tbuckley/cabot-search huggingface dataset:
Human papillomavirus type 5 is commonly present in immunosuppressed and immunocompetent individuals
Authors: None Boxman, None Mulder, None Russell, None Bouwes Bavinck, None Green, None Ter Schegget
Journal: British Journal of Dermatology (1999)

DNA of a wide spectrum of epidermodysplasia verruciformis‐associated human papillomavirus (HPV) types (EV–HPV) has been detected in skin lesions and plucked hairs from both immunosuppressed and a considerable proportion of non‐immunosuppressed persons. Recently, the skin of psoriatic patients was claimed to be an important reservoir for a particular EV–HPV type, HPV 5, which is considered as a high‐risk HPV type for skin carcinomas. In the present study, we analysed plucked hairs from immunosuppressed renal transplant patients and immunocompetent individuals, utilizing an HPV 5‐specific nested polymerase chain reaction. HPV 5 was detected in hairs derived from 14 of 31 (45%) immunosuppressed patients and 21 of 135 (16%) immunocompetent individuals. Both the immunosuppressed and the immunocompetent groups consisted of individuals with and without non‐melanoma skin cancer. HPV 5 DNA was detected in similar proportions of hair samples plucked from individuals with and without skin cancer in either group. Our results indicate that HPV 5 is commonly present in the population. The role of HPV 5 in the pathogenesis of skin carcinomas and psoriasis remains to be established.
rAAV-mediated apo a-1 Milano gene transfer results in significant inhibition of atherogenesis
Authors: Sarah Hardy, Prediman K. Shah, Svapna Patel, Juliana Yano, Tripathi B. Rajavashisth, K. K. Wong
Journal: Molecular Therapy (2004)

Apo A-1 Milano, an Arg173 to Cys point mutation of apo A-1, has demonstrated marked efficacy in the reduction of atherosclerotic lesions in animal models. A recent human trial testing recombinant apo A-1Milano infusions has similarly shown significant and rapid reduction in coronary atheroma volumes. In this project, we tested the utility of rAAV vectors encoding apo A-1 Milano for gene therapy of atherosclerosis in vivo following either intra-muscular injection or transplantation of rAAV-transduced bone marrow cells. ApoE-/- mice were injected with approximately 1012 vector genomes/kg at 6–8 weeks of age and placed on a high fat diet two weeks later. No major differences in body weight were observed between the treatment groups. 20–24 weeks after injection, the mice were harvested, aortas were cleaned, fixed, mounted, stained with oil red O and atherosclerotic plaque areas quantified. Control untreated mice or mice treated with an irrelevant rAAV vector showed marked atherosclerotic lesion formation. In contrast, the rAAV-2-apo A-1Milano and rAAV-5-apo A-1Milano injected groups showed significant reductions in plaque formation, 58% and 50% respectively, despite a lack of major differences in total plasma cholesterol levels. Since marrow-derived monocytes and macrophages play a pivotal role in atherogenesis, we tested the hypothesis that transplantation of rAAV apo A-1 Milano-transduced marrow cells would also result in a decline in plaque formation, possibly due to the localization of transduced macrophages within atherosclerotic lesions. Lethally irradiated Apo E-/- mice were transplanted with rAAV transduced cells, and high fat diet was initiated two weeks later. Twenty two to 24 weeks after transplantation, the mice were euthanized, and aortas were analyzed for atherosclerotic plaques. Untransplanted mice, and mice transplanted with untransduced and control rAAV transduced marrow served as negative controls. Wild type B6 to Apo E-/- transplants served as positive controls for plaque reduction. Results revealed a 41% and 47% reduction in atheroma formation following transplantation with cells transduced with rAAV-2 and rAAV5 vectors encoding apo A-1 Milano, respectively. These results suggest that either intramuscular injection of rAAV Apo A-1 Milano or transplantation of rAAV transduced marrow cells results in significant long-term inhibition of atherogenesis following a single treatment with an rAAV vector.
Abstract 13576: Difference in Right Ventricular Loading Between Patients With Pulmonary Hypertension and Patients With Left Sided Heart Failure
Authors: Soichiro Fuke, Kengo F Kusano, Natsuki Takahashi, Masamichi Tanaka, Aiko Ogawa, Satoshi Nagase, Kazufumi Nakamura, Tetsuya Sato, Toru Ujihira, Hiroshi Ito
Journal: Circulation (2010)

Purpose: Patients with pulmonary hypertension (PH) associated with right ventricular (RV) dysfunction show poor prognosis. To elucidate the mechanism of RV dysfunction, we compared RV function, RV ...
Abstract B05: Recurrence and hormone therapy resistance of cervical cancer in a transgenic mouse model
Authors: Fabiola Mehta, Sang-Hyuk Chung
Journal: Clinical Cancer Research (2015)

Abstract Persistent HPV infection and other cofactors are required for the progression of cervical cancer. Oral contraceptive use or multiple parities increases risk for cervical cancer in HPV-positive women. These risk factors have hormonal balance skewed toward estrogen (i.e., an increase in estrogen levels is much greater than an increase in progesterone levels). It is consistent that transgenic mice expressing HPV16 E6 and E7 (K14E6/K14E7) develop cervical cancer only when treated with physiological levels of estrogen. Using this validated mouse model, we demonstrated that estrogen receptor alpha (ERα) antagonists (e.g., raloxifene) or a progesterone receptor (PR) agonist [e.g. medroxyprogesterone acetate (MPA)] is efficient in treating cervical cancer. Cervical cancer recurs after raloxifene therapy, and recurring disease remains sensitive to raloxifene. The present study investigates whether cervical cancer recurs after stopping MPA treatment. Consistent with our prior results, K14E6/K14E7 mice (7 of 7) developed cervical cancer after 6-month estrogen treatment (initial cancer), which regressed in 14 of 14 mice upon 2-month MPA treatment (i.e., complete response). When the mice were re-treated for 2 months with estrogen after MPA therapy, cervical cancer was observed in 6 of 6 mice (100%). As a control, a group of mice were left untreated for first 6 months, and then treated with MPA for 2 months followed by 2-month estrogen treatment. We defined cervical disease in this group as newly arising disease. Cancer incidence in this group (25%; 4 of 16 mice) was significantly lower. These results indicate that cervical cancer recurs if MPA treatment is discontinued. Interestingly, recurrence was also observed in 8 of 8 mice without readministration of estrogen, indicating that recurring cancers are independent of exogenous estrogen (we do not know whether they depend on endogenous estrogen). Strikingly, when mice bearing recurring cancers were re-treated with MPA, cancer incidence (100%, 5 of 5 mice) and cancer multiplicity remained similar to a control group, and moderate reduction in cancer size was observed. These results indicate that recurring cervical cancers acquired resistance to PR agonist therapy. This resistance was not due to loss of PR because PR status in recurring cancers was similar to that in initial cancers. Further study is warranted to determine a mechanism of therapy resistance in this mouse model, which is anticipated to facilitate development of a more efficient therapy for the disease. Citation Format: Fabiola Mehta, Sang-Hyuk Chung. Recurrence and hormone therapy resistance of cervical cancer in a transgenic mouse model. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B05.
2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the Use of Percutaneous Mechanical Circulatory Support Devices in Cardiovascular Care
Authors: Charanjit S. Rihal, Srihari S. Naidu, Michael M. Givertz, Wilson Y. Szeto, James A. Burke, Navin K. Kapur, Morton Kern, Kirk N. Garratt, James A. Goldstein, Vivian Dimas, Thomas Tu
Journal: Journal of the American College of Cardiology (2015)
Identification of amino acids critical for IgE‐binding to sequential epitopes of bovine κ‐casein and the similarity of these epitopes to the corresponding human κ‐casein sequence
Authors: N. Han, K. M. Järvinen, R. R. Cocco, P. J. Busse, H. A. Sampson, K. Beyer
Journal: Allergy (2008)

Background: The delineation of allergenic (i.e. IgE‐binding) epitopes in cow’s milk proteins and the amino acids (AAs) critical for IgE‐binding is necessary to understand better the structural properties of an allergen and to develop more efficacious immunotherapeutic reagents. Furthermore, this information may enable us to understand better cross‐sensitivity between different allergens. Methods: Eleven peptides, 10–14 AAs in length, representing the IgE‐binding epitopes of κ‐casein were synthesized on a derivatized cellulose membrane with single AA substitutions at each position. Membranes were incubated with pooled sera from 15 milk‐allergic patients and individual sera from 10 of the patients included in the pool. Results: For 10/11 allergenic peptides, one to five different single AA substitutions resulted in elimination of IgE‐binding of pooled patient sera. Overall at least one mutated peptide could be found for these 10 IgE‐binding sites that resulted in a reduction of IgE‐binding in at least 80% of the patients who recognized the native protein. Furthermore, the IgE‐binding region at AA104–112 on bovine κ‐casein showed a high degree of similarity with the human κ‐casein, respectively, including the AAs critical for IgE‐binding. Conclusion: This finding suggests that critical AAs should be assessed with both pooled and individual patient sera to account for the B‐cell epitope heterogeneity between patients, with cow’s milk allergy. In addition, we identified two potentially cross‐reactive peptides between bovine and human caseins of unknown clinical relevance.
Recurrent Clostridium difficile infection is associated with increased mortality
Authors: M.A. Olsen, Y. Yan, K.A. Reske, M.D. Zilberberg, E.R. Dubberke
Journal: Clinical Microbiology and Infection (2014)

Clostridium difficile infections (CDI) are associated with decreased survival, and up to 30% of CDI patients may experience a recurrence. Data on the impact of recurrent CDI on mortality are scarce. The purpose of this study was to determine whether recurrent CDI was independently associated with decreased 6-month survival compared with patients with CDI who did not develop a recurrence. We performed a retrospective cohort study at an academic, urban, tertiary care hospital. Data were collected from the electronic medical record and chart review. CDI patients were followed for 180 days from the end of their index hospital discharge or end of index CDI antibiotic treatment, whichever was later, to determine mortality. Kaplan-Meier analysis was used to compare patient mortality by recurrent CDI status. Cox proportional hazards models were used to determine independent risk factors for death within 180 days. In all, 3958 patients aged ≥ 18 years who developed an initial CDI episode from 2003 to 2009, including 421 patients with recurrent CDI, were included in the study. Thirty-six per cent of persons with recurrent CDI died within 180 days, compared with 26% of persons without CDI recurrence (log-rank p <0.001). Recurrent CDI was associated with significantly higher hazards of death within 180 days, adjusting for demographics, comorbidities and medications received during the index CDI hospitalization (hazard ratio 1.33; 95% CI 1.12-1.58). Recurrent CDI is associated with significantly increased risk of death within 6 months after completion of their initial CDI treatment compared with CDI patients who do not develop a recurrence.
Molecular mechanistic explanation for the spectrum of cholestatic disease caused by the S320F variant of ABCB4
Authors: Edward J. Andress, Michael Nicolaou, Marta R. Romero, Sandhia Naik, Peter H. Dixon, Catherine Williamson, Kenneth J. Linton
Journal: Hepatology (2013)

ABCB4 flops phosphatidylcholine into the bile canaliculus to protect the biliary tree from the detergent activity of bile salts. Homozygous-null ABCB4 mutations cause the childhood liver disease, progressive familial intrahepatic cholestasis, but cause and effect is less clear, with many missense mutations linked to less severe cholestatic diseases. ABCB4S320F, in particular, is described in 13 patients, including in heterozygosity with ABCB4A286V, ABCB4A953D, and null mutants, whose symptoms cover the spectrum of cholestatic disease. We sought to define the impact of these mutations on the floppase, explain the link with multiple conditions at the molecular level, and investigate the potential for reversal. ABCB4S320F, ABCB4A286V, and ABCB4A953D expression was engineered in naïve cultured cells. Floppase expression, localization, and activity were measured by western blot, confocal microscopy, and lipid transport assays, respectively. ABCB4S320F was fully active for floppase activity but expression at the plasma membrane was reduced to 50%. ABCB4A286V expressed and trafficked efficiently but could not flop lipid, and ABCB4A953D expressed poorly and was impaired in floppase activity. Proteasome inhibition stabilized nascent ABCB4S320F and ABCB4A953D but did not improve plasma membrane localization. Cyclosporin-A improved plasma membrane localization of both ABCB4S320F and ABCB4A953D, but inhibited floppase activity. Conclusion : The level of ABCB4 functionality correlates with, and is the primary determinant of, cholestatic disease severity in these patients. ABCB4S320F homozygosity, with half the normal level of ABCB4, is the tipping point between more benign and potentially fatal cholestasis and makes these patients more acutely sensitive to environmental effects. Cyclosporin-A increased expression of ABCB4S320F and ABCB4A953D, suggesting that chemical chaperones could be exploited for therapeutic benefit to usher in a new era of personalized medicine for patients with ABCB4-dependent cholestatic disease. (Hepatology 2014;59:1921–1931)
Abstract 16492: A Common Gene Network Governs the Cellular Phenotypes in Acute Aortic Dissection
Authors: Satoko Ohno, Hiroki Aoki, Michihide Nishihara, Aya Furusho, Saki Hirakata, Norifumi Nishida, Sohei Ito, Hideo Yasukawa, Yoshihiro Fukumoto
Journal: Circulation (2014)

Acute aortic dissection (AAD) is a common disease with sudden onset and high mortality, for which pathogenesis is largely unknown. To better understand AAD pathogenesis, we examined three mouse models of AAD; knockout mice for tenascin C, an extracellular glycoprotein that is secreted by vascular smooth muscle cells (VSMCs), macrophage-specific knockout of SOCS3 (mSOCS3-KO), a negative regulator of JAK/STAT signaling, and infusion of beta-aminopropionitrile, that blocks crosslinking of elastin and collagens. All of three models develop AAD upon the continuous infusion of angiotensin II (AngII). We performed transcriptome analyses at the early time point of AngII infusion when the aortic structure showed no obvious abnormality. Interestingly, the gene expression patterns showed common changes; induction of proinflammatory molecules and cell cycle machinery, and suppression of the structural extracellular matrix (ECM) and cytoskeletal molecules of VSMCs. Such a pattern is consistent with that in human AAD as previously reported. We performed detailed analysis in mSOCS3-KO. Bayesian network model revealed that upregulation of cell cycle machinery precedes other changes in the gene expression. Cell cycle analyses using Ki67 staining and BrdU uptake assay showed that AngII caused proliferative response before AAD development both in macrophages and in VSMCs, indicating the macrophage-VSMC interaction. In addition, the proliferative response of macrophages was associated with the preferential differentiation into the proinflammatory M1 phenotype as determined by the high expression of Ly6C. Our findings showed a gene expression network of AAD that is common to human and mouse models. The findings in mouse models suggest that cell cycle activation precedes both the proinflammatory response in macrophages and the functional deterioration of VSMCs, which in turn would weaken the aortic wall strength. In addition, tissue-specific knockout studies revealed that interactions between macrophages and VSMCs underlie the gene expression network in AAD. Deciphering such cellular interactions and gene expressions would lead to better understanding of this fatal disease.
Limited engraftment capacity of bone marrow–derived mesenchymal cells following T-cell–depleted hematopoietic stem cell transplantation
Authors: Daniela Cilloni, Carmelo Carlo-Stella, Franca Falzetti, Gabriella Sammarelli, Ester Regazzi, Simona Colla, Vittorio Rizzoli, Franco Aversa, Massimo F. Martelli, Antonio Tabilio
Journal: Blood (2000)
FATAL APLASTIC ANEMIA OCCURRING DURING ANTICONVULSANT THERAPY: PROBABLE IDIOSYNCRASY TO PHENURONE
Authors: T W SIMPSON, E B WILSON, S L ZIMMERMAN
Journal: Annals of Internal Medicine (1950)

Case Reports1 June 1950FATAL APLASTIC ANEMIA OCCURRING DURING ANTICONVULSANT THERAPY: PROBABLE IDIOSYNCRASY TO PHENURONETHOMAS W. SIMPSON, M.D., EDWIN B. WILSON JR., M.D., S. L. ZIMMERMAN, M.D., F.A.C.P.THOMAS W. SIMPSON, M.D.Search for more papers by this author, EDWIN B. WILSON JR., M.D.Search for more papers by this author, S. L. ZIMMERMAN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-32-6-1224 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA fatal case of aplastic anemia has recently been observed in which idiosyncracy to phenurone (acetylurea) appears to have been the cause or precipitating factor. Phenurone shows considerable promise in the treatment of epilepsy1 and is being used with increasing frequency in selected cases. The observation that severe bone marrow depression may occur during its use seems worthy of note.CASE REPORTA 33-year-old white married farmer had been in good general health until shortly after discharge from the Army in 1945, when he began to have recurrent epileptic seizures. There was no history of previous convulsive attacks or head...Bibliography1. GibbsEverettRichards FAGMRK: Phenurone in epilepsy, read before the Am. Br. Internat. League against Epilepsy, June 13-14, 1948. Toman, J. P.: The neuropharmacology of antiepileptics, Electroencephalography and Clinical Neurophysiology 1: 33-44, 1949. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Columbia, South Carolina*Received for publication July 9, 1949.From the Medical Service of the Veterans Administration Hospital, Columbia, South Carolina, Dr. S. L. Zimmerman, Chief. Sponsored by the Veterans Administration and published with the approval of the Chief Medical Director. The statements and conclusions published by the authors are a result of their own study and do not necessarily reflect the opinion or policy of the Veterans Administration. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe use of phenacemide for intractable partial complex epilepsy in childrenElevated Serum Creatinine Levels in Three Patients Treated with PhenacemideAcetylurea DerivativesDie Behandlung der EpilepsienDrug therapy for childhood epilepsyPhenacemide in the Treatment of EpilepsyDRUG INDUCED HYPOPLASTIC ANEMIAS AND RELATED SYNDROMES*EDWIN E. OSGOOD, M.D., F.A.C.P. 1 June 1950Volume 32, Issue 6Page: 1224-1228KeywordsAnticonvulsantsAplastic anemiaBone marrowEpileptic seizuresMedical services ePublished: 1 December 2008 Issue Published: 1 June 1950 PDF downloadLoading ...
A memorable dinner party: Eavesdropping on the great and the good
Authors: J. H. Baron
Journal: BMJ (2000)

explain the rarity of tinea capitis in adults. 2 Dermatophytic colonisation of the scalp disappears at puberty. [1]2][3] Colonisation by Pityrosporum orbiculare may interfere with dermatophyte contamination, and the thicker calibre of adult hair may protect against dermatophytic invasion. 1Tinea capitis in adults generally occurs in patients who are immunosuppressed and those infected with HIV. 1 In immunocompetent adults, the clinical features are often atypical. 1 The disease may resemble bacterial folliculitis, folliculitis decalvans, dissecting cellulitis, or the scarring related to lupus erythematosus. 3 4 In recent years, the incidence of tinea capitis has increased in the United Kingdom, particularly among Afro-Caribbean children living in large cities. 5 6 The mean age of patients is 5-6 years, and several siblings may be affected. 5 The mean prevalence of culture positive tinea capitis in a 1996 school study from south east London was 2.5% (range 0%-12%). 7A further 4.9% of
Abstract P6-02-03: SUMO Inhibitors affect tumorigenesis of novel breast cancer xenograft model
Authors: Maria V Bogachek, Jung M Park, James P De Andrade, Mikhail V Kulak, Jeffrey R White, Tong Wu, Philip M Spanheimer, George W Woodfield, Thomas B Bair, Alicia K Olivier, Ronald J Weigel
Journal: Cancer Research (2015)

Abstract A novel basal breast cancer cell line IOWA-1T was derived from chemotherapy resistant locally advanced breast cancer tumor. The cells rapidly form large, skin-eroding xenografts in nude mice. The SUMO inhibitor anacardic acid (AA) effectively cleared CD44+/hi/CD24-/low cancer stem cell (CSC) population in IOWA-1T and BT-20 basal cancer cell lines and delayed tumor outgrowth of basal cancer xenografts. The effect of SUMO inhibitors to clear the CSC population was dependent upon the SUMO unconjugated form of TFAP2A (Bogachek MV et al, Cancer Cell, 2014). Herein we show that tumors that eventually form from IOWA-1T xenografts in mice treated with AA are not capable of developing secondary xenografts, confirming eradication of the CSC population by SUMO inhibitors. As further mechanistic evidence for the SUMO pathway, transient knockdown of UBC9 and PIAS1 SUMOylation enzymes repressed CD44 expression and increased tumor free and overall survival in mice inoculated with IOWA-1T xenografts. Furthermore, CD44 downregulation was demonstrated in IOWA-1T cells after treatment in vitro with UBC9 inhibitor PYR-41 and PIAS1 inhibitor NSC-207895. Overall survival of mice with IOWA-1T xenografts was increased to 43±0.5 and 39±2 days with PYR-41 and NSC-207895 i.p. injections, respectively, compared to a vehicle treated control group 33±1 days (p&amp;lt;0.05). By contrast, doxorubicin treatment was not able to extend survival of mice with IOWA-1T xenografts. These findings establish the class of SUMO inhibitors as potential therapeutic drugs that eliminate the breast CSC population and may be effective in basal breast cancer cases resistant to conventional chemotherapy. Citation Format: Maria V Bogachek, Jung M Park, James P De Andrade, Mikhail V Kulak, Jeffrey R White, Tong Wu, Philip M Spanheimer, George W Woodfield, Thomas B Bair, Alicia K Olivier, Ronald J Weigel. SUMO Inhibitors affect tumorigenesis of novel breast cancer xenograft model [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-02-03.