tbuckley/cabot-search huggingface dataset:
Structure and Mechanics of Healing Myocardial Infarcts
Authors: Jeffrey W. Holmes, Thomas K. Borg, James W. Covell
Journal: Annual Review of Biomedical Engineering (2005)

Therapies for myocardial infarction have historically been developed by trial and error, rather than from an understanding of the structure and function of the healing infarct. With exciting new bioengineering therapies for myocardial infarction on the horizon, we have reviewed the time course of structural and mechanical changes in the healing infarct in an attempt to identify key structural determinants of mechanics at several stages of healing. Based on temporal correlation, we hypothesize that normal passive material properties dominate the mechanics during acute ischemia, edema during the subsequent necrotic phase, large collagen fiber structure during the fibrotic phase, and cross-linking of collagen during the long-term remodeling phase. We hope these hypotheses will stimulate further research on infarct mechanics, particularly studies that integrate material testing, in vivo mechanics, and quantitative structural analysis.
Clinical relevance of IgE to recombinant Gly m 4 in the diagnosis of adult soybean allergy
Authors: Yuma Fukutomi, Sigrid Sjölander, Takuya Nakazawa, Magnus P. Borres, Toyota Ishii, Satoshi Nakayama, Akira Tanaka, Masami Taniguchi, Akemi Saito, Hiroshi Yasueda, Hiroyuki Nakamura, Kazuo Akiyama
Journal: Journal of Allergy and Clinical Immunology (2012)
A NEW CLASS OF HUMAN IMMUNOGLOBULINS
Authors: David S. Rowe, John L. Fahey
Journal: The Journal of Experimental Medicine (1965)

The unique myeloma protein from S. J., a patient with multiple myeloma, was isolated and characterized. It resembled other myeloma proteins in many respects. The S. J. myeloma protein migrated in a distinct peak in the slow beta-globulin region on zone electrophoresis, appeared as a single band on starch gel electrophoresis, and sedimented at 7.04S in the ultracentrifuge. Papain and cysteine treatment produced Fc (fast) and Fab (slow) fragments. Reduction and alkylation of the myeloma protein produced heavy and light chains in a ratio of approximately 3:1. The S. J. myeloma protein had type L (type II) light chains. These were antigenically similar to the Bence Jones protein also found in this patient. The S. J. myeloma protein was unique in the properties of its heavy chains. The myeloma protein (and its heavy chains and Fc pieces) did not contain antigenic determinants specific for IgG, IgA, or IgM. The myeloma protein (and its heavy chains), however, did contain antigenic determinants which are characteristic of a new class of immunoglobulin. The S. J. myeloma protein was unusual also in its effect on the metabolism of normal IgG and in the electrophoretic mobility of the Fc fragment produced by papain digestion. No evidence was obtained to indicate that the entire heavy polypeptide of the S. J. protein was a grossly abnormal product of malignant cell metabolism. The unique properties of the S. J. myeloma protein (and its heavy chains) are believed to represent, in large measure, properties to be found in a small part of the normal immunoglobulin population.
A Randomized Comparison of Pioglitazone to Inhibit Restenosis After Coronary Stenting in Patients With Type 2 Diabetes
Authors: Kazuaki Nishio, Masayuki Sakurai, Taro Kusuyama, Meiei Shigemitsu, Tomoyasu Fukui, Kitaro Kawamura, Seiji Itoh, Noburu Konno, Takashi Katagiri
Journal: Diabetes Care (2006)

OBJECTIVE—Recent studies have demonstrated that the treatment with thiazolidinediones reduces in-stent restenosis. The aim of this study was to elucidate the mechanism of the efficacy of pioglitazone for preventing in-stent restenosis in type 2 diabetic patients. RESEARCH DESIGN AND METHODS—We conducted a prospective, randomized trial involving 54 type 2 diabetic patients referred for coronary stenting who were randomly assigned to either the control or the pioglitazone group. Quantitative coronary angiography was performed at study entry and at 6 months follow-up. Endothelial nitric oxide synthase (eNOS), tumor necrosis factor α, interleukin-6, leptin, and adiponectin were measured at study entry and at 6 months follow-up. RESULTS—A total of 28 patients were randomly assigned to the control group, and 26 patients were assigned to the pioglitazone group. There were no significant differences in glycemic control levels or in lipid levels in the two groups at baseline or at follow-up. Insulin, homeostasis model assessment of insulin resistance, eNOS, and leptin at follow-up were significantly reduced in the pioglitazone group compared with the control group. The late luminal loss and in-stent restenosis were significantly less in the pioglitazone group than in the control group. Leptin independently correlated with late luminal loss at multiple regression analysis. CONCLUSIONS—The treatment with pioglitazone in type 2 diabetic patients significantly reduced leptin. This decreased leptin improved insulin resistance and endothelial function with the reduction of insulin. The improved endothelial function affected the reduction of in-stent restenosis.
Hyperparathyroid bone disease--an unusual and memorable condition
Authors: D J Pradeep, G P R Clunie, R A Watts, R C Nightingale
Journal: Annals of the Rheumatic Diseases (2006)

An 81-year-old man presented with reduced mobility and severe proximal muscle pain and weakness. He reported having frequent falls. His medical history included osteoarthritis of the knees, hypertension and L2 vertebral wedge collapse in 1987. A clinical examination showed swollen ankles and synovitis in his left knee and bilateral quadriceps muscle wasting. Muscle power was grade 4 or 5, and tone, reflexes and …
Clinical prognostic indicators of high-grade pre-invasive bronchial lesions
Authors: D. Moro‐Sibilot, F. Fievet, M. Jeanmart, S. Lantuejoul, F. Arbib, M.H. Laverrière, E. Brambilla, C. Brambilla
Journal: European Respiratory Journal (2004)

Lung cancer arises from multistep genetic damage of bronchial epithelium, driving multifocal progressive dysplastic lesions. However, the risk of progression of high-grade pre-invasive bronchial lesions to cancer is poorly assessed. The purpose of this study was to better define the parameters that predict the outcome of these lesions. The current authors prospectively studied 27 patients with 31 histologically proven severe dysplasia (SD) and carcinoma in situ (CIS), with repeated bronchoscopy and endobronchial treatment. The influence of respiratory-cancer history, histopathological classification, tobacco consumption, and number of biopsies on the progression rate into cancer was studied. The actuarial progression rate to cancer was 17% at 1 yr and 63% at 3 yrs. A total of 11 cases of CIS progressed to invasive cancer, 17 were stable or regressed during the study, two with SD regressed and one progressed to invasive cancer. Progression of CIS appeared more frequent in lesions diagnosed as "questionable CIS". Persistence of smoking did not influence high-grade lesion outcome. The existence of synchronous lung cancer did not seem to impact on progression. The number of biopsies did not influence the outcome. In conclusion, the current study suggests that the outcome of high-grade pre-invasive lesions is not modified by the number of biopsies performed on these lesions. Careful pathological examination of these lesions and pathological revision seem necessary, since questionable cases have the worse progression rate.
"Safe havens" for unwanted babies could reduce infanticide
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

An estimated 85 newborn infants are killed or left to die in the United States each year, according to new research. More “safe havens,” where unwanted babies could be left, would reduce the rate of infanticide, says the study, in the Journal of the American Medical Association (2003;289:1425-9).

Researchers from the University of North Carolina, Chapel Hill, examined all reports in the state between 1985 and 2000 of liveborn babies who died aged less than five days old. The 34 cases of infanticide they found was the equivalent of 2.1 infanticides per 100 000 births a year. Extrapolating from the figures, …
Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome
Authors: Irene A Aligianis, Colin A Johnson, Paul Gissen, Dongrong Chen, Daniel Hampshire, Katrin Hoffmann, Esther N Maina, Neil V Morgan, Louise Tee, Jenny Morton, John R Ainsworth, Denise Horn, Elisabeth Rosser, Trevor R P Cole, Irene Stolte-Dijkstra, Karen Fieggen, Jill Clayton-Smith, André Mégarbané, Julian P Shield, Ruth Newbury-Ecob, William B Dobyns, John M Graham, Klaus W Kjaer, Mette Warburg, Jacqueline Bond, Richard C Trembath, Laura W Harris, Yoshimi Takai, Stefan Mundlos, David Tannahill, C Geoffery Woods, Eamonn R Maher
Journal: Nature Genetics (2005)
Cholesterol Derivatives Based Charged Liposomes for Doxorubicin Delivery: Preparation, <i>In Vitro </i>and <i>In Vivo</i> Characterization
Authors: Yu Nie, Li Ji, Hong Ding, Li Xie, Li Li, Bin He, Yao Wu, Zhongwei Gu
Journal: Theranostics (2012)

Cholesterol plays a critical role in liposome composition.It has great impact on the behavior of liposome in vitro and in vivo.In order to verify the possible effects from cholesterol charge, surface shielding and chemical nature, two catalogs of liposomes with charged and PEGylated cholesterols were synthesized.Anionic liposomes (AL) and cationic liposomes (CL) were prepared, with charges from hemisuccinate and lysine in cholesterol derivatives, respectively.Characteristics of different formulated liposomes were investigated after doxorubicin encapsulation, using neutral liposomes (NL) as control.Results showed that after PEGylation, AL and CL liposomes displayed prolonged retention release profile, while kept similar size distribution, encapsulation efficiency, low cytotoxicity and hemolysis comparing with NL.Confocal laser scanning microscopy and flow cytometry experiments confirmed the significantly higher cell uptake from AL and CL vesicles than the NL in mouse breast carcinoma and melanoma cells, human epithelial carcinoma and hepatoma cells.It was in accordance with our corresponding cellular mortality studies of DOX-loaded liposomes.The in vivo anti-tumor effect experiments from charged liposomes also presented much higher tumor inhibition effect (70% vs 45%, p < 0.05) than NL liposomes.This is the first time reporting anti-cancer effect from charged cholesterol liposome with/without PEGylation.It may give deeper understanding on the liposome formulation which is critical for liposome associated drug research and development.
Small-molecule XIAP inhibitors derepress downstream effector caspases and induce apoptosis of acute myeloid leukemia cells
Authors: Bing Z. Carter, Marcela Gronda, Zhiliang Wang, Kate Welsh, Clemencia Pinilla, Michael Andreeff, Wendy D. Schober, Adel Nefzi, Gregory R. Pond, Imtiaz A. Mawji, Richard A. Houghten, John Ostresh, Joseph Brandwein, Mark D. Minden, Andre C. Schuh, Richard A. Wells, Hans Messner, Kathy Chun, John C. Reed, Aaron D. Schimmer
Journal: Blood (2005)
Benefits of Early Hypertension Control on Cardiovascular Outcomes in Patients With Diabetes
Authors: Patrick J. O’Connor, Gabriela Vazquez-Benitez, Julie A. Schmittdiel, Emily D. Parker, Nicole K. Trower, Jay R. Desai, Karen L. Margolis, David J. Magid
Journal: Diabetes Care (2012)

OBJECTIVE To assess the impact of early hypertension (HT) control on occurrence of subsequent major cardiovascular events in those with diabetes and recent-onset HT. RESEARCH DESIGN AND METHODS Study subjects were 15,665 adults with diabetes but no diagnosed coronary or cerebrovascular disease at baseline who met standard criteria for new-onset HT. Poisson regression models assessed whether adequate blood pressure control within 1 year of HT onset predicts subsequent occurrence of major cardiovascular events with and without adjustment for baseline Framingham Risk Score (FRS) and other covariates. RESULTS Mean age was 51.5 years, and mean blood pressure at HT onset was 136.8/80.8 mmHg. In the year after HT onset, mean blood pressure decreased to 131.4/78.0 mmHg and was &amp;lt;130/80 mmHg in 32.9% of subjects and &amp;lt;140/90 mmHg in 80.2%. Over a mean follow-up of 3.2 years, age-adjusted rates of major cardiovascular events in those with mean 1-year blood pressure measurements of &amp;lt;130/80, 130–139/80–89, and ≥140/90 mmHg were 5.10, 4.27, and 6.94 events/1,000 person-years, respectively (P = 0.004). In FRS-adjusted models, rates of major cardiovascular events were significantly higher in those with mean blood pressure ≥140/90 mmHg in the first year after HT onset (rate ratio 1.30 [95% CI 1.01–1.169]; P = 0.04). CONCLUSIONS Failure to adequately control BP within 1 year of HT onset significantly increased the likelihood of major cardiovascular events within 3 years. Prompt control of new-onset HT in patients with diabetes may provide important short-term clinical benefits.
DSM-5 Field Trials in the United States and Canada, Part III: Development and Reliability Testing of a Cross-Cutting Symptom Assessment for DSM-5
Authors: William E Narrow, Diana E Clarke, S Janet Kuramoto, Helena C Kraemer, David J Kupfer, Lisa Greiner, Darrel A Regier
Journal: American Journal of Psychiatry (2013)

Objective The authors sought to document, in adult and pediatric patient populations, the development, descriptive statistics, and test-retest reliability of cross-cutting symptom measures proposed for inclusion in DSM-5. Method Data were collected as part of the multisite DSM-5 Field Trials in large academic settings. There were seven sites focusing on adult patients and four sites focusing on child and adolescent patients. Cross-cutting symptom measures were self-completed by the patient or an informant before the test and the retest interviews, which were conducted from 4 hours to 2 weeks apart. Clinician-report measures were completed during or after the clinical diagnostic interviews. Informants included adult patients, child patients age 11 and older, parents of all child patients age 6 and older, and legal guardians for adult patients unable to self-complete the measures. Study patients were sampled in a stratified design, and sampling weights were used in data analyses. The mean scores and standard deviations were computed and pooled across adult and child sites. Reliabilities were reported as pooled intraclass correlation coefficients (ICCs) with 95% confidence intervals. Results In adults, test-retest reliabilities of the cross-cutting symptom items generally were good to excellent. At the child and adolescent sites, parents were also reliable reporters of their children’s symptoms, with few exceptions. Reliabilities were not as uniformly good for child respondents, and ICCs for several items fell into the questionable range in this age group. Clinicians rated psychosis with good reliability in adult patients but were less reliable in assessing clinical domains related to psychosis in children and to suicide in all age groups. Conclusions These results show promising test-retest reliability results for this group of assessments, many of which are newly developed or have not been previously tested in psychiatric populations.
Phylogeography of three closely related African bovids (tribe Alcelaphini)
Authors: P Arctander, C Johansen, M A Coutellec-Vreto
Journal: Molecular Biology and Evolution (1999)

The phylogeography of three species of African bovids, the hartebeest (Alcelaphus buselaphus), the topi (Damaliscus lunatus), and the wildebeest (Connochaetes taurinus), is inferred from sequence variation of 345 sequences at the control region (d-loop) of the mtDNA. The three species are closely related (tribe Alcelaphini) and share similar habitat requirements. Moreover, their former distribution extended over Africa, as a probable result of the expansion of open grassland on the continent during the last 2.5 Myr. A combination of population genetics (diversity and structure) and intraspecific phylogeny (tree topology and relative branch length) methods is used to substantiate scenarios of the species history. Population dynamics are inferred from the distribution of sequence pairwise differences within populations. In the three species, there is a significant structuring of the populations, as shown by analysis of molecular variance (AMOVA) pairwise and hierarchical differentiation estimations. In the wildebeest, a pattern of colonization from southern Africa toward east Africa is consistent with the asymmetric topology of the gene tree, showing a paraphyletic position of southern lineages, as well as their relatively longer branch lengths, and is supported by a progressive decline in population nucleotide diversity toward east Africa. The phylogenetic pattern found in the topi and the hartebeest differs from that of the wildebeest: lineages split into monophyletic clades, and no geographical trend is detected in population diversity. We suggest a scenario where these antelopes, previously with wide pan-African distributions, became extinct except in a few refugia. The hartebeest, and probably also the topi, survived in refugia north of the equator, in the east and the west, respectively, as well as one in the south. The southern refugium furthermore seems to have been the only place where the wildebeest has survived.
PF-03732010: A Fully Human Monoclonal Antibody against P-Cadherin with Antitumor and Antimetastatic Activity
Authors: Cathy C. Zhang, Zhengming Yan, Qin Zhang, Kyle Kuszpit, Kenneth Zasadny, Ming Qiu, Cory L. Painter, Anthony Wong, Eugenia Kraynov, Maria E. Arango, Pramod P. Mehta, Ian Popoff, Gerald F. Casperson, Gerrit Los, Steve Bender, Kenna Anderes, James G. Christensen, Todd VanArsdale
Journal: Clinical Cancer Research (2010)

P-cadherin is a membrane glycoprotein that functionally mediates tumor cell adhesion, proliferation, and invasiveness. We characterized the biological properties of PF-03732010, a human monoclonal antibody against P-cadherin, in cell-based assays and tumor models.The affinity, selectivity, and cellular inhibitory activity of PF-03732010 were tested in vitro. Multiple orthotopic and metastatic tumor models were used for assessing the antitumor and antimetastatic activities of PF-03732010. Treatment-associated pharmacodynamic changes were also investigated.PF-03732010 selectively inhibits P-cadherin-mediated cell adhesion and aggregation in vitro. In the P-cadherin-overexpressing tumor models, including MDA-MB-231-CDH3, 4T1-CDH3, MDA-MB-435HAL-CDH3, HCT116, H1650, PC3M-CDH3, and DU145, PF-03732010 inhibited the growth of primary tumors and metastatic progression, as determined by bioluminescence imaging. Computed tomography imaging, H&E stain, and quantitative PCR analysis confirmed the antimetastatic activity of PF-03732010. In contrast, PF-03732010 did not show antitumor and antimetastatic efficacy in the counterpart tumor models exhibiting low P-cadherin expression. Mechanistic studies via immunofluorescence, immunohistochemical analyses, and 3'-[(18)F]fluoro-3'-deoxythymidine-positron emission tomography imaging revealed that PF-03732010 suppressed P-cadherin levels, caused degradation of membrane β-catenin, and concurrently suppressed cytoplasmic vimentin, resulting in diminished metastatic capacity. Changes in the levels of Ki67, caspase-3, and 3'-[(18)F]fluoro-3'-deoxythymidine tracer uptake also indicated antiproliferative activity and increased apoptosis in the tested xenografts.These findings suggest that interrupting the P-cadherin signaling pathway may be a novel therapeutic approach for cancer therapy. PF-03732010 is presently undergoing evaluation in Phase 1 clinical trials.
P7170, a novel inhibitor of mTORC1/mTORC2 and Activin receptor-like Kinase 1 (ALK1) inhibits the growth of non small cell lung cancer
Authors: Venkatasubbaiah A Venkatesha, Asavari Joshi, Magesh Venkataraman, Vinay Sonawane, Dimple Bhatia, Prashant Tannu, Julie Bose, Sarika Choudhari, Ankita Srivastava, Prashant Kumar Pandey, Vaibhavi J Lad, Ramachandra Sangana, Tausif Ahmed, Anagha Damre, Vijaykumar Deore, Bichismita Sahu, Sanjay Kumar, Somesh Sharma, Veena R Agarwal
Journal: Molecular Cancer (2014)

Lung cancer is the major cause of cancer-related deaths and many cases of Non Small Cell Lung Cancer (NSCLC), a common type of lung cancer, have frequent genetic/oncogenic activation of EGFR, KRAS, PIK3CA, BRAF, and others that drive tumor growth. Some patients though initially respond, but later develop resistance to erlotinib/gefitinib with no option except for cytotoxic therapy. Therefore, development of novel targeted therapeutics is imperative to provide improved survival benefit for NSCLC patients. The mTOR cell survival pathway is activated in naïve, or in response to targeted therapies in NSCLC.We have discovered P7170, a small molecule inhibitor of mTORC1/mTORC2/ALK1 and investigated its antitumor efficacy using various in vitro and in vivo models of human NSCLC.P7170 inhibited the phosphorylation of AKT, S6 and 4EBP1 (substrates for mTORC2 and mTORC1) levels by 80-100% and growth of NSCLC cells. P7170 inhibited anchorage-independent colony formation of NSCLC patient tumor-derived cells subsistent of disease sub-types. The compound also induced apoptosis in NSCLC cell lines. P7170 at a well-tolerated daily dose of 20 mg/kg significantly inhibited the growth of NSCLC xenografts independent of different mutations (EGFR, KRAS, or PIK3CA) or sensitivity to erlotinib. Pharmacokinetic-pharmacodynamic (PK-PD) analysis showed sub-micro molar tumor concentrations along with mTORC1/C2 inhibition.Our results provide evidence of antitumor activity of P7170 in the erlotinib -sensitive and -insensitive models of NSCLC.
Colorectal Cancer Cell Lines Are Representative Models of the Main Molecular Subtypes of Primary Cancer
Authors: Dmitri Mouradov, Clare Sloggett, Robert N. Jorissen, Christopher G. Love, Shan Li, Antony W. Burgess, Diego Arango, Robert L. Strausberg, Daniel Buchanan, Samuel Wormald, Liam O'Connor, Jennifer L. Wilding, David Bicknell, Ian P.M. Tomlinson, Walter F. Bodmer, John M. Mariadason, Oliver M. Sieber
Journal: Cancer Research (2014)

Human colorectal cancer cell lines are used widely to investigate tumor biology, experimental therapy, and biomarkers. However, to what extent these established cell lines represent and maintain the genetic diversity of primary cancers is uncertain. In this study, we profiled 70 colorectal cancer cell lines for mutations and DNA copy number by whole-exome sequencing and SNP microarray analyses, respectively. Gene expression was defined using RNA-Seq. Cell line data were compared with those published for primary colorectal cancers in The Cancer Genome Atlas. Notably, we found that exome mutation and DNA copy-number spectra in colorectal cancer cell lines closely resembled those seen in primary colorectal tumors. Similarities included the presence of two hypermutation phenotypes, as defined by signatures for defective DNA mismatch repair and DNA polymerase ε proofreading deficiency, along with concordant mutation profiles in the broadly altered WNT, MAPK, PI3K, TGFβ, and p53 pathways. Furthermore, we documented mutations enriched in genes involved in chromatin remodeling (ARID1A, CHD6, and SRCAP) and histone methylation or acetylation (ASH1L, EP300, EP400, MLL2, MLL3, PRDM2, and TRRAP). Chromosomal instability was prevalent in nonhypermutated cases, with similar patterns of chromosomal gains and losses. Although paired cell lines derived from the same tumor exhibited considerable mutation and DNA copy-number differences, in silico simulations suggest that these differences mainly reflected a preexisting heterogeneity in the tumor cells. In conclusion, our results establish that human colorectal cancer lines are representative of the main subtypes of primary tumors at the genomic level, further validating their utility as tools to investigate colorectal cancer biology and drug responses.