tbuckley/cabot-search huggingface dataset:
Hybrid Lentiviral Vectors
Authors: Waseem Qasim, Conrad A Vink, Adrian J Thrasher
Journal: Molecular Therapy (2010)

Lentiviral vectors have remarkable cell entry and gene delivery properties that make them highly attractive for gene therapy. However, all integration-competent gene delivery systems have come under scrutiny for possible adverse insertional events. Circumventing the risk of insertional mutagenesis, integration-deficient human immunodeficiency virus (HIV)-1–derived vectors have been shown to support durable transcription of transgenes in certain nonmitotic cell lineages. In mitotic cell populations, such nonintegrated viral forms are lost during cell division and so have time-limited effects. Hybrid lentiviral vectors that harness the cell entry properties of HIV to facilitate carriage of alternative DNA modification systems into cells may allow durable genetic modification with more favorable integration profiles. Thus, systems, which have previously been plasmid-based such as those based on nuclease-enhanced homologous recombination (HR) and artificial transposons, have been incorporated into the viral genome to allow them to "hitch-hike" into cells that are difficult to transfect. Here, we review recent progress in the development of such hybrid lentiviral systems and consider potential applications of such vectors. Lentiviral vectors have remarkable cell entry and gene delivery properties that make them highly attractive for gene therapy. However, all integration-competent gene delivery systems have come under scrutiny for possible adverse insertional events. Circumventing the risk of insertional mutagenesis, integration-deficient human immunodeficiency virus (HIV)-1–derived vectors have been shown to support durable transcription of transgenes in certain nonmitotic cell lineages. In mitotic cell populations, such nonintegrated viral forms are lost during cell division and so have time-limited effects. Hybrid lentiviral vectors that harness the cell entry properties of HIV to facilitate carriage of alternative DNA modification systems into cells may allow durable genetic modification with more favorable integration profiles. Thus, systems, which have previously been plasmid-based such as those based on nuclease-enhanced homologous recombination (HR) and artificial transposons, have been incorporated into the viral genome to allow them to "hitch-hike" into cells that are difficult to transfect. Here, we review recent progress in the development of such hybrid lentiviral systems and consider potential applications of such vectors.
Successful use of acitretin in conjunction with narrowband ultraviolet B phototherapy in a child with severe pustular psoriasis, von Zumbusch type
Authors: T. Kopp, F. Karlhofer, Z. Szepfalusi, A. Schneeberger, G. Stingl, A. Tanew
Journal: British Journal of Dermatology (2004)

Journal Article Successful use of acitretin in conjunction with narrowband ultraviolet B phototherapy in a child with severe pustular psoriasis, von Zumbusch type Get access T. Kopp, T. Kopp Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Department of Paediatrics, Division of General Paediatrics Tamara Kopp. E‐mail: tamara.kopp@akh‐wien.ac.at Search for other works by this author on: Oxford Academic Google Scholar F. Karlhofer, F. Karlhofer Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Department of Paediatrics, Division of General Paediatrics Search for other works by this author on: Oxford Academic Google Scholar Z. Szépfalusi, Z. Szépfalusi Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Department of Paediatrics, Division of General Paediatrics Search for other works by this author on: Oxford Academic Google Scholar A. Schneeberger, A. Schneeberger Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Department of Paediatrics, Division of General Paediatrics Search for other works by this author on: Oxford Academic Google Scholar G. Stingl, G. Stingl Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Department of Paediatrics, Division of General Paediatrics Search for other works by this author on: Oxford Academic Google Scholar A. Tanew A. Tanew Division of Special and Environmental Dermatology, Vienna Medical University, Währinger Gürtel 18–20, A‐1090 Vienna, Austria Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 4, 1 October 2004, Pages 912–916, https://doi.org/10.1111/j.1365-2133.2004.06181.x Published: 01 October 2004 Article history Accepted: 28 March 2004 Published: 01 October 2004
Immunoassay of Glycoprotein in Gastric Cancer Secretion.
Authors: Emmanuel Deutsch
Journal: Annals of Internal Medicine (1969)

s1 May 1969Immunoassay of Glycoprotein in Gastric Cancer Secretion.Emmanuel Deutsch, M.D., F.A.C.P., Haruki Mori, M.D.Emmanuel Deutsch, M.D., F.A.C.P.Search for more papers by this author, Haruki Mori, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1105_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn the differentiation of benign from malignant ulcer of the stomach a gastric secretion protein, specific for human gastric cancer, would have great practical diagnostic value. When antisera are prepared against gastric cancer secretion, it is possible to make an antiserum by suitable absorptions which is highly specific for this lesion. An alpha-2 glycoprotein that migrates in the globulin range has been found on immunoelectrophoretic analysis in gastric secretion of patients with gastric carcinoma.Ninety-nine coded and randomized gastric juice specimens from patients with major lesions of the stomach were assayed against this absorbed antiserum. Of 18 known gastric cancer... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Emmanuel Deutsch, M.D., F.A.C.P.; Haruki Mori, M.D.Affiliations: Boston, Massachusetts PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1105-1106KeywordsGastric cancerGastric ulcersGlobulinsGlycoproteinsImmunoassaysImmunohistochemistryLesionsProteinsStomach ePublished: 1 December 2008 Issue Published: 1 May 1969 PDF downloadLoading ...
Dialysis arthropathy: amyloid or iron?
Authors: N R Cary, D Sethi, E A Brown, C C Erhardt, D F Woodrow, P E Gower
Journal: BMJ (1987)

The clinical, biochemical, radiological, and pathological features in five cases of dialysis arthropathy were analysed. All patients were receiving long term haemodialysis and had had multiple blood transfusions. The arthropathy affected both large and small joints, was predominantly bilateral, and in all cases was associated with the carpal tunnel syndrome. In some instances joint pain was exacerbated during dialysis. In four cases the serum ferritin concentration was raised. Radiological examination showed a few juxta-articular cysts and erosions but most affected joints looked normal. All synovial tissue examined showed amyloid, which stained immunohistochemically for beta 2 microglobulin. Large amounts of iron were present in synovial tissue from affected joints. It is suggested that the deposits of iron, rather than amyloid, in synovial tissue may be the cause of the arthropathy. Iron may be derived locally as a result of haemarthrosis or it may be a manifestation of systemic iron overload.
ASSESING CORONARY ARTERY DISEASE IN PATIENTS WITH ANGINAL CHEST PAIN AND LEFT BUNDLE BRANCH BLOCK &amp;ndash; AN EMERGING ROLE FOR A NEW PARAMETER OF CARDIOPULMONAR EXERCISE TESTING
Authors: Alberto Dominguez-Rodriguez, Eduardo Arroyo-Ucar, Maria Angeles Gomez, Maria del Carmen Garcia-Baute, Pedro Abreu-Gonzalez, Pablo Avanzas, Antonio Lara-Padron
Journal: Journal of the American College of Cardiology (2012)
428 Lamivudine-refractory hepatitis B patients can be safely switched directly to entecavir 1 mg daily therapy
Authors: R.G. Gish, T.T. Chang, S. Hadziyannis, J. Cianciara, M. Rizzetto, E. Schiff, G. Pastore, R. Jackson, A. Thiry, R. Hindes
Journal: Journal of Hepatology (2004)
Anaphylatoxin C3a enhances mucous glycoprotein release from human airways in vitro.
Authors: Z Marom, J Shelhamer, M Berger, M Frank, M Kaliner
Journal: The Journal of Experimental Medicine (1985)

Because C3a may be generated during the course of pulmonary inflammatory reactions, we investigated the ability of C3a to affect mucous glycoprotein (MGP) secretion from cultured human airways. C3a, but not C3a des Arg, caused a dose-related increase in MGP release (maximal after 4-6 h), with as little as 15 micrograms of C3a per milliliter stimulating a 40% increase. The experimental evidence suggested that immunologically specific C3a was required for the secretagogue actions, as monospecific anti-C3a inhibited the reaction, as well as specifically absorbing the secretagogue from solution. Moreover, it appeared that C3a does not require mast cell activation, eicosanoid generation, or macrophage-derived mucus secretagogue synthesis for its effect, since (a) no evidence of histamine release accompanied C3a-induced MGP release, and dibutyryl cAMP failed to affect C3a-induced MGP release, while reducing the actions of reversed anaphylaxis; (b) MGP release caused by C3a was not influenced by eicosatetraynoic acid or specific cyclooxygenase inhibitors, and no leukotrienes were detectable on the supernatants of C3a-stimulated airways; and (c) cycloheximide failed to affect C3a secretion-stimulating actions. Thus, C3a is a potent mucus secretagogue, and, possibly, acts directly as a glandular stimulant. It seems likely that C3a generated in the course of pulmonary inflammation might contribute to the mucus secretion associated with pulmonary infections.
Myocardial and Body Metabolism in Fatal Cardiogenic Shock after Valvular Replacement
Authors: EMERSON A. MOFFITT, GEORGE D. MOLNAR, DWIGHT C. MCGOON
Journal: Circulation (1971)

Cellular energy substrates and metabolites, electrolytes, oxygenation, and acid-base balance, in arterial and coronary sinus blood of seven adult patients who died after valvular replacements, were studied and compared with these measurements from five patients having aortic replacement who survived. Six of the patients were in New York Heart Association class IV. All but one died within 24 hr of acute circulatory failure, with excessive bleeding being a contributing factor. Plasma potassium and osmolality remained higher in the first postoperative hours in nonsurvivors. Ketone bodies, growth hormone, and lactate levels rose precipitously as shock became severe. Increased arterial blood osmolality and potassium, plus a still-rising lactate concentration, were evident 2 hr after operation in patients who died in the next 24 hr. Low cardiac output, hyperosmolality, and the degree of lactic acidosis were the only early changes predicting the fatal outcome.
Next-Generation Sequencing for Clinical Diagnostics
Authors: Howard J. Jacob
Journal: New England Journal of Medicine (2013)

Yang et al.1 report in the Journal the results of using whole-exome sequencing to make a molecular diagnosis in 62 of 250 cases (25%) sequenced by the clinical sequencing laboratory at the Baylor College of Medicine, which is accredited by the College of American Pathologists and certified through the Clinical Laboratory Improvement Amendments program. This level of success is a marked improvement over that obtained by testing single genes or gene panels currently used in standard care. The exome is the portion of the genome known to encode proteins (approximately 1% of the human genome2). Whole-exome sequencing has the . . .
Multiple ulcers in the small and large intestines occurred during tocilizumab therapy for rheumatoid arthritis
Authors: T. Iwasa, K. Nakamura, H. Ogino, S. Itaba, H. Akiho, R. Okamoto, Y. Iboshi, A. Aso, H. Murao, K. Kanayama, T. Ito, R. Takayanagi
Journal: Endoscopy (2010)

Tocilizumab is a monoclonal antibody against human interleukin-6 receptor which blocks the binding of interleukin-6 to its receptor. Tocilizumab is effective for the treatment of inflammatory disorders including rheumatoid arthritis. We report a case of multiple ulcers in the small and large intestines, which occurred during tocilizumab therapy. A 57-year-old woman started to use tocilizumab for rheumatoid arthritis. Three months later, she complained of hematochezia. Double-balloon endoscopy revealed multiple small aphthoid ulcers in the small and large intestines. One month after the woman had recovered, she was given tocilizumab again. The woman had hematochezia and abdominal pain again 2 weeks later. Colonoscopy revealed multiple round, discrete punched-out ulcers in the terminal ileum, and vast deep ulcers from the cecum to the descending colon. Bioptic histopathology and cultivation showed non-specific findings. Six weeks after discontinuation of tocilizumab, ulcers in the small and large intestine dramatically improved, leaving ulcer scars. This disease course and the results of examination made us strongly suspect that tocilizumab induced multiple ulcers in the small and large intestines. Interleukin-6 is a pleiotropic cytokine and involved in intestinal mucosal wound healing as well as in inflammatory processes. It is possible that tocilizumab inhibited tissue repair of the intestine and caused intestinal ulcers.
Canada plans new regulations on hepatitis B
Authors: D. Spurgeon
Journal: BMJ (1997)

Canadian surgeons and other healthcare workers could face forced career changes if new recommendations on hepatitis B come into force. Federal, provincial, and territorial health authorities have produced a draft consensus statement recommending that health workers who are infected with the hepatitis B virus should be barred from taking part in procedures prone to exposure, such as deep surgery, closing major wounds, vaginal or caesarian deliveries, and the removal of teeth.

If …
Apolipoproteins and lipoprotein receptors in glomeruli in human kidney diseases
Authors: Tsukasa Takemura, Kazuo Yoshioka, Naobumi Aya, Katsumi Murakami, Akiyo Matumoto, Hiroshige Itakura, Tatsuhiko Kodama, Hiroshi Suzuki, Sunao Maki
Journal: Kidney International (1993)
Prenatal susceptibility to carcinogenesis by xenobiotic substances including vinyl chloride.
Authors: J M Rice
Journal: Environmental Health Perspectives (1981)

The carcinogenicity of vinyl chloride for experimental animals when administered transplacentally is reviewed in comparison with known transplacental carcinogens, including those that, like vinyl chloride, are dependent on enzyme-mediated metabolic conversion to a reactive intermediate in maternal or fetal tissues. Vinyl chloride is converted by mixed-function oxidases to the reactive metabolite chlorooxirane, the carcinogenicity of which is also reviewed. Vinyl chloride is unequivocally a transplacental carcinogen for the rat. No evidence exists, however, to support the hypothesis that exposure of male rats to vinyl chloride or any other carcinogen confers an increased risk of tumor development on their progeny. Many structural analogs of vinyl chloride, i.e., substituted ethylenes, are also carcinogenic for adult animals, and can with confidence likewise be predicted to be effective transplacental carcinogens.
Detection of Hypertension in Childhood
Authors: W. E. Hadden
Journal: BMJ (1973)

treatment is indicated when retrograde ven- ous pressure is not very marked.With both types of therapy the patient should be am- bulatory since this is the best way to prevent complications.If each patient is indivi- dualized and treated according to specific in- dications, excellent results will be obtained both from injection therapy and from sur- gery.-Weare, etc.,
Irritant susceptibility and weal and flare reactions to bioactive agents in atopic dermatitis. II. Influence of season
Authors: R.A. TUPKER, P.J. COENRAADS, V. FIDLER, M.C.J.M. JONG, J.B. MEER, J.G.R. MONCHY
Journal: British Journal of Dermatology (1995)

Many atopic dermatitis (AD) patients have exacerbations of their skin disease in winter. These exacerbations may be caused by non-immunological 'non-specific' factors, such as low sun exposure and low temperature. To date, the influence of season on non-specific skin reactivity in AD has not been studied. The aim of the present investigation was to assess the influence of season on two skin parameters which may be used as quantitative measures of non-specific skin reactivity in AD: (i) susceptibility to repeated epicutaneous irritant (sodium lauryl sulphate, SLS) exposure, and (ii) weal and flare responses to intracutaneous injection of bioactive agents (codeine, FMLP, histamine, methacholine, substance P, trypsin). Four of 16 AD patients had dermatitis which was more severe in November than in July. Susceptibility to SLS was increased in November, both in AD patients and in control subjects. AD patients were more susceptible to SLS than control subjects in both July and November. Pre-exposure barrier function and skin hydration were reduced in November. The increased irritant susceptibility in November may be attributed to reduced barrier function, reduced skin hydration, and/or absence of the beneficial effects of ultraviolet light on cellular targets beneath the stratum corneum. Flare responses to codeine, methacholine, substance P and trypsin were also increased in November compared with July, especially in AD patients. However, smaller flares were observed in AD patients than in control subjects, in both July and November. Flare values were negatively correlated with dermatitis severity, probably because of down-regulation. Weal responses did not show a clear seasonal variation. Hence, susceptibility to epicutaneous irritants and reactivity to intracutaneously injected bioactive agents are parameters which may be used to monitor season-dependent changes in non-specific skin reactivity.
Down-regulation of Phospho-Akt Is a Major Molecular Determinant of Bortezomib-Induced Apoptosis in Hepatocellular Carcinoma Cells
Authors: Kuen-Feng Chen, Pei-Yen Yeh, Kun-Huei Yeh, Yen-Shen Lu, Shang-Yi Huang, Ann-Lii Cheng
Journal: Cancer Research (2008)

Abstract Bortezomib, a proteasome inhibitor, has been clinically approved for the treatment of myeloma and lymphoma. Here, we report a differential effect of bortezomib on apoptosis in four hepatocellular carcinoma (HCC) cell lines and identify the major molecular event that determines sensitivity. Although bortezomib inhibited proteasome activity to a similar extent in all HCC cell lines, it showed differential effects on their viability: Huh-7 (IC50 196 nmol/L), Sk-Hep1 (IC50 180 nmol/L), Hep3B (IC50 112 nmol/L), and resistant PLC5 (IC50 &amp;gt;1,000 nmol/L). Bortezomib caused cell cycle arrest at G2-M phase in all HCC cells tested whereas apoptotic induction was found only in sensitive cells but not in PLC5 cells. No significant bortezomib-induced NF-κB changes were noted in Huh-7 and PLC5. Bortezomib down-regulated phospho-Akt (P-Akt) in a dose- and time-dependent manner in all sensitive HCC cells whereas no alterations of P-Akt were found in PLC5. Down-regulation of Akt1 by small interference RNA overcame the apoptotic resistance to bortezomib in PLC5 cells, but a constitutively activated Akt1 protected Huh-7 cells from bortezomib-induced apoptosis. Furthermore, bortezomib showed suppression of tumor growth with down-regulation of P-Akt in Huh-7 tumors but not in PLC5 tumors. Down-regulation of P-Akt represents a major molecular event of bortezomib-induced apoptosis in HCC cell lines and may be a biomarker for predicting clinical response to HCC treatment. Targeting Akt signaling overcomes drug resistance to bortezomib in HCC cells, which provides a new approach for the combinational therapy of HCC. [Cancer Res 2008;68(16):6698–707]
History of chickenpox and steroid cards: a new warning?
Authors: M D Feher, J P Simms, A F Lant
Journal: BMJ (1996)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following History of chickenpox and steroid cards: a new warning? Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Farnesol-Induced Apoptosis in Human Lung Carcinoma Cells Is Coupled to the Endoplasmic Reticulum Stress Response
Authors: Joung Hyuck Joo, Grace Liao, Jennifer B. Collins, Sherry F. Grissom, Anton M. Jetten
Journal: Cancer Research (2007)

Abstract Farnesol (FOH) and other isoprenoid alcohols induce apoptosis in various carcinoma cells and inhibit tumorigenesis in several in vivo models. However, the mechanisms by which they mediate their effects are not yet fully understood. In this study, we show that FOH is an effective inducer of apoptosis in several lung carcinoma cells, including H460. This induction is associated with activation of several caspases and cleavage of poly(ADP-ribose) polymerase (PARP). To obtain insight into the mechanism involved in FOH-induced apoptosis, we compared the gene expression profiles of FOH-treated and control H460 cells by microarray analysis. This analysis revealed that many genes implicated in endoplasmic reticulum (ER) stress signaling, including ATF3, DDIT3, HERPUD1, HSPA5, XBP1, PDIA4, and PHLDA1, were highly up-regulated within 4 h of FOH treatment, suggesting that FOH-induced apoptosis involves an ER stress response. This was supported by observations showing that treatment with FOH induces splicing of XBP1 mRNA and phosphorylation of eIF2α. FOH induces activation of several mitogen-activated protein kinase (MAPK) pathways, including p38, MAPK/extracellular signal–regulated kinase (ERK) kinase (MEK)-ERK, and c-jun NH2-terminal kinase (JNK). Inhibition of MEK1/2 by U0126 inhibited the induction of ER stress response genes. In addition, knockdown of the MEK1/2 and JNK1/2 expression by short interfering RNA (siRNA) effectively inhibited the cleavage of caspase-3 and PARP and apoptosis induced by FOH. However, only MEK1/2 siRNAs inhibited the induction of ER stress–related genes, XBP1 mRNA splicing, and eIF2α phosphorylation. Our results show that FOH-induced apoptosis is coupled to ER stress and that activation of MEK1/2 is an early upstream event in the FOH-induced ER stress signaling cascade. [Cancer Res 2007;67(16):7929–36]
Building a Better Physician — The Case for the New MCAT
Authors: Robert M. Kaplan, Jason M. Satterfield, Raynard S. Kington
Journal: New England Journal of Medicine (2012)

Interview with Dr. Raynard Kington on the importance to medicine of the behavioral and social sciences. (00:00)Download Beginning in 2015, the Medical College Admission Test (MCAT) will include sections on behavioral and social sciences and critical analysis and reasoning. These revisions reflect the recognition that behavioral and social factors play major roles in health and illness.