tbuckley/cabot-search huggingface dataset:
An invertebrate model of the developmental neurotoxicity of insecticides: effects of chlorpyrifos and dieldrin in sea urchin embryos and larvae.
Authors: G A Buznikov, L A Nikitina, V V Bezuglov, J M Lauder, S Padilla, T A Slotkin
Journal: Environmental Health Perspectives (2001)

Chlorpyrifos targets mammalian brain development through a combination of effects directed at cholinergic receptors and intracellular signaling cascades that are involved in cell differentiation. We used sea urchin embryos as an invertebrate model system to explore the cellular mechanisms underlying the actions of chlorpyrifos and to delineate the critical period of developmental vulnerability. Sea urchin embryos and larvae were exposed to chlorpyrifos at different stages of development ranging from early cell cleavages through the prism stage. Although early cleavages were unaffected even at high chlorpyrifos concentrations, micromolar concentrations added at the mid-blastula stage evoked a prominent change in cell phenotype and overall larval structure, with appearance of pigmented cells followed by their accumulation in an extralarval cap that was extruded from the animal pole. At higher concentrations (20-40 microM), these abnormal cells constituted over 90% of the total cell number. Studies with cholinergic receptor blocking agents and protein kinase C inhibitors indicated two distinct types of effects, one mediated through stimulation of nicotinic cholinergic receptors and the other targeting intracellular signaling. The effects of chlorpyrifos were not mimicked by chlorpyrifos oxon, the active metabolite that inhibits cholinesterase, nor by nonorganophosphate cholinesterase inhibitors. Dieldrin, an organochlorine that targets GABA(A )receptors, was similarly ineffective. The effects of chlorpyrifos and its underlying cholinergic and signaling-related mechanisms parallel prior findings in mammalian embryonic central nervous system. Invertebrate test systems may thus provide both a screening procedure for potential neuroteratogenesis by organophosphate-related compounds, as well as a system with which to uncover novel mechanisms underlying developmental vulnerability.
Circulating Levels of Soluble Interleukin-6 Receptor in Patients with Bronchial Asthma
Authors: AKIHITO YOKOYAMA, NOBUOKI KOHNO, KIMIKO SAKAI, KEI-ICHI KONDO, YUTAKA HIRASAWA, KUNIO HIWADA
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

In the search for markers of airway inflammation, we investigated the role of soluble interleukin-6 receptor (sIL-6R) in patients with bronchial asthma. Serum levels of sIL-6R were measured in 20 patients with stable asthma and in 18 healthy control subjects by means of a sandwich enzyme-linked immunosorbent assay. Such levels were also evaluated during a spontaneous attack of asthma (n = 10) as well as that after allergen inhalation (n = 7). Results were compared with those observed during the stable state and after the inhalation of methacholine. Serum levels of sIL-6R in asthmatic patients (132 +/- 31 ng/ml) significantly exceeded those of control subjects (111 +/- 16 ng/ml) (p < 0.05). These levels showed no correlation with such clinical variables as nonspecific bronchial hyperreactivity, atopic status, or serum concentration of IgE. Serum sIL-6R levels observed during an asthmatic attack versus those during the stable state (4 wk later) differed significantly. After a severe attack of asthma, such levels were significantly elevated on the second and third days, but not on Day 5. After challenge, circulating levels of sIL-6R were significantly increased 24 h after the inhalation of allergen but not of methacholine. Results suggest that serum levels of sIL-6R are increased in patients with asthma and are further increased during a spontaneous attack or that provoked by the inhalation of allergen. Thus, serum sIL-6R may reflect inflammation of the airway. Further studies are indicated to determine the clinical significance and the application of serum levels of sIL-6R in evaluating asthmatic patients.
Comparing tobacco cigarette dependence with other drug dependencies. Greater or equal 'difficulty quitting' and 'urges to use,' but less 'pleasure' from cigarettes
Authors: L. T. Kozlowski
Journal: JAMA (1989)

About 1000 persons seeking treatment for alcohol or drug dependence were asked, relative to cigarettes, about the difficulty of quitting the use of the substance for which they were seeking treatment, the strength of their strongest urges to use, and the pleasure they derived from use. Fifty-seven percent said that cigarettes would be harder to quit using than their problem substance. These ratings were related to the level of cigarette dependence and the perceived difficulty of quitting the use of the problem substance. The alcohol-dependent persons were about four times more likely than the drug-dependent persons to say that their strongest urges for cigarettes were at least as great as their strongest urges for their problem substance. Cigarettes were generally rated as less pleasurable than alcohol or other drugs. Thus, experiential experts on dependence judge cigarette dependence as at least as "addictive" as other drug use, but not as pleasurable, indicating important similarities and differences between cigarette dependence and other forms of dependence on psychoactive substances.
Abstract 3915: α-Fetoprotein-producing hepatoma cells have increased Jagged1 gene copy numbers and their growth can be suppressed by gamma secretase inhibitor
Authors: Kazunori Kawaguchi, Masao Honda, Taro Yamashita, Hajime Takatori, Teruyuki Ueda, Masataka Kanno, Shuichi Kaneko
Journal: Cancer Research (2011)

Abstract Background: Approximately 70% of patients with hepatocellular carcinoma (HCC) have abnormally high α-fetoprotein (AFP) levels, which increase with tumor progression and angiogenesis. We previously used cDNA microarray comparative genomic hybridization (aCGH) to demonstrate an association between hepatoma AFP-producing status and genomic copy number gain and loss. Although genomic copy number change is reported to be associated with some oncogenic factors, its relationship with molecular pathway aberration has not been elucidated. Here, we examined whether signal pathways are associated with both expression and genomic gain for the purpose of discovering clinically useful molecular targets in hepatoma patients. Method: Changes in DNA copy number of hepatoma cells were analyzed using bacterial artificial chromosome (BAC)-aCGH and compared with gene expression profiles. Candidate genes were identified, and real-time PCR was used to confirm gene expression changes in AFP-producing cells. siRNA was used to inhibit gene expression and the effect of this on hepatoma cell growth was determined. Confirmation of genomic alteration was performed by real-time PCR on clinical HCC samples. Growth of hepatoma cells was examined following the application of an inhibitor of the identified signal transduction-related gene. Results: The BAC clone was significantly amplified in some regions of chromosome 20p from hepatoma cells. This amplified region included the ligand for Notch signal transduction, Jagged1, which was shown to be up-regulated by microarray analysis and real-time PCR in AFP-producing hepatoma cells. Surgically treated AFP-up-regulated HCC samples were used to demonstrate the significant correlation between AFP and Jagged1 gene expression. Interestingly, tissue Jagged1 genomic gain and AFP expression were also correlated. The suppression of Jagged1 using siRNA in an AFP-producing cell line significantly repressed cell growth compared with an AFP-negative cell line. The inhibitor of the Notch pathway, gamma secretase inhibitor (GSI), is currently undergoing clinical trials for the treatment of Alzheimer's disease, and its effectiveness has been shown as a cancer therapy for solid tumors. Here, continuous application of GSI to hepatoma cells resulted in a significant suppression of cell growth. Conclusion: The genomic amplification of Jagged1 contributes to the continuous mRNA expression that activates the Jagged1-Notch signaling pathway in hepatomas. GSI may be a promising candidate for use in the therapy of AFP-producing advanced HCC. 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 3915. doi:10.1158/1538-7445.AM2011-3915
The effect of lithium carbonate on chemotherapy‐induced neutropenia and thrombocytopenia
Authors: Carol M. Richman, Michael M. Makii, Patricia A. Weiser, Arthur L. Herbst
Journal: American Journal of Hematology (1984)

Abstract Lithium carbonate ameliorates neutropenia associated with cancer chemotherapy. The effect of lithium on platelet suppression has not, however, been well established. In the present study, five patients with ovarian carcinoma received daily lithium during alternate cycles of treatment with hexamethylmelamine, cyclophosphamide, adriamycin, and cis‐platinum. Analysis of myelosuppression was performed on 24 paired consecutive cycles given at identical doses, one with and one without lithium. During lithium cycles, nadir leukocyte, neutrophil, and platelet counts were significantly higher (P&lt;0.01, &lt;0.01, &lt;0.05 respectively) and the interval between treatments was shorter (P&lt;0.01). One patient who has received 11 cycles of chemotherapy continues to receive 100% doses owing to the beneficial effect of lithium on chemotherapy‐induced thrombocytopenia. Lithium was poorly tolerated by some patients because of either tremor or nausea and vomiting, in spite of nontoxic serum lithium levels. The amelioration of drug‐induced platelet suppression as well as neutrophil suppression noted in this study suggests that lithium's effect on hematopoiesis is not limited to stimulation of neutrophil production. The ability of lithium to decrease chemotherapyinduced myelosuppression suggests that lithium administration may facilitate escalation of chemotherapy doses in selected patients.
Injuries in 13 international Athletics championships between 2007–2012
Authors: Nina Feddermann-Demont, Astrid Junge, Pascal Edouard, Pedro Branco, Juan-Manuel Alonso
Journal: British Journal of Sports Medicine (2014)

Background The International Association of Athletics Federation has systematically surveyed all Athletics injuries in their competitions since 2007 in order to develop strategies for health protection of their athletes. Aims Analysis of frequency and characteristics of injuries during 13 international Athletics championships from 2007 to 2012 regarding different types of championships and discipline categories. Methods The team physicians and the Local Organizing Committee reported daily all injuries on a standardised injury report form during each championship. Results A total of 1470 injuries were reported, equivalent to 81.1±4.2 injuries per 1000 registrations of which 36.7±2.9 were expected to result in absence from sports. The incidence of time-loss injuries was significantly higher in competition (29.0±2.6) than in training (5.8±1.9), and in outdoor (46.4±4.0) than in indoor (23.7±6.2) or youth/junior championships (13.2±4.0). While most in-competition time-loss injuries were reported during short distance events (32.5%), combined events had the highest incidence of in-competition time-loss injuries (106±26.5). The most frequent diagnosis was thigh strain (28.2%), followed by lower leg strain and ankle sprain. Injury location varied between different discipline categories: in long distances the lower leg, in Marathon the foot and in throws the upper extremity were mainly affected. Conclusions The incidence of injuries varied substantially between different types of Athletics championships and between discipline categories. Special attention should be paid to combined events, running disciplines and (thigh) strain to better understand the injury mechanisms and risk factors and develop related preventive measures.
Topical 5-aminolaevulinic acid-photodynamic therapy for the treatment of urethral condylomata acuminata
Authors: X.L. Wang, H.W. Wang, H.S. Wang, S.Z. Xu, K.H. Liao, P. Hillemanns
Journal: British Journal of Dermatology (2004)

Background Electrocoagulation and laser evaporation for urethral condylomata acuminata have high recurrence rates and can be associated with urethral malformations. Objectives To investigate the effect of photodynamic therapy (PDT) with topical 5‐aminolaevulinic acid (ALA) on urethral condylomata acuminata and to examine the histological changes in lesions of condylomata acuminata after ALA‐PDT. Methods Patients with urethral condylomata (n = 164) were given topical ALA followed by intraurethral PDT through a cylindrical fibre. Patients included 11 individuals with 16 penile or vulval condylomatous lesions which were biopsied before or after treatment; the histological changes were then evaluated by light microscopy and electron microscopy. Results The complete response rate was 95% and the recurrence rate was 5% after 6–24 months of follow‐up. Light microscopy revealed keratinocytes in the middle and upper layers of the epidermis showing marked vacuolation and some necrocytosis 1 and 3 h after PDT. Necrosis in all layers of the epidermis was noted 5 h after PDT. Electron microscopy of keratinocytes revealed distinct ultrastructural abnormalities of mitochondria and the endoplasmic reticulum, and membrane damage. Apoptotic bodies were detected 3 h after PDT and a large number of keratinocytes exhibited necrosis 5 h after PDT. Conclusions Results suggest that, compared with conventional therapies, topical ALA‐PDT is a simple, effective, safe and well‐tolerated treatment for urethral condylomata acuminata that is associated with a low recurrence rate. The mechanism might be the triggering of both apoptosis and necrosis by ALA‐PDT in human papillomavirus‐infected keratinocytes.
Osteopontin selectively regulates p70S6K/mTOR phosphorylation leading to NF-κB dependent AP-1-mediated ICAM-1 expression in breast cancer cells
Authors: Mansoor Ahmed, Gopal C Kundu
Journal: Molecular Cancer (2010)

Breast cancer is one of the most frequently diagnosed cancer and accounts for over 400,000 deaths each year worldwide. It causes premature death in women, despite progress in early detection, treatment, and advances in understanding the molecular basis of the disease. Therefore, it is important to understand the in depth mechanism of tumor progression and develop new strategies for the treatment of breast cancer. Thus, this study is aimed at gaining an insight into the molecular mechanism by which osteopontin (OPN), a member of SIBLING (Small Integrin Binding LIgand N-linked Glycoprotein) family of protein regulates tumor progression through activation of various transcription factors and expression of their downstream effector gene(s) in breast cancer. In this study, we report that purified native OPN induces ICAM-1 expression in breast cancer cells. The data revealed that OPN induces NF-κB activation and NF-κB dependent ICAM-1 expression. We also observed that OPN-induced NF-κB further controls AP-1 transactivation, suggesting that there is cross talk between NF-κB and AP-1 which is unidirectional towards AP-1 that in turn regulates ICAM-1 expression in these cells. We also delineated the role of mTOR and p70S6 kinase in OPN-induced ICAM-1 expression. The study suggests that inhibition of mTOR by rapamycin augments whereas overexpression of mTOR/p70S6 kinase inhibits OPN-induced ICAM-1 expression. Moreover, overexpression of mTOR inhibits OPN-induced NF-κB and AP-1-DNA binding and transcriptional activity. However, rapamycin further enhanced these OPN-induced effects. We also report that OPN induces p70S6 kinase phosphorylation at Thr-421/Ser-424, but not at Thr-389 or Ser-371 and mTOR phosphorylation at Ser-2448. Overexpression of mTOR has no effect in regulation of OPN-induced phosphorylation of p70S6 kinase at Thr-421/Ser-424. Inhibition of mTOR by rapamycin attenuates Ser-371 phosphorylation but does not have any effect on Thr-389 and Thr-421/Ser-424 phosphorylation of p70S6 kinase. However, OPN-induced phosphorylation of p70S6 kinase at Thr-421/Ser-424 is being controlled by MEK/ERK pathway. These results suggest that blocking of OPN-induced ICAM-1 expression through mTOR/p70S6 kinase signaling pathway may be an important therapeutic strategy for the treatment of breast cancer.
Treating Dementia and Agitation
Authors: Gary W. Small
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Psoriasiform dermatitis is driven by IL-36–mediated DC-keratinocyte crosstalk
Authors: Luigi Tortola, Esther Rosenwald, Brian Abel, Hal Blumberg, Matthias Schäfer, Anthony J. Coyle, Jean-Christoph Renauld, Sabine Werner, Jan Kisielow, Manfred Kopf
Journal: Journal of Clinical Investigation (2012)

Psoriasis is a chronic inflammatory disorder of the skin affecting approximately 2% of the world’s population. Accumulating evidence has revealed that the IL-23/IL-17/IL-22 pathway is key for development of skin immunopathology. However, the role of keratinocytes and their crosstalk with immune cells at the onset of disease remains poorly understood. Here, we show that IL-36R–deficient (Il36r–/–) mice were protected from imiquimod-induced expansion of dermal IL-17–producing γδ T cells and psoriasiform dermatitis. Furthermore, IL-36R antagonist-deficient (Il36rn–/–) mice showed exacerbated pathology. TLR7 ligation on DCs induced IL-36–mediated crosstalk with keratinocytes and dermal mesenchymal cells that was crucial for control of the pathological IL-23/IL-17/IL-22 axis and disease development. Notably, mice lacking IL-23, IL-17, or IL-22 were less well protected from disease compared with Il36r–/– mice, indicating an additional distinct activity of IL-36 beyond induction of the pathological IL-23 axis. Moreover, while the absence of IL-1R1 prevented neutrophil infiltration, it did not protect from acanthosis and hyperkeratosis, demonstrating that neutrophils are dispensable for disease manifestation. These results highlight a central and unique IL-1–independent role for IL-36 in control of the IL-23/IL-17/IL-22 pathway and development of psoriasiform dermatitis.
Hepatitis C: Risk of a Haircut
Authors: Norman Gitlin
Journal: Annals of Internal Medicine (1997)

Letters1 March 1997Hepatitis C: Risk of a HaircutNorman Gitlin, MD, Frederick S. Nolte, MD, and Michael Weiss, MDNorman Gitlin, MDEmory University School of Medicine, Atlanta, GA 30322Search for more papers by this author, Frederick S. Nolte, MDEmory University School of Medicine, Atlanta, GA 30322Search for more papers by this author, and Michael Weiss, MDEmory University School of Medicine, Atlanta, GA 30322Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-5-199703010-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Hepatitis C virus (HCV) infection has a prevalence of 1.8% in the United States. The mode of acquisition of HCV is unclear in nearly 40% of patients with chronic HCV infection. Various social practices are currently under scrutiny, including sharing razors, snorting cocaine through the same straw another person has used, and sexual practices [1].We questioned whether a haircut that includes a trim of the sideburns and back of the neck using a straight razor might lacerate the skin and thereby spread hepatitis C. We obtained the fluid used in five different male hairdresser salons to ...References1. Conry-Cantilena C, Van Raden M, Gibble J, Melpolder J, Obaid-Shakil A, Viladomiv L, et al. Routes of infection, viremia and liver disease in blood donors found to have hepatitis C virus infection. N Engl J Med. 1996; 334:1691-6. Google Scholar2. Nolte FS, Thurmond C, Fried MW. Preclinical evaluation of amplicor hepatitis C virus test for detection of hepatitis C virus RNA. J Clin Microbiol. 1995; 33:1775-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: Emory University School of Medicine, Atlanta, GA 30322 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByChromium Supplementation Does Not Improve Glucose Tolerance, Insulin Sensitivity, or Lipid Profile: A Randomized, Placebo-Controlled, Double-Blind Trial of Supplementation in Subjects With Impaired Glucose Tolerance: Response to Komorowski and JuturuRole of Chromium in Human Health and in Diabetes 1 March 1997Volume 126, Issue 5Page: 410-411KeywordsCocaineHepatitis AHepatitis CHepatitis C virusMedical risk factorsPolymerase chain reactionRNAReverse transcriptase polymerase chain reactionReverse transcription Issue Published: 1 March 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Brucellar arthritis: a study of 39 Peruvian families.
Authors: E Gotuzzo, C Seas, J G Guerra, C Carrillo, T S Bocanegra, A Calvo, O Castaneda, G S Alarcon
Journal: Annals of the Rheumatic Diseases (1987)

A study was conducted to characterise the articular manifestation of Brucella melitensis within a family in Peru. From January 1981 to June 1986, 39 families with 232 individuals were evaluated. Brucellosis was diagnosed in 118 family members (attack rate of 50.9%). A lower attack rate was observed in children less than 10 years9 old compared with other age groups (p less than 0.02). Complete clinical data were available in 92 of the 118 affected members. Moderate and severe forms of the diseases were more prevalent in women than in men (41.8% v 13.5%; p less than 0.001). Twenty eight of the 92 patients developed some brucellar complications; the articular involvement was the most prevalent (23.9%). Arthritis was also more common in women than in men (34.5% v 8.1%; p less than 0.01). Children appeared to have less articular involvement. Overall, the following pattern was observed: peripheral arthritis (54.5%); unilateral sacroiliitis (23.0%); mixed arthritis (4.5%), and spondylitis (9.1%). Spondylitis was seen only in the elderly with chronic brucellosis. Four patients developed extra-articular rheumatism. Within members of family groups, brucellar arthritis occurred less frequently than in individual patients from the same hospital. This suggests that many family cases were diagnosed in the early stages.
‘e’ Antigen defective hepatitis B virus and course of chronic infection
Authors: M.R. Brunetto, M. Giarin, F. Oliveri, G. Saracco, C. Barbera, T. Parrella, M.L. Abate, E. Chiaberge, P.L. Calvo, P. Manzini, G. Verme, F. Bonino
Journal: Journal of Hepatology (1991)