tbuckley/cabot-search huggingface dataset:
Adequacy of Glycemic, Lipid, and Blood Pressure Management for Patients With Diabetes in a Managed Care Setting
Authors: Sarah J. Beaton, Soma S. Nag, Margaret J. Gunter, Jeremy M. Gleeson, Shiva S. Sajjan, Charles M. Alexander
Journal: Diabetes Care (2004)

We conducted a retrospective study to evaluate the adequacy of glycemic, lipid, and blood pressure (BP) management for diabetic patients in a managed care organization (MCO).Patients aged > or =18 years with diabetes (n=7,114) were retrospectively identified over a 2-year period from the MCO's administrative database based on the Health Plan Employer Data and Information Set 2000 selection criteria using pharmacy, laboratory, and encounter data. Analyses examined demographics and percentages of patients tested and meeting American Diabetes Association goals for HbA1c, lipids, and BP, both overall and for those receiving medication treatment versus no treatment.Testing rates for A1C, LDL cholesterol, and BP were 77, 54, and 95%, respectively. The percentage of patients tested who were at goal were 37% for A1C, 23% for LDL cholesterol, and 41% for systolic BP. Of the patients in our sample, 72% were treated for glycemic control, 64% were treated for BP control, and only 28% were treated for lipid control. Of the patients who received medication treatment, less than one-third were at goal for A1C (29%) and LDL cholesterol (32%), whereas 40% were at goal for systolic BP.We found that although a large percentage of diabetic patients were tested for A1C, LDL cholesterol, and systolic BP, a much smaller percentage had reached their respective goals. More aggressive glycemic, lipid, and BP management appears to be needed to improve care for these patients.
Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117 411 patients
Authors: D. Keene, C. Price, M. J. Shun-Shin, D. P. Francis
Journal: BMJ (2014)

<b>Objective</b> To investigate the effects on cardiovascular outcomes of drug interventions that increase high density lipoprotein levels. <b>Design</b> Meta-analysis. <b>Studies reviewed</b> Therapeutic benefit of niacin, fibrates, and cholesteryl ester transfer protein (CETP) inhibitors on cardiovascular events (all cause mortality, coronary heart disease mortality, non-fatal myocardial infarction, and stroke). <b>Results</b> 117 411 patients were randomised in a total of 39 trials. All interventions increased the levels of high density lipoprotein cholesterol. No significant effect was seen on all cause mortality for niacin (odds ratio 1.03, 95% confidence interval 0.92 to 1.15, P=0.59), fibrates (0.98, 0.89 to 1.08, P=0.66), or CETP inhibitors (1.16, 0.93 to 1.44, P=0.19); on coronary heart disease mortality for niacin (0.93, 0.76 to 1.12, P=0.44), fibrates (0.92, 0.81 to 1.04, P=0.19), or CETP inhibitors (1.00, 0.80 to 1.24, P=0.99); or on stroke outcomes for niacin (0.96, 0.75 to 1.22, P=0.72), fibrates (1.01, 0.90 to 1.13, P=0.84), or CETP inhibitors (1.14, 0.90 to 1.45, P=0.29). In studies with patients not receiving statins (before the statin era), niacin was associated with a significant reduction in non-fatal myocardial infarction (0.69, 0.56 to 0.85, P=0.0004). However, in studies where statins were already being taken, niacin showed no significant effect (0.96, 0.85 to 1.09, P=0.52). A significant difference was seen between these subgroups (P=0.007). A similar trend relating to non-fatal myocardial infarction was seen with fibrates: without statin treatment (0.78, 0.71 to 0.86, P&lt;0.001) and with all or some patients taking statins (0.83, 0.69 to 1.01, P=0.07); P=0.58 for difference. <b>Conclusions</b> Neither niacin, fibrates, nor CETP inhibitors, three highly effective agents for increasing high density lipoprotein levels, reduced all cause mortality, coronary heart disease mortality, myocardial infarction, or stroke in patients treated with statins. Although observational studies might suggest a simplistic hypothesis for high density lipoprotein cholesterol, that increasing the levels pharmacologically would generally reduce cardiovascular events, in the current era of widespread use of statins in dyslipidaemia, substantial trials of these three agents do not support this concept.
Enhanced Systemic Immune Reactivity to a Basal Cell Carcinoma Associated Antigen Following Photodynamic Therapy
Authors: Edith Kabingu, Allan R. Oseroff, Gregory E. Wilding, Sandra O. Gollnick
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Numerous preclinical studies have shown that local photodynamic therapy (PDT) of tumors enhances systemic antitumor immunity. However, other than single-case and anecdotal reports, this phenomenon has not been examined following clinical PDT. To determine whether PDT in a clinical setting enhances systemic recognition of tumor cells, we examined whether PDT of basal cell carcinoma resulted in an increased systemic immune response to Hip1, a tumor antigen associated with basal cell carcinoma. Experimental Design: Basal cell carcinoma lesions were either treated with PDT or surgically removed. Blood was collected from patients immediately before or 7 to 10 days following treatment. Peripheral blood leukocytes were isolated from HLA-A2–expressing patients and reactivity to a HLA-A2–restricted Hip1 peptide was measured by INF-γ ELISpot assay. Results: Immune recognition of Hip1 increased in patients whose basal cell carcinoma lesions were treated with PDT. This increase in reactivity was significantly greater than reactivity observed in patients whose lesions were surgically removed. Patients with superficial lesions exhibited greater enhancement of reactivity compared with patients with nodular lesions. Immune reactivity following PDT was inversely correlated with treatment area and light dose. Conclusions: These findings show for the first time that local tumor PDT can enhance systemic immune responses to tumors in patients, and validate previous preclinical findings.
Helper T cell recognition of the variable domains of a mouse myeloma protein (315). Effect of the major histocompatibility complex and domain conformation.
Authors: T Jørgensen, K Hannestad
Journal: The Journal of Experimental Medicine (1982)

We have examined the recognition of the variable (V) domain of the heavy (VH) and light (V lambda 2) chains of mouse myeloma protein 315 by helper T cells. Mice were primed with the isolated V domain in complete Freund's adjuvant, and carrier (V domain)-primed spleen cells were transferred together with hapten (NIP)-primed spleen cells to recipient mice that were boosted with NIP3-Fab-315. The helper cell response to both domains was governed by H-2-linked immune response (Ir) genes, and VH-315 and V lambda 2 displayed different Ir phenotypes. H-2k conferred high responsiveness to VH on three different genetic backgrounds, BALB/c, C3H, and B10; mice of the d and b haplotypes were low responders. Conversely, H-2d conferred high responsiveness to V lambda 2 on two backgrounds, BALB/c and C3H, whereas mice of the k haplotype were low responders to this domain. Non-H-2 genes of the B10 background extinguished the helper cell response to V lambda 2 in animals with the high responder d haplotype. The VH Ir gene mapped to the K-A interval of the H-2 complex. Unfolded (completely reduced and alkylated) V domains primed helper cells as efficiently as folded domains for responses to NIP3-Fab-315, indicating that the helper cells recognized an antigenic determinant that was not conformation-dependent. The data indicate that there exists helper T cells which recognize each member of the M315 pair of V domains independent of the other, and that these V domains are recognized like conventional extrinsic protein antigens.
A transgenic mouse model for "lipid hang-up", or why pathologists need to be involved in genetically engineered mouse modelling
Authors: G J A Offerhaus, A N A Milne, I M Oving, M E van Gijn, R H Hruban, H Clevers
Journal: Gut (2008)

Current technology can be used to knock out specific genes in the offspring of mice, to knock in genes with specific mutations, to selectively silence or express gene products in certain tissues, and, if desirable, to do all of these on demand.1 It has made Mus musculus a favourite tool in the modern biomedical research laboratory.

The idea that the mouse is a researcher’s aide is not a new one. More than a century ago Dr William Welch, one of the four founding “fathers” of The Johns Hopkins Hospital and Chief of Pathology, directed his trainee to the mouse laboratory for “broadening... knowledge of pathology as well as deepening it...”.2 Today, many pathologists have become intimately familiar with mouse pathology, but the tides have changed; these days the mouse is brought by the researcher to the pathologist to determine how closely the changes in that genetically engineered mouse mimic human disease.

Disruption in bone morphogenetic protein (BMP) signalling in genetically engineered mice led to insights into the human …
<i>MLL</i>-Rearranged B Lymphoblastic Leukemias Selectively Express the Immunoregulatory Carbohydrate-Binding Protein Galectin-1
Authors: Przemyslaw Juszczynski, Scott J. Rodig, Jing Ouyang, Evan O'Donnell, Kunihiko Takeyama, Wojciech Mlynarski, Katarzyna Mycko, Tomasz Szczepanski, Anna Gaworczyk, Andrei Krivtsov, Joerg Faber, Amit U. Sinha, Gabriel A. Rabinovich, Scott A. Armstrong, Jeffery L. Kutok, Margaret A. Shipp
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Patients with mixed lineage leukemia (MLL)–rearranged B-lymphoblastic leukemias (B-ALL) have an unfavorable prognosis and require intensified treatment. Multiple MLL fusion partners have been identified, complicating the diagnostic evaluation of MLL rearrangements. We analyzed molecular markers of MLL rearrangement for use in rapid diagnostic assays and found the immunomodulatory protein, Galectin-1 (Gal-1), to be selectively expressed in MLL-rearranged B-ALL. Experimental Design: Transcriptional profiling of ALL subtypes revealed selective overexpression of Gal-1 in MLL-rearranged ALLs. For this reason, we analyzed Gal-1 protein expression in MLL-germline and MLL-rearranged adult and infant pediatric B-ALLs and cell lines by immunoblotting, immunohistochemistry, and intracellular flow cytometry of viable tumor cell suspensions. Because deregulated gene expression in MLL-rearranged leukemias may be related to the altered histone methyltransferase activity of the MLL fusion protein complex, we also analyzed histone H3 lysine 79 (H3K79) dimethylation in the LGALS1 promoter region using chromatin immunoprecipitation. Results: Gal-1 transcripts were significantly more abundant in MLL-rearranged B-ALLs. All 32 primary MLL-rearranged B-ALLs exhibited abundant Gal-1 immunostaining, regardless of the translocation partner, whereas only 2 of 81 germline-MLL B-ALLs expressed Gal-1. In addition, Gal-1 was selectively detected in newly diagnosed MLL-rearranged B-ALLs by intracellular flow cytometry. The LGALS1 promoter H3K79 was significantly hypermethylated in MLL-rearranged B-ALLs compared with MLL-germline B-ALLs and normal pre-B cells. Conclusion: In B-ALL, Gal-1 is a highly sensitive and specific biomarker of MLL rearrangement that is likely induced by a MLL-dependent epigenetic modification. Clin Cancer Res; 16(7); 2122–30. ©2010 AACR.
Predictors of Reocclusion After Successful Drug-Eluting Stent–Supported Percutaneous Coronary Intervention of Chronic Total Occlusion
Authors: Renato Valenti, Ruben Vergara, Angela Migliorini, Guido Parodi, Nazario Carrabba, Giampaolo Cerisano, Emilio Vincenzo Dovellini, David Antoniucci
Journal: Journal of the American College of Cardiology (2012)
The Cancer Genome Atlas Clinical Explorer: a web and mobile interface for identifying clinical–genomic driver associations
Authors: HoJoon Lee, Jennifer Palm, Susan M. Grimes, Hanlee P. Ji
Journal: Genome Medicine (2015)

The Cancer Genome Atlas (TCGA) project has generated genomic data sets covering over 20 malignancies. These data provide valuable insights into the underlying genetic and genomic basis of cancer. However, exploring the relationship among TCGA genomic results and clinical phenotype remains a challenge, particularly for individuals lacking formal bioinformatics training. Overcoming this hurdle is an important step toward the wider clinical translation of cancer genomic/proteomic data and implementation of precision cancer medicine. Several websites such as the cBio portal or University of California Santa Cruz genome browser make TCGA data accessible but lack interactive features for querying clinically relevant phenotypic associations with cancer drivers. To enable exploration of the clinical–genomic driver associations from TCGA data, we developed the Cancer Genome Atlas Clinical Explorer. The Cancer Genome Atlas Clinical Explorer interface provides a straightforward platform to query TCGA data using one of the following methods: (1) searching for clinically relevant genes, micro RNAs, and proteins by name, cancer types, or clinical parameters; (2) searching for genomic/proteomic profile changes by clinical parameters in a cancer type; or (3) testing two-hit hypotheses. SQL queries run in the background and results are displayed on our portal in an easy-to-navigate interface according to user's input. To derive these associations, we relied on elastic-net estimates of optimal multiple linear regularized regression and clinical parameters in the space of multiple genomic/proteomic features provided by TCGA data. Moreover, we identified and ranked gene/micro RNA/protein predictors of each clinical parameter for each cancer. The robustness of the results was estimated by bootstrapping. Overall, we identify associations of potential clinical relevance among genes/micro RNAs/proteins using our statistical analysis from 25 cancer types and 18 clinical parameters that include clinical stage or smoking history. The Cancer Genome Atlas Clinical Explorer enables the cancer research community and others to explore clinically relevant associations inferred from TCGA data. With its accessible web and mobile interface, users can examine queries and test hypothesis regarding genomic/proteomic alterations across a broad spectrum of malignancies.
THE COURSE OF EXPERIMENTAL AUTOALLERGIC THYROIDITIS IN INBRED GUINEA PIGS
Authors: Edwin M. Lerner, Philip R. B. McMaster, Eurmal D. Exum
Journal: The Journal of Experimental Medicine (1964)

Experimental allergic thyroiditis produced in strain 13 histocompatible guinea pigs after a single immunization with thyroid extract and Freund's adjuvant was followed for more than 2 years. The disease appeared as early as 5 days and persisted for the entire period studied, although it regressed in the later stages. Circulating antithyroid antibody was detected at low levels as early as 7 days after immunization, and increased to a peak at the time of most severe disease. Thereafter, antibody decreased, but was still detectable in most animals as late as 2 years. There was no correlation between antibody levels and extent of disease except at the 7 week stage. Delayed sensitivity to thyroid antigen was found as early as 5 days after immunization, and appeared to precede the development of thyroiditis in many animals. It correlated closely with thyroiditis at 5 days and 7 weeks. At 6 months, the delayed skin reaction was decreased, and a modified type of reaction appeared which persisted as long as 26 months. The time relationship of delayed sensitivity, thyroiditis, and circulating antibody continue to confirm the role of delayed sensitivity in the pathogenesis of this disease. The accumulated data demonstrating production of thyroiditis without antibody, and the converse, tend to strengthen this view.
High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study
Authors: A. Josting, M. Sieniawski, J.-P. Glossmann, O. Staak, L. Nogova, N. Peters, M. Mapara, B. Dörken, Y. Ko, B. Metzner, J. Kisro, V. Diehl, A. Engert
Journal: Annals of Oncology (2005)
Reply to: “Review of drug-related causes of oculocutaneous disease”
Authors: Jonathan E. Mayer, M. Alan Menter
Journal: Journal of the American Academy of Dermatology (2015)

To the Editor: Thank you for the letter regarding the oculocutaneous side effects of epidermal growth factor receptor inhibitors (EGFRIs). We appreciate the increasing use of this class of drugs and the importance of understanding their side effects. A section of the original review was indeed devoted to covering the most common oculocutaneous side effects caused by EGFRIs. In that section, in addition to exploring trichomegaly, we mentioned the common ophthalmic side effects of pruritus, erythema of the periorbital skin and eyelids, purulent secretion, and dryness. Cameron et al mention meibomitis, which is a common entity that can cause several of the above signs and symptoms. We thank them for highlighting this diagnosis and the potential use of systemic doxycycline. In regard to the other side effects mentioned by Cameron et al, such as ectropion and iridocyclitis, these have been only rarely reported and therefore were not included in our broad review. Finally, we agree with the authors that long-term use of periocular mid-high potency topical steroids warrants an ophthalmology referral. We believe all dermatologists are cognizant of this issue. However, for a topical calcineurin inhibitor such as tacrolimus, where there are no issues relating to atrophy or intraocular pressure, a referral would not be necessary. Review of drug-related causes of oculocutaneous diseaseJournal of the American Academy of DermatologyVol. 72Issue 2PreviewTo the Editor: We read with interest Part II of the CME review on oculocutaneous disease by Day et al in the May 2014 issue of the journal entitled “Neoplastic and drug-related causes of oculocutaneous disease.” Medications have a wide variety of oculocutaneous side effects, and we commend the authors for creating a thorough review of this topic. However, we believe epidermal growth factor receptor inhibitors (EGFRIs) deserve further attention with regard to unmentioned oculocutaneous toxicities and their management, as well the increasing prevalence of these side effects due to increased use of EGFRIs. Full-Text PDF
Wingless: developmentally important genes that respond adversely to smoking
Authors: Denise Al Alam, David Warburton
Journal: Thorax (2013)

It has been observed by many authors that cigarette smoking results in long standing epithelial damage and interstitial inflammation within the lung. Quitting strongly reduces the risk of smoking associated lung diseases such as chronic obstructive pulmonary disease (COPD), but the underlying inflammation of the airways does not go away completely even after quitting smoking. So, a critical question for the pulmonary physician is: why is smoking cigarettes so bad for the airway lining and why are the inflammatory effects so long lasting?

Heijink et al , working with cultures of human primary bronchial epithelial cell (PBEC) biopsy specimens, now come with an intriguing new finding that cigarette smoking has significant adverse affects on certain members of the Wingless family, entraining a feed forward mechanism that increases epithelial cytokine production in response to cigarette smoke extract.1 

The Wingless family comprises an important class of developmentally critical signalling ligands that conduct signals from the cell surface through the cytoplasm to the nucleus, where they activate coordinated sets of genes. These genes in turn regulate cell–cell communication in the embryonic through the adult stages of human and animal development and continue to be very important in airway epithelial differentiation as well as during airway epithelial healing (see Warburton et al 2 for a recent review).

The colourful name Wingless was coined to describe the loss of function phenotype of fruit flies that lack this gene (they have no wings). Fruit fly geneticists, being somewhat perverse, always delight in giving active voice picaresque names to their loss of function phenotypes. Thus, conversely, signalling by Wingless ligands actually induces the correct differentiation of epithelial cells that form the wing structures in flies and this basic developmental function is conserved, but has been adapted during evolution all the way up …
Evaluation of Therapeutic Efficacy of Trimethoprim-sulphamethoxazole and Chloramphenicol in Enteric Fever
Authors: S. A. Kamat
Journal: BMJ (1970)

In a clinical trial on 220 patients with bacteriologically proved enteric fever trimethoprim-sulphamethoxazole was compared with chloramphenicol. All patients in both groups responded, and the mean periods of defervescence after starting therapy were similar in both groups. Trimethoprim-sulphamethoxazole was much superior to chloramphenicol in rapidity and uniformity of relief of toxaemia. “Toxic crisis” occurred in 10 out of 120 patients in the chloramphenicol group and was absent in the trimethoprim-sulphamethoxazole group. No major side-effects due to specific drug therapy were observed in either group.
Abstract B18: Non-thermal plasma, tirapazamine, and gap junctions: A novel approach to melanoma therapy through ROS induction
Authors: Shoshanna N. Zucker, Cory Higley, Zethan Koch, Haneesha Goli, Peter Casey, Akeem Francis, Kevin Burke, Jennifer Zirnheld
Journal: Cancer Research (2015)

Abstract Melanoma cells typically have high levels of superoxide anion which may increase their susceptibility to cell death by reactive oxygen species (ROS). We have used this information to establish a system whereby melanoma cells are saturated with ROS through treatment with non-thermal plasma (NTP). NTP is formed from a mixture of highly charged helium and atmospheric gases to emit a total of 45 molecular species, many of which are ROS. We have recently demonstrated that NTP causes selective apoptotic cell death of melanoma cells as compared to normal skin keratinocytes when plated in co-culture. Since tumors flourish under low oxygen (hypoxic) conditions, we tested the effects of NTP under hypoxia. In order to enhance the effects of NTP, we combined this therapy with the experimental anticancer drug, tirapazamine, which promotes cell toxicity through DNA damage only under hypoxic conditions. The question then remains as to how to increase the target area of melanoma therapy. Our previous studies have demonstrated that gap junctions act via the bystander effect to enable the passage of cell-death promoting signals by NTP. We utilized stably transfected 1205Lu metastatic melanoma cells that express three different levels of gap junctions: endogenous low levels, increased levels through expression of connexin 43, or an absence of gap junctions due to expression of a dominant negative mutant connexin 43. We have shown that the cells with the mutant connexin 43 showed increased invasive potential as well as enhanced expression of HIF1α. The combination therapy with NTP and tirapazamine under hypoxic conditions caused a synergistic effect which increased cell death in all cells, yet was most apparent in the 1205Lu cells overexpressing the functional gap junctions. In addition, the target area of the NTP torch was dramatically increased under these conditions. This suggests that the ROS generated by NTP and tirapazamine induced the bystander effect and promoted the spreading of cell death signals well beyond the area of the plasma treatment. These results are indicative a novel future approach to melanoma therapy through selective ROS induction and modification of gap junction phenotype. Citation Format: Shoshanna N. Zucker, Cory Higley, Zethan Koch, Haneesha Goli, Peter Casey, Akeem Francis, Kevin Burke, Jennifer Zirnheld. Non-thermal plasma, tirapazamine, and gap junctions: A novel approach to melanoma therapy through ROS induction. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr B18.