tbuckley/cabot-search huggingface dataset:
Neuropsychiatric Illness in Systemic Lupus Erythematosus: Insights From a Patient With Erotomania and Geschwind's Syndrome
Authors: Mark T. Wright
Journal: American Journal of Psychiatry (2010)

Individuals suffering from systemic lupus erythematosus (SLE) can develop a number of psychiatric conditions, including psychosis. It is often unclear in SLE patients with psychiatric illness whether their illness is primary, due to SLE brain disease, and/or due to treatments for SLE. This article describes a patient with SLE who developed erotomania and personality changes. The differential diagnosis and possible pathogenesis of psychiatric illnesses occurring in SLE patients are discussed.
Tissue Specific Cytotoxicity of Colon Cancer Cells Mediated by Nanoparticle-delivered Suicide Gene <i>In vitro</i> and <i>In vivo</i>
Authors: Guiying Zhang, Ting Liu, Yong-Heng Chen, Yuxiang Chen, Meihua Xu, Jie Peng, Shuyi Yu, Jianwei Yuan, Xiuwu Zhang
Journal: Clinical Cancer Research (2008)

Abstract Purpose: This study aimed to develop an efficient and safe strategy to introduce suicide genes into colon cancer cells. Experimental Design: In this study, we fused an enhanced carcinoembryonic antigen promoter (CEA) to a suicide gene, cytosine deaminase (CD). This construct was delivered into colon cancer cells using calcium phosphate nanoparticles (CPNP). The cells were then treated with the prodrug 5-FC. The therapeutic effect was evaluated in vitro and in vivo. Results: Our study showed that the CEA promoter–driven, CPNP-delivered suicide gene was only expressed in CEA-positive colon cancer cells, and resulted in significant cytotoxicity after administration of the prodrug 5-FC in vitro. Moreover, our in vivo study showed that CPNP-mediated CEA-CD delivery, together with 5-FC treatment, resulted in significant tumor growth delay in xenograft human colon carcinoma. Conclusions: Our study indicates that the combination of CPNP and CEA-CD gene expression represents a novel approach for CEA-positive tumor gene therapy.
Relationship between improved pulmonary arterial pressure and changes in interventricular septal configuration by 320-slice CT in patients under pulmonary endarterectomy
Authors: Toshihiko Sugiura, Nobuhiro Tanabe, Yukiko Matsuura, Hajime Kasai, Naoko Kawata, Ayako Shigeta, Seiichiro Sakao, Yasunori Kasahara, Koichiro Tatsumi
Journal: European Respiratory Journal (2014)

Purpose: We retrospectively determined whether changes of the curvature of the interventricular septum measured by ECG-gated 320-slice CT were influenced by improved pulmonary artery (PA) pressure in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA).  Materials and Methods: Thirty-six patients (13 male, 59±9 yrs) with proven CTEPH underwent right heart catheterization (RHC) and double-volume retrospective ECG-gated enhanced volume scanning using 320-slice CT before and after PEA. CT images were reconstructed every 5% from 0-95% of the R-R interval, and a series of short-axis images of the heart at the level of the left ventricle papillary muscle was acquired using double-oblique multiplanar reformation. Septal bowing expressed as end-systolic curvature (reciprocal of radius [/cm]) was measured (a leftward curvature was denoted as a negative value). The relationships between septal curvature (SC) and hemodynamics measured by RHC before and after PEA were evaluated by linear regression analysis.  Results: The correlation coefficients of SC with systolic PA pressure (sPAP) before and after PEA were -0.83 (P  Conclusions: SC based on ECG-gated 320-slice CT can be used to accurately estimate improved hemodynamics in patients undergoing PEA.
Tristetraprolin regulation of interleukin 23 mRNA stability prevents a spontaneous inflammatory disease
Authors: Céline Molle, Tong Zhang, Laure Ysebrant de Lendonck, Cyril Gueydan, Mathieu Andrianne, Félicie Sherer, Gaetan Van Simaeys, Perry J. Blackshear, Oberdan Leo, Stanislas Goriely
Journal: The Journal of Experimental Medicine (2013)

Interleukin (IL) 12 and IL23 are two related heterodimeric cytokines produced by antigen-presenting cells. The balance between these two cytokines plays a crucial role in the control of Th1/Th17 responses and autoimmune inflammation. Most studies focused on their transcriptional regulation. Herein, we explored the role of the adenine and uridine–rich element (ARE)–binding protein tristetraprolin (TTP) in influencing mRNA stability of IL12p35, IL12/23p40, and IL23p19 subunits. LPS-stimulated bone marrow–derived dendritic cells (BMDCs) from TTP−/− mice produced normal levels of IL12/23p40. Production of IL12p70 was modestly increased in these conditions. In contrast, we observed a strong impact of TTP on IL23 production and IL23p19 mRNA stability through several AREs in the 3′ untranslated region. TTP−/− mice spontaneously develop an inflammatory syndrome characterized by cachexia, myeloid hyperplasia, dermatitis, and erosive arthritis. We observed IL23p19 expression within skin lesions associated with exacerbated IL17A and IL22 production by infiltrating γδ T cells and draining lymph node CD4 T cells. We demonstrate that the clinical and immunological parameters associated with TTP deficiency were completely dependent on the IL23–IL17A axis. We conclude that tight control of IL23 mRNA stability by TTP is critical to avoid severe inflammation.
Binding of purified, soluble major histocompatibility complex polypeptide chains onto isolated T-cell receptors. I. Reactivity against allo- and self-determinants.
Authors: H Binz, H Frischknecht, C Mercolli, S Dunst, H Wigzell
Journal: The Journal of Experimental Medicine (1979)

In this study, we tried to get information about the fine antigen-binding ability of purified, soluble, idiotype-positive T-cell receptor molecules. Lewis anti-DA T-cell receptors were purified from normal Lewis serum by the use of anti-idiotypic immunosorbent and sodium dodecyl sulfate-polyacrylamide gel, and were coupled to cyanogen bromide-activated Sepharose 4B. In parallel, Lewis anti-DA, Lewis anti-BN, and DA anti-Lewis alloantibody immunosorbents were prepared. The major Ag-B chain (44,000 daltons) and the two polypeptide chains (34,000 and 27,000 daltons) of Ia were purified from Lewis, DA, and BN lymphocytes and absorbent on the above-mentioned immunosorbents. We found that the major Ag-B chain as well as the two Ia chains were bound to the alloantibody columns if they were derived from the corresponding allogeneic strain. No retaining ability for self-major histocompatibility complex (MHC) or third-party MHC chains was noted with the alloantibody immunosorbents. When using immunosorbents made up of idiotypic T-cell receptors, only two MHC polypeptides of the relevant allo-MHC type were retained, namely, the Ag-B and the heavy Ia chains. No detectable activity was observed when testing the same column for reactivity against third-party MHC polypeptide chains. However, the Lewis anti-DA T-cell receptors could be shown to display weak, but significant, reactivity toward one Lewis MHC polypeptide chain, that is, the heavy chain of Ia type.
Diabetes
Authors: David M. Nathan
Journal: JAMA (2015)

<h3>Importance</h3> Chronic diseases have overtaken acute diseases, such as infections, as the major cause of premature mortality worldwide. Diabetes mellitus, a chronic degenerative metabolic disease, has reached epidemic proportions in the past 30 years, with worldwide prevalence approaching 400 million people. <h3>Observations and Advances</h3> The epidemic is largely secondary to an increasing sedentary lifestyle and highly prevalent overweight and obesity contributing to the development of type 2 diabetes. Clinical research efforts have developed and demonstrated effective strategies for prevention, and the annual incidence of diabetes in the United States may be decreasing for the first time in 3 decades. The long-term complications of diabetes cause severe morbidity and mortality. Here too the means of reducing the burden of microvascular and cardiovascular disease have been proved. <h3>Conclusions and Relevance</h3> Improved glycemic control and better management of other identified risk factors for the complications of diabetes and more effective treatment of cardiovascular disease and microvascular complications have resulted in a more optimistic outlook for people with diabetes. This review focuses on recent advances in diagnosis and management and the remaining challenges in the prevention and treatment of diabetes mellitus.
Acquired palmoplantar keratoderma and immunobullous disease associated with antibodies to desmocollin 3
Authors: M.C. Bolling, J.R. Mekkes, W.F.M. Goldschmidt, C.J.M. van Noesel, M.F. Jonkman, H.H. Pas
Journal: British Journal of Dermatology (2007)

We present a case of immunobullous disease with an impressive acquired palmoplantar keratoderma (PPK) and unique antigenicity. The palms of the patient showed hyperkeratotic ridges with a tripe pattern that decreased with the amelioration of the immunobullous condition. The histopathology of perilesional skin (blister) demonstrated eosinophilic spongiosis and suprabasal blistering as in pemphigus vulgaris. In palmar skin, acantholysis, intraepidermal pustules, papillomatosis and marked hyperkeratosis were observed. Direct and indirect immunofluorescence displayed intraepidermal intercellular IgG staining as well as linear IgG staining along the epidermal basement membrane zone. Immunochemical assays revealed IgG antibodies to the desmosomal protein desmocollin 3 and to the hemidesmosomal proteins BP230 and LAD-1. Affinity-purified antidesmocollin 3 serum IgG bound to monkey oesophagus in the typical pemphigus pattern. Desmocollins are transmembrane proteins of the desmosome. Desmosome diseases may cause hereditary PPK. In our patient with acquired PPK, we hypothesize that the antibodies to desmocollin 3 were, apart from their role in eliciting the pemphigus-like blistering disease, also implicated in the pathogenesis of the PPK.
Communication skills &amp; overseas medical graduates
Authors: Richard Quinton
Journal: Journal of the Royal Society of Medicine (2012)

Formal communication skills teaching and training has been a feature of undergraduate medical education now for over two decades and, for postgraduate training, for over a decade in the UK, North America and Australasia. However, as the authors point out, it is generally not a core component of medical education elsewhere in the world. Quite apart from the idealistic aim of providing a better service to patients, there is also a financial imperative for organizations employing or indemnifying medical practitioners to ensure high-level communication skills, given that a large proportion of patient complains are at least in part attributable to issues of failed communication early on in the process.

Either one believes (as I do and the GMC purports to do) that formally-taught modules are an important part of developing doctors' and medical students' communications skills (in which case there has to be some kind of remedial training established for overseas doctors graduating from medical schools or postgraduate specialty training programmes where this was not the case), or one has to believe that communication skills training is a modern ‘educationalists fad’ and that actually learning ‘on the job’ through interacting with patients and colleagues is the only worthwhile way forward.

If one believes the former (as I do and the GMC purports to do), then the present situation exposes foreign medical graduates to an unnecessarily high risk of stress, litigation and disciplinary action, at least during initial phase of their working careers in the UK. If one doesn't believe it (as these non-UK medical schools presumably feel) then it has to be assumed that UK medical graduates are missing out on invaluable elements of education in human disease that have been displaced from the UK curriculum through greater focus on ‘soft skills’.
Hypoxia inducible factor-1-dependent up-regulation of BMP4 mediates hypoxia-induced increase of TRPC expression in PASMCs
Authors: Jian Wang, Xin Fu, Kai Yang, Qian Jiang, Yuqin Chen, Jing Jia, Xin Duan, Elizabeth W. Wang, Jianxing He, Pixin Ran, Nanshan Zhong, Gregg L. Semenza, Wenju Lu
Journal: Cardiovascular Research (2015)

Previously we demonstrated that both hypoxia inducible factor-1 (HIF-1) and bone morphogenetic protein-4 (BMP4) up-regulate transient receptor potential canonical (TRPC) 1 and TRPC6, resulting in increased basal intracellular Ca2+ concentration ([Ca2+]i) in pulmonary arterial smooth muscle cells (PASMCs), driving development of chronic hypoxia (CH)-induced pulmonary hypertension (CHPH). This study aims to determine whether HIF-1 regulates BMP4, and whether BMP4 mediates TRPC and basal [Ca2+]i increases in hypoxic PASMCs. The level of BMP4 mature protein was increased for ∼183% in distal pulmonary arterial smooth muscle (PA) from CH (10% O2 for 21 days; CH) exposed rats, and 143% in PASMCs cultured under prolonged hypoxia (4% O2 for 60 h). In rat PASMCs, HIF-1α overexpression up-regulated, whereas HIF-1α knockdown under hypoxia decreased BMP4 expression; site-mutation identified two functional HIF-1-binding sites in Bmp4 gene promoter; noggin or BMP4 siRNA treatment blocked hypoxia-induced increases of TRPC1 and TRPC6 expression and basal [Ca2+]i. Likewise, in mice, exposure to CH increased BMP4 expression in distal PA for ∼80%, which was absent in HIF-1α heterozygous mutant mice. Comparing with wild-type littermates, BMP4 heterozygous mutant mice exposed to CH displayed lower BMP4 and TRPC levels in PA, decreased basal [Ca2+]i in PASMCs, and attenuated CHPH. In human PASMCs, HIF-1α knockdown attenuated hypoxia-induced BMP4 expression and knockdown of either HIF-1α or BMP4 abolished hypoxia-induced TRPC expression and basal [Ca2+]i. BMP4 acts downstream of HIF-1 and mediates hypoxia-induced up-regulation of TRPC, leading to increased basal [Ca2+]i in PASMCs, promoting CHPH pathogenesis.
PARTICIPATION OF THREE CELL TYPES IN THE ANTI-SHEEP RED BLOOD CELL RESPONSE IN VITRO
Authors: Teresita Tan, Julius Gordon
Journal: The Journal of Experimental Medicine (1971)

Spleen cells of unprimed CBA mice were shown to produce anti-sheep red blood cell antibodies comparable in amount in vivo and in vitro. Under identical culture conditions spleen cells of C57BL mice did not respond. CBA spleen cells, passed through columns of cotton wool (CBAf), were equally inactive in vitro. However combined cultures containing both CBAf and C57BL cells yielded as many or more plaque-forming cells than the same number of unfractionated CBA spleen cells. Analysis of the contribution of each cell population to the synthesis of antibody in the combined cultures has disclosed the participation of three cell types. A thymus-dependent, radiosensitive cell was derived from the CBAf population, while the C57BL was the source of the precursor of the antibody-forming cell and of a radioresistant cell. The latter two were partially separated in a Staput apparatus.
Appraisal of sinus node artery disease.
Authors: T R Engel, S G Meister, G S Feitosa, H A Fischer, W S Frankl
Journal: Circulation (1975)

The relationship of depressed sinus node function to coronary artery disease (CAD) was evaluated. The sinus node artery (SNA) was easily identified in all of 80 unselected normal coronary arteriograms. Angiographic disease of, or significant obstruction proximal to, the SNA was seen in 21% of 80 unselected CAD patients. Heart rate and sinoatrial recovery times (SART) were obtained in 50 consecutive unmedicated patients prior to arteriography. There was no difference between the SART of 23 CAD patients free of SNA involvement (1092 msec +/- 55 sem) and 18 normals (1070 +/- 40 msec). Nine patients with SNA involvement had shorter SART (941 +/- 52 MSEC) than normals (P less than 0.05) or other CAD patients (NS). Similar results were obtained for heart rate. No patient with SNA involvement had a prolonged SART or sick sinus syndrom (SSS). six of the 50 patients studied were symptomatic with SSS. Five of these SSS patients had CAD but none had angiographic evidence of SNA involvement. Obstructions involving the SNA were common in CAD but were not associated with altered heart rate or SART. Patients with SSS exhibited no angiographic evidence of SNA involvement. Therefore, it is unlikely that SSS is related to CAD of the SNA.
Increased spontaneous release of tumour necrosis factor-alpha by alveolar macrophages from wheezy infants
Authors: I Azevedo, J de Blic, CH Dumarey, P Scheinmann, BB Vargaftig, M Bachelet
Journal: European Respiratory Journal (1997)

We determined if alveolar macrophages (AMs) from infants with severe recurrent wheezing episodes release increased amounts of tumour necrosis factor-alpha (TNF-alpha), as described in adults with asthma. We compared TNF-alpha release by unstimulated and lipopolysaccharide-stimulated AMs obtained by bronchoalveolar lavage in 13 wheezy and seven nonwheezy infants (aged 6-36 months) and analysed its regulation by dexamethasone. Metabolites in cell supernatants were quantified by enzyme-linked immunosorbent assay (ELISA) (TNF-alpha) or radioimmunoassay (thromboxane B2 and prostaglandin E2). Comparison of results was performed by the Mann-Whitney U-test and values were expressed as median (interquartile range) in ng x 10(6) cells(-1). Resting AMs from wheezy infants released larger amounts of TNF-alpha and thromboxane B2 as compared to controls: 2.67 (0.89-8.33) vs 0.48 (0.25-1.08) and 75.63 (38.07-158.91) vs 10.03 (7.36-76.08), respectively (p&lt;0.05). When stimulated overnight with bacterial lipopolysaccharide, AMs from both groups released similar amounts of metabolites. Dexamethasone induced a consistent inhibition of the lipopolysaccharide-stimulated release of all the mediators. Our results show that alveolar macrophages from wheezy infants are activated to release increased amounts of tumour necrosis factor-alpha, as in asthma, and suggest that infants with recurrent wheezing may eventually benefit from treatment with glucocorticoids.
Ionotropic Glutamate Receptors and Expression of<i>N</i>-Methyl-<scp>d</scp>-Aspartate Receptor Subunits in Subregions of Human Hippocampus: Effects of Schizophrenia
Authors: Xue-Min Gao, Kazuo Sakai, Rosalinda C. Roberts, Robert R. Conley, Brian Dean, Carol A. Tamminga
Journal: American Journal of Psychiatry (2000)

Multiple quantifiable biologic abnormalities have been localized to the hippocampus in schizophrenia. Alterations in glutamate-mediated transmission at N-methyl-D-aspartic acid (NMDA)-sensitive receptors in hippocampus have been implicated in the pathophysiology of the illness. The authors tested the hypothesis that glutamatergic transmission within and efferent from hippocampus is altered in schizophrenia.The authors analyzed postmortem hippocampal tissue from individuals with schizophrenia and from healthy individuals. The tissue samples had been collected by two brain tissue banks, one in Maryland and the other in Melbourne, Australia. lonotropic receptor binding for the NMDA, kainate, and (3)H-amino-3-hydroxy-5-methylisoxazol-4-propionate (AMPA) receptors was quantified by using usual radioligand techniques. In situ hybridization autoradiography was used to quantify mRNA for the NMDA receptor subunits NR1, NR2A, and NR2B.Ligand binding to the ionotropic glutamate receptors (NMDA, kainate, and AMPA) did not differ significantly overall or in any subregion between the schizophrenia tissue and the healthy comparison tissue. The only exception was AMPA receptor binding in hippocampal subregion CA2, which was slightly but significantly less in schizophrenia. However, the level of mRNA for the NMDA receptor subunits NR1 and NR2B was significantly different between groups; in several hippocampal subregions, the level of NR1 mRNA was lower and the level of NR2B mRNA higher in schizophrenia.Because the NR1 subunit of the NMDA receptor is critical to full receptor activity, a reduction of NR1 in hippocampus in schizophrenia suggests a functional impairment in glutamatergic transmission at the NMDA receptor, resulting in reduced glutamatergic transmission within and possibly efferent from the hippocampus in schizophrenia. This defect could underlie a hypoglutamatergic state in regions of limbic cortex, consistent with published results from other lines of research in schizophrenia.
Associations between genetic factors, tobacco smoking and autoantibodies in familial and sporadic rheumatoid arthritis
Authors: L Michou, V H Teixeira, C Pierlot, S Lasbleiz, T Bardin, P Dieudé, B Prum, F Cornélis, E Petit-Teixeira
Journal: Annals of the Rheumatic Diseases (2007)

Objectives: The objective of this study was to investigate the association between genes ( HLA-DRB1 and PTPN22 ) and tobacco smoking, separately as well as combined, and serological markers of rheumatoid arthritis (RA) in a French population with RA. Methods: 274 patients with RA with half of them belonging to RA multicase families, were genotyped for HLA-DRB1 allele and for PTPN22-1858 polymorphism. IgM rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies were determined by ELISA method. The search for association relied on χ 2 test and odds ratio with 95% confidence interval calculation. The interaction study relied on the departure-from-additivity-based method. Results: The presence of at least one shared epitope ( SE ) allele was associated with anti-CCP antibodies presence (82.5% vs. 68.4%, p = 0.02), particularly with HLA-DRB1*0401 allele (28.0% vs. 16.4%, p = 0.01). Tobacco exposure was associated with anti-CCP antibodies, but only in presence of SE. A tendency toward an interaction was found between tobacco, the presence of at least one HLA-DRB1*0401 allele and anti-CCP antibodies (attributable proportion due to interaction = +0.24 (−0.21+0.76)). The cumulative dose of cigarette smoking was correlated with anti-CCP antibody titres (r = 0.19, p = 0.04). The presence of both SE and 1858T alleles was associated with a higher, but not significantly different, risk for anti-CCP antibodies presence than for each separately. No association was found between PTPN22-1858T allele and tobacco smoking for autoantibody positivity. Conclusions: Our findings suggest an association between SE alleles and tobacco smoking for anti-CCP positivity and a tendency toward an interaction between the HLA-DRB1*0401 allele and smoking for anti-CCP positivity in this sample of RA.