying that it also inhibited the kinase activity of cdk-9. Transcriptional repression by FP via inhibition of cdk-9 resulted in inhibition of uridine incorporation, similar to that of a reversible transcription inhibitor, 5,6-dichloro-1-beta-D- ribobenzimidazole (DRB). Investigations on the efficacy of triple agent combination therapy with FP, docetaxel and radiation in the treatment of EC cells in vitro showed that FP significantly enhanced the chemoradiosensitivity when given after chemoradiation treatments. In conclusion, targeting cdks improved the SEG-1 cell sensitivity to chemoradiation treatment. (Supported in part by MDACC MRP esophageal grant and Aventis Pharmaceuticals).
327. Retargetable Oncolytic Measles Viruses for Cancer Virotherapy
Authors: Takafumi Nakamura, Kah-Whye Peng, Mary Harvey, Stephen J. Russell
Journal: Molecular Therapy (2004)

Replication-competent attenuated Edmonston B vaccine strains of measles virus (MV-Edm) have demonstrated potent anti-tumor activity against xenograft models of human multiple myeloma, ovarian cancer, lymphoma and glioma. The virus is selectively oncolytic in tumor cells, exhibiting extensive cell to cell fusion and finally leading to cell death. However, MV-Edm is not entirely tumor-specific and can infect a variety of cell types via its native receptors, CD46 and SLAM. Receptor recognition is mediated by the viral attachment protein H, which then triggers virus-cell fusion via the fusion protein F. CD46 is a ubiquitous regulator of complement activation found on all human nucleated cells whereas SLAM (signaling lymphocyte activation molecule) is expressed on activated T and B cells, dendritic cells and macrophages. Thus, although not yet tested clinically, it is expected that oncolytic measles viruses may cause immunosupression and unwanted damage to normal tissues. We have therefore engineered the H protein of measles virus to restrict and retarget membrane fusion through various antibody-receptor interactions (See abstract “Targeted cell fusion”). However, ablation of the native receptor interactions is incompatible with virus growth in Vero cells which greatly impedes our ability to rescue fully retargeted viruses. To address this question, we have developed a pseudoreceptor system “STAR”, which allows rescue and propagation of fully retargeted viruses that no longer bind to the native measles receptors. We have generated a Vero-αHis cells expressing membrane-anchored single-chain antibody that recognizes a six histidine peptide (H6). Viruses incorporating H6 at the C-terminus of their ablated H proteins could be rescued and propagated on pseudoreceptor expressing Vero-αHis cells under conditions where interaction between H protein and native receptor CD46 was absent. Three different single chain antibodies against CD38, epidermal growth factor receptor (EGFR), or EGFR mutant vIII were displayed at the intermediate site between the ablated H protein and H6 peptides. In all cases the viruses could be easily rescued and propagated on Vero-αHis cells and had the expected host range properties (blind to CD46 and SLAM but efficiently entering cells through their respective targeted receptors). When administered intravenously to athymic mice bearing human EGFR-positive tumor xenografts, only the EGFR-targeted MV-Edm was able to home to the tumor and express its GFP reporter gene. Tumor transduction was not observed in tumors from mice receiving viruses retargeted to CD38 or EGFR-vIII. Our data provide a first convincing in vivo demonstration of measles retargeting and suggest that it will be possible to target a variety of tumors through a broad array of cell surface antigens.
Food Inspection and Analysis. For the Use of Public Analysts, Health Officers, Sanitary Chemists and Food Economists.
Authors: Albert Ernest Leach
Journal: JAMA (1921)

The fact is generally familiar to those concerned with public health matters that Massachusetts was the pioneer in establishing, some twenty years ago, a practical system of food and drug inspection. It is also universally recognized that the Massachusetts State Board of Health has in various ways given a powerful impetus to sanitary work of all kinds. Its activity has been displayed both in the original investigation of scientific problems and in the promotion of the publication of books and monographs dealing with the various undertakings in which it has been engaged. The present work on food inspection and analysis must rank as one of the most important that has issued from its laboratories. The book deals with the following topics: Food analysis and state control; the laboratory and its equipment; food, its functions, proximate components and nutritive value; general analytical methods; the microscope in food analysis; milk and milk
The inhibition of the estrogenic effects of pesticides and environmental chemicals by curcumin and isoflavonoids.
Authors: S P Verma, B R Goldin, P S Lin
Journal: Environmental Health Perspectives (1998)

Many environmental chemicals and pesticides have been found to be estrogenic and have been shown to stimulate the growth of estrogen receptor-positive (ER-positive) human breast cancer cells. Since it is difficult to avoid human exposure to environmental estrogens, a potentially important area of research is the development of dietary strategies to prevent the stimulated growth of breast tumors by environmental estrogens. In this context, the inhibitory action of curcumin and a combination of curcumin and isoflavonoids were studied in ER-positive human breast cancer cells (MCF-7 and T47D) and ER-negative MDA-MB-231 cells induced by the pesticide o,p'-DDT and the environmental pollutants 4-nonylphenol and 4-octylphenol. The median inhibitory concentration (IC50) for curcumin in T47D cells was 10 microM when measured at either a 48-hr or a 6-day incubation time. The IC50 value for curcumin was within the 8-10 microM range for inhibiting the growth of T47D cells induced by a 10- microM concentration each of 4-nonylphenol, 4-octylphenol, and o, p'-DDT. The IC50 for curcumin in MCF-7 cells induced by 10 microM of either o,p'-DDT, 4-octylphenol, or 4-nonylphenol were 9, 39, and >50 microM, respectively. A combination of curcumin and isoflavonoids was able to inhibit the induced growth of ER-positive cells up to 95%. For MDA-MB-231 cells, the IC50 for curcumin was 17 microM, which was reduced to 11 microM in the presence of 25 microM genistein. Curcumin and genistein induce drastic changes in the morphological shape of both ER-positive and ER-negative cells. Data presented here indicate that a mixture of curcumin and isoflavonoids is the most potent inhibitor against the growth of human breast tumor cells. These data suggest that combinations of natural plant compounds may have preventive and therapeutic applications against the growth of breast tumors induced by environmental estrogens.
The American Board of Internal Medicine Maintenance of Certification Program
Authors: Lee R. Berkowitz
Journal: JAMA Surgery (2015)

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Cystic fibrosis and physical activity: Is there a significant difference to healthy individuals?
Authors: Anika Jantzen, Miriam Opoku-Pare, Katharina Ruf, Helge Hebestreit, Alexander Möller
Journal: European Respiratory Journal (2014)

Introduction:  Exercise and habitual physical activity are important components in the care of patients with cystic fibrosis (CF). Regular exercise and physical activity improve physical fitness, exercise tolerance, quality of life and reduce the rate of lung function decline.   Aim:  To compare habitual physical activity between CF patients and healthy age matched controls and to investigate possible predictors for reduced physical activity in CF patients.   Methods:  66 patients with CF (3-44 yrs) and 65 healthy controls (3-55 yrs) were asked to wear an accelerometer (Actigraph GT1M) on their right hip for 9 days during daytime, at min. 10h/day. Physical activity was classified in 5 categories from low (cat. 1) to very strenuous (cat 5) activity.   Results:  In general there was no difference in physical activity between CF-Patients and healthy controls. However, young CF patients (3-9yrs) spent less time with strenuous and very strenuous activity than age-matched controls (p= 0.007 and 0.022). Boys with CF had reduced times with activity cat. 4 and 5 (p= 0.047 and 0.002) and girls with CF spent less time in cat. 3 and 4 (p= 0.005 and 0.013) compared to their counterparts. Activity categories 2-5 were all correlated to FEV1%pred in the CF patients.   Conclusions:  Overall we found no significant differences in the physical activity of patients with CF compared to healthy controls, which is very encouraging. However, healthy small children spend more time with strenuous and very strenuous physical activity than the children with CF. This may be due to overprotection by the parents and underlines the importance to continuously motivate the children to participate in sports activities.
Merkel cell carcinoma, Bowen's disease and chronic occupational arsenic poisoning
Authors: None Tsuruta, None Hamada, None Mochida, None Nakagawa, None Kobayashi, None Ishii
Journal: British Journal of Dermatology (1998)

We diagnosed a unique case of Merkel cell carcinoma (MCC) coexisting with Bowen's disease on the sole of the foot of a 72‐year‐old man who had worked for about 4 years in a factory handling inorganic arsenic. He had a past history of arsenical keratosis and multiple Bowen's disease. The tumour first appeared as a reddish macule and then showed marked growth over the next month. The tumour was excised and the specimen was examined histopathologically. The tumour consisted of two components: a group of atypical cells representing Bowen's disease in the epidermis and another group of atypical cells with a trabecular pattern characteristic of MCC in the dermis. Neither group of cells showed transitional findings, and the tumour elements were divided by a clear basement membrane. The tumour cells in the dermis were positive for neurone‐specific enolase, and on electron microscopy had dense core granules in the cytoplasm. Inorganic arsenic can cause various cutaneous neoplasms, but to our knowledge, this is the first report of a case of MCC associated with Bowen's disease.