tbuckley/cabot-search huggingface dataset:
ADAR1-Mediated RNA Editing, A Novel Mechanism Controlling Phenotypic Modulation of Vascular Smooth Muscle Cells
Authors: Jia Fei, Xiao-Bing Cui, Jia-Ning Wang, Kun Dong, Shi-You Chen
Journal: Circulation Research (2016)

Rationale : Vascular smooth muscle cell (SMC) phenotypic modulation is characterized by the downregulation of SMC contractile genes. Platelet-derived growth factor-BB, a well-known stimulator of SMC phenotypic modulation, downregulates SMC genes via posttranscriptional regulation. The underlying mechanisms, however, remain largely unknown. Objective : To establish RNA editing as a novel mechanism controlling SMC phenotypic modulation. Methods and Results : Precursor mRNAs (pre-mRNA) of SMC myosin heavy chain and smooth muscle α-actin were accumulated while their mature mRNAs were downregulated during SMC phenotypic modulation, suggesting an abnormal splicing of the pre-mRNAs. The abnormal splicing resulted from SMC marker pre-mRNA editing that was facilitated by adenosine deaminase acting on RNA 1 (ADAR1), an enzyme converting adenosines to inosines (A→I editing) in RNA sequences. ADAR1 expression inversely correlated with SMC myosin heavy chain and smooth muscle α-actin levels; knockdown of ADAR1 restored SMC myosin heavy chain and smooth muscle α-actin expression in phenotypically modulated SMC, and editase domain mutation diminished the ADAR1-mediated abnormal splicing of SMC marker pre-mRNAs. Moreover, the abnormal splicing/editing of SMC myosin heavy chain and smooth muscle α-actin pre-mRNAs occurred during injury-induced vascular remodeling. Importantly, heterozygous knockout of ADAR1 dramatically inhibited injury-induced neointima formation and restored SMC marker expression, demonstrating a critical role of ADAR1 in SMC phenotypic modulation and vascular remodeling in vivo. Conclusions : Our results unraveled a novel molecular mechanism, that is, pre-mRNA editing, governing SMC phenotypic modulation.
Some correlates of prospectively defined premenstrual syndrome
Authors: P P Schnurr
Journal: American Journal of Psychiatry (1988)

Correlates of prospectively defined premenstrual syndrome were investigated in 50 women who visited a premenstrual syndrome clinic. To assess premenstrual symptom change relative to daily change, the author used effect size, the difference in mood ratings between the post- and premenstrual phases divided by the standard deviation of the entire cycle. Only 12 women had an effect size greater than or equal to 1.0 in two cycles. The probability of having premenstrual syndrome was positively related to working outside the home and negatively related to age. The results underscore the need to use prospective diagnostic criteria in research on premenstrual syndrome.
A Cytopathologic Study of Tobacco Tar-Induced Lesions of Uterine Cervix of Mouse&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;4&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;5&lt;/xref&gt;
Authors: Koprowska, Irena, Bogacz, John
Journal: JNCI Journal of the National Cancer Institute (1959)

Journal Article A Cytopathologic Study of Tobacco Tar-Induced Lesions of Uterine Cervix of Mouse Get access Irena Koprowska, Irena Koprowska Department of Pathology, The Hahnemann Medical College and Hospital of Philadelphia, Philadelphia, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar John Bogacz John Bogacz Department of Pathology, The Hahnemann Medical College and Hospital of Philadelphia, Philadelphia, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 23, Issue 1, July 1959, Pages 1–19, https://doi.org/10.1093/jnci/23.1.1 Published: 01 July 1959 Article history Received: 09 July 1958 Revision received: 29 December 1958 Published: 01 July 1959
Lupus Nephritis IgG Induction of Calcium/Calmodulin-Dependent Protein Kinase IV Expression in Podocytes and Alteration of Their Function
Authors: Kunihiro Ichinose, Takeshi Ushigusa, Ayako Nishino, Yosikazu Nakashima, Takahisa Suzuki, Yoshiro Horai, Tomohiro Koga, Shin‐ya Kawashiri, Naoki Iwamoto, Mami Tamai, Kazuhiko Arima, Hideki Nakamura, Yoko Obata, Kazuo Yamamoto, Tomoki Origuchi, Tomoya Nishino, Atsushi Kawakami, George C. Tsokos
Journal: Arthritis & Rheumatology (2015)

Kidney podocytes and their slit diaphragms prevent urinary protein loss. T cells from patients with systemic lupus erythematosus display increased expression of calcium/calmodulin-dependent protein kinase IV (CaMKIV). The present study was undertaken to investigate the role of CaMKIV in podocyte function in lupus nephritis (LN).We treated kidney podocytes with IgG derived from healthy individuals or patients with LN and then analyzed gene expression using a DNA microarray. The localization of IgG in podocytes was analyzed by immunofluorescence staining, with or without silencing of neonatal Fc receptor (FcRn). In addition, we silenced CAMK4 in podocytes and analyzed the expression of selected genes. We also examined the expression of CD86 in kidney podocytes from MRL/lpr, MRL/lpr.camkiv(-/-), and MRL/MPJ mice by in situ hybridization.We found that exposure of podocytes to IgG resulted in entry of IgG into the cytoplasm. IgG entered podocytes via the FcRn because less IgG was found in the cytoplasm of podocytes treated with FcRn small interfering RNA. DNA microarray studies of podocytes exposed to LN-derived IgG revealed up-regulation of genes related to the activation of immune cells or podocyte damage. Interestingly, CD86 expression decreased after silencing CAMK4 in podocytes. Also, in situ hybridization experiments showed that the expression of CD86 was reduced in podocytes from MRL/lpr.camkiv(-/-) mice.LN-derived IgG enters podocytes and up-regulates CAMK4, which is followed by increased expression of genes known to be linked to podocyte damage and T cell activation. Targeted inhibition of CAMK4 in podocytes may prove to be clinically useful in patients with LN.
The role of sex therapy in marial therapy
Authors: C J Sager
Journal: American Journal of Psychiatry (1976)

Marital and sex therapy are clinically interrelated in most cases because they deal with different symptoms of overlapping aspects of the couple's total relationship. The connection between marital discord and sexual dysfunction determines the emphasis and course of treatment. For example, sex therapy is the immediate treatment of choice when sexual dysfunction produces secondary marital discord but not when severe discord precludes the possibility of good sexual functioning. The author presents case reports to illustrate the relationship of remote and immediate causes of marital and sexual problems and to emphasize the value of a multimodality approach to treatment.
John Locke
Authors: R. A. Norton
Journal: New England Journal of Medicine (1953)

THE seventeenth century was a remarkable period for England. Colonists moved out to occupy the new world discovered in the previous century; Puritan businessmen at home prospered and gradually gained political power, and the ages of blind faith and of fanatic zeal were passing away, to be replaced by tolerance and critical doubt. John Locke, a modest, pious and prudent man, lived among these changes and helped to direct them.He was born three hundred and twenty-one years ago near Bristol, the son of a country attorney. The Civil War was fought during his childhood, but his education took place . . .
Botulism in Norway
Authors: M Kuusi, V Hasseltvedt, P Aavitsland
Journal: Eurosurveillance (1999)

Botulism is a severe neuroparalytic disease caused by toxin produced by Clostridium botulinum, an anaerobic spore-forming bacillus. Physicians in Norway are required to notify the National Institute of Public Health (NIPH) of cases of botulism immediately
CLINICAL PSYCHOLOGY
Authors: OSCAR A. PARSONS, DAVID E. KEMP
Journal: American Journal of Psychiatry (1965)

A review of current research clearly indicates that variables, other than technical skills, within the therapist, clinical judge and experimenter contribute to the outcome of their professional work. Many of the effects of these variables are unintended and operation of the factors, which lead to such effects, unrecognized. The task confronting responsible professionals is clear. We must become increasingly aware of these variables and the specific manner in which they affect our outcomes.
Erratum to: Practical Considerations for the Use of Daratumumab, a Novel CD38 Monoclonal Antibody, in Myeloma
Authors: Philippe Moreau, Niels W. C. J. van de Donk, Jesus San Miguel, Henk Lokhorst, Hareth Nahi, Dina Ben-Yehuda, Michele Cavo, Gordon Cook, Michel Delforge, Hermann Einsele, Sonja Zweegman, Heinz Ludwig, Christoph Driessen, Antonio Palumbo, Thierry Facon, Torben Plesner, Meletios Dimopoulos, Pia Sondergeld, Pieter Sonneveld, María-Victoria Mateos
Journal: Drugs (2016)
Perfusion-induced changes in cardiac contractility and oxygen consumption are not endothelium-dependent
Authors: M DIJKMAN, J HESLINGA, P SIPKEMA, N WESTERHOF
Journal: Cardiovascular Research (1997)

Objective: Are substances released from rat coronary endothelial cells responsible for the increase in contractility and oxygen consumption (Gregg phenomenon) seen with an increase in cardiac perfusion? Methods: In an isovolumically contracting, Langendorff, crystalloid perfused rat heart ( n = 6) at 27 °C, coronary flow was changed (from 4.4 to 15.4 ml · min −1 · g WW−1 ) before and after the endothelium was made dysfunctional by Triton X-100. Vascular endothelium and smooth muscle function were tested with bradykinin (BK, 1 μM, an endothelium-dependent dilator) and papaverine (PAP, 1 μM, an endothelium-independent dilator) in a preconstricted vascular bed (vasopressin, VP, 3 nM). Results: Before Triton X-100, coronary resistance (at constant flow) decreased significantly in response to BK and to PAP. After Triton X-100 treatment the dilatory response to BK was abolished while the PAP response was still present, suggesting endothelial dysfunction with intact smooth muscle function. Due to Triton X-100 treatment, coronary resistance increased significantly. Therefore coronary flow changes were also applied during a similar increase in coronary resistance induced by VP infusion (3 nM) before Triton X-100 treatment. During control, developed left ventricular pressure (dev P lv ) increased with 68 ± 21% and oxygen consumption (Vo 2 ) increased with 122 ± 25% in response to the maximal increase in coronary flow. During increased coronary resistance with and without functional endothelium, dev P lv increased by 57 ± 16 and 64 ± 22%, respectively, and Vo 2 increased by 126 ± 21 and 103 ± 20%, respectively, in response to the maximal increase in flow. These changes were not significantly different from control. Conclusion: The results suggest that the arterial endothelium is not involved in the Gregg phenomenon.
Case of Aneurism of the Abdominal Aorta
Authors: J. C. Lucas
Journal: BMJ (1876)

dence and post mortem examination.Let it not be said that this capacity in the judge for taking the place of his own witness was a gain to the public.I hold it to be entirely the contrary.He acquired the capacity by a special education, which of itself guarantees that he shall not possess the knowledge of law required for the due discharge of his function, and this ignorance of law he has no power of supple- menting by calling, in ordinary cases at least, a legal adviser, and hence gross and irremediable mistakes and omissions frequently occur.The position of a medical coroner must often, I should suppose, be as uncomforlable as it is undignified.Having obtained it by an expensive election and, perhaps, a servile canvass, he finds the remuneration too small for a sole source of income, and has, therefore, to make its duties fit in with the toils and anxieties of private practice ; and he is also restrained in the inquiries lie may think it necessary to make by objec- tions, on the score of expense, made by an irresponsible authority to
Cosmetic outcome two and three years after intraoperative radiotherapy compared with external beam radiotherapy for early breast cancer: An objective assessment of patients from a randomized controlled trial.
Authors: M. R. Keshtgar, N. R. Williams, T. Corica, C. Saunders, D. J. Joseph
Journal: Journal of Clinical Oncology (2010)

570 Background: The international randomized TARGIT Trial, due to finish accrual in 2010, was designed to determine if there is equivalence between the novel technique of IORT (intraoperative radiotherapy with Intrabeam [Carl Zeiss, Germany]) and conventional external beam radiotherapy (EBRT) in women with early breast cancer. The main outcome objective is risk of local relapse within the treated breast. We report here the two- and three-year data from a subprotocol assessing cosmesis in a subset of 105 women over 50 participating in the TARGIT Trial from one center (Perth, Australia). Methods: Frontal digital photographs from patients at one TARGIT center (Perth, Australia) were assessed, blind to treatment, using specialist software (BCCT.core 2.0, INESC Porto, Portugal) that produces a composite score (excellent, good, fair, poor) based on symmetry, color, and scar. Statistical advice was given by the Biostatistics Group, The Joint UCL, UCLH, & Royal Free Biomedical Research Unit. Results: 105 patients have been assessed, median age at randomization 62 years (range 50 to 82). Photographs were taken 2 years (median 23 months, n=105) and 3 years (median 35 months, n=84) after initial breast conserving surgery; none had subsequent breast surgery. The scores were dichotomized into excellent and good, and fair and poor (Table). After 2 years 78% (43/55) of the IORT patients and 74% (37/50) of EBRT patients had excellent or good cosmetic outcome. 84 of these patients were assessed again at 3 years with similar results. Conclusions: These results indicate that there is no evidence of a difference in comesis between IORT and conventional EBRT, two and three years after surgery. Cosmetic outcome by randomized treatment Year 2 assessment (n=105) Year 3 assessment (n=84*) Excellent/good Fair/poor Excellent/good Fair/poor IORT 43 12 36 6 EBRT 37 13 32 10 * Statistical note: These patients are a subset of the 105 patients assessed at year 2 and the two chi-squared tests (below) are not independent: Year 2: Chi- Square = 0.25, df=1, p = 0.62 Year 3: Chi-Square = 1.24, df=1, p = 0.27. No significant financial relationships to disclose.
Surgical Management of Upper Tract Transitional Cell Carcinoma
Authors: Alison M. Lake, William W. Roberts
Journal: Journal of the National Comprehensive Cancer Network (2006)

Upper tract transitional cell carcinoma (TCC) accounts for approximately 5% of urothelial tumors. Surgical therapy for upper tract TCC is based on tumor grade, stage, location, and confounding factors of individual cases. Options for treatment range from minimally invasive procedures, such as ureteroscopy, to open nephroureterectomy. Laparoscopic nephroureterectomy is progressively eclipsing open nephroureterectomy in the surgical management of upper tract TCC. This article discusses the surgical options for managing upper tract TCC and their considerations for use.
A comparison of pimozide and haloperidol in the treatment of Gilles de la Tourette's syndrome
Authors: M S Ross, H Moldofsky
Journal: American Journal of Psychiatry (1978)

In a double-blind placebo-controlled study, both pimozide and haloperidol significantly decreased tic frequency in nine patients with Gilles de la Tourette's syndrome. These findings are consistent with the catecholamine hypothesis of tic generation. Pimozide was associated with significantly fewer complaints of lethargy. Follow-up 4-20 months later showed that six of seven patients receiving pimozide and one of two receiving haloperidol had had greater than 75% improvement in symptoms.
Psychiatrists' beliefs about gender-appropriate behavior
Authors: M J Kaplan, C Winget, N Free
Journal: American Journal of Psychiatry (1990)

Psychiatrists' beliefs regarding gender-appropriate behavior may influence their treatment of patients. Psychiatrists of both sexes (men: N = 76; women: N = 57) were asked to characterize optimal mental health for hypothetical female and male patients on the Bem Sex Role Inventory. The subjects' ratings for men and women were similar with two exceptions: more of the female psychiatrists rated masculine traits as optimal for female patients, and more male psychiatrists chose traits characteristic of Bem's undifferentiated category (low levels of both masculine and feminine traits) as optimal for both male and female patients. The results indicate significant changes in psychiatrists' attitudes toward gender in the past 20 years.
Dextran 40
Authors: ERICH F. SCHINAGL
Journal: Annals of Internal Medicine (1975)

Comments and Correction1 May 1975Dextran 40ERICH F. SCHINAGL, M.D., RIDA ALI, PH.D.ERICH F. SCHINAGL, M.D.Search for more papers by this author, RIDA ALI, PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-5-722_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We believe that the review article on dextran 40 by Data and Nies (Ann Intern Med 81:500-504, 1974) deserves comments on the "paradoxes" reported by the authors from their selective review of the dextran 40 literature.Dextran 40 is neither an anticoagulant nor an antiplatelet agent. Because increased platelet aggregation, blood viscosity, and elevated plasma fibrinogen concentration may lead to disseminated intravascular coagulation or shock lung, or both, in severely traumatized patients (1), many clinicians would regard decreased concentration of factors V, VIII, and IX (due largely to hemodilution) and decreased platelet adhesiveness (but not count) after...References1. BLAISDELL R: Intravascular coagulation and pulmonary changes following shock and trauma, in Acute Fluid Replacement in the Therapy of Shock, edited by MALINEN TI, New York, Stratton Intercontinental Medical Book Corp., 1974 Google Scholar2. CRONBERGROBERTSONNILLSON FBI: Suppressive effect of dextran on platelet adhesiveness. Thromb Diath Haemorrh 16:384-394, 1966 MedlineGoogle Scholar3. EVARTSFEIL CE: Prevention of thromboembolic disease after elective surgery of the hip. J Bone Joint Surg [Am] 53: 1271-1280, 1971 CrossrefMedlineGoogle Scholar4. SALZMANHARRISDE SANCTIS EWR: Reduction in venous thromboembolism by agents affecting platelet function. N Engl J Med 284:1287-1292, 1971 CrossrefMedlineGoogle Scholar5. MATHESON N: Renal effects of low molecular weight dextran. Monogr Surg Sci 3:303-364, 1966 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Pharmacia Laboratories, Inc. 800 Centennial Ave. Piscataway, New Jersey 08854 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byColloids Vs. Crystalloids—A Continuing Controversy 1 May 1975Volume 82, Issue 5Page: 722-723KeywordsAcute respiratory distress syndromeAnticoagulantsAttentionBlood plasmaDextranDisseminated intravascular coagulationFibrinogenPlatelet aggregationPlatelets Issue Published: 1 May 1975 PDF downloadLoading ...
Drug Allergy
Authors: Charles W. Parker
Journal: New England Journal of Medicine (1975)

Laboratory DiagnosisThe fact that there is no single, universally applicable test for drug allergy is not surprising since a number of different pathogenetic mechanisms can lead to allergic symptoms. In penicillin allergy, and to a lesser extent in other types of drug allergy, antibodies can often be detected by direct skin testing. Anaphylactic sensitivity is indicated by the development of a wheal and erythema skin response. A positive reaction usually reaches maximal intensity within a matter of 15 to 20 minutes, making routine skin testing immediately before drug therapy a practical possibility. Even when marked . . .
Abstract A04: Modulation of SAGA mediated nucleosome acetylation by linker DNA and activator
Authors: Chitvan Mittal
Journal: Cancer Research (2016)

Abstract The SAGA family of co-activators are highly conserved eukaryotic protein complexes that play a major role in regulating gene expression. These complexes facilitate transcription of inducible genes, in part, by acetylating the histone H3 tails of nucleosomes. While the factors that influence nucleosome acetylation are qualitatively understood, quantitative approaches offer the potential to better understand how the interaction between complex nucleosomal substrates, a multi-subunit SAGA complex, and regulatory proteins, combine to remodel the chromatin landscape of gene promoters. Toward this end, we have developed an initial rate, steady-state, acetylation assay using immobilized nucleosomes. For a minimal 147 bp mononucleosome, we find that acetylation activity saturates at a low nucleosome concentration (50 nM KM), and that turnover is quite slow (0.25 min-1 kcat). Addition of linker DNA to the nucleosome enhances acetylation activity up to 8-fold, and does so both by changing the apparent binding constant (2x decrease in KM) and the turnover step (4x increase in kcat). This dual mechanism of stimulation is recapitulated by addition of free DNA in trans, and we are investing the minimum lengths of DNA required for stimulation, as well as the mechanism of stimulation. When the transcriptional activator Gal4-VP16 becomes bound specifically to a recognition site within the linker DNA, additional stimulation of acetylation activity is observed. We are currently working towards gaining more insights into the mechanistic basis of this effect. The results give a more in depth perspective of how different factors work in conjunction to ultimately tune inducible transcription. Citation Format: Chitvan Mittal. Modulation of SAGA mediated nucleosome acetylation by linker DNA and activator. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr A04.
Catecholamine Receptor Function in Depressed Patients
Authors: Dennis L. Murphy, Cynthia Donnelly, Jay Moskowitz
Journal: American Journal of Psychiatry (1974)

The authors compared the effects of norepinephrine on catecholamine alpha receptors in platelets obtained from bipolar and unipolar depressed patients and from normal subjects. They found no differences, although reduced catecholamine receptor function has been suggested as one specific mechanism to account for a deficit in catecholamine function in depression.
Captopril
Authors: Jan Koch-Weser, Donald G. Vidt, Emannuel L. Bravo, Fetnat M. Fouad
Journal: New England Journal of Medicine (1982)

Captopril (D-3-mercapto-2-methylpropranoyl-L-proline [SQ 14,225, Capoten]) is the first orally active inhibitor of angiotensin-converting enzyme, the enzyme responsible for conversion of inactive angiotensin I to the potent pressor peptide angiotensin II. It is a potent, relatively specific competitive inhibitor of angiotensin-converting enzyme (kininase II), as well as an effective antihypertensive agent. Prior experience with the nonapeptide inhibitor of angiotensin-converting enzyme, teprotide (SQ 20,881), demonstrated that this parenterally administered agent was effective in the treatment of most patients with hypertension.1 , 2 The search for an orally effective inhibitor led to the development of captopril (Fig. 1),3 which has since undergone intensive clinical investigation . . .