tbuckley/cabot-search huggingface dataset:
Abstract 683: Evaluating the therapeutic potential of a peptide derivative of cancer-associated PCNA in DNA repair deficient breast cancers
Authors: Elizabeth A. Phipps, Lacey E. Dobrolecki, Robert J. Hickey, George W. Sledge, Brittney-Shea Herbert, Linda H. Malkas
Journal: Cancer Research (2010)

Abstract Our laboratory was the first to isolate and purify an intact mammalian cell multiprotein DNA replication complex, termed the synthesome, from a variety of human cell types that was both stable and fully functional. Subsequent work revealed that the synthesome of malignant breast epithelial cells exhibits a more error-prone synthesis process than that of nonmalignant breast epithelial cells. We recently correlated the low replication fidelity of malignant cells was due at least in part to a post-translational modification of a specific protein component of the synthesome: proliferating cell nuclear antigen, or PCNA. Our laboratory developed an antibody (cancer-associated or caPCNAab) specific to the cancer-associated PCNA isoform (cancer-associated or caPCNA), providing hope of an effective diagnostic marker of malignancy. Additionally, peptides were derived from the caPCNA sequence (caPeptides) and these peptides were shown to augment the action of doxorubicin (DOX) in leukemia cells while leaving nonmalignant cells intact. caPeptides may possess anti-cancer therapeutic potential through blocking the association of caPCNA with its binding partners involved in DNA replication and repair. The objective of this study was to determine the mechanism by which caPeptides directed against caPCNA induced cancer cell cytotoxicity. Breast cancer cells from a patient harboring a hereditary mutation in BRCA1, a major component of DNA double strand break repair (HCC1937 cells), were used in this study. As a genetically matched control, the wild-type breast cancer 1 early onset gene (BRCA1) was transduced into HCC1937 cells (referred to as HCC1937 + wild-type BRCA1). MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays were conducted with caPeptides at a variety of timepoints both alone and in combination with DNA damaging agent cisplatin in HCC1937 and HCC1937 + wild-type BRCA1 cells. The data suggests cells lacking wild-type BRCA1 show increased sensitivity to caPeptides in comparison to isogenic controls transduced with wild-type BRCA1. We show that caPeptides augment the action of DNA damaging agent cisplatin. Furthermore, caPeptides containing amino acid substitutions in specific sites within the peptide show enhanced cytotoxicity over wild-type caPeptides. This work may provide information useful in a clinical setting as caPeptides could benefit a particular subset of breast cancer patients. Additionally, caPeptide studies may shed light on the deregulated replication and repair processes common in cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 683.
Relationship between asthma and gastro-oesophageal reflux.
Authors: R J Goodall, J E Earis, D N Cooper, A Bernstein, J G Temple
Journal: Thorax (1981)

Establishing the cause of unilateral leg pain is difficult in the settings of tibial diaphyseal sclerosis. This patient, a 36-year-old woman presented with unilateral pretibial leg pain for past 7 months without history of trauma, infections, systemic or metabolic disease. Besides local deep tenderness, other clinical findings and blood investigations were normal. Radiograph and CT scan showed both periosteal and endosteal cortical thickening with obliteration of medulla of the tibial midshaft. MRI scan detected marrow oedema and bone scan revealed increased tracer uptake at the affected site of tibia. She was treated by saucerisation and re-establishment of the medullary canal. Biopsy of the harvested tissue had trabecular bone without any sign of inflammation. Patient was pain free after 3 months of operation and was able to perform her activity of daily living without any difficulties. Ribbing disease is a disease of exclusion and need high degree of suspicion for its diagnosis.
Molecular Pathways: IL11 as a Tumor-Promoting Cytokine—Translational Implications for Cancers
Authors: Matthias Ernst, Tracy L. Putoczki
Journal: Clinical Cancer Research (2014)

Emerging evidence suggests that cytokines produced by inflammatory cells act as rheostats to link the degree of wounding and local inflammation to epithelial cell survival, proliferation, and metabolism that collectively underpin the repair response. Among these cytokines, the GP130 family, which encompasses, among others, IL6 and IL11, plays a major role in orchestrating these complex processes through the activation of the latent signal transducer and activator of transcription 3 (STAT3) in the epithelium. However, many of the molecular mechanisms that govern and ensure effective epithelial wound healing and regeneration renewal also promote tumorigenesis and the progression of established cancers. Accordingly, GP130 cytokines endow the inflammatory tumor microenvironment with a capacity to promote "cancer hallmark capabilities" of the malignant epithelium, while simultaneously suppressing the antitumor response of innate and adaptive immune cells. Here, we review some recent insights derived from genetic and therapeutic inhibition of the IL6/IL11-GP130-STAT3 signaling cascade in the context of preclinical mouse models of cancer, which are likely to have implications to other solid malignancies.
Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes.
Authors: M Watanabe, Y Ueno, T Yajima, Y Iwao, M Tsuchiya, H Ishikawa, S Aiso, T Hibi, H Ishii
Journal: Journal of Clinical Investigation (1995)

The interaction of mucosal lymphocytes and intestinal epithelial cells is thought to be important in regulating immune response in the intestinal mucosa, but conclusive evidence is limited. Here we demonstrate the expression of IL-7 mRNA in human intestinal mucosa by combined reverse transcription PCR and Southern blot hybridization. Immunohistochemistry and in situ hybridization confirm the presence of IL-7 in intestinal epithelial cells, especially in epithelial goblet cells. Moreover, IL-7 receptor expression in mucosal lymphocytes is demonstrated by immunohistochemistry and in situ hybridization, as well as by Southern blot and flow cytometric analysis of freshly isolated lamina propria lymphocytes. In contrast, IL-7 receptor could not be detected in the cell surface of freshly isolated PBLs. The functional activity of IL-7 receptor is demonstrated by the utility of recombinant IL-7 to stimulate the growth of lamina propria lymphocytes, and conversely inhibit CD3-dependent proliferation of these cells. In contrast, IL-7 caused no significant increase in DNA synthesis and cell numbers when added to PBLs. These findings suggest that human intestinal epithelial cells and epithelial goblet cells produce IL-7, and locally produced IL-7 may serve as a potent regulatory factor for intestinal mucosal lymphocytes.
Charcot-Marie-Tooth Disease
Authors: L. William McLain
Journal: JAMA (1974)

To the Editor.—  Charcot-Marie-Tooth disease has traditionally been regarded as a pure neuropathic disease, and Siegel (228:873, 1974) suggested that the myopathic changes in two brothers with this disease could be caused by the neuropathy, in accordance with the  hypothesis of muscle disease. Myopathic changes in Charcot-Marie-Tooth disease have already been very well documented by Haase and Shy, 1 who reported them in biopsy specimens of 12 of 17 patients. Ten of these showed both myopathic and neuropathic changes, and two showed only myopathic changes. This finding of myopathic changes in neuropathic diseases (as well as the opposite) has been used to support the neurogenic hypothesis. The a priori assumption is made that the disease in question, eg, Charcot-Marie-Tooth disease, is purely neuropathic; hence, any myopathic changes must be secondary.  An alternative explanation, as Haase and Shy suggested, is that the disease process, whatever it is, affects both nerve
Typhoid Fever; Another Witness.
Authors: C. N. Udell
Journal: JAMA (1896)

Blakesburg, Iowa, May 16, 1896. <h3>To the Editor:</h3> —Prove all things; hold fast that which is good. Whilst the mortality from typhoid fever continues to run so appallingly high, the true physician should never tire of reading any and all articles within his reach that will tend to throw light upon the subject, or aid him in reducing that mortality. The great number of deaths still reported from the ravages of typhoid fever is a stigma upon the whole medical fraternity— is truly mortifying in the extreme. It may be true that some of our brethren jump at conclusions too hastily—are to ready to accept new theories and adopt new remedies: yet it is also true that many are too slow to admit that " there is anything new under the sun." They manifest a stoical indifference—even a dogmatic sarcasm and a stubborn skepticism, regarding all new discoveries, even when they
Endoscopic Ultrasound Features of Protein-Losing Gastropathy with Hypertrophic Gastric Folds
Authors: K. Hizawa, None Kawasaki, T. Yao, K. Aoyagi, H. Suekane, K. Kawakubo, M. Fujishima
Journal: Endoscopy (2000)

Background and Study Aims: We aim to clarify the endoscopic ultrasound (EUS) features of protein-losing gastropathy with hypertrophic gastric folds (PLGH), including Ménétrier's disease.
Necl-5/Poliovirus Receptor Interacts With VEGFR2 and Regulates VEGF-Induced Angiogenesis
Authors: Mitsuo Kinugasa, Hisayuki Amano, Seimi Satomi-Kobayashi, Kazuhiko Nakayama, Muneaki Miyata, Yoshiki Kubo, Yuichi Nagamatsu, Yusuke Kurogane, Fumie Kureha, Shota Yamana, Ken-ichi Hirata, Jun Miyoshi, Yoshimi Takai, Yoshiyuki Rikitake
Journal: Circulation Research (2012)

Vascular endothelial growth factor (VEGF), a major proangiogenic agent, exerts its proangiogenic action by binding to VEGF receptor 2 (VEGFR2), the activity of which is regulated by direct interactions with other cell surface proteins, including integrin α(V)β(3). However, how the interaction between VEGFR2 and integrin α(V)β(3) is regulated is not clear.To investigate whether Necl-5/poliovirus receptor, an immunoglobulin-like molecule that is known to bind integrin α(V)β(3), regulates the interaction between VEGFR2 and integrin α(V)β(3), and to clarify the role of Necl-5 in the VEGF-induced angiogenesis.Necl-5-knockout mice displayed no obvious defect in vascular development; however, recovery of blood flow after hindlimb ischemia and the VEGF-induced neovascularization in implanted Matrigel plugs were impaired in Necl-5-knockout mice. To clarify the mechanism of the regulation of angiogenesis by Necl-5, we investigated the roles of Necl-5 in the VEGF-induced angiogenic responses in vitro. Knockdown of Necl-5 by siRNAs in human umbilical vein endothelial cells (HUVECs) inhibited the VEGF-induced capillary-like network formation on Matrigel, migration, and proliferation, and conversely, enhanced apoptosis. Coimmunoprecipitation assays showed the interaction of Necl-5 with VEGFR2, and knockdown of Necl-5 prevented the VEGF-induced interaction of integrin α(V)β(3) with VEGFR2. Knockdown of Necl-5 suppressed the VEGFR2-mediated activation of downstream proangiogenic and survival signals, including Rap1, Akt, and endothelial nitric oxide synthase.These results demonstrate the critical role of Necl-5 in angiogenesis and suggest that Necl-5 may regulate the VEGF-induced angiogenesis by controlling the interaction of VEGFR2 with integrin α(v)β(3), and the VEGFR2-mediated Rap1-Akt signaling pathway.
Government will suspend MTAS for second round of job interviews
Authors: Lynn Eaton
Journal: BMJ (2007)

An influential group of MPs has claimed that widespread financial incompetence is adding to the cost of the United Kingdom's controversial private finance initiative (PFI).The House of Commons Committee of Public Accounts made its new attack on the PFI after it discovered that the government had clawed back £100m (€145m; $200m) less than was predicted from the new private-public profit sharing schemes.The committee's chairman, the Conservative MP Edward Leigh, blamed the loss on the failure of Treasury officials to oversee key refinancing arrangements.In 2002 ministers introduced changes so that public sector bodies could share in some of the financial gains when big PFI loans were rearranged.Typically, these loans were renegotiated on a more favourable basis once PFI projects had been completed and the risks involved were lower.However, left to their own devices, officials in local hospitals had been out of their depth negotiating with their counterparts in the private sector, the committee says.In 2003 the Office of Government Commerce, which then had responsibility for PFI policy, told the public accounts committee that it expected the public sector to receive between £175m and £200m from the voluntary sharing arrangements in early PFI deals.However, up to December 2006 the government had secured the right to gains of only £93m."Proceeds gained by the public sector from PFI debt refinancing under the voluntary code for the sharing of gains are currently well short of expectations" said Mr Leigh.
miR-221 and miR-155 regulate human dendritic cell development, apoptosis, and IL-12 production through targeting of p27kip1, KPC1, and SOCS-1
Authors: Changming Lu, Xin Huang, Xiaoxiao Zhang, Kristin Roensch, Qing Cao, Keiichi I. Nakayama, Bruce R. Blazar, Yan Zeng, Xianzheng Zhou
Journal: Blood (2011)
Double isotype production by a neoplastic B cell line. II. Allelically excluded production of mu and gamma 1 heavy chains without CH gene rearrangement.
Authors: Y W Chen, C Word, V Dev, J W Uhr, E S Vitetta, P W Tucker
Journal: The Journal of Experimental Medicine (1986)

In our accompanying paper, we described a switch variant (BCL1.2.58) that expresses membrane and secreted forms of IgM and IgG1. Both IgM and IgG1 share the same idiotype and use the same VDJ rearrangement. Here, a detailed Southern blot analysis of the entire constant region of the Ig heavy chain (Ig CH) locus of parental (BCL1.B1) and variants (BCL1.B2) DNA showed no detectable rearrangement. Similar analysis of the JH-C mu region led to the conclusion that two heavy chain alleles present in the IgM/IgG1-producing variants carried the same VDJ rearrangement but differed in their 3' flanking regions. One chromosome 12 did not carry any Ig CH genes, whereas, the other chromosome 12 carried one copy of CH genes. In BCL1.B1, however, each of the chromosome 12 alleles carried a full copy of CH genes. Karyotypic analysis confirmed the presence of two translocated t(12;16) chromosomes in both BCL1.2.58 and BCL1.B1 cells, with a break 5' to the VH locus at the distal region (12F2) of chromosome 12, and at the proximal region below the centromere (16B3) of chromosome 16. We conclude that double production of IgM and IgG1 in BCL1.B2 is accomplished by transcription of the corresponding CH genes in germline configuration using a single VDJ on the same chromosome 12.
The potential impacts of climate variability and change on temperature-related morbidity and mortality in the United States.
Authors: M A McGeehin, M Mirabelli
Journal: Environmental Health Perspectives (2001)

Heat and heat waves are projected to increase in severity and frequency with increasing global mean temperatures. Studies in urban areas show an association between increases in mortality and increases in heat, measured by maximum or minimum temperature, heat index, and sometimes, other weather conditions. Health effects associated with exposure to extreme and prolonged heat appear to be related to environmental temperatures above those to which the population is accustomed. Models of weather-mortality relationships indicate that populations in northeastern and midwestern U.S. cities are likely to experience the greatest number of illnesses and deaths in response to changes in summer temperature. Physiologic and behavioral adaptations may reduce morbidity and mortality. Within heat-sensitive regions, urban populations are the most vulnerable to adverse heat-related health outcomes. The elderly, young children, the poor, and people who are bedridden or are on certain medications are at particular risk. Heat-related illnesses and deaths are largely preventable through behavioral adaptations, including the use of air conditioning and increased fluid intake. Overall death rates are higher in winter than in summer, and it is possible that milder winters could reduce deaths in winter months. However, the relationship between winter weather and mortality is difficult to interpret. Other adaptation measures include heat emergency plans, warning systems, and illness management plans. Research is needed to identify critical weather parameters, the associations between heat and nonfatal illnesses, the evaluation of implemented heat response plans, and the effectiveness of urban design in reducing heat retention.
What Is Surgical Mortality?
Authors: Albert W. Cook
Journal: JAMA (1970)

Depending upon regional attitudes, "surgical mortality" may be defined as death from the time of initiation of an operation to ten days or to many months thereafter. Specifically, in the latter instance, it has been considered by some mandatory that the patient not leave the hospital and that death in the hospital at any time after an operation must be included in surgical mortality statistics. Such thinking has been extended also to include instances in which an operation is planned but death occurs before it can be executed. Designations of this character obviously assign a statistical significance to death related only to the time of surgery with complete disregard of all other items which, in truth, may have been more important. Indeed, the question can be rightfully asked, "What is a surgical death?" There can be no question that certain events can be related to a surgical procedure and require
rt-PA within 6 hours of acute ischemic stroke did not improve clinical outcomes at 6 months
Authors: Brian van Adel, Wieslaw Oczkowski
Journal: Annals of Internal Medicine (2012)

Source Citation IST-3 collaborative group; Sandercock P, Wardlaw JM, Lindley RI, et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet. 2012;379:2352-63. 22632908
The appropriateness of tympanostomy tubes for children
Authors: G. A. Gates
Journal: JAMA (1995)

To the Editor.  —The current national preoccupation with health care costs has fostered a new research genre. Instead of prospective randomized clinical trials or evidence-based guidelines, we now have politicized research pitting the opinions of a group of physicians against the clinical judgment of individual physicians caring for specific patients. Even that approach might have merit if fully developed and carefully applied. However, in the report by Dr Kleinman and colleagues, 1 the physician's judgments for surgical therapy were categorized by insurance company employees using a hitherto secret computer algorithm developed by a for-profit corporation (VHS). While I am concerned about the obvious conflicts of interest, the accuracy of the data (which were collected for insurance rather than research purposes), and the substantial lack of agreement among the members of the physician panel on which the algorithm was based, I am more distressed by the major conceptual flaw of this
Long-Term Outcome of Aortic Dissection With Patent False Lumen
Authors: Artur Evangelista, Armando Salas, Aida Ribera, Ignacio Ferreira-González, Hug Cuellar, Victor Pineda, Teresa González-Alujas, Bart Bijnens, Gaietà Permanyer-Miralda, David Garcia-Dorado
Journal: Circulation (2012)

Background— Patent false lumen in aortic dissection has been associated with poor prognosis. We aimed to assess the natural evolution of this condition and predictive factors. Methods and Results— One hundred eighty-four consecutive patients, 108 surgically treated type A and 76 medically treated type B, were discharged after an acute aortic dissection with patent false lumen. Transesophageal echocardiography was performed before discharge, and computed tomography was performed at 3 months and yearly thereafter. Median follow-up was 6.42 years (quartile 1 to quartile 3: 3.31–10.49). Forty-nine patients died during follow-up (22 type A, 27 type B), 31 suddenly. Surgical or endovascular treatment was indicated in 10 type A and 25 type B cases. Survival free from sudden death and surgical-endovascular treatment was 0.90, 0.81, and 0.46 (95% CI, 0.36–0.55) at 3, 5, and 10 years, respectively. Multivariate analysis identified baseline maximum descending aorta diameter (hazard ratio [HR]: 1.32 [1.10–1.59]; P =0.003), proximal location (HR: 1.84 [1.06–3.19]; P =0.03), and entry tear size (HR: 1.13 [1.08–1.2]; P &lt;0.001) as predictors of dissection-related adverse events, whereas mortality was predicted by baseline maximum descending aorta diameter (HR: 1.36 [1.08–1.70]; P =0.008), entry tear size (HR: 1.1 [1.04–1.16]; P =0.001), and Marfan syndrome (HR: 3.66 [1.65–8.13]; P =0.001). Conclusions— Aortic dissection with persistent patent false lumen carries a high risk of complications. In addition to Marfan syndrome and aorta diameter, a large entry tear located in the proximal part of the dissection identifies a high-risk subgroup of patients who may benefit from earlier and more aggressive therapy.
Acetylator phenotype and adverse effects of sulphasalazine in healthy subjects
Authors: H. Schroder, D. A. P. Evans
Journal: Gut (1972)

Sulphasalazine (salicyl-azo-sulphapyridine) was ingested by 27 healthy subjects for five days at a dosage of 4 g daily. The acetylator phenotype of each subject had been established previously. The serum concentrations of the parent drug and its sulphapyridine-metabolites were determined and the adverse effects were recorded. There was no correlation between the serum concentrations of sulphasalazine and the adverse effects. The slow acetylators obtained enhancement of serum concentrations of sulphapyridine earlier than the rapid acetylators. They also reported adverse effects earlier and of more pronounced nature than the rapid acetylators. The data as a whole suggest that the adverse effects observed were caused by the metabolite sulphapyridine and that they are influenced by the polymorphic acetylation.