tbuckley/cabot-search huggingface dataset:
Cytosolic domain of the type I interleukin-1 receptor spontaneously recruits signaling molecules to activate a proinflammatory gene.
Authors: R Singh, S Huang, T Guth, M Konieczkowski, J R Sedor
Journal: Journal of Clinical Investigation (1997)

Immediate postreceptor events activated by IL-1-IL-1R interaction remain undefined. We have initiated studies to identify candidate signal transducers that associate with the cytosolic domain (cd) of the IL-1R. Immunocomplex kinase assays demonstrated an IL-1-activated myelin basic protein kinase activity that coprecipitated with the IL-1R from rat mesangial, mouse EL-4, and HeLa cells. Using glutathione-S-transferase (GST) fusion proteins, HeLa cell lysates next were assayed for kinases that associated with IL-1R cytoplasmic sequences. A GST-IL-1R fusion protein containing the entire cd (amino acids 369-569; GST-IL-1Rcd) recruited a kinase activity in the absence and presence of IL-1 stimulation. In contrast, a GST-IL-1R membrane-proximal region mutant (amino acids 369-501; GST-IL-1RcdDelta), which lacks COOH-terminal amino acid residues required for nuclear factor-kappaB activation, poorly phosphorylated MBP. In gel, kinase assays demonstrated 63-, 83-, and 100-kD kinases that specifically coprecipitated with the HeLa IL-1R and the GST-IL-1Rcd, but not GST-IL-1RcdDelta. 35S-labeled proteins, with Mrs identical to the kinase activities, stably associated with GST-IL-1Rcd. Transient transfection assays of 293 cells were used to evaluate the functional significance of these findings. Simply increasing IL-1cd expression in 293 cells stimulated 5'-IL-6 flanking region-regulated CAT activity threefold above control, an effect blocked by the kinase inhibitors staurosporine and calphostin C. In summary, we have identified two previously unrecognized 63- and 83-kD kinases as well as a protein with an Mr similar to the recently cloned IL-1R-associated kinase, all of which associate spontaneously with the IL-1Rcd. Ectopic IL-1Rcd expression was sufficient to trigger cellular activation, suggesting that the extracellular domain of the intact receptor represses signal transduction until IL-1 is bound. Given that the IL-1Rcd signaling domain has been conserved in a functionally diverse group of transmembrane receptors, further characterization of this signaling process may define novel molecular mechanisms controlling cellular function and differentiation.
Management of Underwater Accidents
Authors: John B. Weeth
Journal: JAMA (1965)

The growing popularity of underwater swimming has brought with it an increasing incidence of underwater accidents. Any physician who lives near water more than 30 feet deep may be suddenly faced with the problem of diagnosis and management of an underwater accident. Injuries from spear-guns or propeller blades present no diagnostic problem. Similarly, most physicians have no difficulty recognizing and using appropriate medications to counteract fish poisons and stings. The enigma for many physicians is the patient whose injury is related to gas or pressure phenomenon, popularly known as "the bends." Despite a number of excellent reviews of underwater swimming accidents, some with outstanding illustrations,<sup>1-6</sup>including the authoritative and comprehensive<i>US Navy Diving Manual</i>,<sup>7</sup>most physicians are not familiar with the management of these casualties. It seems desirable, therefore, to review the management of underwater accidents and to cite illustrative cases. Drowning is still the major cause of
Effect of long-term PUVA treatment of psoriasis on the collagen and elastin gene expression and growth of skin fibroblasts in vitro
Authors: A. OIKARINEN, L. ALA-KOKKO, M. TAMMINEN, J. KARVONEN, T. REUNALA, M. KALLIOINEN, M. HANNUKSELA
Journal: British Journal of Dermatology (1990)

The proliferation rate, collagen metabolism and collagen and elastin messenger-RNA levels were studied in fibroblasts derived from patients who had received many courses of either systemic 8-methoxypsoralen or topical trioxsalen PUVA treatment. The proliferation rate of fibroblasts as measured by the incorporation of 3H-thymidine or by cellular division was decreased in those obtained from patients who had PUVA treatment as compared with controls. Collagen synthesis was slightly increased in the cells from PUVA-treated patients, but the relative collagen synthesis and the ratio between types I and III collagen were unchanged. The levels of collagen and elastin mRNAs were increased in fibroblasts derived from the PUVA-treated patients. No significant differences in histology or immunochemistry could be found in the biopsies taken from topical and systemic PUVA-treated patients.
Relationship between nonphenacetin combined analgesics and nephropathy: A review
Authors: Alvan R. Feinstein, Lothar A.J. Heinemann, Gary C. Curhan, Elizabeth Delzell, Paul J. DeSchepper, Johannes M. Fox, Helmut Graf, Friedrich C. Luft, Paul Michielsen, Michael J. Mihatsch, Samy Suissa, Fokko van der Woude, Stefan Willich
Journal: Kidney International (2000)
Hypoxia differentially regulates stress proteins in cultured cardiomyocytes Role of the p38 stress-activated kinase signaling cascade, and relation to cytoprotection
Authors: R Kacimi
Journal: Cardiovascular Research (2000)

Objective: Stress proteins (heat shock proteins, HSPs) are molecular chaperones that have been shown to enhance the survival of cells exposed to environmental stress. We sought to investigate the effects of hypoxia on the levels of HSP27 and heme oxygenase-1 (HO-1 or HSP32) in an established model of rat neonatal cardiac myocytes in culture. Methods: Myocytes were subjected to hypoxia (<0.5% O2 for 16 h). Studies of cell viability and nuclear morphology showed no evidence of cell death under these conditions. Results: Messenger RNA analysis demonstrated constitutive expression of HSP27 and low levels of HO-1. Hypoxia strongly induced HO-1 mRNA without affecting HSP27 mRNA. In parallel to mRNA levels, hypoxia increased HO-1 protein level without affecting HSP27. To further assess the signaling pathways implicated in HO-1 induction, we used inhibition experiments. The tyrosine kinase inhibitor tyrphostin and the mitogen-activated protein kinase inhibitor PD98059 did not prevent HO-1 induction, while the protein kinase C inhibitor chelerythrine partially blocked this response. The p38 stress-activated kinase inhibitor SB203580 was the most potent in suppressing hypoxia-induced HO-1. In vitro kinase assays, cell labeling and immunoprecipitation showed activation of signaling pathways downstream of p38 stress-activated kinase as revealed by an increase in phosphorylation of MAPKAPK-2/3 kinases and HSP27. Conclusions: These data show a differential pattern of hypoxia-induced HSP expression and implicate the stress kinase in HO-1 induction. Thus, selective regulation of HSP levels may play a role in the cardioprotective mechanisms that participate in the adaptive response to hypoxia-induced stress.
Glycemic Response to Pasta: Effect of Surface Area, Degree of Cooking, and Protein Enrichment
Authors: T M S Wolever, D J A Jenkins, J Kalmusky, C Giordano, S Giudici, A L Jenkins, L U Thompson, G S Wong, R G Josse
Journal: Diabetes Care (1986)

To see whether food form, the degree of cooking, or protein enrichment affected the glycemic response to pasta, we gave test-meal breakfasts to 13 diabetic patients. Macaroni had a significantly greater glycemic index (GI) (68 ± 8) than spaghetti (45 ± 6, P &amp;lt; .01); the GI of star pastina was intermediate (54 ± 6). The GI of spaghetti was not significantly affected by cooking for 5 or 15 min (45 ± 6 and 46 ± 5, respectively), or by protein enrichment (38 ± 4). The GI of spaghetti was similar in 11 noninsulin-dependent and 6 insulin-dependent diabetic patients (49 ± 7 compared with 57 ± 8). We conclude that different types of pasta may produce different glycemic responses but that these are not necessarily related to differences in cooking or surface area.
Characterizing Healthy Adolescent Development; Distinguishing It From Possible Disturbances
Authors: Jody W. Zylke
Journal: JAMA (1989)

ANNA FREUD once said, "To be normal during the adolescent period is by itself abnormal." At the American Medical Association—sponsored National Congress on Adolescent Health, experts in the field disputed this portrayal. For example, Irving Weiner, PhD, vice president for academic affairs at Fairleigh Dickinson University in Rutherford (Teaneck), NJ, said: "The notion of normative adolescent turmoil is purely and simply a myth." Such claims are not only inaccurate but potentially dangerous, he asserted, if emerging psychopathology is dismissed as normal variability. The myth has been created by clinicians, nurtured by the news media, and sustained by "the penchant in all of us to retain dramatic and distressing images while barely registering more benign ones," Weiner says. But another reason for the persistence of this image is suggested by Grayson Holmbeck, PhD, assistant professor of psychology at Loyola University in Chicago, Ill. "After giving up some of the storm and
General and Pulmonary Hemodynamic Effects of Pure Decapeptide Angiotensin in Normotensive Man
Authors: SALVATORE M. SANCETTA
Journal: Circulation Research (1960)

Purified natural decapeptide angiotensin was infused intravenously at a constant rate for 32 minutes in 5 normotensive subjects. There was no significant change in the cardiac output. There were significant increases in the pulmonary artery, the pulmonary wedge, and the brachial artery pressures. There were significant increases in the systemic vascular and the total pulmonary resistances. There was no significant change in the pulmonary arteriolar resistance. The data indicate that angiotensin I produces peripheral arteriolar constriction and fail to demonstrate a concomitant pulmonary arteriolar constriction. Thus, they are consistent with an hypothesis implicating angiotensin as a causative agent in human essential hypertension.
GSK backs BMJ's new policy to publish only studies with full access to data
Authors: Z. Kmietowicz
Journal: BMJ (2012)

The announcement this week that the BMJ will publish clinical trials only if the researchers have agreed to provide detailed patient level data when requested has been applauded by the drug firm GlaxoSmithKline.

Fiona Godlee, editor in chief of the BMJ , said in an editorial that the journal “will require this commitment for all clinical trials of drugs and devices—whether industry funded or not—from January 2013.”1

In response, Patrick Vallance, president of pharmaceuticals research and development at GSK, said: “GSK fully supports the commitment made today by BMJ to drive greater transparency of clinical trial data. Moves like this should help medical research by allowing scientists to …
The Whole Pediatrician Catalog: A Compendium of Clues to Diagnosis and Management
Authors: Irwin Polk
Journal: JAMA (1982)

This volume might be better subtitled, "All You Ever Wanted to Know About Pediatrics But Were Too Busy to Look Up." The soft-cover volume includes more than 500 pages of the kind of pediatric trivia that is of no consequence until it is needed, at which time it becomes crucial. Examples of this include tables of normal values for plasma pancreatic and salivary-type amylase, normal clitoral size in the newborn, size of gas-filled bowel loops in infants, and a table of 1,000 drug names that look alike or sound alike and therefore have the potential for causing confusion in telephoned prescriptions. A table of fast foods indicates the weight and kilocalorie and sodium content of fast foods by manufacturer; a hamburger from McDonald's can be compared with one from Burger King, a serving of shrimp with batter from Long John Silver's compared with a fish sandwich with cheese from Dairy
Creatine Kinase Is the Main Target of Reactive Oxygen Species in Cardiac Myofibrils
Authors: Hassane Mekhfi, Vladimir Veksler, Philippe Mateo, Véronique Maupoil, Luc Rochette, Renée Ventura-Clapier
Journal: Circulation Research (1996)

Abstract Reactive oxygen species (ROS) have been reported to alter cardiac myofibrillar function as well as myofibrillar enzymes such as myosin ATPase and creatine kinase (CK). To understand their precise mode and site of action in myofibrils, the effects of the xanthine/xanthine oxidase (X/XO) system or of hydrogen peroxide (H 2 O 2 ) have been studied in the presence and in the absence of phosphocreatine (PCr) in Triton X-100–treated cardiac fibers. We found that xanthine oxidase (XO), with or without xanthine, induced a decrease in maximal Ca 2+ -activated tension. We attributed this effect to the high contaminating proteolytic activity in commercial XO preparations, since it could be prevented by a protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), and it could be mimicked by trypsin. In further experiments, XO was pretreated with 1 mmol/L PMSF. Superoxide anion production by the X/XO system, characterized by electron paramagnetic resonance spin-trapping technique, was not altered by PMSF. A slight increase in maximal force was then observed either with X/XO (100 μmol/L per 30 mIU/mL) or H 2 O 2 . pMgATP–rigor tension relationships have been established in the presence and in the absence of PCr to separate the effects of ROS on myosin ATPase and myofibrillar-bound CK. In the presence of PCr, pMgATP 50 , the pMgATP necessary to induce half-maximal rigor tension, was reduced from 5.03±0.17 (n=21) to 4.22±0.22 (n=4) after 25 minutes of incubation in the presence of 30 mIU/mL XO and 100 μmol/L xanthine or to 4.04±0.1 (n=11) after incubation in the presence of 2.5 mmol/L H 2 O 2 . The ROS effects were partially prevented or antagonized by 1 mmol/L dithiothreitol. No effect was observed on pMgATP 50 when PCr was absent. pCa-tension relationships have been evaluated to assess the effects of ROS on active tension development. Incubations with H 2 O 2 induced an increase in Ca 2+ sensitivity and resting tension when MgATP was provided through myofibrillar CK (PCr and MgADP as substrates) but not when MgATP was added directly. These results suggest that myofibrillar CK was inhibited by ROS. Active stiffness and the time constant of tension changes after quick stretches applied to the fibers were dose-dependently increased by H 2 O 2 only in the presence of PCr. In addition, myofibrillar CK but not myosin ATPase enzymatic activity was depressed after incubation with either ROS. These results suggest that ROS mainly alters CK in myofibrils, probably by the oxidation of its essential sulfhydryl groups. Such CK inactivation results in a decrease in the intramyofibrillar ATP-to-ADP ratio. The effects of ROS on cytosolic and bound CKs may take part in the overall process of myocardial stunning after cardiac ischemia and reperfusion.
New formulation of vasoactive intestinal peptide using liposomes in hyaluronic acid gel for uveitis
Authors: Laure Lajavardi, Serge Camelo, Florence Agnely, Wei Luo, Brigitte Goldenberg, Marie-Christine Naud, Francine Behar-Cohen, Yvonne de Kozak, Amélie Bochot
Journal: Journal of Controlled Release (2009)
Identification of Unique MEK-Dependent Genes in GNAQ Mutant Uveal Melanoma Involved in Cell Growth, Tumor Cell Invasion, and MEK Resistance
Authors: Grazia Ambrosini, Christine A. Pratilas, Li-Xuan Qin, Madhavi Tadi, Oliver Surriga, Richard D. Carvajal, Gary K. Schwartz
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Metastatic uveal melanoma represents the most common intraocular malignancy with very poor prognosis and no effective treatments. Oncogenic mutations in the G-protein α-subunit q and 11 have been described in about 85% of uveal melanomas and confer constitutive activation. Multiple signaling pathways are induced as a consequence of GNAQ/11 activation, which include the MEK/ERK kinase cascade. We analyzed the transcriptional profile of cell lines treated with a mitogen-activated protein (MAP)/extracellular signal–regulated (ERK) kinase (MEK) inhibitor to identify gene targets of activated GNAQ and to evaluate the biologic importance of these genes in uveal melanoma. Experimental Design: We conducted microarray analysis of uveal melanoma cell lines with GNAQ mutations treated with the MEK inhibitor selumetinib. For comparison, we used cells carrying BRAFV600E and cells without either mutation. Changes in the expression of selected genes were then confirmed by quantitative real-time PCR and immunoblotting. Results: We found that GNAQ mutant cells have a MEK-dependent transcriptional output and identified a unique set of genes that are downregulated by MEK inhibition, including the RNA helicase DDX21 and the cyclin-dependent kinase regulator CDK5R1 whereas Jun was induced. We provide evidence that these genes are involved in cell proliferation, tumor cell invasion, and drug resistance, respectively. Furthermore, we show that selumetinib treatment regulates the expression of these genes in tumor tissues of patients with metastatic GNAQ/11 mutant uveal melanoma. Conclusions: Our findings define a subset of transcriptionally regulated genes by selumetinib in GNAQ mutant cells and provide new insights into understanding the biologic effect of MEK inhibition in this disease. Clin Cancer Res; 18(13); 3552–61. ©2012 AACR.
Increased Incidence of Gout and Hyperuricemia in Adrenalectomy Patients.
Authors: H. D. Itskovitz
Journal: Annals of Internal Medicine (1962)

s1 April 1962Increased Incidence of Gout and Hyperuricemia in Adrenalectomy Patients.H. D. Itskovitz, M.D., A. M. Sellers, M.D., F.A.C.P.H. D. Itskovitz, M.D.Search for more papers by this author, A. M. Sellers, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-675_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAcute gouty arthritis has been observed in eight of 104 patients surviving adrenalectomy and sympathectomy performed during the past ten years for treatment of severe arterial hypertension. An additional three patients have symptoms of arthritis not wholly typical of gout, but accompanied by elevated uric acid levels. Hyperuricemia has been found in 28 of 35 patients tested.The incidence of gout in this series is greater than ten times that observed in other surveys; this increase is statistically significant. Similarly, the 75% occurrence of hyperuricemia without gout is substantially greater than the expected incidence of 5% found in the general... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pa. (CI) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHypertension and HyperuricæmiaResults of sympathectomy and adrenalectomyACUTE GOUT—UNSOLVED 1 April 1962Volume 56, Issue 4Page: 675-675KeywordsAdrenalectomyArthritisGoutHypertensionPatientsSympathectomyUric acid Issue Published: 1 April 1962 PDF downloadLoading ...
Successful endoscopic ultrasound-guided fine-needle aspiration through a gastroduodenal stent for the diagnosis of recurrent gallbladder carcinoma
Authors: Anoop Prabhu, Maoxin Wu, Christopher DiMaio
Journal: Endoscopy (2015)

A 55-year old woman presented with epigastric pain and vomiting of 4 days' duration. She had a history of T2N0 gallbladder adenocarcinoma incidentally identified at cholecystectomy 6 months prior, for which she subsequently underwent resection of the cystic duct remnant. The patient declined adjuvant chemotherapy.
Long-Term Follow-Up of Diabetes in Two Patients With Thiamine-Responsive Megaloblastic Anemia Syndrome
Authors: Giuliana Valerio, Adriana Franzese, Vincenzo Poggi, Alfred Tenore
Journal: Diabetes Care (1998)

OBJECTIVE To describe a 15-year follow-up of diabetes and to present data regarding pancreatic β-cell function in two adolescents affected by the thiamine-responsive megaloblastic anemia (TRMA) syndrome. CASE REPORTS The first patient (PMR) is a 17.5-year-old Italian girl who presented megaloblastic anemia at 7.5 months of age. At age 2.5 years, because of the presence of diabetes and sensorineural deafness, she was diagnosed with TRMA syndrome and started treatment with thiamine-HCl, followed very early by benzoyloxymethyl-thiamine (BOM-T). The second patient (PF) is a 16.8-year-old Italian boy born to consanguineous parents. Sensorineural deafness was diagnosed at age 1.5 years, while diabetes with ketoacidosis and megaloblastic anemia were diagnosed at age 3 years. Treatment with thiamine HCl was started immediately after diagnosis and changed to BOM-T 2 months later. Subsequent to the initiation of the vitamin, the two patients did not require insulin for ∼ 7 and 10 years, respectively. Puberty was determinant in deteriorating the metabolic control in these patients, leading to treatment with an oral hypoglycemic agent and finally to a reinstitution of insulin therapy. CONCLUSIONS The hormonal assessment in our patients (normal insulin response to oral glucose in childhood, preserved C-peptide secretion in case 2) and the good response to an oral hypoglycemic agent would indicate that the pancreatic disease may initiate as type 2 diabetes and may progress after several years to an insulin-requiring diabetes, as indicated by the exhaustion of the insulin secretory capacity.
"Swallowed" Endotracheal Tube
Authors: M. G. Prinn
Journal: BMJ (1967)

Lyelrs Toxic Epidermal Necrolysis SIR,--We were very interested to read the article on Lyell's disease by Dr. J. Jefferson (24 June, p. 802), particularly as we admitted a similar case on 12 June which caused a great deal of diagnostic difficulty.This was a 2-week-old female child who had been restless and irritable for two days.On the day of admission the mother had taken her to the local child welfare clinic, where it was noted that she had a blepharitis, and was given sulpha- cetamide eye ointment to apply.Five hours later the mother noticed the skin was peeling off the child's buttocks and brought her to hos- pital.The main clinical findings were a tem- perature of 990 F. (37.50 C.), general erythema of the skin (boiled lobster appearance), patchy areas of moist erythema with yellow crusts on the face, particularly around the mouth, nose, and eyes, and large patches of what appeared to be scalds of the perineum, buttocks, and trunk.In view of the appearance of the child's skin and the state of agitation of the mother (who was 17 years old, and this was her first child) it was suspected that she had been accidentally scalded, but the mother was emphatic that there was no possibility of this.In addition, the child showed no evidence of shock, dehydration, or systemic disturbance.A swab from the facial lesions yielded a heavy growth of Staphylococcus aureus resistant to benzylpenicillin.Treatment was on the same lines as that described by Dr. Jefferson, except that the child was nursed in a gallows splint to keep the perineum exposed.All the skin lesions healed completely within two weeks, and at no time throughout her stay did the child show any evidence of systemic disturbance.-We are, etc.,