tbuckley/cabot-search huggingface dataset:
169. Patterned Substrate-Mediated DNA Delivery Using Soft Lithography for Neural Tissue Engineering
Authors: Tiffany L. Houchin, Lonnie D. Shea
Journal: Molecular Therapy (2006)

Combining tissue-engineering scaffolds with gene therapy can provide versatile systems to physically support cellular processes and locally stimulate tissue growth. The engineering of tissues with complex architectures, such as the nervous system, will likely require spatial patterning of molecular signals resulting in concentration gradients of extracellular proteins that organize cells into functional tissues. We believe that substrate-mediated gene delivery, which involves immobilizing DNA complexes to a cell-adhesive substrate, provides the ability to spatially pattern molecular signals that can guide cell migration and organize tissue formation. We have combined substrate-mediated gene delivery with soft lithography to pattern DNA complex deposition and therefore cellular transfection. Non-specific interactions between lipoplexes and a polystyrene surface allow immobilized complexes to remain in the pattern and transfect only cells in the region of the pattern. Polydimethylsiloxane (PDMS) microfluidic devices with channels ranging in width from 100 to 1000 μm were utilized to pattern lipoplexes on the polystyrene surface. Complex binding efficiency in the pattern, as determined using 32P-labeled plasmid, was dependent on PDMS treatment, with no treatment allowing for 15% binding efficiency, and both O2 plasma and Pluronic L35 treated permitting 25% binding efficiency (1000 μm channels). The percentage of transfected HEK293T cells in the pattern was dependent on the PDMS treatment, concentration of DNA in the microchannels, and size of the microchannels. Substantial levels of transfection were observed only with Pluronic treated PDMS microchannels. The percentage of transfected cells ranged from 30% to 40% for the different sized channels with varying DNA concentrations. The capacity of patterned transfection to guide neuron growth cones during axonal extension was investigated using a neuronal co- culture system. Primary dorsal root ganglia (DRG) neurons were dissected from 8-day chicken embryos, dissociated, and cultured on patterns of RK5-NGF transfected HEK293T cells. Neurite outgrowth was greater at the location of transfected cells as compared to regions outside the pattern. Additionally, high transfection efficiencies were not necessary to achieve patterns of neurite extension, suggesting that cell types that are more difficult to transfect can be utilized with this system. We present a system for patterning gene delivery on a two-dimensional tissue culture surface that was used to enhance axonal growth and guidance. The system has applications beyond neural tissue engineering, and is an enabling technology to correlate the patterned expression of tissue inductive factors with subsequent tissue formation.
Systemic and Specific Delivery of Small Interfering RNAs to the Liver Mediated by Apolipoprotein A-I
Authors: Soo In Kim, Duckhyang Shin, Tae Hyun Choi, Jong Chan Lee, Gi-Jeong Cheon, Ki-Yong Kim, Mahnhoon Park, Meehyein Kim
Journal: Molecular Therapy (2007)

Tissue-targeted delivery of small interfering RNA (siRNA) must be achieved before RNA interference (RNAi) technology can be used in practical therapeutic approaches. In this study, the potential of apolipoprotein A-I (apo A-I) for the systemic delivery of nucleic acids to the liver is demonstrated using real-time in vivo imaging. As a proof of concept, synthetic siRNAs against hepatitis B virus (HBV) were formulated into complexes of apo A-I and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (DTC-Apo) and injected intravenously (IV) into a mouse model carrying replicating HBV. We show that administration of these nanoparticles can significantly reduce viral protein expression by receptor-mediated endocytosis. The advantages of the apo A-I–mediated siRNA delivery method are its liver specificity, its effectiveness at low doses (≤2 mg/kg) in only a single treatment, and its persistent antiviral effect up to 8 days. The liver-targeted gene silencing was also shown by in vivo images, in which bioluminescent signals emitted from the liver were efficiently reduced after IV administration of luciferase-specific siRNA and DTC-Apo lipoplex. Thus, our unique approach to siRNA delivery creates a foundation for the development of a new class of promising therapeutics against hepatitis viruses or hepatocyte genes related to tumor growth. Tissue-targeted delivery of small interfering RNA (siRNA) must be achieved before RNA interference (RNAi) technology can be used in practical therapeutic approaches. In this study, the potential of apolipoprotein A-I (apo A-I) for the systemic delivery of nucleic acids to the liver is demonstrated using real-time in vivo imaging. As a proof of concept, synthetic siRNAs against hepatitis B virus (HBV) were formulated into complexes of apo A-I and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (DTC-Apo) and injected intravenously (IV) into a mouse model carrying replicating HBV. We show that administration of these nanoparticles can significantly reduce viral protein expression by receptor-mediated endocytosis. The advantages of the apo A-I–mediated siRNA delivery method are its liver specificity, its effectiveness at low doses (≤2 mg/kg) in only a single treatment, and its persistent antiviral effect up to 8 days. The liver-targeted gene silencing was also shown by in vivo images, in which bioluminescent signals emitted from the liver were efficiently reduced after IV administration of luciferase-specific siRNA and DTC-Apo lipoplex. Thus, our unique approach to siRNA delivery creates a foundation for the development of a new class of promising therapeutics against hepatitis viruses or hepatocyte genes related to tumor growth.
Umbrella test
Authors: David L Bradford
Journal: BMJ (2007)

stent thrombosisAntiplatelets alone won't do the job Gershlick and Richardson say that premature discontinuation of clopidogrel is the greatest risk factor for thrombosis of drug eluting stents. 1 In Iakovou's series thrombosis occurred in five of 17 patients (29%) who prematurely discontinued dual antiplatelet therapy. 2 One of them discontinued only clopidogrel, and the others stopped both antiplatelets (aspirin and clopidogrel or ticlopidine).We do not know whether continuation of aspirin alone would have been adequate to prevent thrombosis associated with drug eluting stents.In only a minority of patients (five out of 29; 17%) did discontinuation of antiplatelets seem to have a role in the occurrence of stent thrombosis.The tragedy of drug eluting stents is not the risk of late stent thrombosis but the fact that these devices have only a limited effect on patients' wellbeing.In several randomised trials they did not lead to a lower mortality and did not affect the incidence of acute myocardial infarction. 3Recently presented meta-analyses and data from registries show that they might increase the occurrence of acute infarctions and even late mortality. 4 5
MEHP/DEHP: gonadal toxicity and effects on rodent accessory sex organs.
Authors: J A Thomas, K A Curto, M J Thomas
Journal: Environmental Health Perspectives (1982)

The phthalate acid esters (PAEs), and, in particular, di(2-ethylhexyl) phthalate (DEHP) and its monoester, monoethylhexyl phthalate (MEHP), can adversely affect rodent testes but only at high doses. Rat gonadal zinc levels can be decreased by the injection of DEHP, but not MEHP. The rat prostate gland seems to be particularly sensitive to PAE-induced zinc depletion. PAE-induced changes in male reproductive organs were more evident in the rat than in the mouse. Some of the effects of MEHP can be demonstrated in vitro since it can alter the uptake of 65Zn in rodent gonads and accessory sex organs.
T cell receptor usage and fine specificity of human immunodeficiency virus 1-specific cytotoxic T lymphocyte clones: analysis of quasispecies recognition reveals a dominant response directed against a minor in vivo variant.
Authors: S A Kalams, R P Johnson, M J Dynan, K E Hartman, T Harrer, E Harrer, A K Trocha, W A Blattner, S P Buchbinder, B D Walker
Journal: The Journal of Experimental Medicine (1996)

Numerous virus-specific, class I-restricted cytotoxic T lymphocyte (CTL) epitopes have been identified, yet little information is available regarding the specificity of the CTL response in persons of the same human histocompatibility leukocyte antigen (HLA) type. In this study, the human immunodeficiency virus (HIV) 1 envelope-specific CTL response was evaluated in five HLA-B14-positive persons. CTL responses specific for a previously described nine-amino acid epitope in gp41 (aa 584-592, ERYLKDQQL) could be identified in all subjects, and CTL clones specific for this epitope could be isolated from four persons. Despite heterogeneous T cell receptor usage, the fine specificity of the clones was similar, as defined by recognition of alanine-substituted peptides as well as peptides representing natural HIV-1 sequence variants. Correlation with in vivo virus sequences revealed that the dominant species in two of the subjects represented poorly recognized variants, with a K--&amp;gt;Q substitution at amino acid 588, whereas no variants were observed in the other two subjects. Although clonal type-specific responses to these dominant variants could be identified, the magnitude of these responses remained small, and the dominant CTL response was directed at the minor in vivo variant. These studies indicate that despite similar epitope-specific immunologic pressure in persons of the same HLA type, the in vivo quasispecies may differ, and that the major in vivo immune response to a given CTL epitope can be directed at a minor variant.
Comparison of Quantitative Coronary Angiography, Intravascular Ultrasound, and Coronary Pressure Measurement to Assess Optimum Stent Deployment
Authors: Clara E. E. Hanekamp, Jacques J. Koolen, Nico H. J. Pijls, H. Rolf Michels, Hans J. R. M. Bonnier
Journal: Circulation (1999)

Although intravascular ultrasound (IVUS) is the present standard for the evaluation of optimum stent deployment, this technique is expensive and not routinely feasible in most catheterization laboratories. Coronary pressure-derived myocardial fractional flow reserve (FFRmyo) is an easy, cheap, and rapidly obtainable index that is specific for the conductance of the epicardial coronary artery. In this study, we investigated the usefulness of coronary pressure measurement to predict optimum and suboptimum stent deployment.In 30 patients, a Wiktor-i stent was implanted at different inflation pressures, starting at 6 atm and increasing step by step to 8, 10, 12, and 14 atm, if necessary. After every step, stent deployment was evaluated by quantitative coronary angiography (QCA), IVUS, and coronary pressure measurement. If any of the 3 techniques did not yield an optimum result, the next inflation was performed, and all 3 investigational modalities were repeated until optimum stent deployment was present by all of them or until the treating physician decided to accept the result. Optimum deployment according to QCA was finally achieved in 24 patients, according to IVUS in 17 patients, and also according to coronary pressure measurement in 17 patients. During the step-up, a total of 81 paired IVUS and coronary pressure measurements were performed, of which 91% yielded concordant results (ie, either an optimum or a suboptimum expansion of the stent by both techniques, P<0.00001). On the contrary, QCA showed a low concordance rate with IVUS and FFRmyo (48% and 46%, respectively).In this study, using a coil stent, both IVUS and coronary pressure measurement were of similar value with respect to the assessment of optimum stent deployment. Therefore, coronary pressure measurement can be used as a cheap and rapid alternative to IVUS for that purpose.
Splenectomy for Hypersplenism in Sickle Cell Anemia
Authors: Richard H. Egdahl
Journal: JAMA (1963)

Marked symptomatic improvement followed splenectomy in five patients with sickle cell anemia in whom there was evidence of hypersplenism. Tests on hemoglobin revealed hemoglobin S concentrations over 89% and hemoglobin A 2 concentrations ranging between 1.5% and 3.6%. These results established the diagnosis of sickle cell anemia, in contrast to sickle cell thalassemia and other sickle cell variants. It is suggested that splenectomy is a valuable procedure in patients with the combination of sickle cell anemia, hypersplenism, and hyperhemolysis.
yet another child
Authors: Mark S Haendel
Journal: JAMA (1992)

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
Carbohydrate, Fiber, and Disease
Authors: K. K. KIMURA
Journal: Annals of Internal Medicine (1976)

Comments and Correction1 January 1976Carbohydrate, Fiber, and DiseaseK. K. KIMURA, PH.D., M.D.K. K. KIMURA, PH.D., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-1-99_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The Life Sciences Research Office of the Federation of American Societies for Experimental Biology is conducting a study for the Bureau of Foods, Food and Drug Administration, on the "Nutritional Significance of Refined Carbohydrates and Dietary Fiber and Their Role in the Prevention or Induction of Gastrointestinal Pathology." In addition to the effects on the gastrointestinal tract, attention will be given to cardiovascular-renal and oncologic considerations, as well as to the question of hypersensitivity to dietary carbohydrates and fiber in children and adults. In connection with the study, we would like to learn the prevalence of sensitivity... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1976Volume 84, Issue 1Page: 99-99KeywordsCarbohydratesChildrenFoodFood and Drug AdministrationGastrointestinal tractHypersensitivityNutrition Issue Published: 1 January 1976 PDF DownloadLoading ...
Tumor–Immune Dynamics Regulated in the Microenvironment Inform the Transient Nature of Immune-Induced Tumor Dormancy
Authors: Kathleen P. Wilkie, Philip Hahnfeldt
Journal: Cancer Research (2013)

Cancer in a host induces responses that increase the ability of the microenvironment to sustain the growing mass, for example, angiogenesis, but cancer cells can have varying sensitivities to these sustainability signals. Here, we show that these sensitivities are significant determinants of ultimate tumor fate, especially in response to treatments and immune interactions. We present a mathematical model of cancer-immune interactions that modifies generalized logistic growth with both immune-predation and immune-recruitment. The role of a growing environmental carrying capacity is discussed as a possible regulatory mechanism for tumor growth, and this regulation is shown to modify cancer-immune interactions and the possibility of achieving immune-induced tumor dormancy. This mathematical model qualitatively matches experimental observations of immune-induced tumor dormancy as it predicts dormancy as a transient period of growth that necessarily ends in either tumor elimination or tumor escape. As dormant tumors may exist asymptomatically and may be easier to treat with conventional therapy, an understanding of the mechanisms behind tumor dormancy may lead to new treatments aimed at prolonging the dormant state or converting an aggressive cancer to the dormant state.
Interleukin-10 modulates the sensitivity of peritoneal B lymphocytes to chemokines with opposite effects on stromal cell–derived factor-1 and B-lymphocyte chemoattractant
Authors: Karl Balabanian, Arnaud Foussat, Laurence Bouchet-Delbos, Jacques Couderc, Roman Krzysiek, Ali Amara, Françoise Baleux, Alain Portier, Pierre Galanaud, Dominique Emilie
Journal: Blood (2002)
Gastric Acid–Inhibiting Medications and Vitamin B<sub>12</sub>Deficiency
Authors: Cristian Gonzalez-Gonzalez, Adolfo Figueiras
Journal: JAMA (2014)

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
Vertical transmission rates for HIV in the British Isles: estimates based on surveillance data
Authors: T. Duong, A E Ades, D. M Gibb, P. A Tookey, J. Masters
Journal: BMJ (1999)

To estimate and interpret time trends in vertical transmission rates for HIV using data from national obstetric and paediatric surveillance registers.Prospective study of HIV infected women reported through obstetric surveillance. HIV infection status of the child and onset of AIDS were reported through paediatric surveillance. Rates of vertical transmission and progression to AIDS rate were estimated by methods that take account of incomplete follow up of children with indeterminate infection status and delay in AIDS reporting.British Isles.Pregnant women infected with HIV whose infection was diagnosed before delivery, and their babies.Mother to child transmission of infection and progression to AIDS in children.By January 1999, 800 children born to diagnosed HIV infected women who had not breast fed had been reported. Vertical transmission rates rose to 19.6% (95% confidence interval 8. 0% to 32.5%) in 1993 before falling to 2.2% (0% to 7.8%) in 1998. Between 1995 and 1998 use of antiretroviral treatment increased significantly each year, reaching 97% of live births in 1998. The rate of elective caesarean section remained constant, at around 40%, up to 1997 but increased to 62% in 1998. Caesarean section and antiretroviral treatment together were estimated to reduce risk of transmission from 31.6% (13.6% to 52.2%) to 4.2% (0.8% to 8.5%). The proportion of infected children developing AIDS in the first 6 months fell from 17.7% (6.8% to 30.8%) before 1994 to 7.2% (0% to 15. 7%) after, coinciding with increased use of prophylaxis against Pneumocystis carinii pneumonia.In the British Isles both HIV related morbidity and vertical transmission are being reduced through increased use of interventions.
Evidence based diagnosis: Terminology is unsatisfactory
Authors: G H Hall
Journal: BMJ (2006)

Evidence based diagnosis We may need to be open to new ideasEditor-If evidence based diagnosis is still in the dark ages, as Delamothe writes, 1 then so is evidence based treatment.The doctor's job is to choose the right treatment.If the diagnosis is wrong then the treatment will be wrong.Inaccurate diagnoses will also affect clinical trials.A treatment may be "evidence based" because it has worked in a published study, but some patients who would have responded might have been left out because of diagnostic inaccuracy while some patients with no prospect of responding might have been included incorrectly. 2vidence based diagnosis is about convincing others using shared rules of evidence that a diagnosis (and its implications in terms of treatment) should be accepted by others.Evidence is gathered from the individual and from groups of patients. 3Evidence based diagnosis means specifying the individual's facts in addition to pointing to facts relating to that diagnosis in the literature. 4ayes's theorem uses unconditional initial prior probabilities.Diagnostic leads are based on conditional probabilities and are used to initiate diagnostic thought processes. 4owever, closely related theorems can be used to interpret diagnostic leads, which allow doctors to reason with diagnostic evidence in a more familiar way, 3 thus reducing misunderstandings. 5So to improve evidence based diagnosis we also need to collect better data on diagnostic leads.The published evidence given for a diagnosis and any related actions cannot realistically be assembled when actually seeing a patient.A draft evidence based rationale might be prepared in advance.It would have to be capable of being accessed in seconds to provide evidence in support of a suspected diagnosis and decision arrived at by using kindness, imagination, and common sense.It could be put into context by inserting the patient's details into the draft evidence summoned up from a computer.If we are to make progress and allow evidence based diagnosis to emerge from the dark ages then in addition to doing more of the same, we may also have to be receptive to new ideas.