tbuckley/cabot-search huggingface dataset:
FRI0004 Discovery of potent and selective retinoid related orphan receptor gamma (ror-gamma) inverse agonists for the treatment of th17 mediated diseases
Authors: K. Nellore, M. Bejugam, A. Ramanathan, W. R. Balasubramaian, S. Mukherjee, S. S. Dodheri, R. K. B. Damarla, A. M. Sathyanandan, A. Lakshminarasimhan, N. Rao, V. R. Erigala, N. Mahalingam, S. Samajdar, H. Subramanya
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Th17 cells play a key pro-inflammatory role in a variety of autoimmune diseases such as Arthritis, Inflammatory Bowel Disease, Psoriasis and Multiple Sclerosis. The nuclear hormone receptor RORγ controls the differentiation of Th17 cells and expression of IL-17. Antibodies against IL-17R (Brodalumab) and IL-17 (Ixekizumab) have demonstrated promising efficacy in clinical trials for psoriasis. <h3>Objectives</h3> To identify novel and selective inverse agonists of RORγ, as well as to demonstrate efficacy in relevant disease models. <h3>Methods</h3> Novel RORγ inverse agonists were designed using a combination of approaches including structure and knowledge based methods. Compounds were screened in a RORγ radio-ligand binding assay using <sup>3</sup>H 25- Hydroxycholesterol, as well as in a cell based reporter assay to demonstrate inverse agonism (fusion of Gal4-DBD and RORγ-LBD in one vector, and UAS of Gal4 upstream of luciferase reporter in another vector). Selected compounds were screened against RORα to evaluate selectivity. Crystal structure of RORγ in complex with known inverse agonists as well as novel compounds, were solved. Th17 differentiation assay was developed using primary mouse CD4+ve T-cells to determine functional effect of the compounds. Pharmacokinetic profile in mice was determined for selected compounds with good ADME properties. <h3>Results</h3> Novel hits from multiple structural classes have been identified, with IC<sub>50</sub> in the range of 5 – 500 nM in binding assay. Compounds from the lead series demonstrated good activity (&lt; 1 μM) in reporter assay. Co-crystal structure of novel compounds clearly showed the mode of binding. Several compounds demonstrated &gt; 10 fold selectivity against RORα in a reporter assay. Compounds from multiple series have shown significant inhibition of IL-17 release from differentiated Th17 cells. Lead compounds have shown good pharmacokinetic properties in mice. <h3>Conclusions</h3> We have identified novel and structurally diverse small molecule inverse agonists of RORγ. Selectivity against RORα and cell based activity has been demonstrated for compounds from multiple series. Relevant efficacy models have been established and profiling of lead compounds in these models in on-going. <h3>Disclosure of Interest</h3> None Declared
Surgical Management of Cerebrovascular Insufficiency
Authors: H. C. Stansel, M. Hume, W. W. L. Glenn
Journal: New England Journal of Medicine (1963)

THE patient with signs and symptoms of cerebro-vascular insufficiency presents specific problems relating to diagnosis and treatment. Realizing that widely divergent opinions exist regarding the management of these cases, we consider this report of our experience in the diagnosis and surgical treatment of the extracranial vascular lesions justified.The concept that occlusive disease of the extra-cranial cerebral arteries may produce significant Central-nervous-system dysfunction now appears well founded. Chiari,1 in 1905, emphasized the frequency of atherosclerosis in the region of the carotid bifurcation, believing that these lesions produced cerebral symptoms and lesions by atheromatous embolization. Hunt,2 nine years later, recognized the . . .
Outpatient Tonsil and Adenoid Surgery
Authors: Richard L. Fields
Journal: JAMA (1986)

To the Editor.—  I take strong exception to the position expressed in MEDICAL NEWS & PERSPECTIVES in the July 18, 1986, issue ofJAMAregarding the safety and economic benefits of outpatient tonsil and adenoid surgery.1While I do not favor the policy of mandating outpatient surgery for these procedures being promulgated by insurance companies and other thirdparty payers, the comments in that article only serve to perpetuate the fear that such surgery cannot safely be done on an outpatient basis and the myth that it is not economically beneficial.  In the past eight years, I have performed more than 1500 adenoidectomies and more than 600 tonsillectomies with or without adenoidectomy in a freestanding ambulatory surgery center. The patients receive excellent intensive postoperative nursing care, and the adenoidectomy patients are discharged in two hours and the tonsillectomy patients in four hours. During all this time, only one patient has
Marrying Immunotherapy with Chemotherapy: Why Say IDO?
Authors: Alexander J. Muller, George C. Prendergast
Journal: Cancer Research (2005)

Abstract Activation of the tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) in cancer cells facilitates immune escape. A recent study now shows how small-molecule inhibitors of IDO can be used to leverage the efficacy of traditional chemotherapeutic drugs that are used to treat cancer in the clinic. By promoting antitumor immune responses in combination with cytotoxic chemotherapy, IDO inhibitors may offer a drug-based strategy to more effectively attack systemic cancer.
Diabetes Mellitus in Pregnancy: Principles and Practice
Authors: Stanley H. Tischler
Journal: JAMA (1989)

This book is indeed a gem. What makes it so is that every facet of diabetes in pregnancy, and I mean every facet, is explored and explained thoroughly. This book belongs in the libraries of hospitals and departments of obstetrics and gynecology, and obstetricians and gynecologists should have it in their personal libraries. Metabolism should be normalized even prior to conception. Certainly, diabetes mellitus requires close supervision during pregnancy. This book tells us<i>how</i>. What is gestational diabetes? How does one manage labor and delivery in a diabetic? How to decide if delivery is to be from below or by cesarean section? How to prevent or at least manage macrosomia and shoulder dystocia successfully? To help answer these questions are 31 sections by 37 contributors, guided most successfully by Drs Reece and Coustan. The sections begin with "General Medical Considerations," then "The Fetus and Placenta," followed by "Management of Carbohydrate
Orthoptic Methods for Concomitant Squint
Authors: G. G. Penman
Journal: BMJ (1937)

In this paper I propose to deal with some general con- siderations in the use of orthoptic treatment in con- comitant squint.Details of treatment and the question of heterophoria are being discussed by other speakers. Cases Suitable for the TreatmentIn the first place we may consider what requirements the patient must fulfil to be acceptable for orthoptic treatment.1.
Alterations in cardiac beta-adrenergic receptors in chagasic mice and their association with circulating beta-adrenoceptor-related autoantibodies
Authors: L Sterin-Borda
Journal: Cardiovascular Research (1999)

Objetive: Cardiac tissue from chagasic mice was studied to evaluate the expression and biological activity of β-adrenoceptors in association with circulating β-adrenoceptor-related autoantibodies. Methods: BALB/c inbred mice that were either treated or not treated with atenolol (2.5 mg/kg) and infected or not infected with 1×104 trypomastigotes (CA-1 strain) were sacrificed weekly up to week nine. Morphological, binding and contractility studies were performed on the four different groups of animals. The effect of their serum antibodies was also assayed in binding and contractility studies on normal heart preparations. Results: Hearts from chagasic myocarditis mice showed a β-adrenoceptor-related dysfunction, with a decrease in heart contractility, impaired response to exogenous β-adrenoceptor agonist and a significant reduction in β-adrenergic binding sites. Those effects were maximum at eight–nine weeks post-infection and were improved by treating infected mice with atenolol. In addition, serum or IgG from chagasic myocarditis mice was capable of interacting with cardiac β-adrenoceptors, reducing the number of binding sites and inhibiting the contractile response to exogenous norepinephrine. IgG effects that were observed in normal myocardium, were highest in sera from mice eight–nine weeks post-infection and correlate with the degree of myocarditis. Moreover, chagasic autoantibodies from infected mice recognized a peptide corresponding to the sequence of the second extracellular loop of the human β1-adrenoceptor. Conclusions: (1) The development of alterations in β-adrenergic receptors, related to cardiac dysfunction, may be associated with the presence of circulating antibodies against these receptors and (2) it is possible that the chronic deposits of these autoantibodies in cardiac β-adrenoceptors could lead to a progressive blockade with sympathetic denervation, a phenomenon that has been described in the course of chagasic myocarditis.
Response to Letter Regarding Article, “High-Density Substrate Mapping in Brugada Syndrome: Combined Role of Conduction and Repolarization Heterogeneities in Arrhythmogenesis”
Authors: P.D. Lambiase, A.K. Ahmed, R. Ben-Simon, A.W. Chow, M.D. Lowe, W.J. McKenna, E.J. Ciaccio, R. Brugada, E. Lizotte, None Chaubey
Journal: Circulation (2010)
Interrelationship of spontaneous growth hormone axis activity, body fat, and serum lipids is healthy elderly women and men
Authors: Kieran G. O'Connor, S.Mitchell Harman, Thomas E. Stevens, Jocelyn J. Jayme, Michele F. Bellantoni, M.Janette Busby-Whitehead, Colleen Christmas, Thomas Münzer, Jordan D. Tobin, Tracey A. Roy, Ernest Cottrell, Carol St. Clair, Katherine M. Pabst, Marc R. Blackman
Journal: Metabolism (1999)

Aging is associated with decreased growth hormone (GH) secretion and plasma insulin-like growth factor-I (IGF-I) levels, increased total and abdominal fat, total and low-density lipoprotein (LDL) cholesterol, and triglycerides, and reduced high-density lipoprotein (HDL) cholesterol. Similar changes in lipids and body composition occur in nonelderly GH-deficient adults and are reversed with GH administration. To examine whether GH/IGF-I axis function in the elderly is related to the lipid profile independently of body fat, we evaluated GH secretion, serum IGF-I and IGF binding protein-3 (IGFBP-3) levels, adiposity via the body mass index (BMI), waist to hip ratio (WHR), dual-energy x-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI), and circulating lipids in 101 healthy subjects older than 65 years. Integrated nocturnal GH secretion (log IAUPGH) was inversely related (P < .005) to DEXA total and abdominal fat and MRI visceral fat in both genders. Log IAUPGH was inversely related to visceral fat in women (P < .005) and men (P < .0001), but was not significantly related to total fat in either gender. In women, log IAUPGH was related inversely to total and LDL cholesterol and positively to HDL cholesterol (P < .008). In men, log IAUPGH was inversely related to total cholesterol and triglycerides (P < .005). In women, HDL cholesterol was inversely related to the WHR (P < .005). In men, triglycerides were positively related (P < .001) to the WHR and DEXA abdominal and MRI visceral fat. Multivariate regression revealed log IAUPGH, but not DEXA total body fat, to be an independent determinant of total (P < .001 for women and P = .01 for men) and LDL (P < .007 and P = .05) cholesterol in both sexes and of HDL cholesterol (P < .005) and triglycerides (P < .03) in women. Log IAUPGH, but not DEXA abdominal fat, was related to total (P < .005 and P < .03) and LDL (P < .03 and P = .05) cholesterol in both genders and to HDL in women (P < .05). Log IAUPGH, but not MRI visceral fat, was related to total cholesterol (P < .03 and P = .05) in women and men. Age, IGF-I, and IGFBP-3 were not significantly related to any body fat or lipid measures, except for a positive correlation of IGF-I with triglycerides in men. Thus, endogenous nocturnal GH secretion predicts total, LDL, and HDL cholesterol levels independently of total or abdominal fat, suggesting that it is an independent cardiometabolic risk factor in healthy elderly people.
Damage to Haiti's infrastructure is "almost unbelievable," says WHO chief
Authors: P. Moszynski
Journal: BMJ (2010)

As the scale of the devastation in Haiti gradually emerges, with 200 000 people feared dead and one and half million left homeless, healthcare workers are struggling to cope. Not only is this one of the worst natural disasters in recent years, the earthquake wiped out much of the limited infrastructure of one of the world’s poorest countries.

The World Health Organization is coordinating the healthcare sector of the massive international relief operation. WHO’s director general, Margaret Chan, said, “This disaster ranks among the most devastating and logistically challenging in recent history. We are seeing the difficulties that arise when disaster strikes an already disastrous public health situation.

“We have every reason to be concerned …
A clinical and follow-up study of right and left bundle branch block.
Authors: M Rotman, J H Triebwasser
Journal: Circulation (1975)

The experience with bundle branch block at the USAF School of Aerospace Medicine was reviewed. The clinical and follow-up status was evaluated in 394 subjects with right bundle branch block (RBBB) and 125 subjects with left bundle branch block (LBBB). The majority of subjects were asymptomatic at the time of bundle branch block diagnosis. The subjects were divided into subfroups based on electrocardiographic (EEG) findings to determine if any one subfroup was at higher risk for initial or follow-up morbidity of cardiobascular disease or follow-up mortality. At initial diagnosis and clinical evaluation, 94% of RBBB and 89% of LBBB subjects had no evidence of cardiobascular disease. In the RBBB group, 3 and 2% had cornary heart disease and hypertension, respectively; in LBBB subjects, 9 and 7% had cornary heart disease and hypertension, respectively. No one ECG subfroup in either the RBBB or LBBB group had a higher incidence of cardiobascular disease. Complete follow-up information was available in 94% of the RBBB subgroup subjects and 91% of the LBBB group. In the follow-up period, new cases of coronary heart disease and hypertension occurred in 6% of the RBBB group and 5 and 8%, respectively, in the LBBB group. Fourteen (4%) RBBB and nine (8%) LBBB subjects died during the follow-up period. No differences for follow-up groups. Progressive electrical dysfunction in the form of complete heart block occurred in one subject each absence, and degree of associated cardiobascular disease. Furthermore, within the age limits of the present aeromedical implications of bundle block are discussed.
Anti-CTLA4 Antibody Therapy Related Complications on FDG PET/CT
Authors: Phillip J. Koo, William C. Klingensmith, Karl D. Lewis, Brian M. Bagrosky, Rene Gonzalez
Journal: Clinical Nuclear Medicine (2013)

Anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody therapy is a new class of drug which has demonstrated increased overall survival in patients with metastatic melanoma. Anti-CTLA-4 antibody therapy inhibits the CTLA-4 inhibitory signal, thereby enhancing the anti-tumor response of the cytotoxic T lymphocytes. This response can lead to a variety of immune-related adverse events. Many of these events are present on follow-up PET/CT examinations performed to assess response to therapy. It is important for the interpreting physician to be aware of the findings on PET/CT to avoid diagnosing adverse events as progressive disease and to alert clinicians regarding these complications.
Still-Life: Past Revisited
Authors: Thomas B. Cole
Journal: JAMA (2012)

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
A MOUSE B-CELL ALLOANTIGEN DETERMINED BY GENE(S) LINKED TO THE MAJOR HISTOCOMPATIBILITY COMPLEX
Authors: David H. Sachs, James L. Cone
Journal: The Journal of Experimental Medicine (1973)

Antibodies cytotoxic for only a subpopulation of C57Bl/10 lymph node and spleen cells were detected when rat antiserum against B10.D2 was exhaustively absorbed with B10.A lymphocytes. Antibodies of similar specificity were also detected in B10.A anti-B10.D2 and in B10.A anti-C57Bl/10 alloantisera. Reactions with recombinant strains of mice indicate that the cell-surface antigen(s) responsible for this specificity is determined by gene(s) in or to the left of the Ir-1 region of the major histocompatibility complex. A variety of criteria implicate B cells as the subpopulation of lymphocytes bearing this antigen. In view of these data and the recent report by others of a T-cell alloantigen determined by gene(s) in the major histocompatibility complex, it seems possible that there may be a variety of H-2-linked alloantigens expressed preferentially on subclasses of lymphocytes.
Abstract 5175: Survivin Suppression by YM155 involves downregulation of Cyclin Ds and Activation of Rb.
Authors: Eswar Shankar, Sarah L. Corum, Scott M. Welford, David Danielpour
Journal: Cancer Research (2013)

Abstract The pro-metastatic and survival protein Survivin is robustly overexpressed in carcinomas compared to normal or benign tissue. The imadazolium based small molecule YM155, which was discovered in a chemical library screen of compounds that effectively suppressed the Survivin promoter, induces apoptosis of castration-resistant prostate cancer (CRPC) cells. Despite the current use of YM155 in phase II clinical trials, the mechanisms by which YM155 inhibits the expression of Survivin and kills cancer cells remain unclear. Our laboratory previously reported that the pocket proteins (Rb, p107, p130) suppress Survivin expression by recruiting E2F4 to CDE/CHR promoter elements of the Survivin promoter. Here we studied early signaling responses in a panel of prostate and kidney cancer cell lines and showed that YM155 rapidly decreases the levels of cyclin Ds and activates Rb, preceding the suppression of Survivin expression. We hypothesize that YM155 down-regulates Survivin expression by activating the pocket proteins and promoting their recruitment along with E2F4 to the proximal region of the Survivin promoter. In addition, we provide evidence that the induction of apoptosis by YM155 may be mediated not only by the downregulation of Survivin but also through induced expression of the proapoptotic protein Bim, repression of the anti-apoptotic protein Mcl-1, followed by activation of caspases. Citation Format: Eswar Shankar, Sarah L. Corum, Scott M. Welford, David Danielpour. Survivin Suppression by YM155 involves downregulation of Cyclin Ds and Activation of Rb. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5175. doi:10.1158/1538-7445.AM2013-5175
UNCOMPLICATED FORWARD LUXATION OF THE ULNA
Authors: William A. Horan
Journal: JAMA (1928)

Traumatic deformities of the carpus and of the wrist have been discussed so thoroughly and so often that it is with hesitancy that I again bring the subject to the reader's attention. I was surprised in reviewing the literature and in hunting for a description of uncomplicated forward luxation of the ulna at the wrist to find so little concerning it. The condition was first described probably by Desault and Palletta. Their cases were presented from the dissecting room, without a history. In 1906, Thon described an actual case in detail. Later on, in 1926, Brissett described a similar condition. There is a great deal to be said concerning this deformity when it is treated secondary to some other condition, and undoubtedly there is a great deal more in the literature concerning the actual deformity that has not come to my attention. The excruciating pain, the extreme disability
ERYTHROMELALGIA.A STUDY OF SEVENTY CASES REPORTED IN THE LITERATURE.
Authors: IRVING WILSON VOORHEES
Journal: JAMA (1907)

nephritis, I have learned that two effects of renal de- capsulation may be-regarded as practically invariable and constant.First, renal decapsulation invariably and at once increases the daily urea output of the kidney or kidneys; and second, renal decapsulation enables any kidney to do the best work possible for that particular kidney to perform.Both these results act directly to prevent a renal death.And, as a matter of fact, I nave had no renal deaths in my nephrectomies of the past seven years, during which I have consistently practiced decapsulation of the remaining kidney.There can be but two possible objections advanced to the routine practice of exploration and decapsulation of the remaining kidney when performing nephrectomy, one objection partly including the other.These are
CRITERIA OF THERAPY OF WAR NEUROSES
Authors: J. S. KASANIN, EMANUEL WINDHOLZ, MISS CHARL RHODE
Journal: American Journal of Psychiatry (1947)

The rehabilitation techniques used in this Veterans' Clinic varied from case to case. The success was not dependent on the type of psychiatric diagnosis but rather on the psychodynamics in each individual case. Effective help was given to veterans suffering from paranoid, homosexual or other severe conflicts provided these were closely related to the present situation. This could be achieved even in cases with serious pre-war problems. A thorough knowledge of the service experiences, the reactions to discharge and the immediate adjustment situation as well as the family background was necessary for intensive therapy. In other cases, the aim of treatment had to be limited to problems of readjustment, to giving immediate but limited support, or to protecting the veterans from harming themselves under emergency conditions. The earlier the veterans came after discharge, the better were the conditions for help. Where there was no stability in at least one area of the veterans' environment—his home, his job, his friends —rehabilitation became extremely difficult. In such cases the secondary gain from illness might become a serious obstacle. The same applied to some cases suffering from purely physical complaints covering up their need for dependency. Only 3 cases developed a real compensation neurosis. The success of rehabilitation depended largely on the degree to which the disability was related to the present situation and also on our ability to discover the proper point of attack. Many veterans came in for treatment of their long standing or revived problems such as stuttering, alcoholism, homosexuality, psychopathic maladjustment, etc. Close analysis always revealed some new and hidden conflict, related to the present situation, which could be dealt with.
Preimplantation-stage stem cells induce long-term allogeneic graft acceptance without supplementary host conditioning
Authors: Fred Fändrich, Xiongbin Lin, Gui X. Chai, Maren Schulze, Detlev Ganten, Michael Bader, Julia Holle, Dong-Sheng Huang, Reza Parwaresch, Nicholaus Zavazava, Bert Binas
Journal: Nature Medicine (2002)