tbuckley/cabot-search huggingface dataset:
The Cell-Autonomous Role of Excitatory Synaptic Transmission in the Regulation of Neuronal Structure and Function
Authors: Wei Lu, Eric A. Bushong, Tiffany P. Shih, Mark H. Ellisman, Roger A. Nicoll
Journal: Neuron (2013)

Highlights•Genetic silencing of synaptic transmission in single neurons in vivo•Cell-autonomous role of excitatory synaptic transmission in individual neurons•Dichotomic role of synaptic transmission in neuronal structure and function•Synaptic excitation is not essential for spine development and maintenanceSummaryThe cell-autonomous role of synaptic transmission in the regulation of neuronal structural and electrical properties is unclear. We have now employed a genetic approach to eliminate glutamatergic synaptic transmission onto individual CA1 pyramidal neurons in a mosaic fashion in vivo. Surprisingly, while electrical properties are profoundly affected in these neurons, as well as inhibitory synaptic transmission, we found little perturbation of neuronal morphology, demonstrating a functional segregation of excitatory synaptic transmission from neuronal morphological development.
Pseudotumor Cerebri Associated With Danazol Withdrawal
Authors: Maher Fanous
Journal: JAMA (1991)

<h3>To the Editor.</h3> —Danazol is an androgenic compound used in the treatment of endometriosis, benign cystic breast disease, and some hematologic disorders. Danazol therapy has been implicated in the pathogenesis of pseudotumor cerebri in some patients.<sup>1,2</sup>We describe a patient who developed symptoms and signs of increased intracranial pressure (ICP) shortly after cessation of danazol. <h3>Report of Case.</h3> —A 36-year-old woman was prescribed 200 mg/d of danazol for endometriosis. She received the drug from December 1989 to July 1990. Two days after discontinuing danazol, she developed bifrontal headaches with nausea and tinnitus, accompanied by transient visual obscurations. She was examined 3 weeks later because of progressive worsening of her symptoms. Corrected visual acuity was 20/25 in each eye. Results of pupillary and slit-lamp examination and applanation tonometry were normal. Fundus examination showed bilateral papilledema, peripapillary hemorrhages, and absent spontaneous venous pulsations. The blind spots were enlarged on Goldmann visual
Topical Idoxuridine in the Treatment of Genital Herpes
Authors: Tibor A. Rozman
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The effectiveness of 5% idoxuridine in dimethyl sulfoxide for the treatment of herpes zoster and herpes simplex virus (HSV) infections has been documented in several well-controlled trials.<sup>1-4</sup> By comparing the actual subject of the investigation carried out by Silvestri et al (1982;248:953) and the claim stated in the title, there is a wide gap of missing links. The criteria used for selecting 30% idoxuridine in dimethyl sulfoxide are somewhat obscure. Detailed information concerning the duration of the tolerance-testing procedure and the changes taking place on the cellular level is not available (in part 1). The absence of immediate side effects like burning and erythema does not prove that 30% idoxuridine in dimethyl sulfoxide is no more irritating or toxic to the nonkeratinizing epithelium of the vagina or penis than the formulation with 5% active ingredient. Since it is well known that therapy with high concentrations of
Activation of HER family members in gastric carcinoma cells mediates resistance to MET inhibition
Authors: Simona Corso, Elena Ghiso, Virna Cepero, J RAFAEL Sierra, Cristina Migliore, Andrea Bertotti, Livio Trusolino, Paolo M Comoglio, Silvia Giordano
Journal: Molecular Cancer (2010)

Gastric cancer is the second leading cause of cancer mortality in the world. The receptor tyrosine kinase MET is constitutively activated in many gastric cancers and its expression is strictly required for survival of some gastric cancer cells. Thus, MET is considered a good candidate for targeted therapeutic intervention in this type of tumor, and MET inhibitors recently entered clinical trials. One of the major problems of therapies targeting tyrosine kinases is that many tumors are not responsive to treatment or eventually develop resistance to the drugs. Perspective studies are thus mandatory to identify the molecular mechanisms that could cause resistance to these therapies.Our in vitro and in vivo results demonstrate that, in MET-addicted gastric cancer cells, the activation of HER (Human Epidermal Receptor) family members induces resistance to MET silencing or inhibition by PHA-665752 (a selective kinase inhibitor). We provide molecular evidences highlighting the role of EGFR, HER3, and downstream signaling pathways common to MET and HER family in resistance to MET inhibitors. Moreover, we show that an in vitro generated gastric cancer cell line resistant to MET-inhibition displays overexpression of HER family members, whose activation contributes to maintenance of resistance.Our findings predict that gastric cancer tumors bearing constitutive activation of HER family members are poorly responsive to MET inhibition, even if this receptor is constitutively active. Moreover, the appearance of these alterations might also be responsible for the onset of resistance in initially responsive tumors.
Glycemic Responses to Exercise in IDDM After Simple and Complex Carbohydrate Supplementation
Authors: Karen Soo, Stuart M Furler, Katherine Samaras, Arthur B Jenkins, Lesley V Campbell, Donald J Chisholm
Journal: Diabetes Care (1996)

OBJECTIVE Subjects with IDDM should take carbohydrate before exercise to avoid hypoglycemia. However, there is little information on the glycemic effect of recommended supplementation. This study is aimed to determine the glycemic effects of oral glucose or bread (30 g carbohydrate) before 45 min of moderate exercise. RESEARCH DESIGN AND METHODS Nine subjects with uncomplicated IDDM did 45 min of bicycle ergometer exercise at 60% VO2max in the morning before insulin injection on three occasions: 1) with no carbohydrate supplement, 2) with 30 g glucose in water at −5 min, and 3) with 30 g carbohydrate as white bread with water at −20 min. The glycemic responses were determined. The glycemic responses to glucose and bread were also determined without exercise in six subjects. RESULTS Without carbohydrate, exercise caused a small fall (−1.2 ± 0.6 mmol/l, mean ± SE) in plasma glucose (PG). With either glucose or bread, PG rose (the change in plasma glucose relative to basal [Δ PG] = 5.1 ± 0.8 and 2.6 ± 0.8, respectively). The rise was greater (P &amp;lt; 0.01) without exercise (Δ PG = 6.9 ± 0.7 and 4.5 ± 0.7, respectively). During exercise, glucose increased PG levels more than bread increased glucose levels P &amp;lt; 0.05). CONCLUSIONS Before morning insulin injection, the fall in PG during moderate exercise in IDDM subjects is generally small or absent. The glycemic effects of complex carbohydrate are slightly &amp;lt; glucose before exercise. Under these circumstances, the usually recommended amount of carbohydrate tends to cause an unwanted elevation of PG; thus, IDDM subjects should anticipate reducing or even omitting carbohydrate supplementation after monitoring their individual glycemic response.
Hepatitis C virus eradication in intravenous drug users maintained with subcutaneous naltrexone implants
Authors: Gary P. Jeffrey, Gerry MacQuillan, Fern Chua, Sam Galhenage, Judith Bull, Emma Young, Gary Hulse, George O'Neil
Journal: Hepatology (2006)

The effectiveness of HCV antiviral therapy in patients who have undergone recent drug dependency treatment and continue to inject drugs sporadically is presently not clear. Patients attending a community-based drug rehabilitation and naltrexone implant clinic from October 2002 until March 2005 were screened for HCV infection and if positive offered further assessment and treatment with interferon and ribavirin therapy. The first 50 patients to commence HCV therapy and complete at least 6 months follow-up were prospectively studied. ETR response (HCV PCR negative) was 34/50 (68%) and SVR 6 months post-treatment was 31/50 (62%). Viral eradication was maintained in those 22 patients that have had 12 months or more post-treatment follow-up. Eleven (22%) patients stopped therapy early due to side effects or poor compliance. Only two patients with an ETR likely reinfected due to unsafe injection practices. One was re-treated and achieved an SVR. Of the patients achieving a 6-month SVR, 17 of 31 patients reported no further IDU and 13 of 31 patients occasional IDU during treatment and this was maintained after HCV treatment cessation. 46% of patients received antidepressant and/or antipsychotic medication during treatment. Conclusion: This study of HCV treatment in a community-based subcutaneous naltrexone implant clinic found antiviral therapy resulted in a 62% SVR. This result is comparable to that reported in hospital-based clinics in non-IDU patients. The side effect profile and compliance was also similar. HCV antiviral therapy should be offered to this large and currently under treated group. (Hepatology 2007;45:111–117.)
An insertion/deletion polymorphism in the α2b-adrenergic receptor gene is a novel genetic risk factor for acute coronary events
Authors: Amir Snapir, Paula Heinonen, Tomi-Pekka Tuomainen, Pia Alhopuro, Matti K Karvonen, Timo A Lakka, Kristiina Nyyssönen, Riitta Salonen, Jussi Kauhanen, Veli-Pekka Valkonen, Ullamari Pesonen, Markku Koulu, Mika Scheinin, Jukka T Salonen
Journal: Journal of the American College of Cardiology (2001)
The Association Button.
Authors: T. S Dabney
Journal: JAMA (1906)

New Orleans,, April 26, 1906. <h3>To the Editor:</h3> —I hope that you will again and again urge the advisability of every member wearing the button, for by this means the public will soon learn to distinguish us from the many irregulars who infest every large city and call themselves doctors. Besides, the constant sight of these buttons will give the wearers power and influence in the public eye.
'In the Ballpark' Not Good Enough
Authors: Paul Cotton
Journal: JAMA (1990)

A ROBOT laboring away in a cramped room may be hammering the last coffin nails into public smoking. The impersonal machine is mundane by Hollywood standards. But like much of the technology in the laboratory at the CDC's Center for Environmental Health and Injury Control in Atlanta, Ga, it defines the state of the art. For the next several years, the robot will test 35 samples at a time, day and night, for cotinine, a metabolite of nicotine. Some of its test tubes are centrifuged while others are bathed, shaken, or allowed to settle. The robot opens one, gripping the cap and turning the tube. It pours off a layer of methylene chloride, screws the tube back into the cap, returns it to its preordained place in the rack, and waits for the program, written by CDC researcher Dana Sheeley, PhD, to tell it what to do next. The CDC
Age and Routine Invasive Management of Acute Coronary Syndromes
Authors: Nasseer A. Masoodi
Journal: Annals of Internal Medicine (2004)

Letters21 December 2004Age and Routine Invasive Management of Acute Coronary SyndromesNasseer A. Masoodi, MDNasseer A. Masoodi, MDFrom Florida State University College of Medicine and Advent Christian Village Inc., Dowling Park, FL 32064.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-141-12-200412210-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In their article on early invasive management of elderly patients with acute coronary syndromes (1), Bach and colleagues did not mention the cognitive status of their patients at baseline, especially those older than 75 years of age. Cognitive impairment plays a vital role in charting the plan of care, more so when invasive procedures are considered. Bach and colleagues' findings would be more convincing if the authors had mentioned how many patients were older than age 75 years in both of their study groups. Age 65 years is rarely considered elderly anymore, except for research purposes. Since ...Reference1. Bach RG, Cannon CP, Weintraub WS, DiBattiste PM, Demopoulos LA, Anderson HV, et al. The effect of routine, early invasive management on outcome for elderly patients with non-ST-segment elevation acute coronary syndromes. Ann Intern Med. 2004;141:186-95. [PMID: 15289215] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Nasseer A. Masoodi, MDAffiliations: From Florida State University College of Medicine and Advent Christian Village Inc., Dowling Park, FL 32064. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Effect of Routine, Early Invasive Management on Outcome for Elderly Patients with Non–ST-Segment Elevation Acute Coronary Syndromes Richard G. Bach , Christopher P. Cannon , William S. Weintraub , Peter M. DiBattiste , Laura A. Demopoulos , H. Vernon Anderson , Paul T. DeLucca , Elizabeth M. Mahoney , Sabina A. Murphy , and Eugene Braunwald Age and Routine Invasive Management of Acute Coronary Syndromes Richard G. Bach , Christopher P. Cannon , and Eugene Braunwald Metrics 21 December 2004Volume 141, Issue 12Page: 967KeywordsAcute coronary syndromeCognitive impairmentDeliriumElderlyMortality ePublished: 21 December 2004 Issue Published: 21 December 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Reliability assessment and correlation analysis of evaluating orthodontic treatment outcome in Chinese patients
Authors: Guang-Ying Song, Zhi-He Zhao, Yin Ding, Yu-Xing Bai, Lin Wang, Hong He, Gang Shen, Wei-Ran Li, Sheldon Baumrind, Zhi Geng, Tian-Min Xu
Journal: International Journal of Oral Science (2013)

This study aimed to assess the reliability of experienced Chinese orthodontists in evaluating treatment outcome and to determine the correlations between three diagnostic information sources. Sixty-nine experienced Chinese orthodontic specialists each evaluated the outcome of orthodontic treatment of 108 Chinese patients. Three different information sources: study casts (SC), lateral cephalometric X-ray images (LX) and facial photographs (PH) were generated at the end of treatment for 108 patients selected randomly from six orthodontic treatment centers throughout China. Six different assessments of treatment outcome were made by each orthodontist using data from the three information sources separately and in combination. Each assessment included both ranking and grading for each patient. The rankings of each of the 69 judges for the 108 patients were correlated with the rankings of each of the other judges yielding 13 873 Spearman rs values, ranging from –0.08 to +0.85. Of these, 90% were greater than 0.4, showing moderate-to-high consistency among the 69 orthodontists. In the combined evaluations, study casts were the most significant predictive component (R2=0.86, P<0.000 1), while the inclusion of lateral cephalometric films and facial photographs also contributed to a more comprehensive assessment (R2=0.96, P<0.000 1). Grading scores for SC+LX and SC+PH were highly significantly correlated with those for SC+LX+PH (r(SC+LX)vs.(SC+LX+PH)=0.96, r(SC+PH)vs.(SC+LX+PH)=0.97), showing that either SC+LX or SC+PH is an excellent substitute for all three combined assessment. A comprehensive survey of six orthodontic treatment centers in China indicates a high level of consistency with which Chinese orthodontic specialists assess treatment outcomes. The study, led by Tian-Min Xu of Peking University, is the first of its kind to compare the values of different combinations of methods for such assessments. The three most commonly used approaches to evaluate the success of orthodontic procedures are: study, or plaster, casts; cephalometric films, or head images (traditionally x-rays); and facial photographs. Previous studies examined the predictive potential of each of these methods in isolation. Xu and colleagues showed that study casts were the most reliable predictors of successful treatment. The additional use of cephalometric films and facial photographs increased the likelihood of a reliable assessment. More than 300, 000 Chinese patients undergo orthodontic procedures annually.
Dragon Within the Gates: The Once and Future AIDS Epidemic
Authors: Robert M. Wachter
Journal: JAMA (1993)

The first time I saw Dr Stephen Joseph, he was not having a good day. As the New York City Health Commissioner rose to give his plenary talk at the 1989 Fifth International Conference on AIDS in Montreal, Quebec, hundreds of AIDS activists rose with him. When Joseph began to speak, outlining his plan to encourage more aggressive HIV testing and contact tracing, the activists turned their backs on the Commissioner and began to shout   Resign! Joseph ignored the hecklers and went on with his talk; the shouts became Murder! and Shame! At the conclusion of the address, I joined the thousands of physicians and scientists in the hall in rewarding Joseph with a standing ovation in tribute to his courage and perseverance.  an extra hurdle for the successful scientist, physician, and health official to overcome: the need to persuade a skeptical public  Both of these qualities shine
Dermal fibroblasts are one of the therapeutic targets for topical application of 1α,25‐dihydroxyvitamin D<sub>3</sub>: the possible involvement of transforming growth factor‐β induction
Authors: N. Oyama, K. Iwatsuki, M. Satoh, H. Akiba, F. Kaneko
Journal: British Journal of Dermatology (2000)

Transforming growth factor (TGF) -beta has been suggested to be an effective inhibitor for abnormal keratinocyte growth in psoriasis. As a majority of the secreted TGF-beta are biologically latent complexes, activation is essential for TGF-beta-mediated cellular responses in vitro and in vivo. Objectives Here we report the response of the TGF-beta regulation system to 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], an active vitamin D3 analogue Patients/methods We studied two types of fibroblasts derived from normal and psoriatic lesional skin, using an enzyme-linked immunosorbent assay and Northern blotting techniques.1,25(OH)2D3 caused a dose-dependent induction of latent and active TGF-beta1 proteins in both cell cultures. The increases were significant over 72 h, but not within 48 h after stimulation. The time course of TGF-beta1 mRNA expression showed a biphasic response consisting of early ( approximately 1 h) and late phases ( approximately 96 h) of induction. Concomitant increases of TGF-beta2 and -beta3, other mammalian isoforms, were observed in the 1,25(OH)2D3-treated cells, but the kinetics were all different. Co-incubation with metabolic inhibitors, actinomycin D and cycloheximide, revealed that the early induction of TGF-beta1 mRNA by 1,25(OH)2D3 is dependent on de novo RNA synthesis, but not on RNA stabilization or protein synthesis. It seems likely to be a transient and negligible response given the absence of TGF-beta1 protein production. The late induction of TGF-beta1 mRNA was partially blocked by adding isoform-specific antibodies to TGF-beta1, -beta2 and -beta3, indicating TGF-beta autoregulation. Despite these marked responses, there were no significant differences in the TGF-beta expression between normal and psoriatic fibroblasts.These results suggest that antiproliferative and anti-inflammatory effects of 1,25(OH)2D3 on psoriatic lesional skin may be mediated, at least in part, by a complex TGF-beta regulation in local dermal fibroblasts.
The Pathogenic Role of <i>Staphylococcus epidermidis</i> Capsular Polysaccharide/Adhesin in a Low-Inoculum Rabbit Model of Prosthetic Valve Endocarditis
Authors: Hiroyuki Shiro, Gloria Meluleni, Andreas Groll, Eugene Muller, Tor D. Tosteson, Donald A. Goldmann, Gerald B. Pier
Journal: Circulation (1995)

Background The capsular polysaccharide/adhesin (PS/A) antigen of Staphylococcus epidermidis was required to produce endocarditis in a rabbit model in which infection resulted from hematogenous spread of bacteria from a contaminated catheter in the jugular vein. However, many prosthetic valve endocarditis (PVE) infections probably result from direct contamination of the valve with small numbers of bacteria during surgery. The role of PS/A in this situation was evaluated by modifying a rabbit model of endocarditis to partially mimic PVE. Methods and Results A Teflon catheter was contaminated with graded inocula of either PS/A-positive S epidermidis strain M187sp11 or the PS/A-negative, isogenic strain M187sn3 and inserted into the left ventricle through the aortic valve. The PS/A-positive strain had a 50% infectious dose of 1.1×10 2 cfu (95% CI, 3.3 to 3.7×10 3 ) compared with 8.5×10 4 cfu of the PS/A-negative strain (95% CI, 8.6×10 3 to 8.5×10 5 ). The odds for developing endocarditis were estimated to be 42 times higher for any given inoculum level of the PS/A-positive strain ( P =.1). When the PS/A-positive strain was adherent to a catheter surface it survived in rabbit blood, whereas under the same conditions the PS/A-negative strain was killed ≈90% in 1 hour. Conclusions Direct contamination of an intraventricular foreign body by low levels of PS/A-positive S epidermidis results in endocarditis in rabbits, but at suitably high doses PS/A-negative strains have sufficient virulence to infect cardiac vegetations. PS/A enhances but is not absolutely required for bacterial virulence in a rabbit model of PVE.
Pseudocancer Symptoms and Mourning
Authors: HARRY D. KERR
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 May 1985Pseudocancer Symptoms and MourningHARRY D. KERR, M.D.HARRY D. KERR, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-5-720_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Schnaper and Wiernik (1) saw a defense pattern among the spouses of patients with cancer in which the spouses presented with various physical symptoms and the belief that they too had cancer. These symptoms evidently were part of their attempts to grapple with their own emotional strain.A 55-year-old man had intense pruritus (especially nocturnal), malaise, anorexia, mild weight loss, and epigastric discomfort for several months. Results of a thorough physical examination were normal except for numerous excoriations on the arms, legs, buttocks, and upper back. Results of screening laboratory testing and radiographs were normal. Hydroxyzine gave...References1. SCHNAPERWIERNIK NP. Pseudocancer symptoms in coping. Ann Intern Med. 1982;96:257. LinkGoogle Scholar2. HEIMLICHKUTSCHER HA. The family's reaction to terminal illness. In: SCHOENBERG B, CARR AC, PERETZ D, KUTSCHER AH, eds. Loss and Grief. New York: Columbia University Press; 1970:275-9. Google Scholar3. RODIN G. Somatization and the self: psychotherapeutic issues. Am J Psychother. 1984;38:257-62. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: HARRY D. KERR, M.D.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1985Volume 102, Issue 5Page: 720-720KeywordsEmotionsPruritusResearch laboratoriesWeight loss ePublished: 1 December 2008 Issue Published: 1 May 1985 PDF downloadLoading ...