tbuckley/cabot-search huggingface dataset:
Phylogenetic analysis of the South American electric fishes (order Gymnotiformes) and the evolution of their electrogenic system: a synthesis based on morphology, electrophysiology, and mitochondrial sequence data.
Authors: J A Alves-Gomes, G Ortí, M Haygood, W Heiligenberg, A Meyer
Journal: Molecular Biology and Evolution (1995)

The order Gymnotiformes (South American electric fishes) is a fascinating assemblage of freshwater fishes that share the unusual ability to produce and sense electric fields used for electrolocation and social communication. In the last few decades, the electrogenic and electrosensory systems (EES) of these fish have served as an excellent model to study motor and sensory physiology in vertebrates. In an attempt to the evolution of characters associated with the EES in the group, we applied maximum-parsimony (MP), minimum-evolution (ME), and maximum-likelihood (ML) methods to analyze 302 aligned bases of the mitochondrial 12S rRNA and 416 bases of the mitochondrial 16S rRNA of 19 gymnotiform genera representing all six recognized families. Six catfish genera (order Siluriformes) were also sequenced and used as outgroups. The phylogenetic hypothesis resultant from molecular data analysis differs in some respects from previous hypotheses based on morphological studies. Our results were most informative within the family level, as we were unable to elucidate the relationships among deeper branches in this order with sufficient confidence by using molecular data alone. The phylogenetic information of both mitochondrial DNA segments appears to be affected by functional constraints, and the resultant topologies were sensitive to different weighting schemes and the algorithm used. Nonetheless, we found unanimous support for the following phylogenetic relationships: (1) the family Sternopygidae is an unnatural group, and Sternopygus is the sole representative of a unique lineage within the order; (2) the family Hypopomidae is not monophyletic; and (3) the order Gymnotiformes is composed of at least six natural clades: Sternopygus, family Apteronotidae, a new clade consisting of the remaining sternopygids, families Hypopomidae + Rhamphicthyidae, family Electrophoridae, and family Gymnotidae. By combining molecular, morphological, and physiological information, we propose a new hypothesis for the phylogeny of this group and suggest a new family Eigenmanniidae n. (order Gymnotiformes).
EXPERIMENTAL DEHYDRATION: CHEMICAL CHANGES IN THE BLOOD OF THE DOG CONTRASTED WITH THOSE FOLLOWING OBSTRUCTION OF THE CARDIAC END OF THE STOMACH
Authors: Russell L. Haden, Thomas G. Orr
Journal: The Journal of Experimental Medicine (1929)

A comparative chemical study of the blood and the urine of the dog with experimental dehydration and with obstruction of the cardiac end of the stomach is reported. The average duration of life is slightly longer with dehydration than with obstruction. The urine output per kilo of body weight is almost twice as great in dehydration as with obstruction. The increase in non-protein nitrogen and urea nitrogen is much the same in the two groups although somewhat more marked with obstruction. The chlorides of the blood are markedly increased with dehydration and slightly decreased with obstruction. The increase in fibrinogen and total protein is twice as great with obstruction as with dehydration. These findings indicate that there must be some factor or factors in addition to dehydration producing the toxemia of cardiac obstruction.
Gene Networks and microRNAs Implicated in Aggressive Prostate Cancer
Authors: Liang Wang, Hui Tang, Venugopal Thayanithy, Subbaya Subramanian, Ann L. Oberg, Julie M. Cunningham, James R. Cerhan, Clifford J. Steer, Stephen N. Thibodeau
Journal: Cancer Research (2009)

Prostate cancer, a complex disease, can be relatively harmless or extremely aggressive. To identify candidate genes involved in causal pathways of aggressive prostate cancer, we implemented a systems biology approach by combining differential expression analysis and coexpression network analysis to evaluate transcriptional profiles using lymphoblastoid cell lines from 62 prostate cancer patients with aggressive phenotype (Gleason grade >or= 8) and 63 prostate cancer patients with nonaggressive phenotype (Gleason grade <or= 5). From 13,935 mRNA genes and 273 microRNAs (miRNA) tested, we identified significant differences in 1,100 mRNAs and 7 miRNAs with a false discovery rate (FDR) of <0.01. We also identified a coexpression module demonstrating significant association with the aggressive phenotype of prostate cancer (P = 3.67 x 10(-11)). The module of interest was characterized by overrepresentation of cell cycle-related genes (FDR = 3.50 x 10(-50)). From this module, we further defined 20 hub genes that were highly connected to other genes. Interestingly, 5 of the 7 differentially expressed miRNAs have been implicated in cell cycle regulation and 2 (miR-145 and miR-331-3p) are predicted to target 3 of the 20 hub genes. Ectopic expression of these two miRNAs reduced expression of target hub genes and subsequently resulted in cell growth inhibition and apoptosis. These results suggest that cell cycle is likely to be a molecular pathway causing aggressive phenotype of prostate cancer. Further characterization of cell cycle-related genes (particularly, the hub genes) and miRNAs that regulate these hub genes could facilitate identification of candidate genes responsible for the aggressive phenotype and lead to a better understanding of prostate cancer etiology and progression.
The effect of indomethacin blockade of prostaglandin synthesis on blood pressure of normal rabbits and rabbits with renovascular hypertension.
Authors: J C Romero, C G Strong
Journal: Circulation Research (1977)

Indomethacin inhibits the synthesis of prostaglandin and the release of renin. These effects were studied in normal rabbits and rabbits with two-kidney Goldblatt hypertension (2KGH) and one-kidney Goldblatt hypertension (1KGH) by giving daily intravenous injections of indomethacin (3mg/kg after two initial doses of 9 mg/kg), and in appropriate control rabbits given diluent phosphate buffer without indomethacin. In normal rabbits, indomethacin significantly decreased immunoreactive plasma prostaglandin E-like substance (IPGE) and plasma renin activity (PRA). Indomethacin did not change plasma creatinine (PCr) or mean blood pressure but it decreased renal blood flow (RBF) and glomerular filtration rate (GFR). In 2KGH rabbits, responses depended on the level of renal function and, to a lesser extent, on the level of PRA. In six of10 2KGH rabbits in which hypertension developed without significant changes in PRA, IPGE, PCr, RBF, and GFR, indomethacin produced changes similar to those seen in normals. In the other four rabbits, development of 2KGH was accompanied by increased PRA, increased IPGE, and decreased RBF and GFR, and indomethacin produced renal failure, oliguria, malignant hypertension, and death within 5 days. In 1KGH rabbits, indomethacin decreased IPGE, PRA, and renal function but increased mean blood pressure. These observations suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.
Embryonic Stem Cells As an Alternate Marrow Donor Source
Authors: Richard K. Burt, Larissa Verda, Duck-An Kim, Yu Oyama, Kehuan Luo, Charles Link
Journal: The Journal of Experimental Medicine (2004)

A single embryonic stem cell (ESC) line can be repetitively cryopreserved, thawed, expanded, and differentiated into various cellular components serving as a potentially renewable and well-characterized stem cell source. Therefore, we determined whether ESCs could be used to reconstitute marrow and blood in major histocompatibility complex (MHC)-mismatched mice. To induce differentiation toward hematopoietic stem cells (HSCs) in vitro, ESCs were cultured in methylcellulose with stem cell factor, interleukin (IL)-3, and IL-6. ESC-derived, cytokine-induced HSCs (c-kit+/CD45+) were isolated by flow cytometry and injected either intra bone marrow or intravenously into lethally irradiated MHC-mismatched recipient mice. From 2 wk to 6 mo after injection, the peripheral blood demonstrated increasing ESC-derived mononuclear cells that included donor-derived T and B lymphocytes, monocytes, and granulocytes without clinical or histologic evidence of graft-versus-host disease (GVHD). Mixed lymphocyte culture assays demonstrated T cell tolerance to both recipient and donor but intact third party proliferative responses and interferon gamma production. ESCs might be used as a renewable alternate marrow donor source that reconstitutes hematopoiesis with intact immune responsiveness without GVHD despite crossing MHC barriers.
Human Nuclease/Helicase DNA2 Alleviates Replication Stress by Promoting DNA End Resection
Authors: Guang Peng, Hui Dai, Wei Zhang, Hui-Ju Hsieh, Mei-Ren Pan, Yun-Yong Park, Robert Yu-Lin Tsai, Isabelle Bedrosian, Ju-Seog Lee, Grzegorz Ira, Shiaw-Yih Lin
Journal: Cancer Research (2012)

In precancerous and cancerous lesions, excessive growth signals resulting from activation of oncogenes or loss of tumor suppressor genes lead to intensive replication stress, which is recognized by a high level of replication-associated DNA double-strand breaks (DSB). However, the molecular mechanism by which cells alleviate excessive replication stress remains unclear. In this study, we report that the human nuclease/helicase DNA2 facilitates homologous recombination to repair replication-associated DNA DSBs, thereby providing cells with survival advantages under conditions of replication stress. The nuclease activity of DNA2 was required for DSB end resection, which allowed subsequent recruitment of RPA and RAD51 to repair DSBs and restart replication. More importantly, DNA2 expression was significantly increased in human cancers and its expression correlated with patient outcome. Our findings therefore indicate that enhanced activity of DSB resection likely constitutes one mechanism whereby precancerous and cancerous cells might alleviate replication stress.
Propylthiouracil-induced antineutrophil cytoplasmic antibodies in a patient with Graves' disease and a neutrophilic dermatosis
Authors: R.M. Miller, T.A. Darben, J. Nedwich, J. Savige
Journal: British Journal of Dermatology (1999)

S ir, Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against neutrophil granular enzymes that are present in nearly all patients with the small vessel vasculitides, Wegener’s granulomatosis and microscopic polyangiitis. ANCA also occur in the drug‐induced vasculitides, 1 inflammatory bowel disease and rheumatoid arthritis. They are usually only demonstrated in patients with skin conditions when these are manifestations of the above diseases; previous descriptions of ANCA in Sweet’s syndrome have been thought to reflect the underlying diseases rather than an independent association. 2–4 However, we report here a patient who had Graves’ disease treated with propylthiouracil (PTU), in whom the simultaneous development of ANCA and a neutrophilic dermatosis suggested that PTU contributed to the aetiopathogenesis of both. The patient was a 37‐year‐old woman who had been diagnosed with Graves’ disease 3 years previously. She was treated with PTU without any problems for the first 2 years. PTU had been recommenced at a dose of 100 mg three times daily 3 months before this presentation. She had no other significant medical history, no known allergies, and took no other medication. On this occasion the patient presented with a temperature of 38 °C, and 1 week of discrete, annular plum‐coloured nodules and plaques on her face, outer arms, upper back, lateral aspects of her legs and the backs of her hands and fingers. Some of these areas developed bullae and became superficially eroded ( Fig. 1). The patient also had superficial aphthous‐like erosions of the buccal mucosa and tongue, but her lips, eyes, nails and genitals were not involved. There had been no preceding upper respiratory tract infection, and no features to suggest the diagnosis of rheumatoid arthritis, inflammatory bowel disease or malignancy. There were no other significant findings on physical examination except for a goitre and a fine tremor consistent with mild hyperthyroidism.
Breast Cancer Lung Metastasis Requires Expression of Chemokine Receptor CCR4 and Regulatory T Cells
Authors: Purevdorj B. Olkhanud, Dolgor Baatar, Monica Bodogai, Fran Hakim, Ronald Gress, Robin L. Anderson, Jie Deng, Mai Xu, Susanne Briest, Arya Biragyn
Journal: Cancer Research (2009)

Cancer metastasis is a leading cause of cancer morbidity and mortality. More needs to be learned about mechanisms that control this process. In particular, the role of chemokine receptors in metastasis remains controversial. Here, using a highly metastatic breast cancer (4T1) model, we show that lung metastasis is a feature of only a proportion of the tumor cells that express CCR4. Moreover, the primary tumor growing in mammary pads activates remotely the expression of TARC/CCL17 and MDC/CCL22 in the lungs. These chemokines acting through CCR4 attract both tumor and immune cells. However, CCR4-mediated chemotaxis was not sufficient to produce metastasis, as tumor cells in the lung were efficiently eliminated by natural killer (NK) cells. Lung metastasis required CCR4(+) regulatory T cells (Treg), which directly killed NK cells using beta-galactoside-binding protein. Thus, strategies that abrogate any part of this process should improve the outcome through activation of effector cells and prevention of tumor cell migration. We confirm this prediction by killing CCR4(+) cells through delivery of TARC-fused toxins or depleting Tregs and preventing lung metastasis.
Phase I Study of Weekly Mitoxantrone and Docetaxel before Prostatectomy in Patients with High-Risk Localized Prostate Cancer
Authors: Tomasz M. Beer, Mark Garzotto, Bruce A. Lowe, William J. Ellis, Michelle A. Montalto, Paul H. Lange, Celestia S. Higano
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose is to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of mitoxantrone and docetaxel administered weekly before prostatectomy in men with localized prostate cancer at high risk for recurrence. Experimental Design: Twenty-two patients were treated with four cycles of docetaxel 35 mg/m2 and increasing doses of mitoxantrone starting at 2 mg/m2 repeated weekly for 3 weeks of a 4-week cycle before prostatectomy. The MTD was defined as that dose at which fewer than one-third of patients experienced a DLT (≥grade 4 hematological or ≥grade 3 nonhematological toxicity). Changes in serum prostate-specific antigen and serum testosterone, and pathological outcome with surgery were secondary endpoints. Results: The MTD for mitoxantrone in combination with this dose of docetaxel was 4 mg/m2. Neutropenia was the DLT for the combination. Ten of 12 patients treated at the MTD completed the planned 16 weeks of chemotherapy, whereas 2 discontinued therapy early because of toxicity. The median reduction in PSA was 41% (range, 4–88%). Serum testosterone levels remained constant postchemotherapy. Conclusions: In this patient population, the planned Phase II regimen is 4 mg/m2 mitoxantrone and 35 mg/m2 docetaxel weekly for 3 of every 4 weeks. Delivery of this regimen before prostatectomy is feasible with acceptable toxicity. Additional studies are needed to determine whether this combined modality approach will reduce cancer recurrence rates in this high-risk population. Because extent of disease and exposure to prior therapy may impact treatment tolerance these safety data may not be applicable to patients with advanced prostate cancer.
Evaluation of the anti-tumor effects of lactate dehydrogenase inhibitor galloflavin in endometrial cancer cells
Authors: Xiaoyun Han, Xiugui Sheng, Hannah M Jones, Amanda L Jackson, Joshua Kilgore, Jessica E Stine, Monica N Schointuch, Chunxiao Zhou, Victoria L Bae-Jump
Journal: Journal of Hematology & Oncology (2015)

High rates of aerobic glycolysis represent a key mechanism by which endometrial cancer cells consume glucose as its primary energy source. The up-regulated glycolytic pathway is a common therapeutic target whose inhibition has implications for anti-tumor activity in cancer cells. The present study was aimed at evaluating the potential of a novel lactate dehydrogenase (LDH) inhibitor, Galloflavin, as a therapeutic agent for endometrial cancer. Our results revealed that Galloflavin effectively inhibited cell growth in endometrial cancer cell lines and primary cultures of human endometrial cancer through its involvement in multiple signaling pathways that regulate metabolism, cell cycle, apoptosis, cell stress and metastasis.
Differential chemosensitivity to antifolate drugs between RAS and BRAF melanoma cells
Authors: Imanol Arozarena, Ibai Goicoechea, Oihane Erice, Jennnifer Ferguson, Geoffrey P Margison, Claudia Wellbrock
Journal: Molecular Cancer (2014)

The importance of the genetic background of cancer cells for the individual susceptibility to cancer treatments is increasingly apparent. In melanoma, the existence of a BRAF mutation is a main predictor for successful BRAF-targeted therapy. However, despite initial successes with these therapies, patients relapse within a year and have to move on to other therapies. Moreover, patients harbouring a wild type BRAF gene (including 25% with NRAS mutations) still require alternative treatment such as chemotherapy. Multiple genetic parameters have been associated with response to chemotherapy, but despite their high frequency in melanoma nothing is known about the impact of BRAF or NRAS mutations on the response to chemotherapeutic agents. Using cell proliferation and DNA methylation assays, FACS analysis and quantitative-RT-PCR we have characterised the response of a panel of NRAS and BRAF mutant melanoma cell lines to various chemotherapy drugs, amongst them dacarbazine (DTIC) and temozolomide (TMZ) and DNA synthesis inhibitors. Although both, DTIC and TMZ act as alkylating agents through the same intermediate, NRAS and BRAF mutant cells responded differentially only to DTIC. Further analysis revealed that the growth-inhibitory effects mediated by DTIC were rather due to interference with nucleotide salvaging, and that NRAS mutant melanoma cells exhibit higher activity of the nucleotide synthesis enzymes IMPDH and TK1. Importantly, the enhanced ability of RAS mutant cells to use nucleotide salvaging resulted in resistance to DHFR inhibitors. In summary, our data suggest that the genetic background in melanoma cells influences the response to inhibitors blocking de novo DNA synthesis, and that defining the RAS mutation status could be used to stratify patients for the use of antifolate drugs.
Scottish Foot Ulcer Risk Score Predicts Foot Ulcer Healing in a Regional Specialist Foot Clinic
Authors: Graham Leese, Christopher Schofield, Brian McMurray, Gillian Libby, Judith Golden, Ritchie MacAlpine, Scott Cunningham, Andrew Morris, Murray Flett, Gareth Griffiths
Journal: Diabetes Care (2007)

To determine whether patients developing ulcers had previously been identified as being at high risk of ulceration using the Scottish Care Information-Diabetes Collaboration (SCI-DC) ulcer risk score and whether the risk score predicts ulcer healing.All patients attending the diabetes foot clinic with an ulcer had been assessed for foot ulcer risk using the SCI-DC risk calculator, which categorizes patients into low, moderate, or high risk of ulceration. Information on foot pulses, neuropathy, foot deformity, previous ulcer, ulcer site, depth, and presence of sepsis was recorded and related to ulcer outcome. Patients were followed up until outcome was achieved (median 3 months [range 1-33]).Of patients attending the clinic with a foot ulcer (mean [+/-SD] age 67.3 +/- 12.7 years, 68% male), 68% were previously recognized to be at high risk of foot ulceration, and 98% were high or moderate risk. Of 221 ulcers, the healing rate was 75% overall but was lower for high-risk patients compared with other patients (68 vs. 93%; P < 0.0001). Of the remainder, 3% became chronic ulcers, 12% required minor or major amputation, and 10% died with their ulcer. In multivariate analysis, absent pulses, neuropathy, increased age, and deep ulcers were associated with poor healing. The combination of neuropathy and ischemia was particularly associated with poor outcome of an ulcer (61% healing).The Scottish foot ulcer risk score predicts both ulcer development and ulcer healing. The risk score can be a useful initial guide to determine the likelihood of poor healing. The individual criteria contributing to this overall risk are similar to other studies.
Recognition of major histocompatibility complex antigens on cultured human biliary epithelial cells by alloreactive lymphocytes
Authors: Susan L. Saidman, Rene J. Duquesnoy, Adriana Zeevi, John J. Fung, Thomas E. Starzl, Jake A. Demetris
Journal: Hepatology (1991)

We have developed an in vitro system to study the interactions between biliary epithelium and lymphocytes using cultured human biliary epithelial cells. No class II antigens were detected by immunoperoxidase staining of the normal biliary epithelial cells, but alloactivated lymphocyte culture supernatants were able to induce class II expression. The activity of the supernatants was blocked with an anti-gamma-interferon monoclonal antibody. In addition, recombinant human gamma-interferon alone induced the expression of class II antigens and increased the intensity of class I staining of cultured biliary epithelial cells. Biliary epithelial cell-induced proliferation of alloreactive T lymphocytes demonstrated that the major histocompatibility complex molecules carry functional lymphocyte-activating determinants. The recognition of major histocompatibility complex determinants was confirmed by monoclonal antibody-blocking studies and by stimulation of an alloreactive T-cell clone. However, the biliary epithelial cells were much less potent stimulators than arterial endothelial cells tested in the same assay system.
Computed tomography score and pulmonary function in infants with chronic lung disease of infancy
Authors: E.E. Sarria, R. Mattiello, L. Rao, M.R. Wanner, M.E. Raske, C. Tiller, R. Kimmel, R.S. Tepper
Journal: European Respiratory Journal (2011)

Chronic lung disease of infancy (CLDI) remains a common outcome among infants born extremely prematurely. In older children and adults with lung disease, pulmonary function and computed tomography (CT) scores are used to follow up respiratory disease and assess disease severity. For infants and toddlers, however, these outcomes have been used very infrequently and most often, a dichotomous respiratory outcome (presence or absence of CLDI) is employed. We evaluated the performance of CT score and pulmonary function to differentiate infants and toddlers with CLDI from a control group. CT scans, forced expiratory flows and pulmonary diffusing capacity were obtained in 39 CLDI patients and 41 controls (aged 4–33 months). CT scans were quantified using a scoring system, while pulmonary function was expressed as Z-scores. CT score outperformed pulmonary function in identifying those with CLDI. There were no significant correlations between CT score and pulmonary function. CT score had a better performance than pulmonary function in differentiating individuals with CLDI; however, these outcomes may reflect differing components of the pulmonary pathophysiology of CLDI. This new information on pulmonary outcomes can assist in designing studies with these parameters. Future studies will be required to evaluate which of the outcomes can better detect improvement with therapeutic intervention and/or lung growth.
Intrathymic programming of effector fates in three molecularly distinct γδ T cell subtypes
Authors: Kavitha Narayan, Katelyn E Sylvia, Nidhi Malhotra, Catherine C Yin, Gregory Martens, Therese Vallerskog, Hardy Kornfeld, Na Xiong, Nadia R Cohen, Michael B Brenner, Leslie J Berg, Joonsoo Kang
Journal: Nature Immunology (2012)