tbuckley/cabot-search huggingface dataset:
541. Mechanisms of Adenovirus Vector Gene Delivery to the Inner Ear
Authors: Susan S. Tom, Bruce A. Bunnell
Journal: Molecular Therapy (2004)

Top of pageAbstract
Sandhoff Disease, SD, is an autosomal recessive metabolic disorder that manifests in degeneration of nervous system function. The progressive loss in sensory and cognition has been linked to defects in the β subunit of the dimeric isoenzyme, β-Hexosaminidase. A mouse model for SD was previously generated by targeted gene knockout of the β subunit. The model is excellent for studying gene therapy approaches to treat SD. The current study used an HIV-1 retroviral vector to deliver a functional human Hexb gene to cultured Hexb(-/-) mouse fibroblast. Assays for β-Hexosaminidase activity on the transfected Hexb(-/-) fibroblast were positive, demonstrating that HIV-1 mediated Hexb delivery is feasible. Based on these results, HIV-1 vectors will be incorporated into future in utero gene transfer approaches for Sandhoff Disease.
Antibacterial prescribing and antibacterial resistance in English general practice: cross sectional study Commentary: antibiotic resistance is a dynamic process
Authors: P. Priest, P. Yudkin, C. McNulty, D. Mant, R. Wise
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To quantify the relation between community based antibacterial prescribing and antibacterial resistance in community acquired disease. <b>Design:</b> Cross sectional study of antibacterial prescribing and antibacterial resistance of routine isolates within individual practices and primary care groups. <b>Setting:</b> 405 general practices (38 groups) in south west and north west England. <b>Main outcome measures:</b> Correlation between antibacterial prescribing and resistance for urinary coliforms and <i>Streptococcus pneumoniae</i>. <b>Results:</b> Antibacterial resistance in urinary coliform isolates is common but the correlation with prescribing rates was relatively low for individual practices (ampicillin and amoxicillin <i>r<sub>s</sub></i>=0.20, P=0.001; trimethoprim <i>r<sub>s</sub></i>=0.24, P=0.0001) and primary care groups (ampicillin and amoxicillin <i>r<sub>s</sub></i>=0.44, P=0.05; trimethoprim <i>r<sub>s</sub></i>=0.31, P=0.09). Regression coefficients were also low; a practice prescribing 20% less ampicillin and amoxicillin than average would have about 1% fewer resistant isolates (0.94/100; 95% confidence interval 0.02 to 1.85). Resistance of <i>S pneumoniae</i> to both penicillin and erythromycin remains uncommon, and no clear relation with prescribing was found. <b>Conclusions:</b> Routine microbiological isolates should not be used for surveillance of antibacterial resistance in the community or for monitoring the outcome of any change in antibacterial prescribing by general practitioners. Trying to reduce the overall level of antibiotic prescribing in UK general practice may not be the most effective strategy for reducing resistance in the community. <h3>What is already known on this topic</h3> The probability of an individual hosting a resistant organism is increased by recent use of an antibacterial drug Correlation between antibacterial prescribing and coliform resistance in routine microbiological samples from the community has been reported in one study <h3>What this study adds</h3> In English general practice, there are significant but low correlations between antibacterial prescribing and resistance in routine isolates of urinary coliforms Substantial differences in prescribing between high and low prescribing practices are associated with only small differences in resistance Improved methods of assessing national antimicrobial resistance are required
375. The Function of F12-Vif Mutant in the Context of APOBEC3G/Vif Model
Authors: Giuliana Vallanti, Rossella Lupo, Maurizio Federico, Fulvio Mavilio, Chiara Bovolenta
Journal: Molecular Therapy (2004)

Viral infectivity factor (Vif) is required for high HIV-1 infectivity in non-permissive cells, which include the natural targets of HIV-1, whereas it is dispensable in several cell lines called permissive. This requirement depends on the ability of Vif to counteract the action of the cellular inhibitor APOBEC3G, whose expression is restricted to non-permissive cells. APOBEC3G is a cytidine deaminase which is incorporated, in the absence of Vif, into viral particles and induces massive G-to-A hyper mutation in the nascent plus strand cDNA during reverse transcription in new target cells. Vif overcomes the action of APOBEC3G by inducing, without the need of any other viral components, its proteasome-dependent degradation. We have constructed, in the context of a potential new approach of anti-HIV-1 gene therapy, a second generation, VSV-G pseudo-typed lentiviral vector carrying the F12-vif gene, which is transcriptionally regulated by the HIV 5 LTR. F12-Vif derives from the natural variant F12-HIV provirus, which confers homologous interference to HIV-1 super-infection. We have transduced several T cell lines and primary T lymphocytes with F12-vif and WT-vif vectors and then challenged them with either CCR5 or CXCR4 HIV-1 strains. Here, we show that the level of p24 Ag released in the culture medium of infected cells is 5 logs lower in cells expressing F12-Vif, compared to the mock transduced and the control WT-Vif expressing cells. To understand whether F12-Vif inhibits HIV-1 replication in a dominant negative fashion, we have infected with Δvif HIV-1 non-permissive cells, transduced with the Vif vectors. Of note, similarly to WT-Vif, F12-Vif rescues viral replication, suggesting that in the absence of WT-Vif, F12-Vif vicariates its function. Finally, to investigate whether F12-Vif interferes with APOBEC3G function, we have monitored the expression of endogenous APOBEC3G in transduced non-permissive cells infected with either wild type or Δvif HIV-1 strains. Results of this analysis will be presented.
Abstract 660: Pravastatin Ameliorates Hypoxia-Induced Pulmonary Arterial Hypertension Associated Through Down-regulation of Stromal Cell-Derived Factor-1 in Mice
Authors: Makoto Nakano, Kimio Satoh, Yoshihiro Fukumoto, Koichiro Sugimura, Jun Nawata, Jun Demachi, Akihiko Karibe, Yutaka Kagaya, Jun Watanabe, Kunio Shirato, Naoto Ishii, Kazuo Sugamura, Hiroaki Shimokawa
Journal: Circulation (2007)
Immunohistochemical expression of bone morphogenetic protein-2 in pilomatricoma
Authors: I. Kurokawa, K. Kusumoto, K. Bessho, Y. Okubo, H. Senzaki, A. Tsubura
Journal: British Journal of Dermatology (2000)

Background The mechanism of occurrence of calcification and ossification in pilomatricoma remains unclear. Objectives To elucidate the pathogenesis of calcification and ossification in pilomatricoma we examined the role of bone morphogenetic protein (BMP)‐2, which plays important parts in inducing ectopic bone formation both in vivo and in vitro. Methods Twenty cases of pilomatricoma were studied immunohistochemically using anti‐BMP‐2 monoclonal antibody. Results In normal skin, including hair follicles, there was no BMP‐2 expression. In all pilomatricomas, BMP‐2 was found exclusively in the cytoplasm of shadow cells but not in basophilic cells. In two cases of bone formation seen in pilomatricoma, osteoblasts in the periosteal area showed a strong positive reaction, while bone trabeculum (bone matrix) showed no reaction. Conclusions Our findings indicate that shadow cells positive for BMP‐2 may play an important part in generating bone formation in pilomatricoma.
Influence of Body Height on Pulsatile Arterial Hemodynamic Data 11Financial support for this study was provided by Groupe d’Etude Physiopathologie Insuffisance Renale, Fleury Mérogis and by Laboratoires Synthelabo, Meudon-La-Foret, France.
Authors: Harold Smulyan, Sylvain J. Marchais, Bruno Pannier, Alain P. Guerin, Michel E. Safar, Gérard M. London
Journal: Journal of the American College of Cardiology (1998)
Bronchiolitis obliterans as a first manifestation of rheumatoid arthritis – Case report
Authors: Simona Luca, Victorita Mihaela Sandu
Journal: European Respiratory Journal (2011)

Introduction:  Rheumatoid arthritis (RA) is the most common connective tissue disease associated with bronchiolitis obliterans (OB). OB is a clinico-pathologic entity of bronchiolar inflammation which reflects the injury of the small airways and presents symptoms and signs of small airways obstruction. OB can go as a first manifestation of RA in 10–20% of patients.  Case presentation: A 37-year-old woman, non-smoker presented to our clinic accusing: MRC III dyspnea and bronchorrhea and suddenly it developed an obstructive lung disease without any reasonable explanation. Clinical, physiological and radiologic features suggested OB (squeaks and crackles on auscultation, functional evidence of OB). HRCT scan features consisted mostly of indirect signs of bronchiolitis, with a mosaic pattern reflecting air trapping, bronchial wall thickening, centrilobular emphysema,areas of ground-glass attenuation.  She also had extra-respiratory symptoms-asthenia and weight loss (5 percent in 2 months).  3 months after, she developed seropositive RA and a elevate serum rheumatoid factor was found, but with no clinical evidence of active rheumatological disease. All of these findings suggests that the OB was secondary to a rheumatoid process. Oral corticosteroids, associated with immunosuppressive treatment and inhaled bronchodilators was initiated, but without any clinical and functional improvement.   Conclusions:  This case is atypical since usually the diagnosis of RA precedes respiratory symptoms in 88% of cases. In our patient the bronchiolitis obliterans was the initial manifestation of rheumatoid arthritis, attributable to rheumatoid arthritis.
Abstract 2520: Novel inhibitors of β-catenin
Authors: Elmar Nurmemmedov, Anton Cheltsov, Peter K. Vogt
Journal: Cancer Research (2014)

Abstract β-catenin is a key player of the WNT pathway; its aberrant regulation is associated with the onset and progression of numerous types of cancer. β-catenin is therefore an attractive drug target but direct inhibition of β-catenin is a challenging approach toward suppression of β-catenin-driven tumorigenesis. Ideal drug candidates should specifically target nuclear β-catenin, leaving its cytoplasmic and cell junctional functions intact. We have identified several drug-like candidate β-catenin inhibitors using a robust screening method against four allosteric binding sites of β-catenin (TCF4, BCL9 and two novel sites). We show that these inhibitors significantly reduce proliferation of a panel of human β-catenin-driven cancer cell lines, and repress the expression of β-catenin-induced target genes. They cause a shift in the melting temperature of the purified β-catenin protein. We also show that the candidate compounds reduce levels of β-catenin in the nucleus and block β-catenin-driven oncogenic transformation in cell culture. We consider these novel β-catenin inhibitors promising leads that should be further investigated for their molecular mechanism of action and for their potential development as therapeutic drugs. Key words: β-catenin, oncogene, therapeutic, target, small molecule, protein-protein interaction This work was supported by NIH Grant R01 CA078230. This is abstract 26043 of The Scripps Research Institute. Citation Format: Elmar Nurmemmedov, Anton Cheltsov, Peter K. Vogt. Novel inhibitors of β-catenin. [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 2520. doi:10.1158/1538-7445.AM2014-2520
Ultrasound biomicroscopic and conventional ultrasonographic study of ocular dimensions in primary angle-closure glaucoma11Conducted on behalf of the Regional Council of the Veneto Region, Finalized Health Research, Venice, Italy.
Authors: Giorgio Marchini, Andrea Pagliarusco, Andrea Toscano, Roberto Tosi, Chiara Brunelli, Luciano Bonomi
Journal: Ophthalmology (1998)
Abstract 12149: Impact of Elevated Cardiac Troponin and Increased Fibrosis on Clinical Manifestations in Hypertrophic Cardiomyopathy
Authors: Takashi Nakamura
Journal: Circulation (2014)

Introduction: Recently, in patients with hypertrophic cardiomyopathy (HCM), an abnormal serum concentration of cardiac troponin (cTn), which is a sensitive marker of myocyte injury, was reported to be an independent predictor of the adverse outcome. In addition, late gadolinium-enhancement (LGE) cardiac magnetic resonance (CMR) imaging, which has been used to uniquely characterize the extent of myocardial fibrosis, has prognostic value in HCM. However, the relationship between myocyte injury, fibrosis, and clinical events/manifestations remains unclear. Hypothesis: A combined analysis using cTn and LGE by CMR may help to identify the clinical events/manifestations in patients with HCM. Methods: Eighty-seven HCM patients receiving regular outpatient treatment underwent CMR (cine and LGE imaging). LV myocardial fibrosis mass index (FMI) was quantified and the distribution/pattern of LGE was analyzed using 17 segment model. Serum cTnI was measured within a week around CMR testing. cTnI elevation was defined as ≥ 0.05ng/mL. Clinical events were defined as heart failure (HF) admission, ventricular tachycardia (VT), atrial fibrillation, and syncope. Results: In total patients, mean age was 65.7 ± 15.0 years old and female patients were 41.4%. HF and VT events were observed in 22 (25%) and 16 (18%) patients, respectively. Both elevated cTnI and higher FMI were associated with the combined clinical events (P&lt;0.01 and P&lt;0.05, respectively). Elevated cTnI was associated not with HF (P=0.06), but with VT (P&lt;0.001). In contrast, higher FMI was associated with HF (P=0.01), but not with VT (P=0.67). A grouping according to both cTnI and FMI showed the good stratification for clinical events as shown in the figure. Conclusions: In HCM patients, both cTn and FMI were significant markers for clinical events in HCM patients. In particular, elevated cTn was strongly associated with VT. Combined analysis of cTn and CMR may be useful in clinical practice for HCM.
Abstract #LB-160: CXCR4 antagonist as a sensitizing agent for anti-tumor therapies in disseminated lymphoma models
Authors: Yanping Hu, Matthew Gale, Jacqueline Shields, Gary Jacques, Robert Fogle, Carrie Garron, Johanne Kaplan, William Siders
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

CXCR4 is a chemokine receptor frequently over-expressed on hematological cancers and solid tumors. CXCR4 plays an important role in cancer metastasis, regulation of stem cell trafficking and neovascularization. The human B-lymphoma cell lines Raji and B-104 express high levels of human CXCR4 as well as CD52 and CD20, the targets of the monoclonal antibodies Campath and Rituxan, respectively. We hypothesized that the small molecule CXCR4 antagonists AMD3465 and AMD3100 could compromise tumor cell growth by inhibiting the survival signals delivered through the interaction of CXCR4 and SDF-1 in the tumor stroma and increase the susceptibility of the tumor cells to the cytotoxic effects of monoclonal antibody therapy. Lymphoma cells were seeded by intravenous injection and tumor-bearing mice were treated with multiple injections of AMD3465 or AMD3100. Interestingly, treatment with AMD3465 as a single agent was sufficient to increase survival of the animals compared to untreated controls. In addition, the combination of AMD3465 and Campath showed a synergistic effect with a prolongation of survival greater than that obtained with either agent alone. Similarly, combination of the CXCR4 antagonist AMD3100 and Rituxan also resulted in a significantly prolonged survival compared to either agent alone. The impact of treatment on tumor burden was confirmed by Xenogen imaging. These results suggest that there is a potential role for CXCR4 antagonists in combination with a B-cell targeted therapy in the treatment of B-cell malignancies.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-160.
Abstract 16096: The Relationship between Global Longitudinal Strain from Novel Feature Tracking MRI Strain and Echo Strain: Comparison against Ejection Fraction and Scar
Authors: Kazuaki Negishi, Deborah H Kwon, Aderonke Adeniyi, Quasai Selah, Neil L Greenberg, Thomas H Marwick
Journal: Circulation (2012)

Background: Global longitudinal strain (GLS) has prognostic value in pts with suspected LV impairment. MRI strain has traditionally been assessed by tagging, but recent feature tracking software ha...
Overcoming the problem: Take a lodger
Authors: E. O Parbrook
Journal: BMJ (1999)

Dear Amelia, I did enjoy Joe's retirement party and I was honoured that, as your godmother, you have written for advice on your pension position.

You should not have got upset with Joe when he told you that you would be punished if he died first and you decided to take a boyfriend. He was only quoting the official line which states that he must tell his wife that the pensions of doctors' widows are forfeit if the widow remarries or cohabits. A senior pension expert told me that these rules were produced in 1948 when there were few women members of parliament and when in financial and legal matters a wife was regarded as part of the goods and chattels of the husband.

Of course, you are puzzled by the contrary advice we had from Professor Roy …
New developments in the diagnosis and treatment of thyroid cancer
Authors: David F. Schneider, Herbert Chen
Journal: CA A Cancer Journal for Clinicians (2013)

Answer questions and earn CME/CNE Thyroid cancer exists in several forms. Differentiated thyroid cancers include those with papillary and follicular histologies. These tumors exist along a spectrum of differentiation, and their incidence continues to climb. A number of advances in the diagnosis and treatment of differentiated thyroid cancers now exist. These include molecular diagnostics and more advanced strategies for risk stratification. Medullary cancer arises from the parafollicular cells and not the follicular cells. Therefore, diagnosis and treatment differs from those of differentiated thyroid tumors. Genetic testing and newer adjuvant therapies have changed the diagnosis and treatment of medullary thyroid cancer. This review will focus on the epidemiology, diagnosis, workup, and treatment of both differentiated and medullary thyroid cancers, focusing specifically on newer developments in the field. CA Cancer J Clin 2013;63:373‐394. © 2013 American Cancer Society, Inc.
Percutaneous Coronary Intervention versus Coronary-Artery Bypass Grafting
Authors: Jonathan L Edwards
Journal: New England Journal of Medicine (2009)

To the Editor: With regard to the results of the SYNTAX (Synergy between PCI [percutaneous coronary intervention] with Taxus and Cardiac Surgery) study (ClinicalTrials.gov number, NCT00114972) reported by Serruys et al. (March 5 issue),1 we wish to highlight a few factors that require clarification and may influence the differences observed between the study groups. The timing of strokes and rates of atrial fibrillation are not reported. These data, in combination with the differences in pharmacologic therapies between cohorts, may account for the excess number of strokes seen in the coronary-artery bypass grafting (CABG) cohort. Clarification of the timing of strokes may help to explain whether they were thromboembolic or due to surgical handling of the aorta. Furthermore, the range and influence of PCI strategies, including the use of adjuvant intravascular ultrasonography adopted by the investigators for complex lesions, are not reported; these factors could have affected restenosis rates. Ravinay Bhindi, M.D., Ph.D. Gemma A. Figtree, M.D., D.Phil.
Equine Influenza Jumps to Canines
Authors: Tracy Hampton
Journal: JAMA (2005)

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Abstract 17329: Prognostic Value of Coronary Flow Reserve in Patients with Prior Coronary Artery Bypass Surgery
Authors: Takashi Kato, Vikas Veeranna, Nishant R Shah, Viviany R Taqueti, Venkatesh L Murthy, Courtney R Foster, Mariya Gaber, Jon Hainer, Josh Klein, Sharmila Dorbala, Ron Blankstein, Marcelo F DiCarli
Journal: Circulation (2014)

Introduction: Although abnormal coronary flow reserve (CFR) is frequently seen after coronary artery bypass graft (CABG) surgery, little is known about its association with clinical outcomes.

Hypothesis: We tested the hypothesis that CFR quantification will provide improved risk stratification in patients with prior CABG.

Methods: We studied 567 consecutive patients (73.5% male; age 73 ± 11 years) undergoing PET myocardial perfusion imaging (MPI) for evaluation of chest pain and/or dyspnea after CABG from 2006 to 2013. The median time between first CABG and PET MPI was 9.9 years, and 45 patients underwent redo CABG before PET study. Ischemia + Scar score was calculated by dividing summed stress score by 68 and multiplying by 100 to obtain a percentage. Rest and stress myocardial blood flow (MBF, in mL/min/g) were quantified, and CFR was calculated as stress/rest MBF. Primary and secondary endpoints were defined as all cause death, and all cause death plus non-fatal myocardial infarction (MI), respectively. Cox proportional hazards model were used to evaluate the association of CFR and outcomes.

Results: The mean CFR was 1.56 ± 0.56. During a median follow up of 2.4 years, 146 deaths and 43 non-fatal MI occurred. The annualized death rate increased with increasing levels of LV ischemia+scar score on PET MPI, and it was highest with each worsening groups of CFR (Figure). In survival analysis adjusting for clinical risk score (Morise), a history of MI, time from CABG, LV ischemia+scar score, and rest LVEF, higher CFR was associated with lower primary (hazard ratio [HR]: 0.93 [95% CI: 0.90 - 0.97] per 0.1 unit increase, p < 0.001) and secondary endpoints (HR: 0.94, [95% CI: 0.91 - 0.97] per 0.1 unit increase, p < 0.001).

Conclusions: Coronary flow reserve measurements, as measured by PET MPI, provide improved risk stratification in patients with prior CABG.

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