tbuckley/cabot-search huggingface dataset:
Chemosensitivity is controlled by p63 modification with ubiquitin-like protein ISG15
Authors: Young Joo Jeon, Mi Gyeong Jo, Hee Min Yoo, Se-Hoon Hong, Jung-Mi Park, Seung Hyeun Ka, Kyu Hee Oh, Jae Hong Seol, Yong Keun Jung, Chin Ha Chung
Journal: Journal of Clinical Investigation (2012)

Identification of the cellular mechanisms that mediate cancer cell chemosensitivity is important for developing new cancer treatment strategies. Several chemotherapeutic drugs increase levels of the posttranslational modifier ISG15, which suggests that ISGylation could suppress oncogenesis. However, how ISGylation of specific target proteins controls tumorigenesis is unknown. Here, we identified proteins that are ISGylated in response to chemotherapy. Treatment of a human mammary epithelial cell line with doxorubicin resulted in ISGylation of the p53 family protein p63. An alternative splice variant of p63, ΔNp63α, suppressed the transactivity of other p53 family members, and its expression was abnormally elevated in various human epithelial tumors, suggestive of an oncogenic role for this variant. We showed that ISGylation played an essential role in the downregulation of ΔNp63α. Anticancer drugs, including doxorubicin, induced ΔNp63α ISGylation and caspase-2 activation, leading to cleavage of ISGylated ΔNp63α in the nucleus and subsequent release of its inhibitory domain to the cytoplasm. ISGylation ablated the ability of ΔNp63α to promote anchorage-independent cell growth and tumor formation in vivo as well to suppress the transactivities of proapoptotic p53 family members. These findings establish ISG15 as a tumor suppressor via its conjugation to ΔNp63α and provide a molecular rationale for therapeutic use of doxorubicin against ΔNp63α-mediated cancers.
Survivin as a Radioresistance Factor, and Prognostic and Therapeutic Target for Radiotherapy in Rectal Cancer
Authors: Franz Rödel, Jörg Hoffmann, Luitpold Distel, Martin Herrmann, Timmo Noisternig, Thomas Papadopoulos, Rolf Sauer, Claus Rödel
Journal: Cancer Research (2005)

Abstract Apoptosis levels have been shown to predict tumor response to preoperative radiochemotherapy in rectal cancer. Recently, the prominent role of survivin, a structurally unique member of the inhibitor of apoptosis protein family, has been shown in colorectal cancer tumorigenesis and prognosis. In this study, we investigated whether survivin plays a direct role in mediating radiation resistance. We used short interfering RNA molecules to decrease survivin in radioresistant SW480 and intermediately radioresistant HCT-15 colorectal cancer cells. This resulted in a significant decrease of survivin mRNA and protein expression with a maximum at 24 to 48 hours after transfection. If irradiated during this sensitive period, an increased percentage of apoptotic cells and an increased caspase 3/7 activity in parallel with a decreased cell viability and a reduced clonogenic survival was shown. These effects were more pronounced in the radioresistant SW480 cell line with a radiation-induced cytotoxicity enhancement factor at 10% and 50% survival of 1.8 to 2.2 for SW480 and 1.5 to 1.7 for HCT-15, respectively. Furthermore, transfection with survivin short interfering RNA increased levels of G2-M arrest and levels of DNA double-strand breaks in irradiated cells. These observations indicate that cell cycle and DNA repair mechanisms may be associated with apoptosis induction in tumor cells that are otherwise resistant to killing by radiation. In a translational study of 59 patients with rectal cancer treated with a combination of radiotherapy and chemotherapy, increased survivin expression was inversely related to the levels of apoptosis, and was also associated with a significantly higher risk of a local tumor recurrence.
Re: Alexander Kutikov, Boris Rozenfeld, Brian L. Egleston, et al. Academic Ranking Score: A Publication-Based Reproducible Metric of Thought Leadership in Urology. Eur Urol 2012;61:435–9
Authors: Elias S. Hyams, Jeffrey K. Mullins, Mohamad E. Allaf
Journal: European Urology (2012)
Consulting with veiled students
Authors: C. Ellis
Journal: BMJ (2009)

After 35 years in general practice, I have been contracted to teach family medicine at a national university medical school in the Middle East. I thought that changing from clinical practice to full time teaching would be easier, but teaching practice and theory have undergone a sea change since I was at medical school in the 1960s.

On top of this have been the challenges of teaching in a completely different culture where the male and …
Rat carotid neointimal smooth muscle cells reexpress a developmentally regulated mRNA phenotype during repair of arterial injury.
Authors: M W Majesky, C M Giachelli, M A Reidy, S M Schwartz
Journal: Circulation Research (1992)

Smooth muscle cells (SMCs) cultured from the neointima of injured rat carotid arteries have a different shape and organization in vitro than SMCs from the uninjured media. The morphology of neointimal SMCs from adult rats strongly resembles that of a subset of medial SMCs from 12-day-old rat pups. In the present study, we show that adult carotid neointimal SMCs in vitro express the platelet-derived growth factor (PDGF)-B gene but have little or no PDGF alpha-receptor mRNA. In contrast, medial SMCs from contralateral uninjured carotids, grown and passaged under identical conditions, contain abundant PDGF alpha-receptor mRNA but little or no PDGF-B mRNA. Transcript levels for PDGF-A or PDGF beta-receptor were not different in neointimal versus medial SMC cultures. The PDGF mRNA phenotype of adult neointimal SMCs strongly resembles that of an aortic medial SMC subset from newborn rat pups. Although intriguing, the differences in SMC phenotypes we observed in cell culture may depend on unique conditions in vitro and do not necessarily mean that analogous SMC diversity also exists in vivo. To address this question, we constructed and screened a SMC cDNA library for additional molecular markers of the common "pup-intimal" SMC phenotype. Two cDNA clones were identified whose cognate mRNA levels were developmentally regulated in rat aorta in vivo and were present at high levels in the adult carotid neointima formed 2 weeks after balloon catheter injury. Importantly, elevated levels of these two cognate mRNAs in carotid neointima compared with underlying media were maintained in cultures of neointimal versus medial SMCs in vitro. DNA sequence analysis indicated that the cDNA clones encoded rat tropoelastin and alpha 1 procollagen (type I). These results provide further evidence that neointima formation in the adult rat carotid artery depends on reexpression of an SMC phenotype or subpopulation with special properties characteristic of earlier stages of artery wall development. Our studies to date indicate that two of these special properties are paracrine growth factor production and extracellular matrix synthesis.
Acetylcysteine for Bronchial Plugging
Authors: ALLAN P. FREEDMAN
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 September 1978Acetylcysteine for Bronchial PluggingALLAN P. FREEDMAN, M.D., JAMES P. SHINNICK, D.O., PAUL B. SOLNICK, M.D.ALLAN P. FREEDMAN, M.D.Search for more papers by this author, JAMES P. SHINNICK, D.O.Search for more papers by this author, PAUL B. SOLNICK, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-89-3-431_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We were pleased to note the report from the National Naval Medical Center relating their experience with acetylcysteine instillation in cases of bronchial mucous plugging (Ann Intern Med88:656, 1978). For several years we have been instilling 5-ml aliquots of 10% acetylcysteine through the fiber-optic bronchoscope in cases of atelectasis due to thick retained secretions when aggressive chest physiotherapy did not result in significant resolution. In these cases, we have found the subsequent liquefaction of thick mucoid secretions quite helpful. We believe that some of these cases would have required rigid endoscopy had acetylcysteine not been used.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Division of Pulmonary Diseases Hahnemann Medical College and Hospital Philadelphia, PA 19102 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDetermination of electron-diffusion length from photocurrent characteristics of the structure ITO/a-SiC:H(p-type)/a-Si:H/a-Si:H(n-type)/Pd 1 September 1978Volume 89, Issue 3Page: 431-431KeywordsEndoscopyPhysiotherapyThorax Issue Published: 1 September 1978 PDF downloadLoading ...
Abstract 3707: The Multiplier Effect of Telmisartan and Fenofibrate in Patients with Metabolic Syndrome
Authors: Katsuya Maruyama, Yasuo Sutani, Yoshiteru Abe, Masayuki Motohiro, Shuji Katoh
Journal: Circulation (2008)

Background: Telmisartan, a partial agonist of PPARγ, improve insulin resistance with increase adiponectin and especially high molecular weight adiponectin (HMW adipo) in patients with metabolic syndrome. Fenofibrate, an antihyperlipidemic drug, can function as an agonist of PPARα and is increased adiponectin receptors. In this study, we examined that telmisartan with fenofibrate influences multiplier effect of insulin resistance and anti-arteriosclerosis action in patients with metabolic syndrome. Methods: 25 patients with metabolic syndrome took telmisartan (40mg/day) for 6 months (stage 1), and they were measured HOMA-R, high sensitive CRP (hsCRP), adiponectin, HMW adipo, TNFα, both visceral fat (VF) area and subcutaneous fat (SF) area by CT scan and mean intima-media thickness (M-IMT) of common carotid artery. After stage 1 they took telmisartan (40mg/day) together with fenofibrate (100mg/day) for 6 months (stage 2), and they were measured them again. Results: We compared these parameters of stage 1 and stage 2. HOMA-R, hsCRP, and TNFα were decreased for both stage 1 and stage 2. HOMA-R especially was significant (from 3.97 to 3.09; p&lt;0.05) for stage 2. Both adiponectin and HMW adipo were increased for stage 1, but they were decreased for stage 2. Both VF area and SF area were decreased between stage1 and stage2. SF area especially was significant (from 194.9 to 184.3 cm2; p&lt;0.05) for stage 2. M-IMT of common carotid artery significantly was decreased (from 0.97 to 0.84 mm; p&lt;0.01) between stage 1 and stage 2. Conclusion: Our findings indicate that although telmisartan with fenofibrate are decreased both fat area (especially SF area) and secretion of adiponectin, they influences multiplier effect of insulin resistance and anti-arteriosclerosis action through the improvement of adiponectin sensitivity.
Gynecologic Endocrine Emergencies
Authors: John M. Shane
Journal: JAMA (1975)

THE physician dealing with gynecologic and obstetric patients frequently must manage emergencies resulting from faulty endocrine homeostasis (eg, dysfunctional uterine bleeding). In earlier portions of this series, reference had been made to particular problems in the diagnosis and treatment of certain endocrine emergencies as they occur in pregnancy. In this section, we review disruptions of normal gynecologic endocrine function encountered during the reproductive years and early pregnancy: treatment of dysfunctional uterine bleeding, undesirable sequelae of ovulation induction, and finally, a few comments about the use of hormonal agents during gestation. <h3>Dysfunctional Uterine Bleeding</h3><h3>Etiology.—</h3> Dysfunctional uterine bleeding (abnormal uterine bleeding caused by endocrine factors, often defined as such because of its irregular timing and the absence of nonendocrine lesions) is generally synonymous with anovulation. Occasionally, dysfunctional bleeding associated with ovulation does occur, viz, ovulation bleeding, inadequate corpus luteum, prolonged corpus luteum (Halban disease), and irregular shedding.<sup>1</sup> <h3>Diagnosis.—</h3> Differentiating dysfunctional
Delayed hemolytic transfusion reaction due to anti-Goa, an antibody against the low-prevalence Gonzales antigen
Authors: Peter J. Larson, Maria B. Lukas, David F. Friedman, Catherine S. Manno
Journal: American Journal of Hematology (1996)

Go(a) (D(Cor)) is a low-frequency antigen in the Rh system found on red cells lacking part of the D mosaic (category IVa). Anti-Go(a) has not been previously reported to cause hemolytic transfusion reactions. A 27-year-old African American male with sickle-cell disease, maintained on chronic transfusion, was noted to have dark plasma during an erythrocytapheresis, procedure, and the pretransfusion hemoglobin was noted to be 1 g/dl lower than 4 weeks before (with hyperbilirubinemia and a significantly increased LDH). Polyspecific direct antiglobulin test (DAT) was weakly positive (C3-weak, IgG-weak), and indirect antiglobulin tests (IATs) performed on the serum (pre- and posttransfusion reaction) and a red blood cell (RBC) eluate from the postreaction sample were negative. A segment from one of the four implicated units from the prior month's transfusion was strongly reactive at 37 degrees C and using anti-human globulin (AHG) when crossmatched with the postreaction serum and the eluate. The postreaction serum, screened with a panel of red cells positive for low-prevalence antigens, reacted with three Go(a+) cells. The implicated unit was reactive with a previously identified anti-Go(a) serum.
Comparison of reflectance confocal microscopy and standardized skin surface biopsy for three different lesions in a pityriasis folliculorum patient
Authors: C. Yuan, X.-M. Wang, A. Guichard, T. Lihoreau, S. Mac-Mary, L. Khyat, M. Ardigò, P. Humbert
Journal: British Journal of Dermatology (2014)

Journal Article Comparison of reflectance confocal microscopy and standardized skin surface biopsy for three different lesions in a pityriasis folliculorum patient Get access C. Yuan, C. Yuan Department of Skin & Cosmetic Research Shanghai Skin Disease Hospital Shanghai China Search for other works by this author on: Oxford Academic Google Scholar X.‐M. Wang, X.‐M. Wang Department of Skin & Cosmetic Research Shanghai Skin Disease Hospital Shanghai China Search for other works by this author on: Oxford Academic Google Scholar A. Guichard, A. Guichard Research and Studies Center on the Integument (CERT); Clinical Investigation Center (CIC BT506) Department of Dermatology Besançon University Hospital University of Franche‐Comté 3, Boulevard Alexandre Fleming Besancon France Search for other works by this author on: Oxford Academic Google Scholar T. Lihoreau, T. Lihoreau Research and Studies Center on the Integument (CERT); Clinical Investigation Center (CIC BT506) Department of Dermatology Besançon University Hospital University of Franche‐Comté 3, Boulevard Alexandre Fleming Besancon France Search for other works by this author on: Oxford Academic Google Scholar S. Mac‐Mary, S. Mac‐Mary Skinexigence Besançon France Search for other works by this author on: Oxford Academic Google Scholar L. Khyat, L. Khyat Research and Studies Center on the Integument (CERT); Clinical Investigation Center (CIC BT506) Department of Dermatology Besançon University Hospital University of Franche‐Comté 3, Boulevard Alexandre Fleming Besancon France Search for other works by this author on: Oxford Academic Google Scholar M. Ardigò, M. Ardigò San Gallicano Dermatological Institute‐IRCCS Rome Italy Search for other works by this author on: Oxford Academic Google Scholar P. Humbert P. Humbert Research and Studies Center on the Integument (CERT); Clinical Investigation Center (CIC BT506) Department of Dermatology Besançon University Hospital University of Franche‐Comté 3, Boulevard Alexandre Fleming Besancon France Correspondence : Philippe Humbert. E‐mail: philippe.humbert@univ-fcomte.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 5, 1 May 2015, Pages 1440–1442, https://doi.org/10.1111/bjd.13506 Published: 01 May 2015
Haiti launches vaccination campaign against cholera after much debate
Authors: N. Hawkes
Journal: BMJ (2012)

A vaccination campaign against cholera has been launched in Haiti after months of medical and political argument. The final hurdle was approval for the programme from Haiti’s National Ethics Committee, which became involved after a local radio station charged that the campaign was an “experiment” in which the Haitian people were being used as guinea pigs.

The first phase of the campaign is targeting 50 000 people living in Port-au-Prince and will be followed by a further 50 000 in the Artibonite River valley, all of whom will be given the oral cholera vaccine, Shanchol, made in India. The organisers hope to show that it is …
Plasma TSH, T3, T4 and cortisol responses to swimming at varying water temperatures.
Authors: A Deligiannis, M Karamouzis, E Kouidi, V Mougios, C Kallaras
Journal: British Journal of Sports Medicine (1993)

The acute effect of 30-min swimming at a moderate speed, at three water temperatures (20, 26 and 32 degrees C) on plasma thyroid stimulating hormone (TSH), free thyroxine (F.T4), triiodothyronine (T3) and cortisol concentrations was studied in 15 élite male swimmers. Blood was sampled before and immediately after the events. The heart rate, which was continuously monitored during exercise, had the highest response at 32 degrees C and the lowest at 20 degrees C. Blood lactate concentrations were found to be similar after the three tests. Plasma TSH and F.T4 were found to be significantly increased (by 90.4% and 45.7% respectively) after swimming at 20 degrees C, decreased at 32 degrees C (by 22.3% and 10.1% respectively) and unchanged at 26 degrees C. Exercise at these three water temperatures did not significantly affect T3. Finally, plasma cortisol was found to be increased after swimming at 32 degrees C (by 82.8%) and 26 degrees C (by 46.9%), but decreased at 20 degrees C (by 6.1%).
The Killing of Pathogens by Phagocytes
Authors: T G Gabig, B M Babior
Journal: Annual Review of Medicine (1981)

Phagocytes include neutrophils, eosinophils, and monocyte-macrophages. They are cells specialized for destruction. Their name reflects the fact that they routinely ingest large particles during the course of their activities (Gr. 0a:yw, I eat). The objects that they destroy include invading pathogens, damaged and foreign cells, and connective tissue. Small targets such as bacteria and protozoa are destroyed after phagocytosis, a process by which the target is internalized into a cytoplasmic vesicle (the phagocytic vesicle) lined with what was originally plasma membrane (I). Larger targets can be killed without internalization (2-4). Because many of the destructive agents em­ ployed by phagocytes are nonspecifically reactive, normal tissue will be destroyed, especially near a region of inflammation where phagocytes accu­ mulate in large numbers (5-7); this accounts for much of the pathology at sites of inflammation. Pathogens are killed by all three types of phagocytes, though different phagocytes seem to specialize in different types of patho­ gens. Neutrophils appear to have few other major functions, but eosinophils are thought to limit the extent of an allergic response by the destruction of mediators (8), while the mononuclear phagocytes are the major elements
Abstract 3526: Coadministration of nicotinic acid with the Nampt inhibitor MPC-9528 enhances antitumor activity in Naprt deficient cancer cells in culture and in xenografts
Authors: Tracey C. Fleischer, Vijay R. Baichwal, J Jay Boniface, Daniel M. Cimbora, Lynn DeMie, Thomas B. Douce, Andrew D. Gassman, Damon I. Papac, Ashley Peterson, Rosann Robinson, Ryan T. Terry-Lorenzo, Robert O. Carlson
Journal: Cancer Research (2011)

Abstract Background: The tumoricidal small molecule MPC-9528 is a picomolar inhibitor of nicotinamide phosphoribosyltransferase (Nampt). Nampt catalyzes the first and rate-limiting step in NAD synthesis from nicotinamide. Nicotinic acid phosphoribosyltransferase (Naprt) catalyzes the first and rate-limiting step in an alternate pathway of NAD synthesis from nicotinic acid (NA). Cancer cells are particularly dependent on NAD and many cancer cell lines, but not most normal tissues, are deficient in Naprt activity. Therefore administration of NA could prevent MPC-9528-induced NAD depletion in normal tissues, but not in Naprt-deficient tumors, resulting in greater therapeutic index and efficacy. Methods: Cell viability was determined based on ATP levels. Naprt protein expresson was quantified by western blot and qRT-PCR. NAD was acid-extracted from cells and quantified by a coupled reaction based on fluorescent resorufin. Xenograft studies were performed in nu/nu mice. Results: In 44 out of 153 cancer cell lines surveyed, NA did not prevent MPC-9528-induced cell death, which correlated with low to undetectable levels of Naprt. MPC-9528-induced NAD depletion and cell death in HCT116 colon carcinoma cells were prevented by the addition of NA, consistent with high Naprt expression. A single dose of MPC-9528 at the maximum-tolerated dose (MTD) of 75 mg/kg caused tumor regression in HCT116 xenografts and NA coadministration completely blocked this effect. NA also completely blocked mortality in mice induced by 300 mg/kg MPC-9528, consistent with the finding that most mouse tissues have high Naprt expression. In Naprt-deficient MIA PaCa-2 xenografts, NA coadministration allowed tolerance of 200 mg/kg MPC-9528 with a substantially increased anti-tumor response relative to the MTD of 75 mg/kg MPC-9528 alone. Conclusions: Low Naprt expression correlates with the lack of effect of NA on MPC-9528 tumoricidal activity. Because Naprt deficiency is prevalent in cancer cell lines and in primary tumor specimens, but not in normal tissues, NA coadministration with MPC-9528 should increase the tolerability and efficacy of MPC-9528 in patients with Naprt-deficient tumors. A companion diagnostic designed to measure Naprt expression or activity in tumors could be used to identify tumors that would most likely benefit from such combination therapy. 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 3526. doi:10.1158/1538-7445.AM2011-3526
Visualization of clustered IgE epitopes on α-lactalbumin
Authors: Heidrun Hochwallner, Ulrike Schulmeister, Ines Swoboda, Margit Focke-Tejkl, Vera Civaj, Nadja Balic, Mats Nystrand, Annika Härlin, Josef Thalhamer, Sandra Scheiblhofer, Walter Keller, Tea Pavkov, Domen Zafred, Bodo Niggemann, Santiago Quirce, Adriano Mari, Gabrielle Pauli, Christof Ebner, Nikolaos G. Papadopoulos, Udo Herz, Eric A.F. van Tol, Rudolf Valenta, Susanne Spitzauer
Journal: Journal of Allergy and Clinical Immunology (2010)
The "Nasal Crease"
Authors: W. A. Myers
Journal: JAMA (1960)

The term nasal crease, as used here, refers to a persistent transverse hyperpigmented or hypopigmented line extending across the junction of the lower and middle thirds of the bridge of the nose. It is always at the site of the natural crease of the skin that is produced when the tip of the nose is pushed upward, as in the "allergic salute."<sup>1,4</sup>("Allergic salute" refers to the habitual manipulation of the nose, due to chronic obstruction and itching. It is typically accomplished by pushing the tip of the nose upward with the palm of the hand.) This nasal crease varies from a faint, or temporary, line to the distinct atrophic scars illustrated by our adult patients. Several of the faint ones disappeared in a few months after nasal symptoms had been relieved. I am not, of course, referring to the temporary blanching of the skin in this area immediately