tbuckley/cabot-search huggingface dataset:
Sebaceous lipogenesis in human skin.
Authors: MARY F. COOPER, HELEN McGRATH, SAM SHUSTER
Journal: British Journal of Dermatology (1976)

Lipogenesis from [14C] glucose was measured in skin biopsies from the shoulder-blade region of forty-two male subjects. In the acne age range, dermal lipogenesis showed an upward trend with increasing severity of acne; a similar trend was found in forehead sebum excretion rate, but no correlation was obvious between dermal lipogenesis (back) and sebum secretion rate (forehead) in the same subject. In older subjects, dermal lipogenesis was significantly increased in those with a past history of severe acne. At high rates of dermal lipogenesis there was a small but significant increase in wax ester labelling relative to triglyceride and squalene. No increase was found in squalene labelling relative to other lipids, either with increasing lipogenic rate or in severe acne. Dermal and epidermal lipogenesis rates showed no correlation with age. In dermis, however, there was a decrease in wax ester labelling relative to triglyceride, and a marked decrease in squalene labelling relative to both triglyceride and wax esters, with increasing age.
Intraocular lens implants
Authors: B. Allan
Journal: BMJ (2000)

Just over 50 years ago Harold Ridley implanted the first intraocular lens.1 Artificial lens implants have since revolutionised cataract surgery. In 2000 foldable intraocular lenses with a 6 mm lens optic can be delivered through a self sealing 3.2 mm valve incision. Sutured closure is not normally required, the strength of the eye wall is not diminished,2 and the refractive power of the lens can be tailored to minimise the postoperative requirement for glasses. In the absence of comorbidity, most patients can expect to see the driving standard or better without spectacle correction from the day after surgery. Though lens surgery has come a long way, development continues and access to the best new intraocular lens technology needs to be widened.

Ridley was ahead of his time. Developments in lens design and surgical technique were required to make intraocular lens implantation safe, so lens implantation did not become widely adopted as an integral part of cataract surgery until the 1980s. Key advances were the introduction of viscoelastic fluids to …
Abstract 10956: In-vivo Tracking of Mononuclear Cells for Therapeutic Neovascularization in Myocardial Infarction: Comparison Between Manganese-Enhanced Magnetic Resonance Imaging and Single Photon Emission Computed Tomography
Authors: Junji Moriya, Ichio Aoki, Kenichi Odaka, Kaoru Tateno, Hiroyuki Tadokoro, Jeff Kershaw, Tatsuya Kikuchi, Toshimitsu Fukumura, Tohru Minamino, Iwao Kanno, Issei Komuro
Journal: Circulation (2010)

Autologous transplantation of bone marrow or peripheral blood mononuclear-cells (MNCs) has been applied as a strategy for therapeutic angiogenesis after limb ischemia and myocardial infarction. In vivo tracking of MNCs with magnetic resonance imaging (MRI) has attempted to visualize the long term regenerative therapeutic effects and the localization of migrated cells at high spatial resolution in living tissues such as skeletal muscle, heart, and brain. Manganese (Mn2+) is known to be an essential element for living organisms and there has been a recent renewed interest in Mn2+ as a useful ‘positive' MRI contrast agent. We successfully established a Methods to label MNCs with Mn2+ (Mn-MNCs) and performed longitudinal observation of Mn-MNCs in a rat model of myocardial infarction with 7-tesla MRI. Mn-MNCs or saline were intramuscularly injected into a border zone of the ischemic myocardium and were evaluated once a week by T1-weighted imaging. We also injected MNCs labeled with 111-indium oxine (111In-MNCs...
Autophagy precedes caspase-independent cell death in chemo-resistant ovarian cancer cells
Authors: Ayesha Alvero, Michele Montagna, Ki Hyung Kim, Gil Mor
Journal: Cancer Research (2007)

3216   Introduction: The role of autophagy in cancer is controversial. Initially autophagy was thought to represent an alternative pathway for cell death. However, more recently it has been suggested to play a role in tumor survival. In this study we describe how the induction of autophagy by a novel isoflavone derivative, NV128, induce cell death in chemo-resistant ovarian cancer cells. Methods: Eight primary cultures and two established epithelial ovarian cancer (EOC) cell lines were treated with increasing concentrations of NV128 (0.1, 1, and 10 ug/ml) with or without the pan-caspase inhibitor, Z-VAD-FMK. Cell viability was determined after 24h using the Celltiter 96 assay. DNA fragmentation was analyzed by flow cytometry with Hoechst and Propidium iodide staining. Activity of caspases- 3/7, -8, and -9 was measured using Caspase-Glo assay. Autophagic markers LC3-II and Beclin-1 was determined by Western blot analysis. Results: NV128 treatment decreased cell viability in all tested EOC cells lines in a dose-dependent manner with IC50 between 1 and 5 ug/ml. Flow cytometry analysis revealed DNA fragmentation, with Hoechst and Propidium iodide double-positive cells increasing 2-4 fold after NV128 treatment. However, cell death was caspase independent as evidenced by the lack of caspases- 3/7, -8, and -9 activity and the inability of the caspase inhibitor, Z-VAD-FMK, to prevent cell death. Western blot analysis of autophagic markers showed early involvement of LC3-II and Beclin-1. Conclusion: We demonstrate that induction of autophagy by NV128 in chemo-resistant ovarian cancer cells is able to promote caspase- independent cell death. Our results suggest that the autophagic pathway can be an alternative target in EOC cells, especially those that are highly resistant to apoptosis.
Abstract 3631: Elevated In-hospital Glucose Level, and not Known History of Diabetes Mellitus, Predicts 30-day Mortality Following Acute ST-elevation Myocardial Infarction
Authors: Abhinav Goyal, Rafael Diaz, Hertzel C Gerstein, Rizwan Afzal, Shamir R Mehta, Denis Xavier, Jun Zhu, Prem Pais, Liu Lisheng, Khawar A Kazmi, Mohammad Zubaid, Leopoldo S Piegas, Petr Widimsky, Salim Yusuf
Journal: Circulation (2007)

Introduction: According to clinical risk assessment guidelines, a history of diabetes mellitus (DM) portends poor outcomes following acute MI. Elevated in-hospital glucose levels also predict early mortality in acute MI patients, but the degree to which glucose levels and diabetic history independently predict post-MI mortality is unclear. Methods and Hypothesis: We analyzed data from the combined cohort of the CREATE-ECLA and OASIS-6 randomized trials that evaluated the impact of glucose-insulin-potassium (GIK) infusion versus no infusion on 30-day mortality in 22,943 patients hospitalized with acute ST-elevation MI. We calculated the average in-hospital glucose level for each patient (mean of the admission, 6-hour, and 24-hour glucose levels). Logistic regression was performed to determine whether average glucose level and history of DM remained significant mortality predictors after adjusting for age, sex, and GIK allocation. Results: Glucose data were recorded in 22,860 (99.6%) patients; 10,050 (44%) had an average in-hospital glucose level ≥ 8 mmol/L (144 mg/dL), of whom 65% did not have known prior DM. Among patients with glucose &gt;8 mmol/L, 30-day mortality rates were similar in patients with and without known DM (Figure ). In-hospital glucose, but not history of DM, was a significant multivariable predictor of mortality (Table). Conclusions: By considering only history of DM and not in-hospital glucose levels, risk assessment guidelines for acute MI overlook a large proportion of patients at high risk for early death. Therefore, clinicians should emphasize elevated glucose levels in addition to history of DM as a risk marker in patients with acute MI.
Abstract 19757: Severity of Renal Artery Stenosis Predicts Baseline and Residual Renal Function In Patients Undergoing Renal Artery Stenting
Authors: Haifeng Yu, Dong Zhang, Khalil Kanjwal, Satjit Adalakha, William R Colyer, Pamela S Brewster, Mark W Burket, Joseph I Shapiro, Michael Steffes, Christopher J Cooper
Journal: Circulation (2010)
383. Cloning of the Minimal Functional Domain of Human Lim Mineralization Protein-3 Able To Induce Bone Mineralization: In Vitro and In Vivo Study
Authors: Enrico Pola, Wanda Lattanzi, Wentao Go, Huijie Sun, Kaori Okada, Andrea Gambotto, Carlo A. Logroscino, Paul D. Robbins
Journal: Molecular Therapy (2004)

Human LIM mineralization protein (LMP)-3 is one of the three splice variants of LMP recently identified. LMPs are involved in the osteoblast differentiation program and structurally characterized by the two conserved LIM and PDZ domains. Human LMP-1 (hLMP-1) shows one N-terminal PDZ domain and three C-term LIM domains connected by a non-conserved “Unique” region, deleted in the hLMP-2. hLMP-3 misses almost completely the LIM domains along with part of the unique region, due to a frame shift mutation. The three isoforms are expressed almost ubiquitously but show quantitative differences, hLMP-3 being the less expressed in all the analyzed tissues. Both hLMP-1 and hLMP-3 has been demonstrated to induce bone formation in vitro and ectopic bone formation in vivo, while hLMP-2 is not osteoinductive, suggesting that LIM domains are not essential for this function. Thus it has been hypothesized that the osteoinductive domain could reside in the “Unique” region that is partially conserved in hLMP-3. To examine the osteoinductive properties of this minimal domain we have cloned three different length of the Unique region of the hLMP-3 gene, corresponding to 120, 90 and 60 bp, fused to the enhanced green fluorescent protein (eGFP) and named L40-eGFP, L30-eGFP and L20-eGFP respectively. Thus we tested the ability of these constructs to induce bone specific gene expression and bone mineralization in vitro and ectopic bone formation in vivo in comparison to the full-length gene hLMP-3. Here we demonstrate that adenoviral-mediated gene transfer of all the 3 domains induces expression of certain bone-specific genes in a mouse fibroblasts cell line. The up-regulation of osteo-specific genes was assessed in mouse fibroblasts also by means of biolistic transfection using a plasmid containing a L20-eGFP fusion gene. In addition, we demonstrate that all the domains are able to induce mineralization in fibroblast and mesenchymal stem cells. An experiment to evaluate if direct gene transfer of the three constructs into murine skeletal muscle results in ectopic bone formation as efficiently as using LMP-3 is being performed. Finally in order to propose these new constructs as an effective approach to induce bone formation in vivo for clinical applications, we have synthesized a peptide of 20 aminoacid, corresponding to the fragment of 60 bp of the Unique region (named PTD-OD-1). The peptide enter the cells by a protein transduction domain (PTD-5) and its ability to induce in vitro expression of bone-specific genes and bone mineralization both in fibroblast and in human mesenchymal stem cells will be evaluated. PTD-OD-1 could represent a safe and powerful tool for clinical applications, and merit several analysis to evaluate its ability.
M. fortuitum and M. chelonei—fast growing mycobacteria.
Authors: JOANNA M. WARD
Journal: British Journal of Dermatology (1975)

Infection due to opportunist mycobacteria is considered in general and that due to the fast growing mycobacteria in particular. This group is now seen to contain two facultative pathogens, M. fortuitum and M. chelonei (abscessus), all other synonyms for these two species having been shown to be invalid. Both organisms are ubiquitous and normally harmless; however, following injury or injection, they may cause chronic sub‐cutaneous abscesses. Pulmonary lesions have also been described. More recently M. fortuitum has been found to cause osteomyelitis and corneal ulceration and both organisms have been identified in cases of septicaemia associated with renal dialysis. In the past M. chelonei may have been identified as M. fortuitum but although it is more difficult to isolate, it may in fact be the more common cause of disease. A case is reported of an English girl who received a small injury to her shin in Spain. The initial lesion failed to heal and for 18 months there was repeated formation of small sinuses in the area. Healing then occurred spontaneously. Histology showed a chronic granuloma and on two occasions a rapid growing mycobacteria resistant to all antibiotics was isolated. This was initially identified as M. fortuitum but finally as M. chelonei and the latter diagnosis was confirmed by differential skin tests. Difficulties in interpretation of these tests are discussed.
HIV/STD Risk Reduction Interventions for African American and Latino Adolescent Girls at an Adolescent Medicine Clinic
Authors: Jemmott Jb d, Jemmott Ls, Braverman Pk, Fong Gt
Journal: JAMA Pediatrics (2005)

Background: Adolescent girls in the United States and around the world are at a heightened risk for sexually transmitted diseases (STDs) including human immunodeficiency virus (HIV). Objective: To determine the efficacy of a skill-based HIV/STD risk-reduction intervention in reducing self-reported unprotected sexual intercourse among African American and Latino adolescent girls. Design: Randomized controlled trial with 3- 6- and 12-month follow-ups. Setting and Participants: Sexually experienced African American and Latino adolescent girls recruited from the adolescent medicine clinic of a children’s hospital serving a low-income inner-city community (N = 682 mean age 15.5 years); 88.6% were retained at the 12-month follow-up. Interventions: Three 250-minute interventions based on cognitive-behavioral theories and elicitation research: an information-based HIV/STD intervention provided information necessary to practice safer sex; a skill-based HIV/STD intervention provided information and taught skills necessary to practice safer sex; or a health-promotion control intervention concerned with health issues unrelated to sexual behavior. Main Outcome Measures: Primary outcome measure was self-reported frequency of unprotected sexual intercourse; secondary outcomes included the frequency of sexual intercourse while intoxicated the number of sexual partners biologically confirmed STDs and theoretical mediator variables including the intention to use condoms beliefs about using condoms and condom- use knowledge. Results: No differences between the information intervention and the health control intervention were statistically significant. Skills-intervention participants (mean [SE] 2.27 [0.81]) reported less unprotected sexual intercourse at the 12-month follow-up than did information intervention participants (mean [SE] 4.04 [0.80]; P = .03) or health control-intervention participants (mean [SE] 5.05 [0.81]; P = .002). At the 12-month follow-up skills-intervention participants (mean [SE] 0.91 [0.05]) reported fewer sexual partners (P = .04) compared with health control-intervention participants (mean [SE] 1.04 [0.05]) and were less likely to test positive for STD (mean [SE] 10.5% [2.9%]) than were health control-intervention participants (mean [SE] 18.2% [2.8%]; P = .05). No differences in the frequency of unprotected sexual intercourse the number of partners or the rate of STD were observed at the 3- or 6-month follow-up between skill-intervention participants and information- intervention or health control-intervention participants. Conclusion: Skill- based HIV/STD interventions can reduce sexual risk behaviors and STD rate among African American and Latino adolescent girls in clinic settings. (authors)
Organ cooling in liver transplantation and resection: How low should we go?
Authors: Rowan F. van Golen, Megan J. Reiniers, Thomas M. van Gulik, Michal Heger
Journal: Hepatology (2014)

The realization of long-term human organ preservation will have groundbreaking effects on the current practice of transplantation. Herein we present a new technique based on subzero nonfreezing preservation and extracorporeal machine perfusion that allows transplantation of rat livers preserved for up to four days, thereby tripling the viable preservation duration. (Reprinted with permission)
367. Development of Lentiviral Vectors Carrying shRNA, Ribozyme and RNA Decoy for the Inhibition of HIV-1 Infection
Authors: Ming-Jie Li, James Kim, Shirley Li, John Zaia, Jiing-Kuan Yee, John J. Rossi
Journal: Molecular Therapy (2004)

The replication-defective lentiviral vectors are able to transduce a wide array of quiescent cell types with sustained long-term expression of the genes within the vector backbone. These properties make them favorable vectors for anti-HIV-1 therapeutic gene delivery. The recently discovered small interfering RNA(siRNA) mediated RNA interference provides a powerful new tool for gene silencing in a sequence specific manner, which suggest the potential of siRNAs for gene therapy application. A stable expression system of siRNAs and the efficient delivery vehicle of lentiviral vectors would prove an excellent match as a powerful gene therapy tool. We have developed lentiviral vectors expressing U6 pol III promoter-driven short hairpin RNAs (shRNAs) targeting the rev and tat mRNAs of HIV-1. Utilizing these shRNAs we have achieved potent inhibition of HIV-1 replication in primary cells. Up to date, the majority of HIV-1 gene therapy protocols target a single therapeutic gene. Like any therapeutic approach for inhibition of HIV infection, gene therapy is also faced with the problem of development of viral variants that are resistant to therapeutic agents. We hypothesize that if a combination of therapeutic genes targeting different viral products and steps in the viral life cycle is used, the probability of viral escape mutants will be greatly reduced. Furthermore, there is the possibility of synergy between the different gene therapy agents. Previously, we created the pol III expressing cassettes expressing an anti-CCR5 ribozyme or a nucleolar localizing TAR decoy and cloned them into a self-inactivating lentiviral vector. Each of the constructs showed marked anti-HIV-1 activities. In this study, we combined the shRNAs with the ribozyme or the RNA decoy, or all three constructs into a single vector backbone. Each of these therapeutic RNAs targets a different gene and blocks HIV infection by a distinct mechanism. After transduction with the vectors and infection with HIV-1, a potential synergistic effect was apparent in CD34+ hematopoietic stem cells and primary T cells. We have also developed the vectors expressing only the various therapeutic genes but excluding the reporter gene and WPRE sequence to eliminate any elements that potentially interfere with the expression of the therapeutic genes or have adverse effects on target cells. Our long-term goal is to develop vectors suitable for human gene therapy.
Therapeutic Electricity and Ultraviolet Radiation.
Authors: Sidney Herman Licht
Journal: Annals of Internal Medicine (1960)

Electrotherapy. By Arthur L. Watkins, M.D. Price, $5. Pp. 259, with 167 illustrations. Lea & Febiger, 600 S. Washington Sq., Philadelphia, 1958. This book is basically a revision and condensation of Dr. Richard Kovacs' large textbook Electrotherapy and Light Therapy, with the addition of a section describing the use of ultrasonics in physical medicine. Many of the outdated sections have either been completely omitted or radically revised. In some instances, the original was not sufficiently modified to comply with present clinical practices. For example, the large electric heat cabinet for general body radiation is rarely, if ever, medically indicated according to current trends, although, obviously, certain patients feel more relaxed following such a session; the same effect can usually be accomplished more efficiently by other physical or pharmacologic means. The title, A Manual of Electrotherapy, is somewhat misleading, since there is a chapter
Differentiation-dependent expression of sialyl stage-specific embryonic antigen-1 and I-antigens on human lymphoid cells and its implications for carbohydrate-mediated adhesion to vascular endothelium
Authors: K Ohmori, A Takada, T Yoneda, Y Buma, K Hirashima, K Tsuyuoka, A Hasegawa, R Kannagi
Journal: Blood (1993)
Characteristics of patients newly prescribed a long acting bronchodilator in the United Kingdom (UK)
Authors: Sarah Landis, Keele Wurst, Hoa Le, Hana Muellerova, Kourtney Davis
Journal: European Respiratory Journal (2014)

Objective: Characterize patients newly prescribed long acting bronchodilator (LABD) monotherapy for maintenance treatment of COPD and assess treatment changes over 24 months.

Methods: Retrospective cohort of COPD patients aged ≥40yrs and newly prescribed long acting beta-agonists (LABA) or long acting muscarinic (LAMA) monotherapy between 1/1/2009-30/11/2012 identified from UK Clinical Practice Research Datalink and followed for up to 24 months. New use defined as no LABD or inhaled corticosteroid use in 12 months prior to or at initial prescription. Patient characteristics, treatment patterns, and adherence (medication possession ratio [MPR]) examined during 24 months follow-up.

Results: 5,267 COPD patients newly prescribed LAMA (83%) or LABA (17%) monotherapy; mean age 70 years, 56% male. At 24 months, adherence (MPR ≥80%) to initially prescribed therapy was higher for LAMA (43%) compared to LABA (36%).

View this table:

Treatment pattern over 24 months after LAMA or LABA monotherapy





Conclusion: In this UK COPD cohort, less than half of patients adhered to LABD monotherapy; many discontinued treatment. At 24 months, one in three patients initally prescribed LAMA added medication, suggesting additional or alternative therapy may be required to achieve optimal disease control in some patients.
743. Study of Lentiviral Vectors with Two Marker Genes Driven by Two Independent Promoters for Gene Transfer Applications
Authors: Marilyne Dijon, Christian Chabannon, Caroline Torne-Celer
Journal: Molecular Therapy (2004)

Recombinant lentiviruses are widely used vectors for in vitro and in vivo long term gene transfer. Many of the initial gene transfer studies were conducted using single reporter genes. However, for many gene delivery applications, expression and detection of two genes are useful. The goal of this study is to explore the feasibility of directing the independent expression of two marker genes from a single lentiviral vector derived from HIV-1. We used the enhanced green fluorescent protein (EGFP) and the enhanced yellow fluorescent protein (EYFP). Because of spectral overlap of these fluorescent proteins, we modified a FACScalibur flow cytometer with insertion of Omega Optical filters. To coexpress independently two marker genes, we used two different promoter associations in lentiviral vectors. In a first strategy, EGFP transcription was driven by the EF1alpha promoter, and EYFP was translated from spliced RNA transcribed from the LTR promoter. In a second strategy, two internal promoters: EF1alpha and CMV were inserted in a SIN (Self Inactivating) vector.