tbuckley/cabot-search huggingface dataset:
P618PAR2 expression differentially regulates immune response upon treatment with Poly(I:C) and LPS
Authors: A Weithaeuser, HP Schultheiss, U Rauch
Journal: Cardiovascular Research (2014)

Introduction: The protease activated receptor 2 (PAR2) is a G-protein coupled receptor, that is activated by serine proteases such as trypsin, tryptase and the complex composed of tissue factor (TF)/ factor VII (FVII) and factor X (FX). PAR2 is also involved in modulating immune response after infections with pathogens. The activation of PAR2 is associated with the induction of a pro-inflammatory response by induction of gene expression of cytokines, such as IL8. Here we studied role of PAR2 for the innate immune response in the heart.
Abstract A29: Mdm2 E3 ubiquitin ligase function is dispensable for the degradation of Mdm2 itself
Authors: Tae-Hyung Kim, Yanping Zhang
Journal: Cancer Research (2013)

Abstract Mdm2 has long been considered the major negative regulator of both p53 stability and activity. The RING finger domain of Mdm2 confers its E3 ubiquitin ligase activity, and through this function Mdm2 controls p53 stability, additionally, auto-ubiquitination of Mdm2 is believed to be the primary mechanism of Mdm2 degradation. In vitro, mutation or truncation of the RING domain in Mdm2 resulted in loss of ubiquitin ligase activity towards both Mdm2 and its substrate p53. In contrast, recent knock-in mouse models indicate that under physiological conditions the Mdm2 RING-mediated E3 ubiquitin ligase function is dispensable for Mdm2 degradation. To investigate the in vivo significance of Mdm2 auto-ubiquitination, we compared two Mdm2 knock-in mouse strains each harboring a single amino acid substitution in RING domain (C462A) or C-terminus (Y487A). Both knock-in mutants disrupt Mdm2 E3 ligase activity for p53. We observed that (1) mutant Mdm2 protein (C462A or Y487A) fails to degrade p53 protein. (2) Wild type and mutant Mdm2 are degraded similarly. Despite efficient disruption of p53 degradation, half-life assays demonstrated that neither of the Mdm2 mutants affected the rate of degradation of Mdm2 itself indicating not only that Mdm2 auto-ubiquitination is not the primary mechanism for Mdm2 degradation in vivo, but also that an additional mechanism is in action to regulate Mdm2. (3) Inhibition of proteasomal degradation by MG-132 resulted in similar levels of accumulation of both wild type and mutant Mdm2s suggesting Mdm2 degradation is mediated via the proteasome. In vivo ubiquitination assay reconfirmed that Mdm2 RING domain mutation does not affect degradation and accumulation of Mdm2 itself, further implicating the possibility of an outside E3 ligase activity. In conclusion, auto-ubiquitination of Mdm2 is not necessary for Mdm2 degradation in vivo. The identification of E3 ubiquitin ligases with specificity for Mdm2 is an important next step to gain mechanistic insight into the regulation of Mdm2 regulation, and with that, p53. Citation Format: Tae-Hyung Kim, Yanping Zhang. Mdm2 E3 ubiquitin ligase function is dispensable for the degradation of Mdm2 itself. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A29.
GPs will be asked to spearhead mental health care in the next decade
Authors: L. Eaton
Journal: BMJ (2009)

General practitioners in England will be encouraged to sign up to better training in mental health care, as part of the government’s latest mental health policy, said the national director for mental health, Louis Appleby.

Speaking at a conference of the Westminster Health Forum in London on 17 September, Professor Appleby said he …
Sexual Dysfunction in Women With Type 1 Diabetes
Authors: Paul Enzlin, Chantal Mathieu, Annick Van den Bruel, Jan Bosteels, Dirk Vanderschueren, Koen Demyttenaere
Journal: Diabetes Care (2002)

OBJECTIVE—This study aimed to 1) examine the prevalence of sexual problems in women with type 1 diabetes, 2) compare this prevalence rate with that of an age-matched control group, 3) study the influence of diabetes-related somatic factors on female sexuality, and 4) study the influence of psychological variables on the sexual functioning of both groups. RESEARCH DESIGN AND METHODS—A total of 120 women with diabetes visiting the outpatient diabetes clinic completed questionnaires evaluating psychological adjustment to diabetes, marital satisfaction, depression, and sexual functioning. Medical records were used to obtain data on HbA1c, use of medication, BMI, and early-onset microvascular complications. An age-matched control group of 180 healthy women attending an outpatient gynecological clinic for preventive routine gynecological assessment also completed the non–diabetes-related questionnaires. RESULTS—More women with diabetes than control subjects reported sexual dysfunction (27 vs. 15%; P = 0.04), but a significant difference was found only for decreased lubrication. No association was found between sexual dysfunction and age, BMI, duration of diabetes, HbA1c, use of medication, menopausal status, or complications. Women with more complications, however, reported significantly more sexual dysfunctions, and the presence of complications altered treatment satisfaction. Both diabetic and control women with sexual dysfunction mentioned lower overall quality of the marital relation and more depressive symptoms than their respective counterparts without sexual problems. Depression was a significant predictor for sexual dysfunction in both women with diabetes and control subjects. CONCLUSIONS—Sexual problems are frequent in women with diabetes. They affect the overall quality of life and deserve more attention in clinical practice and research.
Atrial natriuretic factor-specific antibody as a tool for physiological studies. Evidence for role of atrial natriuretic factor in aldosterone and renal electrolyte regulation.
Authors: M A Rudd, S Plavin, A T Hirsch, J R Ingelfinger, V J Dzau
Journal: Circulation Research (1989)

Numerous studies have shown that administration of atrial natriuretic factor (ANF) increases urinary sodium excretion and urine flow, decreases blood pressure, and inhibits renin and aldosterone release. However, the role of endogenous ANF in the regulation of renal sodium excretion, blood pressure, plasma renin activity, and aldosterone level remains to be elucidated. To examine this issue, endogenous ANF was blocked by administering rat ANF-(99-126) specific antiserum (Ab) to anesthetized rats (n = 7). Control animals received either no injection (time controls, n = 10) or preimmune serum (n = 8). Blockade of endogenous ANF caused a 28 +/- 0.09%, 47 +/- 0.08%, and 51 +/- 0.08% fall in sodium excretion at 15, 30, and 45 minutes after Ab injection (p less than 0.05, p less than 0.01, p less than 0.01, respectively). Urine flow fell 35 +/- 7% at 45 minutes after ANF inhibition (p less than 0.05). Plasma ANF levels were suppressed to undetectable levels. However, there were no changes in blood pressure throughout the experiment nor plasma renin concentration when measured at 45 minutes after Ab injection. Interestingly, plasma aldosterone concentration increased significantly (by approximately 50%, p less than 0.025), in response to Ab. Completeness of blockade was demonstrated by the absence of sodium excretion response to exogenous ANF (500 ng). In either the time control or the preimmune serum group, urinary excretion, blood pressure, plasma ANF, plasma renin concentration, and plasma aldosterone concentration were unchanged throughout the experiment. In contrast to the Ab group, a challenge with exogenous ANF (500 ng) increased sodium excretion by 2.17 mueq/min in the preimmune serum group.(ABSTRACT TRUNCATED AT 250 WORDS)
High insulin-like growth factor binding protein 1 levels in cirrhosis: Link with insulin resistance
Authors: E Shmueli, J P Miell, M Stewart, K G Alberti, C O Record
Journal: Hepatology (1996)

Hyperinsulinemic euglycemic clamps were performed on six patients with compensated alcoholic cirrhosis and on six normal comparison subjects. As in previous studies, glucose uptake in the cirrhotic patients was only 21% of the comparison value. The cirrhotic patients had high growth hormone (GH) and low insulin-like growth factor-I (IGF-I) levels, with low insulin-like growth factor-binding protein (IGFBP)-3 levels, but surprisingly high IGFBP-I levels (26.8 +/- 8.4 microgH vs. 3.2 +/- 0.2 microm/L, P < .001). The log IGFBP-1 level was inversely correlated with the log insulin sensitivity (r = -.95). The clamps were repeated with a somatostatin infusion to suppress GH secretion. IGFBP-1 increased in both groups, especially in the cirrhotic subjects. Insulin sensitivity increased in the normal subjects but was unchanged in the cirrhotic patients. Following GH treatment (0.13 U/kg/d for 5 days), the clamps were repeated. GH, IGF-1, and IGFBP-3 levels were now similar in the two groups; IGFBP-1 levels decreased in the cirrhotic patients but remained fivefold higher than the comparison value (10.6 +/- 3.7 vs. 2.1 +/- 0.4, P < .05). Glucose uptake in the cirrhotic patients remained only 29% of the comparison value, but the change in their insulin sensitivity was inversely correlated with the change in their IGFB-1 levels (r = -.84). These results suggests an important role for IGFBP-1 in modulating insulin sensitivity in cirrhosis.
Book Review The Kaspar Hauser Syndrome of ”Psychosocial Dwarfism”: Deficient Statural, Intellectual, and Social Growth Induced by Child Abuse By John Money. 290 pp. Buffalo, N.Y., Prometheus Books, 1994. $25.95. 0-87975-754-X
Authors: Joseph Gonzalez-Heydrich
Journal: New England Journal of Medicine (1994)
Disappearance of drugs undermines Uganda's fight against malaria
Authors: P. Moszynski
Journal: BMJ (2010)

<h3>Abstract</h3> The inner ear has a rich population of pericytes, a multi-functional mural cell essential for sensory hair cell heath and normal hearing. However, the mechanics of how pericytes contribute to the homeostasis of the auditory vascular-neuronal complex in the spiral ganglion is not yet known. In this study, using an inducible and conditional pericyte depletion mouse (<i>Pdgfrb</i><sup><i>CreERT2+/-</i></sup>; <i>ROSA26</i><sup><i>iDTR+/-</i></sup>) model, we demonstrate, for the first time, that pericyte depletion causes loss of vascular volume and spiral ganglion neurons (SGNs) and adversely affects hearing sensitivity. Using an <i>in vitro</i> trans-well co-culture system, we show pericytes markedly promote neurite and vascular branch growth in neonatal SGN explants and adult SGNs. The pericyte-controlled neural growth is strongly mediated by pericyte-released exosomes containing vascular endothelial growth factor-A (VEGF-A). Treatment of neonatal SGN explants or adult SGNs with pericyte-derived exosomes significantly enhances angiogenesis, SGN survival, and neurite growth, all of which were inhibited by a selective blocker of the VEGF receptor 2 (Flk1). Our study demonstrates that pericytes in the adult ear are critical for vascular stability and SGN health. Cross-talk between pericytes and SGNs via exosomes is essential for neuronal and vascular health and normal hearing.
Treatment Outcome and Survival Associated With Metastatic Renal Cell Carcinoma of Non–Clear-Cell Histology
Authors: Robert J. Motzer, Jennifer Bacik, Tania Mariani, Paul Russo, Madhu Mazumdar, Victor Reuter
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To define outcome data for patients with metastatic renal cell carcinoma (RCC) with histology other than clear-cell type, including collecting duct (or medullary carcinoma), papillary, chromophobe, and unclassified histologies. PATIENTS AND METHODS: Sixty-four patients with metastatic non–clear-cell RCC histology were the subjects of this retrospective review. Included in the analysis were 22 (8%) of 286 patients from a clinical trials database, 19 of 1,166 patients from a surgery database, and 23 of 357 patients from a pathology database. RESULTS: The prevalent histology was collecting duct, present in 26 (41%) patients. The number of patients with chromophobe and papillary histologies was 12 (19%) and 18 (28%), respectively. Eight (12%) of the patients had tumors that could not be classified for specific tumor histology. Among the 43 patients treated with 86 systemic therapies, including 37 cytokine therapies, two patients (5%) were observed to have a partial response. The median overall survival time was 9.4 months (95% confidence interval, 8 to 14 months). The survival was longer for patients with chromophobe tumors compared with collecting duct or papillary histology, and this group included four patients with survival of greater than 3 years. CONCLUSION: RCC consists of a heterogeneous group of tumors including clear-cell, papillary, chromophobe, collecting duct, and unclassified cell types. Non–clear-cell histologies constitute less than 10% of patients in general populations of patients with advanced RCC treated on clinical trials. Metastatic non–clear-cell RCC is characterized by a resistance to systemic therapy and poor survival, with the survival for patients with chromophobe tumors longer than that for patients with metastatic collecting duct or papillary RCC. Treatment with novel agents on clinical trials is warranted.
Routine Depression Screening for Patients With Diabetes
Authors: Brett D. Thombs
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
Diagnosis and management of maturity onset diabetes of the young (MODY)
Authors: G. Thanabalasingham, K. R. Owen
Journal: BMJ (2011)

#### Summary points

Maturity onset diabetes of the young (MODY) comprises a heterogeneous group of monogenic disorders characterised by β cell dysfunction. It is estimated to be the underlying cause of diabetes in 1-2% of patients diagnosed with diabetes, but prevalence estimates will not be accurate until large population screening studies are performed.1 It is important to distinguish MODY from type 1 and type 2 diabetes because optimal treatments are different. Furthermore, first degree relatives have a 50% probability of inheriting the same mutation, which confers a greater than 95% lifetime risk of developing diabetes.2 Distinguishing people who have rare forms of diabetes such as MODY from those with type 1 or type 2 diabetes is a diagnostic challenge because clinical features are similar. In this review we discuss when the general physician might suspect MODY and how to identify which patients with diabetes should be offered genetic testing. We focus on the recognition of the common forms of MODY in people diagnosed with diabetes in the age range 10-45 years, drawing mainly on evidence from small trials and cross …
Western European Responses to Physician Oversupply
Authors: Steven A. Schroeder
Journal: JAMA (1984)

The supply and specialty distribution of physicians in Belgium, West Germany, the Netherlands, and the United Kingdom were compared with those in the United States. The numbers of physicians per 10,000 population in 1980 was 24 (Belgium), 22.9 (West Germany), 19.1 (United States), 19.0 (the Netherlands), and 16.2 (United Kingdom). Projections for 1990 were 34 (Belgium), 32.6 (West Germany), 24.3 (United States), and 17.1 (United Kingdom). The United States and the United Kingdom produce about half as many physicians per population but have a much higher proportion (26%) of foreign physicians. The United States has a much higher ratio of specialists to generalists. Official recognition of physician oversupply exists in Belgium, which is restricting specialty training, and the Netherlands, which is reducing both medical school intake and specialty training, but not yet in West Germany. The European experience suggests that the United States' most pressing health manpower problem is an oversupply of specialists. (<i>JAMA</i>1984;252:373-384)
Treatment of Alopecia Totalis
Authors: Walter P. Unger
Journal: JAMA (1974)

<h3>To the Editor.—</h3> In my opinion, the dosages that Dr. Orentreich recommended for alopecia (229:204, 1974) are inadequate and would result in the unsuccessful treatment of many patients who could benefit from an increased dosage of both preparations. These patients should be treated initially with at least 30 mg of prednisone per day, tapering rapidly to 10 to 15 mg/day over a period of one month, and thereafter the dosage adjusted according to apparent need. Intralesionally administered steroids should be used so that systemic treatment can be kept to a minimum; however, the amounts I have used have been 3 ml of a 3.33-mg/ml solution of triamcinolone acetonide every two to three weeks. I reported on the successful treatment of two patients with alopecia totalis in the<i>Canadian Medical Association Journal</i>on Jan 20, 1973. Since that time, we have treated a total of ten patients, eight of whom have had
Peptide-conjugated polyamidoamine dendrimer as a nanoscale tumor-targeted T1 magnetic resonance imaging contrast agent
Authors: Liang Han, Jianfeng Li, Shixian Huang, Rongqin Huang, Shuhuan Liu, Xing Hu, Peiwei Yi, Dai Shan, Xuxia Wang, Hao Lei, Chen Jiang
Journal: Biomaterials (2011)
Abstract 1786: Improved survival with gemcitabine and CTLA-4 blockade in a murine model of prostate cancer
Authors: Charlotte E. Ariyan, Segio Quezada, Emily Corse, Welby Montalvo, James Allison
Journal: Cancer Research (2011)

Abstract Introduction: Immunotherapy with CTLA-4 blockade has resulted in dramatic responses in patients with advanced melanoma and prostate cancer. However, only 10-30% of patients have a response, therefore there is a need to increase the efficacy of CTLA-4 blockade. In this work we tested the hypothesis that combinatorial approaches incorporating tumor destruction with conventional chemotherapy and CTLA-4-blockade would synergize to significantly increase anti-tumor activity in vivo. Experimental Procedure: Mice with a transplantable prostate tumor (TRAMPC2) were treated with 5 doses of gemcitabine alone, or followed by immunotherapy with CTLA-4 blockade. Control mice were treated with isotype antibody. Tumor growth was measured by calipers and mice were sacrificed when tumors reached 15mm. Progression was followed over time and CD8 T cell responses to the tumor specific antigen SPAS were examined by tetramer staining and functional assays ex vivo. Data: Mice treated with the combination gemcitabine and α-CTLA-4 had improved survival over mice treated with gemcitabine alone. The majority of mice treated with control Hamster Ig or CTLA-4 blockade died (median survival 59 days for both groups). The median survival of mice treated with gemcitabine was 72 days with 50% having long-term survival. The addition of α-CTLA-4 to gemcitabine treatment increased median survival to &amp;gt; 125 days with 65% of mice with long term survival (p&amp;lt;0.05 for survival of gemcitabine versus gemcitabine + α-CTLA-4). The additive effect of α-CTLA-4 was lost when CD8 T cells were depleted. Analysis of draining lymph nodes revealed a reduced number of T regulatory T cells and myeloid suppressor cells with gemcitabine treatment. Mice receiving combination treatment had increased accumulation of tetramer positive CD8 cells for the SPAS peptide in the spleen and tumor draining lymph node. In addition, the combination treated mice had increased IFNγ production by ELISPOT in response to SPAS peptide re-stimulation ex vivo (p&amp;lt;0.05 for gemcitabine versus gemcitabine and α-CTLA-4). Conclusion: Combination chemo- and immunotherapy with gemcitabine and α-CTLA-4 improves survival. This is associated with an accumulation of CD8 cells that are tumor specific. Depletion of CD8 cells reduces the efficacy of this treatment. This study supports further investigation into the additive effects of chemotherapy with CTLA-4 blockade. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1786. doi:10.1158/1538-7445.AM2011-1786
Growth, behaviour, and educational achievement of Jamaican children with sickle-cell trait.
Authors: M T Ashcroft, P Desai, S A Richardson, None Serjeant
Journal: BMJ (1976)

A longitudinal study of the mental and physical development of 200 children with normal haemoglobin and 21 with the sickle-cell trait was carried out in a small rural community in Jamaica. At about 2 and 10 years of age heights and weights showed no significant differences. At about 10 years of age classroom behaviour, sociability, and educational achievement were similar. The results suggest that the sickle-cell trait does not affect growth and mental development.
Internal Medicine in the National Resident Matching Program 1987: The Ides of March
Authors: JOHN S. GRAETTINGER
Journal: Annals of Internal Medicine (1988)

The number and percentage of graduating seniors from medical schools in the United States who have matched to categorical programs in internal medicine in the National Resident Matching Program have decreased since 1985. Examination of the balance between undergraduate and graduate medical education in the 127 networks of each medical school in the United States and its associated hospitals showed major differences in the retention and recruitment of graduates. The service needs of hospitals rather than the number of graduates from schools in the United States would seem to have controlled the number of positions. Because the positions exceeding the number of graduates from the United States are filled by graduates of foreign schools, these positions are of major importance in determining the supply of internists. The clerkship programs must be restructured to provide students an improved introduction to internal medicine, and the number of entering positions in residencies must be reduced by the substitution of other personnel to do some of the service functions now done by residents.
Suicide Rates and Antidepressant Prescribing: A Casual or Causal Relationship?
Authors: Bernhard Baune, Phillipa Hay
Journal: PLoS Medicine (2006)

In an ecological study in this issue of PLoS Medicine, Milane and colleagues found a temporal association between prescription of specific serotonin reuptake inhibitor (SSRI) antidepressants and suicide rates in the United States [ 1]. Their study addresses a subject of great public health importance and clinical interest. The researchers asked the question: was the use of antidepressants associated with a change in suicide rates in the general population of the United States between 1988 and 2002? There were two underlying hypotheses: (1) antidepressants can trigger suicide and subsequently increase suicide rates, and (2) through the treatment of depression with antidepressants, suicide rates decline over time.