tbuckley/cabot-search huggingface dataset:
Glucocorticoids induce the expression of CD8 alpha chains on concanavalin A-activated rat CD4+ T cells: induction is inhibited by rat recombinant interleukin 4.
Authors: F Ramirez, A J McKnight, A Silva, D Mason
Journal: The Journal of Experimental Medicine (1992)

Rat T lymphocytes, activated in vitro with concanavalin A (Con A), were shown by flow cytofluorographic analysis to contain a population of cells that simultaneously expressed CD4 and the alpha chain of CD8. The inclusion of the glucocorticoid hormone dexamethasone in the culture medium greatly increased both the frequency of these double-positive cells and the level of CD8 alpha chain expression. The level of expression of CD4 was not affected, and the cells that expressed CD8 antigen only also remained unchanged in surface phenotype. Detailed studies demonstrated unequivocally that the CD4+ CD8 alpha + cells were not artifacts produced by the random association of single-positive cells in the flow cytofluorograph, but arose from precursors that were single-positive CD4+ cells before activation. Furthermore, Con A activation of purified CD4+ T cells, in the presence of T cell-depleted accessory cells, showed that CD8+ T cells played no role in the induction process. However, the induction of CD8 alpha chain expression on CD4+ T cells and the enhancement of this expression by dexamethasone were almost completely inhibited by rat recombinant interleukin 4 (IL-4). Detection of mRNA for rat CD8 alpha chain by Northern blot closely paralleled the cell surface expression of CD8 alpha antigen, indicating that dexamethasone and IL-4 had opposing effects on mRNA levels. In contrast, IL-4 and dexamethasone both induced CD8 alpha chain expression on a rat CD4+ T cell clone when this was activated by specific antigen, and, although the effect with IL-4 was relatively weak, it did not antagonize the effect of the glucocorticoid. The possible significance of these results is briefly discussed.
The Impact of Hormone Replacement Therapy on Menopausal Symptoms in Younger High-Risk Women After Prophylactic Salpingo-Oophorectomy
Authors: Joanna B. Madalinska, Marc van Beurden, Eveline M.A. Bleiker, Heiddis B. Valdimarsdottir, Judith Hollenstein, Leon F. Massuger, Katja N. Gaarenstroom, Marian J.E. Mourits, René H.M. Verheijen, Eleonora B.L. van Dorst, Hans van der Putten, Ko van der Velden, Henk Boonstra, Neil K. Aaronson
Journal: Journal of Clinical Oncology (2006)

Preventive health strategies for women at increased hereditary risk of ovarian cancer include gynecologic screening (GS) and/or prophylactic oophorectomy (PBSO). Hormone replacement therapy (HRT) is often prescribed to compensate for postsurgical endocrine deficiencies. This study examined the impact of HRT use on levels of endocrine symptoms and sexual functioning among premenopausal women who have undergone PBSO. Comparisons were made with similar women undergoing GS.Questionnaire data on endocrine symptoms and sexual functioning were obtained from 450 premenopausal, high-risk women who had participated in this nationwide, cross-sectional, observational study.Thirty-six percent of women had undergone PBSO and 64% had opted for GS. In the PBSO group, 47% of the women were current HRT users. They reported significantly fewer vasomotor symptoms than nonusers (P < .05). However, compared with premenopausal women undergoing GS, oophorectomized HRT users were more likely to report vasomotor symptoms (P < .01). HRT users and nonusers reported comparable levels of sexual functioning. Compared with women in the GS group, oophorectomized HRT users reported significantly more sexual discomfort due to vaginal dryness and dyspareunia (P < .01).Although HRT has a positive impact on surgically induced vasomotor symptoms, it may be less effective than is often assumed. Symptom levels remain well above those of premenopausal women undergoing screening, and sexual discomfort is not alleviated by HRT. Physicians need to provide younger high-risk women considering PBSO with realistic information about both benefits and drawbacks of this preventive strategy, including information about premature menopause and HRT.
Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis
Authors: Daniel P Gale, Elena Goicoechea de Jorge, H Terence Cook, Rubén Martinez-Barricarte, Andreas Hadjisavvas, Adam G McLean, Charles D Pusey, Alkis Pierides, Kyriacos Kyriacou, Yiannis Athanasiou, Konstantinos Voskarides, Constantinos Deltas, Andrew Palmer, Véronique Frémeaux-Bacchi, Santiago Rodriguez de Cordoba, Patrick H Maxwell, Matthew C Pickering
Journal: The Lancet (2010)
The Development of the Human Body. A Manual of Human Embryology.
Authors: McMurrich J. Playfair
Journal: JAMA (1920)

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
Development of Neural Systems for Reading
Authors: Bradley L. Schlaggar, Bruce D. McCandliss
Journal: Annual Review of Neuroscience (2007)

Functional and structural neuroimaging studies of adult readers have provided a deeper understanding of the neural basis of reading, yet such findings also elicit new questions about how developing neural systems come to support this learned ability. A developmental cognitive neuroscience approach provides insights into how skilled reading emerges in the developing brain, yet also raises new methodological challenges. This review focuses on functional changes that occur during reading acquisition in cortical regions associated with both the perception of visual words and spoken language, and it examines how such functional changes differ within developmental reading disabilities. We integrate these findings within an interactive specialization framework of functional development and propose that such a framework may provide insights into how individual differences at several levels of observation (genetics, white matter tract structure, functional organization of language, cultural organization of writing systems) impact the emergence of neural systems involved in reading ability and disability.
Up‐dosing with bilastine results in improved effectiveness in cold contact urticaria
Authors: K. Krause, A. Spohr, T. Zuberbier, M. K. Church, M. Maurer
Journal: Allergy (2013)

Abstract Background Cold contact urticaria ( CCU ) is characterized by itchy wheal and flare responses due to the release of histamine and other pro‐inflammatory mediators after exposure to cold. The treatment of choice is nonsedating antihistamines, dosages of which may be increased up to fourfold if standard doses are ineffective. Here, we assess the effects of a standard 20 mg dose and up‐dosing to 40 and 80 mg of bilastine in reducing the symptoms of CCU and inflammatory mediator release following cold challenge. Methods Twenty patients with CCU were included in this randomized, crossover, double‐blind, placebo‐controlled 12‐week study. They received placebo, 20, 40 or 80 mg of bilastine daily each for 7 days with 14‐day washout periods. The primary readout was change in critical temperature thresholds ( CTT ). Secondary readouts were changes in pruritus, levels of histamine IL ‐6, IL ‐8 and TNF ‐α collected by skin microdialysis and safety and tolerability of bilastine. Results Bilastine 20 mg was highly effective ( P &lt; 0.0001) in reducing CTT . Up‐dosing to 80 mg significantly ( P &lt; 0.04) increased its effectiveness. At this dose, 19 of 20 (95%) patients responded to treatment, with 12 of 20 (60%) becoming symptom free. Only one patient was refractory to treatment. Microdialysis levels of histamine, IL ‐6 and IL ‐8 assessed 1–3 h after cold challenge were significantly ( P &lt; 0.05) decreased following up‐dosing with 80 mg bilastine. Bilastine treat‐ment was well tolerated without evidence of increased sedation with dose escala‐tion. Conclusions Bilastine was effective in reducing the symptoms of patients with CCU . Increased efficacy of bilastine with fourfold up‐dosing was without sedation and supports urticaria treatment guidelines.
Phase II preradiation R115777 (tipifarnib) in newly diagnosed GBM with residual enhancing disease
Authors: Robert Lustig, Tom Mikkelsen, Glenn Lesser, Stuart Grossman, Xiaobu Ye, Serena Desideri, Joy Fisher, John Wright
Journal: Neuro-Oncology (2008)

Glioblastoma multiforme (GBM) is a lethal primary malignant brain tumor in adults. R115777 (tipifarnib) is an oral agent with antiproliferative effects, being a potent and selective inhibitor of farnesyltransferase. This multicenter, open-label phase II study was designed to evaluate the efficacy and safety of R115777 given after surgery and prior to radiation in patients with newly diagnosed and residual enhancing GBM. Following surgery, an MRI confirmed the presence of residual enhancing tumor. Patients on enzyme-inducing antiseizure drugs (EIASDs) received 600 mg twice per day, and those not on EIASDs received 300 mg twice per day. One to three monthly cycles of R115777 were administered, and radiation was initiated with progression or after three cycles. A cycle consisted of 3 weeks of continuous R115777 followed by a 1-week rest. MRI was done monthly. The primary end point was overall survival; secondary end points were tumor response rate and toxicity. A total of 28 confirmed GBM patients entered the study; 15 patients (54%) were on EIASDs. The overall median time of survival was 7.7 months. There were no tumor responses. Eight patients (29%) had stable disease as the best response. The study was stopped early due to progression of the disease in 12 patients (48%). A total of 24 patients (85%) were off study before the planned treatment schedule for radiation therapy. R115777 administered prior to radiation therapy in patients with newly diagnosed GBM and residual enhancing disease did not result in any measurable responses or improvement in survival. R115777 administered prior to radiation therapy is not recommended for patients with newly diagnosed GBM.
Deletion of 1p32-p36 Is the Most Frequent Genetic Change and Poor Prognostic Marker in Adenoid Cystic Carcinoma of the Salivary Glands
Authors: Pulivarthi H. Rao, Diana Roberts, Yi-Jue Zhao, Diana Bell, Charles P. Harris, Randal S. Weber, Adel K. El-Naggar
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Adenoid cystic carcinoma (ACC) is a relatively uncommon salivary gland malignancy known for its protean phenotypic features and pernicious clinical behavior. Currently, no effective therapy is available for patients with advanced nonresectable, recurrent, and/or metastatic disease. The purpose of this study is to identify prognostic factors other than tumor stage that can be used to predict the outcome of the patients with ACC. Experimental Design: We used comparative genomic hybridization (CGH) to identify copy number aberrations in 53 primary ACCs. Array CGH and fluorescence in situ hybridization analysis was used to validate CGH results on selected cases. We correlated these copy number aberrations with clinicopathologic factors using Pearson's χ2 or by the two-tailed Fisher exact test. The disease-specific survival and disease-free intervals were generated by the Kaplan-Meier product limit method. Results: Chromosomal losses (n = 134) were more frequent than gains (n = 74). The most frequent genetic change was the loss of 1p32-p36 in 44% of the cases followed by 6q23-q27, and 12q12-q14. The most frequently gained chromosomal regions were 8 and 18. Of the chromosomal aberrations, loss of 1p32-p36 was the only abnormality significantly associated with patient's outcome. Conclusions: This study, for the first time, identifies loss of 1p32-p36 as a significant aberration in ACC. Molecular characterization of 1p32-36 region using the available genomic technologies may lead to the identification of new genes critical to the development of novel therapeutic targets for this disease copy number aberration.
Marker genes of decidualization: activation of the decidual prolactin gene
Authors: R Telgmann
Journal: Human Reproduction Update (1998)

Decidualization of human endometrial stromal (ES) cells in vitro is induced by cAMP analogues and ligands that elevate cellular cAMP levels in a manner resembling the gonadotrophins, prostaglandin E2 and relaxin (RLX). This differentiation process is marked by the onset of decidual prolactin (PRL) production in the late luteal phase of the cycle. Using transfection assays and a primary ES cell culture system, we have demonstrated that decidual PRL gene transcription is driven by an alternative upstream promoter (dPRL), approximately 6 kb upstream of the pituitary transcription start site. In primary cell cultures, RLX not only acutely but also permanently elevated cellular cAMP levels and induced PRL secretion after 6 days. Northern and Western blot analyses revealed all regulatory subunit isoforms (RIα, RIβ, RIIα, RIIβ) and catalytic subunits Cα and Cβ of protein kinase A (PKA) in ES cells. Transcript levels of PKA subunit isoforms are not altered during decidualization, but in decidualized ES cells exposed to elevated cellular cAMP levels by stimulation with RLX for >6 days, RIα protein levels were significantly reduced, whereas levels of all other forms remained unchanged. Reducing the availability of R subunits changed the R:C subunit ratio in favour of C and increased kinase activity. In transient transfections of undifferentiated ES cells, the dPRL promoter was activated by 8-Br-cAMP and by C subunit (Cβ) of PKA. This induction, and the differentiation-dependent activity of the dPRL promoter in transfected decidualized cells, was effectively abolished by the co-expression of protein kinase inhibitor (PKI). A fragment of 332 bp of 5'-flanking region of the dPRL transcription start site was sufficient to mediate full inducibility by cAMP. cAMP activation of the dPRL promoter in ES cells was biphasic as an initial weak induction within 12 hours was followed by a subsequent, much more intense induction after 12 hours. The secondary induction was not seen with a control construct driven by a consensus cAMP response element (CRE) linked to a minimal promoter. The early response of the dPRL promoter depended upon a non-palindromic CRE at position-12 and mutation of this sequence led to omission of the early, but not of the delayed, induction. The major activation of the dPRL promoter depended upon a different region between position -332 and -270 since its deletion significantly reduced inducibility by cAMP. Its action was probably indirect as its kinetics differed from classic CRE-mediated responses, and it was specific to ES cells.
THALASSEMIA: Pathophysiology of Red Cell Changes
Authors: Stanley L. Schrier, M.D
Journal: Annual Review of Medicine (1994)

▪ Abstract The thalassemias are extremely heterogeneous in terms of their clinical severity, and their underlying pathophysiology relates directly to the extent of accumulation of excess unmatched globin chains: α in βthalassemia and βin the αthalassemias. However, the accumulation of each separate globin chain affects red cell membrane material properties and the state of red cell hydration very differently. These observations presumably account for the varying extent of ineffective erythropoiesis and peripheral blood hemolysis in the major variants of thalassemia.
Role of Endothelin in Deterioration of Heart Failure Due to Cardiomyopathy in Hamsters
Authors: Rikako Yamauchi-Kohno, Takashi Miyauchi, Tomoko Hoshino, Tsutomu Kobayashi, Hajime Aihara, Satoshi Sakai, Hideo Yabana, Katsutoshi Goto, Yasuro Sugishita, Sakae Murata
Journal: Circulation (1999)

We previously reported that chronic endothelin (ET) receptor blockade ameliorated the survival rate and cardiac hemodynamics in rats with chronic heart failure (CHF) due to myocardial infarction. However, it remains unclear whether ET-1 is involved in the pathophysiology of cardiomyopathy, which is one of the major causes of CHF. Accordingly, we investigated the production of ET-1 in the heart and the effect of chronic ETA receptor blockade on survival rate and cardiac function in the Bio 14.6 hamster, which is an idiopathic model of CHF caused by cardiomyopathy.We used 52-week-old Bio 14.6 cardiomyopathic hamsters and age-matched F1b normal hamsters. The expression of preproET-1 mRNA and the ET-1 level in the hearts were markedly higher in the cardiomyopathic hamsters than in the normal hamsters. The cardiomyopathic hamsters showed severe CHF, illustrated by lower left ventricular (LV) +dP/dt/Pmax and right ventricular (RV) +dP/dt/Pmax and by higher LV end-diastolic pressure (EDP), RVEDP, and central venous pressure compared with the normal hamsters. Long-term (9 weeks) treatment with an ETA antagonist (TA-0201, 1.3 mg. kg-1. d-1) markedly increased survival of cardiomyopathic hamsters (untreated, 16%; TA-0201-treated, 65.2%; P<0.001). After 6 weeks of treatment, LV +dP/dt/Pmax and RV +dP/dt/Pmax were significantly higher and LVEDP and RVEDP were lower in the TA-0201-treated group than in the untreated group, suggesting that chronic TA-0201 treatment effectively prevented deterioration of cardiac dysfunction.In the cardiomyopathic hamsters with CHF, the production of ET-1 in the heart was markedly increased, and chronic ETA receptor blockade greatly ameliorated survival and cardiac dysfunction. These results suggest that ET-1 plays an important role in the deterioration of CHF caused by cardiomyopathy, and ETA antagonists may exert therapeutic effects in CHF due to cardiomyopathy.
Formoterol 24 μg is not associated with an increase in serious asthma exacerbations in patients with persistent asthma
Authors: J. Wolfe, C. LaForce, N.K. Ostrom, P. Korenblat, C. Orevillo, B. Ziehmer, D. Till, S. Stenglein
Journal: Journal of Allergy and Clinical Immunology (2005)
On the shear rate dependence of red cell aggregation in vitro
Authors: H. Schmid-Schönbein, P. Gaehtgens, H. Hirsch
Journal: Journal of Clinical Investigation (1968)

Non-Newtonian viscosity of blood, i.e., the rise in apparent viscosity at low flow, was believed to be a result of reversible aggregation of red cells at low velocity gradients (shear rate). By making a cone-plate viscometer transparent, direct observation was made possible of the blood flowing under defined shear rates. Red cell aggregates, occurring in all cases at low flow, were reversibly dispersed by increasing the shear rate. This behavior was independent of the addition of anticoagulants, but it could be altered by changing the plasma protein composition. Red cells in serum did not form aggregates; such nonaggregating samples did show an increase in viscosity at low shear rates. Since the sedimentation rate can be influenced by many parameters, it is not reliable in describing red cell aggregation. Aggregation of red cells is linked with a marked separation of plasma and cells. Such a separation is of considerable influence on cone-plate viscometry.
Diabetes and Impaired Fasting Glycemia in a Rural Population of Bangladesh
Authors: M. Abu Sayeed, Hajera Mahtab, Parvin Akter Khanam, Zafar Abdul Latif, S. M. Keramat Ali, Akhter Banu, Bo Ahren, A.K. Azad Khan
Journal: Diabetes Care (2003)

To determine the prevalence of type 2 diabetes and impaired fasting glycemia (IFG) in a rural population of Bangladesh.A cluster sampling of 4,923 subjects >/=20 years old in a rural community were investigated. Fasting plasma glucose, blood pressure, height, weight, and girth of waist and hip were measured. BMI and waist-to-hip ratio (WHR) were calculated. Total cholesterol, triglycerides, and HDL cholesterol were also estimated. We used the 1997 American Diabetes Association diagnostic criteria.The crude prevalence of type 2 diabetes was 4.3% and IFG was 12.4%. The age-standardized prevalence of type 2 diabetes (95% CI) was 3.8% (3.12-4.49) and IFG was 13.0% (11.76-14.16). The subjects with higher family income had significantly higher prevalence of type 2 diabetes (5.9 vs. 3.5%, P < 0.001) and IFG (15.6 vs. 10.8%, P < 0.001) than those with lower income. Employing logistic regression in different models, we found that wealthy class, family history of diabetes, reduced physical exercise, and increased age, BMI, and WHR were the important predictors of diabetes. Total cholesterol, triglycerides, and HDL cholesterol showed no association with diabetes and IFG.The prevalence of diabetes and IFG in the rural population was found to be on the increase compared with the previous reports of Bangladesh and other Asian studies. Older age, higher obesity, higher income, family history of diabetes, and reduced physical activity were proved significant risk factors for diabetes and IFG, whereas plasma lipids showed no association with diabetes and IFG. Further study may address whether diabetes is causally associated with insulin deficiency or insulin resistance.