tbuckley/cabot-search huggingface dataset:
Impaired Neurogenic Vascular Response in Patients with Diabetes and Neuropathic Foot Lesions
Authors: Nicholas Parkhouse, Pamela Margaret Le Quesne
Journal: New England Journal of Medicine (1988)

Peripheral neuropathy plays an important part in the development of foot complications in patients with diabetes. We studied the contribution of impairment of the dual sensory and inflammatory function of unmyelinated nociceptive C fibers in the foot complications of diabetes. The integrity of these fibers was assessed objectively by measuring axon reflex vasodilatation in response to stimulation with 10 percent acetylcholine introduced by electrophoresis. This was related to the non-neurogenic capacity of the vessels to dilate in response to a mechanical stroke. These measurements were made on the soles of the subjects' feet. The function of the nociceptive C fibers was abnormal in 1 of 14 patients with long-standing diabetes who had no foot complications, 3 of 9 patients with diabetes and skin sepsis, 8 of 11 patients with typical neuropathic plantar ulcers, and all of 8 patients with neuroarthropathy. In patients with long-standing diabetes but no foot complications, the mean ratio of neurogenic to non-neurogenic vasodilatation was not significantly different from that in controls; however, it was significantly lower in the other three groups (P<0.01 for those with sepsis; P<0.001 for those with ulcer or arthropathy). Impairment of the neurogenic vasodilator response, or flare, correlated with the clinical diminution of pain sensation. This study suggests that the loss of both components of nociceptive C-fiber function — neurogenic inflammation and pain sensation — is an important factor in the development of foot complications in diabetes. (N Engl J Med 1988; 318:1306–9.)
Abstract 2457: Nestin regulates pancreatic cancer stem cell functions
Authors: Yoko Matsuda, Kazuya Yamahatsu, Kiyoko Kawahara, Taeko Suzuki, Takenori Fujii, Tetsushi Yamamoto, Murray Korc, Zenya Naito, Toshiyuki Ishiwata
Journal: Cancer Research (2011)

Abstract Background: Nestin, a class VI intermediate filament protein, was originally described as a neuronal stem cell/progenitor cell marker. Nestin expression has also been shown to be up-regulated in progenitor cells in muscle, testis, teeth and pancreas. In the pancreas, lineage-tracing experiments have indicated that exocrine cells are derived from Nestin-expressing progenitor cells. Moreover, activation of K-ras in the nestin cell lineage is sufficient for the initiation of premalignant pancreatic intraepithelial neoplasia lesions in mice. To examine cancer stem cell (CSC) functions, floating cultures in plates with a low-attachment surface have been widely employed. CSCs are reported to be able to grow in floating spheres in serum-free culture medium supplemented with epidermal growth factor (EGF) and/or fibroblast growth factor-2 (FGF-2), whereas non-CSCs, more differentiated non-CSCs cannot form spheres. In this study, we examined nestin expression in spheres and clarified whether nestin regulates sphere forming activity. Methods: Human pancreatic ductal adenocarcinoma (PDAC) cell lines, PANC-1, KLM-1, MIAPaCa-2 and PK-45H were used to perform sphere-forming assay in ultra-low attachment plates supplemented with EGF and FGF-2. Expression of CSC markers including CD133, CD44, CD24, epithelial specific antigen (ESA), and nestin in spheres were determined by real time RT-PCR and immunocytochemistry. Sphere-forming cells were dispersed with trypsin, and then cell growth and migration were assessed. Next, short hairpin RNA (shRNA) targeting nestin was stably transfected into PANC-1 and PK-45H, human PDAC cells, which express high levels of nestin, in order to assess the effects of decreased nestin expression on sphere-forming ability. Conversely, KLM-1 cells which express low level of nestin were stably transfected with a nestin expression vector and their sphere forming ability was then determined. Results: All the PDAC cell lines formed spheres, and all CSC markers examined were expressed in the spheres. The sphere cells showed low cell growth rates and increased cell migration as compared to non-sphere cells. Expression levels of nestin in the spheres of PDAC cells were higher than those of non-sphere cells. Nestin shRNA transfected PANC-1 and PK-45H cells showed a marked decrease in sphere number and diameter. By contrast, nestin-gene-transfected KLM-1 cells exhibited increased sphere formation. Conclusion: Nestin is a pancreatic CSC marker that promotes the sphere-forming ability of CSCs. Therefore, nestin may represent a novel therapeutic target for CSCs in PDAC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2457. doi:10.1158/1538-7445.AM2011-2457
ALPHA-2C ADRENERGIC RECEPTOR POLYMORPHISM INTERACTS WITH BETA-BLOCKER DOSE EFFECT ON HEART FAILURE OUTCOMES DIFFERENTLY IN BLACK RACE: RESULTS FROM THE HF-ACTION DNA SUBSTUDY
Authors: Kishan S. Parikh, Mona Fiuzat, Megan Neely, Tariq Ahmad, G. Michael Felker, Ileana Pina, Kirkwood Adams, Mark Donahue, William Kraus, David Whellan, Christopher O’Connor
Journal: Journal of the American College of Cardiology (2015)
The Biology of Chronic Myeloid Leukemia
Authors: Stefan Faderl, Moshe Talpaz, Zeev Estrov, Susan O'Brien, Razelle Kurzrock, Hagop M. Kantarjian
Journal: New England Journal of Medicine (1999)

Chronic myeloid leukemia (CML) is a clonal myeloproliferative expansion of transformed, primitive hematopoietic progenitor cells. It involves myeloid, monocytic, erythroid, megakaryocytic, B-lymphoid, and occasionally T-lymphoid lineages.1 CML was the first human disease in which a specific abnormality of the karyotype — the Philadelphia (Ph) chromosome — could be linked to pathogenetic events of leukemogenesis.2 It was among the first neoplastic diseases in which therapy with a biologic agent (interferon) was found to suppress the leukemic clone and prolong survival.3 Although heterogeneous, CML is the best-characterized leukemia at a molecular level, and studies in recent years have helped to define further . . .
Abstract 5031: miR-21 targets TGF-β Pathway in breast cancer
Authors: Liang Chen, Meng Wang, Jin Peng, Christine Teal, Michael Stamatakos, Timothy McCaffrey, Sidney W. Fu
Journal: Cancer Research (2012)

Abstract MicroRNAs (miRNAs) are endogenous non-coding RNAs (∼22 nt), which regulate the stability and translation of coding mRNAs. miRNA dysregulation is observed in a variety of cancers, including breast cancer. Our previous studies, by miRNA expression profiling using archived FFPE tissues, identified a set of miRNAs that are differentially expressed during breast cancer progression. Using ANOVA test, we identified 8 clusters of miRNAs, which discrete the normal and disease lesions, such as ADH, DCIS and IDC. miR-21 has been well documented as an oncogene, while miR-200c/b are reported as biomarkers for primary hepatocellular carcinoma, and miR-200c as an independent prognostic factor in pancreatic cancer. Our study shows that miR-21 consistently expresses high level in pre-cancerous lesions, i.e. ADH and DCIS, which indicates that miR-21 plays an important role in breast cancer initiation and progression. However, the exact mechanism is not clear. To test the effects of miR-21 inhibition in both ER+ and ER- breast cancer cells, we transfected anti-miR-21 oligos and scrambled oligo mocks into human breast cancer cells, MCF-7 (ER+) and Hs578T (ER-). We observed a significantly increased expression of MSH2 and SMAD7, when miR-21 was knocked down by 60%-80%. Both MSH2 and SMAD7 are key players in TGF-β signaling pathway, which is well known for its anti-mitogenic function during tumor initiation. These findings help establish miR-21 as an important oncogene that targets a network of TGF-β in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5031. doi:1538-7445.AM2012-5031
CARDIAC MRI AND PET HAVE COMPLEMENTARY VALUE IN THE ASSESSMENT OF SUSPECTED CARDIAC SARCOIDOSIS
Authors: Tomas Vita, David Okada, Mahdi Veillet-Chowdhury, Rachna Madan, Mukta Agrawal, Erin Mullins, Paco Bravo, Hulten Eddie, Michael Steigner, Hicham Skali, Raymond Kwong, Garrick Stewart, Sharmila Dorbala, Marcelo Di Carli, Ron Blankstein
Journal: Journal of the American College of Cardiology (2016)
P5-21-02: The Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center: The Source for Normal Breast Tissue and Biospecimens.
Authors: SE Clare, T Mathieson, JE Henry, H Zhang, ES Way, KE Ridley, S Badve, B-S Herbert, CA Rufenbarger, AMV Storniolo
Journal: Cancer Research (2011)

Abstract Background Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. This ignorance has been the consequence of the lack of access to richly annotated, high quality normal breast specimens. The Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center (KTB) was established expressly to remedy this deficiency. The KTB is a repository of specimens from volunteer donors with no clinical evidence of breast malignancy. The Bank's mission is to make available specimens that will enable an understanding of the developmental biology of the normal breast, to provide insight into breast oncogenesis, and to provide a normal control for breast cancer research. The purpose of this presentation is to increase the awareness of this unique and rich research resource and to actively solicit the use of its specimens. Methods: The KTB has been prospectively banking fresh frozen breast tissue since mid-2006. Coincident with the tissue donation two tubes of blood are obtained, which are processed for lymphocyte DNA, serum and plasma. These specimens are richly annotated with detailed information regarding the donors’ reproductive history, medical history, family history, and medications. Standard Operating Procedures have been constructed so as to control, limit and identify potential sources of bias. All of this information is recorded in an Oracle-based, searchable database. Results: As of June 2011, the KTB and its predecessor bank, Mary Ellen's Bank, have available fresh frozen breast tissue (10 gauge cores) from 1469 donors; formalin-fixed, paraffin-embedded tissue from 1055; DNA from 7507; serum from 2382; and plasma from 3771 donors. The KTB has also established 28 epithelial and 33 stromal cell lines from the cores; 4 of the epithelial cell lines have been immortalized using hTERT. Donors range in age from 18–86 years of age. 9% of donors to the KTB describe themselves as Hispanic/Latino. 5.2% of donors are Black or African-American. Using the Gail Risk Model, there is a bimodal distribution of life-time breast cancer risk among the donors: the largest peak is at 10% and a smaller one at 18%. Conclusions: The KTB is a unique and invaluable research resource which is now open for business and accessible to researchers across the globe. We encourage researchers to avail themselves of this unique tissue resource and to also acquaint themselves with other sources of healthy breast tissue, i.e., the Love/Avon Army of Women [http://www.armyofwomen.org/]. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-21-02.
Abstract IA20: DNA methylation and nucleosome repositioning in cancer
Authors: Peter A. Jones
Journal: Cancer Research (2011)

Abstract Epigenetic processes are reinforced by interactions between covalent chromatin marks such as DNA methylation, histone modifications, and variants. These marks ultimately specify the locations of nucleosomes particularly with respect to transcriptional start sites and in regulatory regions. Understanding how the epigenome functions therefore requires a coordinated approach so that the mechanisms by which the chemical modifications interact with nucleosomal remodeling machines are achieved to ensure epigenetic inheritance and control of gene expression. We have developed a new methodology to simultaneously map nucleosomal positioning and DNA methylation on individual molecules of DNA. We used this nucleosomal mapping technology to ascertain alterations in nucleosomal positioning during the abnormal silencing of genes by promoter hypermethylation. These experiments show that the methylation of CpG islands at the transcriptional start sites of key tumor suppressor genes results in the stable placement of nucleosomes at the transcription start site. Inhibition of DNA methylation by 5-azanucleoside treatment results in an immediate inhibition of DNA methylation and a sequence of downstream events which ultimately result in the eviction of the nucleosomes from the transcription start site and the activation of gene expression. Interestingly this process requires the insertion of the histone variant H2AZ downstream and upstream of the transcriptional start site for full gene activation to occur. Thus inhibition of DNA methylation by these drugs which are used to treat myelodysplastic syndrome results not only in the removal of DNA methylation but in the resetting of chromatin to an active state. Genes activated in this way often undergo resilencing when the drug is removed so that understanding the precise nature of these alterations is essential in the design of the next generation of epigenetic therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA20.
Abstract 3783: Talin-1 phosphorylation promotes invasion and migration of prostate tumor cells through activation of β1 integrins.
Authors: Jung-Kang Jin, Yu-Chen Lee, Sue-Hwa Lin, Gary E. Gallick
Journal: Cancer Research (2013)

Abstract Integrins have been shown to play a critical role in cell survival. We recently demonstrated that integrins are constitutively activated in highly metastatic prostate cancer cell PC3-mm2. Activation of integrins increases their binding affinity with extracellular matrix, resulting in increased migration and cancer metastasis. Talin is a 270 kDa cytoskeletal protein that has been shown to regulate integrin activity. Previous reports showed that the S425 residue in the N-terminal domain of talin was phosphorylated by Cdk5 to increase talin stability. In this study, we determined whether talin S425 phosphorylation regulates β1 integrin activation. We found that β1 integrin activation in prostate tumor cells correlates with talin S425 phosphorylation but not total talin levels. To examine the role of talin-pS425 in β1 integrin activation, endogenous talin-1 in PC3-mm2 cells was knocked down by shRNA, followed by re-expression of a phosphorylation-deficient S425A or phosphorylation-mimicking S425D talin-1 mutant. Re-expressing phosphorylation-deficient S425A-talin-1 in talin-1-knockdown PC3-mm2 cells showed reduced activation of β1 integrins, and decreased migration and invasion, compared to cells re-expressing wild type talin-1. In contrast, re-expressing the phosphorylation-mimicking S425D mutant in talin-1-knockdown PC3-mm2 cells restored β1 integrin activation and increased migratory and invasive properties of these cells. Inhibition of Cdk5 by roscovitine, a Cdk5 inhibitor, decreases talin-1 S425 phosphorylation and also inhibits downstream integrin signaling, including FAK and Src phosphorylation. Treatment of PC3-mm2 cells with roscovitine decreases β1 integrin activation and migration of PC3-mm2 cells. These results suggest that phosphorylation of talin-1 at S425 plays a role in promoting β1 integrin activation, leading to increased metastatic potential of prostate tumor cells. Citation Format: Jung-Kang Jin, Yu-Chen Lee, Sue-Hwa Lin, Gary E. Gallick. Talin-1 phosphorylation promotes invasion and migration of prostate tumor cells through activation of β1 integrins. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3783. doi:10.1158/1538-7445.AM2013-3783
Changing Blood Pressure in Aortic Insufficiency
Authors: Richard Gorlin, Walter T. Goodale
Journal: New England Journal of Medicine (1956)

MARKED changes in arterial blood pressure and peripheral circulation may occur during the life history of patients with aortic insufficiency. These changes reflect alterations in cardiac function and peripheral vasomotor activity. As such they may be the first clues to progression of the disease and the ultimate development of failure of the left ventricle.Lewis1 has emphasized the fact that the patient with aortic insufficiency is warm and flushed, with bounding arterial, capillary and venous pulsations, and that this is due to associated vasodilatation. He specifically excluded from this description patients with aortic insufficiency in the final stages of congestive . . .
Association of Perioperative Myocardial Ischemia with Cardiac Morbidity and Mortality in Men Undergoing Noncardiac Surgery
Authors: D T Mangano, W S Browner, M Hollenberg, M J London, J F Tubau, I M Tateo
Journal: New England Journal of Medicine (1990)

Adverse cardiac events are a major cause of morbidity and mortality after noncardiac surgery. It is necessary to determine the predictors of these outcomes in order to focus efforts on prevention and treatment. Patients undergoing noncardiac surgery sometimes have postoperative cardiac events. It would be helpful to know which patients are at highest risk.
Functional lung adenocarcinoma risk SNPs identified through positional integration with human alveolar epithelial cell epigenomes
Authors: Chenchen Yang, Theresa Ryan Stueve, Crystal Nicole Marconett, Suhn Kyong Rhie, Jiao Luo, Beiyun Zhou, Zea Borok, Ite A. Laird-Offringa
Journal: Journal of Thoracic Oncology (2016)
Tc-99m MAG3 Evaluation of Recipients with En Bloc Renal Grafts from Pediatric Cadavers
Authors: F Morin, I Côté
Journal: Clinical Nuclear Medicine (2000)

Tc-99m MAG3 scintigraphy is a well-established test to monitor patients who have received renal grafts. The shortage of available kidneys has forced the development of alternative sources of donors. En bloc pediatric renal grafts have been used for more than 10 years with good results, but mechanical complications are still a concern. No reports have illustrated the Tc-99m MAG3 scintigraphic aspect of the most common complications resulting from en bloc pediatric renal grafts. The authors describe three recipients of en bloc renal graft. One patient had thrombosis of one of the two grafts, one patient had postrenal obstruction of only one of the grafts, and a third patient progressed normally.
Gastric rupture before puncture of the stomach in percutaneous gastrostomy
Authors: Y. Matsunaga, A. Goto, H. Kaneko, N. Hasegawa, H. Wakasugi, M. Itoh, K. Fujii, K. Suzuki, K. Nakahata, Y. Shinomura
Journal: Endoscopy (2011)

A 73-year-old man had swallowing difficulties because of a recent cerebrovascular accident, and was on enteral feeding via a nasogastric tube. Percutaneous endoscopic gastrostomy (PEG) was chosen for long-term enteral feeding. Before the PEG tube was inserted, a flexible endoscope was inserted into the stomach for inspection. No gross abnormal lesion was detected in the upper gastrointestinal tract ([Fig. 1]).
Abstract 2664: Pharmacokinetics of a novel fumagillol conjugate XMT-1107 in the rat and the dog
Authors: Alexander Yurkovetskiy, Carolina B. Cabral, Laraine L. Meyers, Robert J. Fram, Timothy B. Lowinger
Journal: Cancer Research (2010)

Abstract XMT-1107 is a novel polymer fumagillol derivative, comprised of the small molecule XMT-1191 conjugated to a 70 kDa biodegradable, hydrophilic polyacetal, poly(1-hydroxymethylethylene hydroxymethylformal) (PHF). The conjugated drug XMT-1107 is a prodrug that improves the pharmacokinetics (PK) of the active compound XMT-1191 and demonstrates significant antitumor activity in multiple rodent xenograft models providing a compelling rationale for clinical development. We evaluated the metabolism and PK of XMT-1107 in the rat and the dog and expect that the preclinical dog toxicokinetic (TK) data provide better guidance than the rat data for the assessment of XMT-1107 safety/PK in humans. XMT-1107 metabolism was studied in rodent, dog and human plasma as well as in liver microsomes. The PK of XMT-1107 was studied in rat and dog at a variety of doses and schedules. The extent and duration of the exposure was monitored over 120 hours post dosing. The analytical determinations of XMT-1107 and small molecule metabolites were carried out by LC/MS/MS. XMT-1107 was metabolized in rodent, dog and human plasma producing XMT-1191 and XMT-1201 (via conjugated XMT-1201) as major and minor metabolites, respectively. Considering that XMT-1201 does not bind to or inhibit MetAP2, the molecular target of XMT-1107, conjugated and free XMT-1191 are of most interest since conjugated XMT-1191 is a prodrug and XMT-1191 is its active release product. In both species the PK of conjugated and free XMT-1191 was approximately dose proportional with no marked gender differences. Consistent 2,000-4,000 fold differences between conjugated XMT-1191 and free XMT-1191 plasma exposure (AUC0–120) and Cmax suggest that observed pharmacological effects may result from extravascular distribution of conjugated XMT-1191 and local release of XMT-1191 rather than from systemic exposure to free XMT-1191. Conjugated XMT-1191 has a low volume of distribution, slow systemic clearance and is characterized by a t1/2 ranging from 27-35 hours in rat and 47-68 hours in dog. The 1.8-2.0-fold increase in conjugated XMT-1191 plasma t1/2 observed in dog relative to rat was accompanied by an approximately proportional increase in dose normalized exposure (AUC0–120) to conjugated XMT-1191 and conjugated XMT-1201. The rates for in vitro release of XMT-1191 and XMT-1201 from XMT-1107 in dog and human plasma were similar and at least 2 times lower than the release rates for corresponding compounds in rat plasma, suggesting that dog TK may be more predictive of human XMT-1107 PK compared to rat TK. 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 2664.
The Red Eye
Authors: Howard M. Leibowitz
Journal: New England Journal of Medicine (2000)

A red eye is the most common ocular disorder that primary care physicians encounter. Most cases are relatively benign. Some, however, herald a vision-threatening or even life-threatening disorder. A detailed description of the full differential diagnosis of a red eye is available elsewhere.1 This overview does not assume that the examiner has access to a slit lamp or has been trained to use it.Subconjunctival HemorrhageA subconjunctival hemorrhage (Figure 1) is often the cause of acute ocular redness. The diagnosis is based on simple observation of the characteristic features of such a hemorrhage: the redness, which is unilateral, is . . .
LEPTIN AND INCIDENT HEART FAILURE IN WOMEN VERSUS MEN: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA)
Authors: Seth S. Martin, Michael Blaha, Evan Muse, Atif Qasim, Muredach Reilly, Roger Blumenthal, Khurram Nasir, Michael Criqui, Robyn McClelland, Tamara B. Harris, Jan Hughes-Austin, Matthew Allison
Journal: Journal of the American College of Cardiology (2013)