tbuckley/cabot-search huggingface dataset:
Anti–Ribosomal P Protein Autoantibodies From Patients With Neuropsychiatric Lupus Impair Memory in Mice
Authors: Marcela Bravo‐Zehnder, Enrique M. Toledo, Fabián Segovia‐Miranda, Felipe G. Serrano, María J. Benito, Claudia Metz, Claudio Retamal, Alejandra Álvarez, Loreto Massardo, Nibaldo C. Inestrosa, Alfonso González
Journal: Arthritis & Rheumatology (2014)

To define whether anti-ribosomal P (anti-P) autoantibodies from patients with neuropsychiatric systemic lupus erythematosus (NPSLE) impair the function of hippocampal neurons that express the neuronal surface P antigen (NSPA) when accessing the brain via circulating blood.We used anti-P antibodies from patients with NPSLE and rabbit-generated anti-P and anti-NSPA antibodies. Primary hippocampal neurons from mice were analyzed to determine antibody cell surface binding (double immunofluorescence), intracellular calcium variations (Fura 2 AM), and apoptosis (caspase 3 activation). Hippocampal-dependent spatial flexible memory was assessed in mice subjected to a water maze test 24 hours after an intravenous injection of anti-P or anti-NSPA, using lipopolysaccharide (LPS) to permeate the blood-brain barrier. Presence of antibodies and apoptosis in the hippocampus was studied using immunohistochemistry and TUNEL assays.Hippocampal neurons expressed NSPA on the cell surface, as revealed by anti-P and anti-NSPA staining colocalization, and responded to both anti-P and anti-NSPA by exhibiting increased intracellular calcium levels. Neuronal apoptosis was induced when anti-P was directly injected by stereotaxis into the hippocampus or added to primary cultures. Upon LPS treatment, intravenously injected anti-P impaired memory but did not elicit neuronal apoptosis in the hippocampus, where it was detectable in low amounts. Anti-NSPA antibodies also impaired memory.Anti-P antibodies interact with NSPA on the surface of hippocampal neurons leading to apoptotic death or to functional perturbations, results that are likely dependent on the concentration of these antibodies. Circulating anti-P can access the hippocampus and impair memory without requiring neuronal death when the blood-brain barrier is disrupted. NSPA can mediate antibody-driven diffuse brain dysfunction, and anti-P might contribute to the cognitive impairment that is frequently observed in SLE.
Abstract 15633: Canonical Wnt Signaling Promotes Pacemaker Cell Specification of Cardiac Mesodermal Cells
Authors: Wenbin Liang, Elizabeth H Kim, Jordan Mak, Rui Zhang, Angelo G Torrente, Joshua I Goldhaber, Eduardo Marbán, Hee Cheol Cho
Journal: Circulation (2014)

Cardiac differentiation of embryonic stem cells (ESCs) gives rise to both chamber (atrial/ventricular) cardiomyocytes and pacemaker cells. Recent findings point to canonical Wnt signaling as a mediator of cardiac sinoatrial node development in chick embryos. We sought to test if early regulation of this pathway may influence cardiac progenitors to bifurcate to either chamber cardiomyocytes or pacemaker cells. The prevailing model of cardiac differentiation of ESCs relies on maintaining a saturating level of Dkk1, added exogenously to inhibit canonical Wnt signaling. We hypothesized that canonical Wnt signaling may lead the progenitor cells to commit to cardiac pacemaker cell fate while its suppression leads differentiation to chamber cardiomyocytes. To this end, Flk-1+/PdgfR-α+ mesodermal progenitor cells were derived from mouse ESCs by treatment with activin-A and BMP-4. Then, the progenitors were subjected to either cardiac differentiation medium (CDM) containing 150 ng/mL of recombinant Dkk1 or the sam...
Genetic variant increases risk of schizophrenia
Authors: Deborah Josefson
Journal: BMJ (2001)

Researchers from the National Institute of Mental Health have found that a common genetic variant in an enzyme involved in dopamine metabolism is linked to poor memory function and increased susceptibility to schizophrenia ( Proceedings of the National Academy of Sciences USA 2001;98:6917-22.)

The study is among the first to show that a normal genetic variant can increase the risk of mental illness. It also opens up another possible treatment option for schizophrenia.

The researchers wanted to study whether variations in catechol-o-methyltransferase, a gene coding for the degradation of dopamine in the prefrontal cortex, was related to risk of schizophrenia.

People with schizophrenia have increased dopamine receptor levels in their brains …
Cutaneous Vascular Malformations in Disappearing Bone (Gorham-Stout) Disease
Authors: Daniela Bruch-Gerharz, Claus-Dieter Gerharz, Helger Stege, Jean Krutmann, Michael Pohl, Rainer Koester, Thomas Ruzicka
Journal: JAMA (2003)

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630. Tamoxifen-Inducible Expansion of Murine Hematopoietic Stem Cells by Retroviral-Mediated Transfer of a HOXB4-ERT2 Fusion Protein
Authors: Yan Shou, Lilia Stepanova, Brian P. Sorrentino
Journal: Molecular Therapy (2004)

Top of pageAbstract
Overexpression of the homeobox transcription factor HOXB4 can increase self-renewal divisions in hematopoietic stem cells (HSCs). As a result, HOXB4 expression is being explored as a gene therapy strategy for increasing the number of genetically modified HSCs. While vectors expressing HOXB4 have not led to any cases of hematopoietic malignancy in transplanted mice, several other HOX family members do cause transformation in this context. An additional concern is that HOXB4 expression can interfere with hematopoietic differentiation in some systems. Therefore, to circumvent any potential adverse effects associated with exogenous HOXB4 expression, we developed an inducible HOXB4 system (HOXB4-ERT2) consisting of a mutated ligand binding domain of the estrogen receptor fused to the carboxyl terminus of HOXB4 via a 10 amino acid linker. Secondary replating assays were used to evaluate the self-renewal capacity of myeloid progenitor cells, and showed that cells transduced with the HOXB4-ERT2 vector generated 3, 5 and 8 fold more secondary colonies than GFP transduced cells in the presence of 100, 200 and 300 nM tamoxifen (TAM) respectively. We next examined whether HOXB4-ERT2 transduced HSCs could be expanded in vivo by treating transplanted mice with TAM. Murine bone marrow (BM) cells expressing the CD45.1 leukocyte antigen were transduced with MSCV-based vectors expressing either GFP, HOXB4 or HOXB4-ERT2. Recipient mice (CD45.2) were lethally irradiated and then transplanted with 2.5105 CD45.1 BM cells, 10% of which were GFP positive, together with 1105 fresh CD45.2 BM cells, giving a total of 7% GFP positive cells in each graft. For the HOXB4-ERT2 group, half of the recipients received TAM treatment daily for 3 weeks starting immediately after the transplant, while the other half received no treatment. Secondary transplants were performed at week 21. The percentages of GFP positive cells in peripheral blood leukocytes (PBLs) are summarized in the table. Our results showed that HSCs transduced with the HOXB4-ERT2 vector expanded in vivo with TAM treatment. Comparing TAM treated with untreated mice, GFP positive cells in PBLs increased 7 and 27 fold in primary and secondary recipients respectively. Hematological parameters were within normal range in all transplanted animals. In summary, these results show that HOXB4 function can be controlled both in vivo and in vitro using our HOXB4-ERT2 system. This may allow for increased safety by allowing inactivation of HOXB4 function after HSC expansion has occurred. In addition, we are using this system to study the kinetics of the HOXB4 effect by inducing HOXB4 function at different time points post-transplant and early results indicated that there was a restricted time frame for HOXB4-induced expansion.
Ultrastructure of acantholysis in pemphigus foliaceus re‐examined from the current perspective
Authors: G. van der Wier, M.F. Jonkman, H.H. Pas, G.F.H. Diercks
Journal: British Journal of Dermatology (2012)

Pemphigus foliaceus (PF) is a chronic cutaneous autoimmune blistering disease that is characterized by superficial blistering of the skin, and according to the current perspective is caused by autoantibodies directed against desmoglein (Dsg) 1.To examine early acantholysis in the skin of patients with PF at an ultrastructural level.Two Nikolsky-negative (N-), five Nikolsky-positive (N+) and two lesional skin biopsies from immunoserologically defined patients with PF were studied by light and electron microscopy.We found no abnormalities in N- PF skin, whereas all the N+ skin biopsies displayed intercellular widening between desmosomes, a decreased number of desmosomes and hypoplastic desmosomes in the lower epidermal layers. Acantholysis was present in two of five N+ biopsies, but only in the upper epidermal layers. The lesional skin biopsies displayed acantholysis in the higher epidermal layers. Hypoplastic desmosomes were partially (pseudo-half-desmosomes) or completely torn off from the opposing cell.We propose the following mechanism for acantholysis in PF: initially PF IgG causes a depletion of nonjunctional Dsg1, leading to intercellular widening between desmosomes starting in the lower layers and spreading upwards. Depletion of nonjunctional Dsg1 impairs the assembly of desmosomes, resulting in hypoplastic desmosomes and a decreased number of desmosomes. In addition, antibodies might promote disassembly of desmosomes. In the upper layers of the epidermis, where Dsg3 is not expressed and cannot compensate for Dsg1 loss, ongoing depletion of Dsg1 will finally result in a total disappearance of desmosomes and subsequent acantholysis.
Ethics review in research
Authors: Ian L P Beales
Journal: BMJ (2004)

EDITOR—Hearnshaw and Glasziou and Chalmers highlight the inconsistencies and arbitrary decision making of UK research ethics committees and show that this may delay and suppress clinical research in the United Kingdom.1 2 I recently submitted a study that required six months, countless emails, and submission of 1443 sheets of A4 paper to gain approval …
Abstract 9223: In vivo Assessment of Pulmonary Arterial Wall Fibrosis by Intravascular optical Coherence Tomography in Pulmonary Arterial Hypertension: A New Prognostic Marker of Adverse Clinical Follow-Up
Authors: Domingo Enric, Juan Carlos Grignola, Rio Aguilar, Christian Arredondo, Maria Angeles Montero, Manuel Lopez, Carlos Bravo, Manuel Vazquez, Nadia Bouteldja, Antonio Roman
Journal: Circulation (2011)

The aim of the study is to quantify pulmonary artery (PA) wall fibrosis by intravascular optical coherence tomography (OCT) in severe pulmonary arterial hypertension (PAH) and to correlate it with clinical follow-up. Histological and OCT study of PA specimens is also performed. OCT is an imaging modality for studying vessel wall structure with higher resolution than intravascular ultrasound. Nineteen consecutive PAH patients , aged 54±16 (4 men) , functional class II-III were studied with simultaneous right heart catheterization and OCT in inferior lobe PA segments (2-4 mm diameter). Relative PA wall fibrosis (%fibrosis) was obtained by OCT (area of fibrosis/PA cross sectional area×100). All patients were prospectively followed up. Physicians who carried out the clinical follow-up were blind to the OCT results. Patients were initially divided into 2 groups, low and high degree of fibrosis, according to the median value of PA wall OCT % fibrosis. Clinical deterioration had been initially defined in terms of either mortality, lung transplantation, need of intravenous prostaglandins or onset of clinical right ventricular failure. OCT measurements showed a high intra and interobserver agreement. There was a good correlation between OCT and histological fibrosis in PA wall from explanted lungs. In the whole group area of fibrosis was 1.4±0.8 mm 2 and % fibrosis was 22.3±8. All patients were prospectively followed-up with an average follow-up of 3.5 years (2.5-4.5 years). Patients were divided into 2 groups, low and high degree of fibrosis, according to the median value of PA wall OCT fibrosis percentage ( 22% ). There were 10 patients with a high degree of fibrosis ( ≥ 22% ) and 9 with a lower degree of fibrosis (&lt;22% ). Clinical events, as previously defined, were present in 6 patients ( 1 death, 1 lung transplantation, 2 intravenous prostaglandins, 2 right heart failure ) out of 10 patients with high fibrosis and in 0 out of 9 patients with low fibrosis ( p&lt;0.01). In PAH, the severity of PA remodeling assessed by quantification of PA wall fibrosis by OCT was significantly predictive of severely unfavorable clinical outcome. There was a good correlation between OCT and histological fibrosis in explanted PA.
Abstract 13414: 5-year Impact of Catheter Ablation for Atrial Fibrillation on Cardiac Function and Heart Failure in Patients With Baseline Moderate-severe Systolic Heart Failure
Authors: Thomas J Bunch, Heidi T May, Tami L Bair, Victoria Jacobs, Brian G Crandall, Michael Cutler, J P Weiss, Charles Mallendar, Jeffrey S Osborn, Jeffrey L Anderson, John D Day
Journal: Circulation (2014)

Backgroud. Catheter ablation of atrial fibrillation (AF) is an established therapeutic rhythm approach. 1-year outcomes of ablation in patients with systolic heart failure (SHF) have shown that ejection fraction(EF), and risk of heart failure progression and death are improved. However, SHF is often a progressive process and as such, long-term data regarding cardiac function and heart failure are needed.

Methods: 3 groups with SHF and 5 years of follow-up were matched 1:4:4 by age(±5 years) and sex. AF ablation patients receiving their first ablation (n=267), AF patients that did not receive an ablation (n=1068), and SHF patient without AF (n=1068). A patient was deemed as having SHF if they had both a clinical diagnosis(ICD-9 code 428.8*) and an EF<35%. Patients were followed for 5-year outcomes of HF and cardiac function.

Results: The average age of the population was 67±13 years and 78% male. The AF was paroxysmal in 25%, persistent in 34.7%, and longstanding persistent in 41%. Serial echocardiogram data were available on a subset of the population, although these were not performed per a routine protocol (AF ablation: 87, AF no ablation: 292, no AF: 213, p=0.17). Cardiac function in the AF ablation group improved the most at 3 years, then all groups were largely similar at 5 years and the composite of the last study ordered within our network (p=0.17). Worsening of an EF compared to an improvement after ablation trended towards an increased risk of AF recurrence (HR 1.65: 95% CI: 0.47-5.83, p=0.33). The AF Ablation and No AF groups had the lowest long-term HF hospitalization rates (14%, 15%, vs. 21%, p<0.0001).

Conclusion: Early improvements in cardiac function in patients with SHF are observed after catheter ablation, but on average are not maintained at 5 years. Despite similarities in EF, long-term heart failure was lower in the AF ablation and no AF groups, a finding that likely reflects maintenance of atrial systolic function and less exposure to antiarrhythmic drugs.

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Costly Surge in Diagnostic Imaging Spurs Debate
Authors: Mike Mitka
Journal: JAMA (2005)

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
Loratadine and terfenadine in perennial allergic rhinitis
Authors: K. H. Carlsen, J. Kramer, H. E. Fagertun, S. Larsen
Journal: Allergy (1993)

The efficacy of loratadine and terfenadine in perennial allergic rhinitis was evaluated in a double‐blind, selected cross‐over study consisting of two phases. During the first phase, 76 patients with perennial allergic rhinitis, 8–67 years old, were included in the study. Of these, 41 patients received loratadine 10 mg daily, and 35 patients received terfenadine 60 mg twice daily, for 2 weeks. According to symptoms and side‐effects, 32 patients were classified as responders to loratadine, and 28 patients as responders to terfenadine. All observed symptoms were significantly reduced in both treatment groups, but with no significant differences between the two groups. Side‐effects were few and mild. In patients with normal IgE, loratadine was significantly superior to terfenadine in relieving nasal secretion, whereas terfenadine was significantly superior to loratadine in relieving nasal congestion. In patients with increased IgE, patients treated with loratadine showed significantly greater reduction in sneezing than patients treated with terfenadine. A positive correlation between total IgE and reduction in overall symptoms was found for patients treated with loratadine, whereas a negative correlation was found for patients treated with terfenadine. During the second study phase, the nonresponders received the other drug for 2 weeks. All seven nonresponders to terfenadine responded to loratadine after crossing over, whereas four of nine nonresponders to loratadine responded to terfenadine. Nonresponders to one drug may respond to the other drug. Thus, more than one antihistamine drug should be tried in perennial allergic rhinitis if the first fails.
Transplantation of human limbal epithelium cultivated on amniotic membrane for the treatment of severe ocular surface disorders1 1The authors do not have any proprietary interest in the products mentioned or used in this study.
Authors: Jun Shimazaki, Masayo Aiba, Eiki Goto, Naoko Kato, Shigeto Shimmura, Kazuo Tsubota
Journal: Ophthalmology (2002)
Abstract 17797: Noninvasive Optical Imaging of Response to On-Demand Antioxidant Therapy in a Model of Peripheral Arterial Disease
Authors: Kristin M Poole, Christopher E Nelson, John R Martin, Devin R McCormack, Rucha V Joshi, Melissa C Skala, Craig L Duvall
Journal: Circulation (2014)

Peripheral arterial disease is often modeled by surgical induction of hind limb ischemia (HLI) in mice to study collateral vessel development. However, there is a need for methodologies that provide intravital, multifunctional, quantitative data on ischemic recovery for robust evaluation of new therapeutics. Here, we apply hyperspectral imaging and optical coherence tomography (OCT) to longitudinally assess hemoglobin oxygen saturation (SaO 2 ) and vessel morphology in response to a novel therapy. Injectable microspheres loaded with curcumin were synthesized from reactive oxygen species (ROS)-responsive poly(propylene) sulfide (PPS) to provide “on demand”, local release of the antioxidant drug curcumin to reduce tissue-damaging oxidative stress in a mouse model of diabetic HLI. Curcumin-PPS microspheres significantly reduced intracellular ROS in LPS-activated RAW 264.7 macrophages and rescued viability of 3T3 fibroblasts treated with cytotoxic levels of H 2 O 2 in vitro . HLI was induced in FVB mice with streptozotocin-induced diabetes, and curcumin-PPS or blank-PPS microspheres were injected into the ischemic limb. Curcumin-PPS significantly improved recovery of SaO 2 in the ischemic footpad relative to blank-PPS and vehicle (saline) groups over a one week time course evaluated with hyperspectral imaging (n≥8/group, p&lt;0.05). Vessel structure in the gastrocnemius was imaged noninvasively with OCT at day 7 (Figure), revealing trends toward increased vessel area density and vessel length fraction in the curcumin-PPS group (n=5/group). The vessel diameter distribution was also extracted from OCT data. Our collective data indicate that sustained, on demand curcumin delivery has significant therapeutic promise for improving ischemic tissue recovery. Also, the hyperspectral and OCT imaging methods showcased provide quantitative, noninvasive monitoring of vasculature and can accelerate screening of novel therapies.
Anti-RhoA and Anti-RhoC siRNAs Inhibit the Proliferation and Invasiveness of MDA-MB-231 Breast Cancer Cells in Vitro and in Vivo
Authors: J.-Y. Pillé, C. Denoyelle, J. Varet, J.-R. Bertrand, J. Soria, P. Opolon, H. Lu, L.-L. Pritchard, J.-P. Vannier, C. Malvy, C. Soria, H. Li
Journal: Molecular Therapy (2004)

Overexpression of RhoA or RhoC in breast cancer indicates a poor prognosis, due to increased tumor cell proliferation and invasion and tumor-dependent angiogenesis. Until now, the strategy of blockage of the Rho-signaling pathway has used either GGTI or HMG-CoA reductase inhibitors, but they are not specific to RhoA or RhoC inhibition. In this study, a new approach with anti-RhoA and anti-RhoC siRNAs was used to inhibit specifically RhoA or RhoC synthesis. Two transfections of either RhoA or RhoC siRNA (8.5 nM) into MDA-MB-231 human breast cancer cells or HMEC-1 endothelial cells induced extensive degradation of the target mRNA and led to a dramatic decrease in synthesis of the corresponding protein. In vitro, these siRNAs inhibited cell proliferation and invasion more effectively than conventional blockers of Rho cell signaling. Finally, in a nude mouse model, intratumoral injections of anti-RhoA siRNA (100 microl at 85 nM) every 3 days for 20 days almost totally inhibited the growth and angiogenesis of xenografted MDA-MB-231 tumors. One may infer from these observations that specific inhibition of the Rho-signaling pathway with siRNAs represents a promising approach for the treatment of aggressive breast cancers.