tbuckley/cabot-search huggingface dataset:
243. Delivery of Igf-I and Dystrophin to Dystrophic mdx Muscle
Authors: Simone Abmayr, Paul Gregorevic, James M. Allen, Shanna M. Sawatzki, Jeffrey S. Chamberlain
Journal: Molecular Therapy (2004)

Duchenne muscular dystrophy is among the most common genetic diseases and is caused by mutations in the dystrophin gene. Dystrophic muscles display an extensive degeneration and regeneration process, whereby muscle fibers progressively lose their self-renewal potential and are gradually replaced by adipose and fibrotic tissue. Gene replacement therapy using truncated versions of dystrophin have been shown to protect dystrophic muscles from contraction-induced injury and partially reverse muscle pathology. An alternative approach involves the activation of satellite cells to maintain the regenerative potential of dystrophic muscle. Igf-I, an important mediator of cell growth and differentiation, has been shown to increase muscle mass and strength and to enhance muscle repair mechanism in dystrophic mdx muscles (Barton et al., 2002). However, Igf-1 is unable to restore mechanical integrity to muscle fibers lacking dystrophin. To determine if the beneficial effect of Igf-I is synergistic with the protective effect of dystrophin in ameliorating dystrophic pathology, we compared the effects of delivering Igf-I alone versus co-delivering both Igf-I and dystrophin to adult, dystrophic mdx mouse muscles. We generated recombinant adeno-associated viral vectors pseudotyped with the serotype 6 capsid protein that carry expression cassettes in which the muscle-specific creatine kinase promoter/enhancer drove either the micro-dystrophin (AAV-udys) or the Igf-I cDNA (AAV-Igf-I). Tibialis anterior muscles of mdx mice were injected with each vector separately, together or with buffer control and then analyzed four months post injection. Immunohistochemical analysis demonstrated persistent expression of dystrophin that reached an average of 40% of the total muscle cross sectional area. We also observed persistent expression of Igf-I mRNA at levels 200-400 fold greater than endogenous mdx Igf-I levels in AAV-Igf-I and AAV-udys co-injected muscles. In contrast, injection of AAV-Igf-I alone resulted in a 4-fold decline of Igf-I mRNA levels in the four months following injection into dystrophic mdx muscles. Functional measurements demonstrated that AAV-udys injected animals were partially protected from contraction-induced injury after two lengthening contractions, whereas animals injected with AAV-Igf-I alone were as susceptible as mdx animals to muscle damage. AAV-Igf-I treated animals, on the other hand, showed an increase in muscle mass, which was not seen after AAV-udys only treatment. In contrast, co-injection of AAV-Igf-I and AAV-udys resulted in increased muscle mass and muscle strength, and in protection from contraction-induced injury. These results suggest that the combination of AAV-Igf-I and AAV-udys acted synergistically and was beneficial for the animal.
Abstract 3977: Molecular reprogramming in high-risk progressive neuroblastoma
Authors: Vijayabaskar Pandian, Faizan H. Khan, Satish K. Ramraj, Sheeja Aravindan, Mohan Natarajan, Terence S. Herman, Natarajan Aravindan
Journal: Cancer Research (2014)

Abstract High risk disease in infants with neuroblastoma significantly contributes to the pediatric cancer death. We investigated the molecular reprogramming in neuroblastoma cells that drives favorable neuroblastoma to aggressive disease. For this, multi-site aggressive tumors from animals that received parental (SH-SY5Y) cell xenotransplantation were assayed and compared to the animals with subtle non-metastatic xenografts. Establishment of highly malignant neuroblastoma cell line (NBP4) and its comparative (with SH-SY5Y) cytogenetic/phenotypic physiognomies were reported elsewhere. Ex vivo whole genome gene expression identified a total of 33 genes upregulated and another 33 genes downregulated (&amp;gt;40 fold change) in NBP4 cells as opposed to parental SH-SY5Y cells. QPCR analysis revealed a conforming upregulation of SEMA3D, MEGF10, GRB10 and suppression of RD3 in multi-site aggressive tumors. Tissue microarray (72 core) constructed with aggressive multiple tumors and non-progressive controls coupled with immunohistochemistry showed robust levels of SEMA3D, GRB10, MEGF10 and complete loss of KCNQ2, KRTAP1-1 and RD3. Consistently, translational modifications of SEMA3D, GRB10, MEGF10, KCNQ2 and RD3 in multi-site aggressive tumors were validated with immunoblotting. More importantly, selective knockdown of KCNQ2 or KRTAP1-1 in parental SH-SY5Y cells robustly modified the cellular phenotype and significantly increased the tumorosphere formation. Conversely, discrete muting of GRB10, KIAA2022, MEGF10 or SEMA3D ex vivo (in aggressive NBP4 cells) endorsed the cellular differentiation, adherence and resulted in complete regulation of tumorosphere formation. Together, these data suggests that the milieu based molecular reprograming of the neuroblastoma cells drives the development of high-risk disease and further implies that GRB10, KIAA2022, MEGF10, SEMA3D, RD3 and KCNQ2 may concert and orchestrate the disease progression. Signal flow-through and molecular driver(s) that orchestrate favorable to high-risk disease are yet to be understood and are currently in progress in our laboratory. Citation Format: Vijayabaskar Pandian, Faizan H. Khan, Satish K. Ramraj, Sheeja Aravindan, Mohan Natarajan, Terence S. Herman, Natarajan Aravindan. Molecular reprogramming in high-risk progressive neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3977. doi:10.1158/1538-7445.AM2014-3977
Abstract P260: Genome-wide Pathway and Network-based Approaches Identify Novel Genetic Loci and Pathways for Cardiovascular Disease and Diabetes in an Ethnically Diverse Cohort of American Women
Authors: Kei Hang K Chan, Yen-Tsung Huang, Yi-Hsiang Hsu, Yiqing Song, Andrea Hevener, Qingying Meng, Chunyuan Wu, Alexander Reiner, Eric M Sobel, Lesley Tinker, Xia Yang, Simin Liu
Journal: Circulation (2014)

Introduction: Despite the success of recent genome-wide association studies (GWAS) in identifying genetic loci associated with cardiovascular disease (CVD) and diabetes (T2D), a comprehensive examination of GWAS data for identifying biological pathways underlying their specific or shared genetic mechanisms is lacking, especially in an ethnicity-specific manner. Hypothesis: We hypothesized that genetic variation clustered in biological pathways is associated with an increased risk of CVD and T2D. Methods: We applied a pathway and network-based approach to characterize GWAS signals in sets of biological pathways for their contribution to CVD and T2D in two separate nation-wide populations of ethnically diverse women from the Women’s Health Initiative (WHI) Cohort, the WHI SNP Health Association Resource(WHI-SHARe) and the Genomics and Randomized Trials Network(WHI-GARNET), involving 8,155 African American, 3,494 Hispanic American, and 3,697 Caucasian American women. Results: Eight pathways were identified to be significantly enriched for CVD, T2D, and combined CVD and T2D across the three ethnic groups at false discovery rate &lt;0.001, including hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, calcium signaling pathway, axon guidance, cell adhesion molecules, focal adhesion, and ECM-receptor interaction pathways. We also identified disease- and ethnicity-specific pathways, such as cell cycle (specific for Hispanic and Caucasian Americans) and tight junction (CVD and combined CVD + T2D in Hispanic Americans). Conclusions: By applying pathway- and network-based analyses to two large GWAS from three ethnic groups of American women, we identified shared biological pathways for CVD and T2D and disease- and ethnicity-specific pathways. These results provide evidence for multiple pathways underlying the pathogenesis of CVD and T2D in three genetically distinct populations and implicate the complex etiology of cardiometabolic disease.
The Medical Management of AIDS
Authors: Merle A. Sande, Paul Volberding
Journal: Annals of Internal Medicine (1989)

Part 1 The virus - its transmission and infection: current trends in the epidemiology of HIV/AIDS molecular insights into HIV-1 infection natural history and immunopathogenesis of HIV-1 disease quantitation of HIV viral load - a tool for clinical practice? limiting the risks of health care workers. Part 2 Management of HIV infections and their complications: primary HIV infection initiating routine care for the HIV-infected adult antiretroviral therapy drug interactions and toxicities in patients with AIDS alternative therapies for HIV dermatologic care in the AIDS patient oral complications of HIV infection gastrointestinal tract manifestations of AIDS management of neurologic complications of HIV-1 infection and AIDS HIV disease - psychosocial issues and psychiatric complications haematologic complications of HIV infection cardiovascular complications of HIV infection endocrinologic manifestations of HIV infection renal complications of HIV infection. Part 3 Specific infections and malignant conditions: pneumocystis carinii pneumonia disseminated mycobacterium avium complex and other bacterial infections tuberculosis in persons with human immunodeficiency virus infection cryptococcosis and other fungal infections (histoplasmosis, coccidiomycosis) AIDS-associated toxoplasmosis bacillary angiomatosis and other unusual infections in HIV-infected individuals management of herpesvirus infections (CMV,HSV, VZV) management of syphilis in HIV-infected persons malignancies associated with AIDS. Part 4 Special aspects of AIDS: the chest film in AIDS management of pregnant women with HIV infection paediatric AIDS - perinatal transmission and early diagnosis gender-specific issues in HIV disease HIV nursing care.
Peter J. Safar, MD
Authors: Mike Mitka
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 11288: Breast Arterial Calcifications and Their Association With Cardiovascular Disease in the Prospect Cohort
Authors: Eva J Hendriks, Joline W Beulens, Willem P Mali, Yolanda van der Graaf, Pim A de Jong, Yvonne T van der Schouw
Journal: Circulation (2014)

Introduction: Breast arterial calcifications (BAC) are a type of medial arterial calcification observed at mammography. They are more prevalent among diabetes patients and thought to be associated with increased cardiovascular risk, but high quality longitudinal studies are scarce. We aimed to investigate the association of BAC with risk of different types of cardiovascular outcomes. Methods: We performed a series of case-cohort studies nested within the PROSPECT-EPIC cohort, including a random subcohort (n = 1672), and incident cases of coronary heart disease (n=1050), stroke (n=399) peripheral artery disease (n=257), cardiovascular mortality (n=250), and type 2 diabetes (n=526). At baseline BAC was scored as absent, mild, moderate or severe by experienced radiologists. The average follow-up time was 12.0(±1.9) years. We calculated hazard ratios(HRs) using Cox proportional hazards models, adapted to the case-cohort design through Prentice-weighting and adjusting for traditional cardiovascular risk factors. Results: Of the women in the sub cohort with mammograms available (n=1540), 133 women (8.6%) had BAC in at least one breast. Grade was scored as mild in 75 women (4.9%), moderate in 39 women (2.5%) and severe in 19 women (1.2%). BAC presence was borderline significantly (0.05&lt;p&lt;0.10) associated with risk of coronary heart disease, stroke and cardiovascular mortality, with adjusted HR estimates ranging from 1.42 to 1.58. Much larger effect sizes were found for women with the most severe grade of BAC, as they had a HR of 3.43 (95% CI 1.85-6.37) for coronary heart disease, a HR of 3.19 (95% CI 1.52-6.72) for stroke, a HR of 2.92 (95%CI 1.02-8.35) for peripheral artery disease and a HR of 3.55 (95%CI 1.48-8.52) for cardiovascular mortality compared to women without BAC. Conclusions: BAC presence is modestly associated with cardiovascular disease, with an approximately 3-fold increased risk for the severest grade of BAC, independent of traditional risk factors. This indicates a possible contribution of a medial, non-atherosclerotic pathway to cardiovascular disease events. Whether BAC is a marker of medial arterial calcification in different vascular beds needs to be further investigated.
Antibiotic‐Killed <i>Staphylococcus aureus</i> Induces Destructive Arthritis in Mice
Authors: Abukar Ali, Xuefeng Zhu, Jakub Kwiecinski, Inger Gjertsson, Catharina Lindholm, Yoichiro Iwakura, Xiaoyang Wang, Nils Lycke, Elisabet Josefsson, Rille Pullerits, Tao Jin
Journal: Arthritis & Rheumatology (2014)

Permanent reduction in joint function is a severe postinfectious complication in patients with Staphylococcus aureus septic arthritis. We undertook this study to determine whether this reduction in joint function might be caused by persistent joint inflammation after the adequate eradication of bacteria by antibiotics. After intraarticular injection of cloxacillin-killed S aureus into mouse knee joints, we investigated whether antibiotic-killed S aureus induced joint inflammation and elucidated the molecular and cellular mechanisms of this type of arthritis. Intraarticular injection of antibiotic-killed S aureus induced mild-to-moderate synovitis and bone erosions that lasted for a minimum of 14 days. Compared with wild-type animals, mice deficient in tumor necrosis factor receptor type I (TNFRI), receptor for advanced glycation end products (RAGE), or Toll-like receptor 2 (TLR-2) had a significantly reduced frequency and severity of synovitis. Combined depletion of monocytes and neutrophils also resulted in a significantly lower frequency of synovitis. Among bacterial factors, insoluble cell debris played a more important role than bacterial DNA or soluble components in inducing joint inflammation. Importantly, anti-TNF therapy abrogated joint inflammation induced by antibiotic-killed S aureus. Antibiotic-killed S aureus induced and maintained joint inflammation mediated through TLR-2, TNFRI, and RAGE. The cross-talk between neutrophils and monocytes is responsible for this type of arthritis. Anti-TNF therapy might be used as a novel strategy, in combination with antibiotics, to treat staphylococcal septic arthritis.
Seasonal influenza vaccination rates in chronic asthma patients
Authors: Rachelle Asciak, Liam Mercieca, Jesmar Buttigieg, Martin Balzan
Journal: European Respiratory Journal (2012)

Aim To document influenza vaccination in asthma patients, to explore factors that influence vaccination.

Method Adult patients with chronic asthma attending a hospital clinic (n=146, Female =103, mean age 49.81±3.2, 29.66 Male) filled in a questionnaire in January 2012 on influenza vaccination.

Results 51.39% used reliever medication less than twice per week. 4.79% were current smokers. 86(58.9%) of patients had experienced acute episodes in the previous year. 80(55%, 40% of Male, 61% of F) received the influenza vaccine this winter. 129 (88.6%) had been vaccinated in the past. 49 patients did not re-vaccinate because of fear of side effects(21), forgotten or had no time(12), were sick when vaccine available(6), adverse media report (1), because of current pregnancy(5) and 4 thought the did not need it. 41 patients who had experienced side effects in the past, 16 re-vaccinated this year. 78 of 125 (62.4%) of all patients who were advised the vaccine were vaccinated, while 10% of those not advised were vaccinated this year (p=<0.0001). 78% of those who were advised to take the vaccine by a doctor were actually vaccinated. The mean age for vaccinated was 54, and 42 in those who were not (p=0.0003). The main reasons for taking the vaccine were advised by a doctor(34%), to protect themselves(60%), to reduce severity and frequency of asthma attacks (39%). Reasons for not having the vaccine were fear of side effects (40%), forgot or had no time to take it (19%), did not know they should take it (12%)

Conclusion The rate of influenza vaccination in asthma patients is low. Medical advice by a medical practitioner resulted in a high vaccination rate. Fear of side-effects was main reason for non-vaccination.
Bortezomib is active as a single agent against multidrug resistant (MDR) leukemia in vitro but does not synergize with cytarabine (Ara-C), daunorubicin (DNR), doxorubicin (Dox) or Idarubicin (Ida).
Authors: Hans Minderman, Kieran L. O’Loughlin, Maria R. Baer
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5416 

The proteasome inhibitor bortezomib has been approved for single-agent treatment of multiple myeloma and is being evaluated in other malignancies. Two prominent effects of bortezomib are inhibition of nuclear factor-kappa-B activation and stabilization of p53, both of which may affect the cellular response to cytotoxic drugs. The purpose of the present study was to assess efficacy of bortezomib in acute myeloid leukemia (AML) by determining its activity as a single agent in AML cell lines with wt (ML-1) and inactive (HL60) p53 and against cells overexpressing MDR proteins prevalent in AML, including P-glycoprotein (Pgp), multidrug resistance protein-1 (MRP-1), breast cancer resistance protein (BCRP) and lung resistance protein (LRP). In addition, interactions between bortezomib and chemotherapy drugs with activity in AML were studied. Cells were cultured for four days in 96-well microculture assays with bortezomib and the chemotherapy drugs Ara-C, DNR, Dox or Ida individually, simultaneously and sequentially with reciprocal sequences, and cell survival was measured by the WST-1 assay. Drug interactions at various constant drug concentration ratios were evaluated by isobologram analysis. All cell lines, regardless of p53 status or overexpression of MDR proteins, were highly sensitive to bortezomib as a single agent, with nanomolar IC50’s, compared to micromolar IC50’s for Ara-C, DNR, Dox and Ida. Simultaneous combination of bortezomib with Ara-C, DNR, Dox or Ida was antagonistic over the full dose-response range (IC10, IC25, IC50, IC75, IC90) at five different constant ratios. Pre-incubation of cells with bortezomib (dose range 2-10 nM) for 24 hours did not sensitize to Ara-C, DNR or Dox, nor did adding bortezomib 24 hours into Ara-C, DNR or Dox exposure. Furthermore, pre-incubation of cells with non-cytotoxic concentrations of Ara-C, DNR or Dox did not sensitize to bortezomib, nor did adding non-cytotoxic concentrations of Ara-C, DNR or Dox 24 hours into bortezomib exposure. Thus bortezomib is highly effective in AML as a single agent and overcomes resistance mechanisms prevalent in AML, but in vitro does not have synergistic drug interactions with standard chemotherapy drugs used in AML. These data do not rule out additive or synergistic drug interactions in vivo , but suggest that benefits of these drug combinations would likely be due to mutually exclusive drug targets leading to additive interactions or altered host/target cell interactions that may lead to synergistic interactions. The antagonistic drug interactions observed in vitro should be taken into account in the design of clinical trials.
Primer ya da Metastatik Akciğer Kanserinde Hipofraksiyone Stereotaktik Radyoterapinin Sonuçları ve Prognostik Belirteçleri
Authors: Haeyoung Kim, Yong Chan Ahn, Hee Chul Park, Do Hoon Lim, Heerim Nam
Journal: Journal of Thoracic Oncology (2010)
Cross-Species Genomics Identifies TAF12, NFYC, and RAD54L as Choroid Plexus Carcinoma Oncogenes
Authors: Yiai Tong, Diana Merino, Birgit Nimmervoll, Kirti Gupta, Yong-Dong Wang, David Finkelstein, James Dalton, David W. Ellison, Xiaotu Ma, Jinghui Zhang, David Malkin, Richard J. Gilbertson
Journal: Cancer Cell (2015)
940. Ribozyme Oligonucleotides Against TGF-β Transferred by Ultrasound Inhibited the Progression of Diseases in Anti-Thy1 Model
Authors: Naruya Tomita, Keita Yamasaki, Kei Yamamoto, Hiromi Koike, Yasuo Kunugiza, Toshio Ogihara, Ryuichi Morishita
Journal: Molecular Therapy (2004)

Top of pageAbstract
Antisense as well as ribozyme oligonucleotides (ODN) are often used to inhibit the specific gene espression by targeting to the transcriptional process resulting in the combat against disease processes. On the other hand, TGF-β has been postulated to play an important role in the pathophysiology of renal diseases. In this study, we first examined the inhibitory effects of ribozyme ODN against TGF-β in mesangial cells (MC). Transfer of TGF-β ribozyme ODN into human and rat MC by cationic liposomes significantly decreased mRNA expression and protein production of TGF-β induced by Ang II as compared to the control (Protein production; TGF-β ribozyme: 116 ± 14.2 pg/ml, Control ribozyme: 162 ± 16.7 pg/ml, P<0.01). The examination of FITC-labeled ribozyme ODN transfer by cationic liposomes in MC revealed that ribozyme ODN are mainly located in the cytoplasm. Then, we examined the feasibility of ultrasound method that we established recently to transfer ribozyme ODN into the kidney in vivo. As we expected, FITC-labeled ribozyme ODN was efficiently transferred in glomeruli, interstitial tissues and tubules with this method. Finally, the inhibitory effect of TGF-β ribozyme ODN transferred by ultrasound method in vivo on TGF-β expression and extracellular matrix accumulation in experimental glomerulonephritis, anti-Thy1 model, was examined. TGF-β ribozyme ODN, not control ribozyme ODN, suppressed the TGF-β expression leading to the inhibition of extracellular matrix accumulation in glomeruli significantly. Overall, the present studies demonstrated that our constructed ribozyme ODN against TGF-β can effectively cleavage TGF-β mRNA in MC in vitro and glomeruli in vivo suggesting the feasibility of ribozyme-mediated therapy to treat renal diseases.
Acceleration of intestinal polyposis through prostaglandin receptor EP2 in ApcΔ716 knockout mice
Authors: Masahiro Sonoshita, Kazuaki Takaku, Nobuya Sasaki, Yukihiko Sugimoto, Fumitaka Ushikubi, Shuh Narumiya, Masanobu Oshima, Makoto M. Taketo
Journal: Nature Medicine (2001)
A Y-encoded subunit of the translation initiation factor Eif2 is essential for mouse spermatogenesis
Authors: Sophie Mazeyrat, Noëmie Saut, Vladimir Grigoriev, Shantha K. Mahadevaiah, Obah A. Ojarikre, Áine Rattigan, Colin Bishop, Eva M. Eicher, Michael J. Mitchell, Paul S. Burgoyne
Journal: Nature Genetics (2001)