tbuckley/cabot-search huggingface dataset:
Oxidative stress–induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease
Authors: Coen H. Wiegman, Charalambos Michaeloudes, Gulammehdi Haji, Priyanka Narang, Colin J. Clarke, Kirsty E. Russell, Wuping Bao, Stelios Pavlidis, Peter J. Barnes, Justin Kanerva, Anton Bittner, Navin Rao, Michael P. Murphy, Paul A. Kirkham, Kian Fan Chung, Ian M. Adcock, Christopher E. Brightling, Donna E. Davies, Donna K. Finch, Andrew J. Fisher, Alasdair Gaw, Alan J. Knox, Ruth J. Mayer, Michael Polkey, Michael Salmon, David Singh
Journal: Journal of Allergy and Clinical Immunology (2015)

BackgroundInflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial oxidative stress might be involved in driving the oxidative stress–induced pathology.ObjectiveWe sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells.MethodsMice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined. Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD. Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ.ResultsMice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression. Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR. ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased. Healthy smokers were intermediate between healthy nonsmokers and patients with COPD. Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects. MitoQ and Tiron inhibited TGF-β–induced ASM cell proliferation and CXCL8 release.ConclusionsMitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell hyperproliferation. Targeting mitochondrial ROS represents a promising therapeutic approach in patients with COPD.
Frequency and Characteristics of Isolated Psychiatric Episodes in Anti–<i>N</i>-Methyl-<scp>d</scp>-Aspartate Receptor Encephalitis
Authors: Matthew S. Kayser, Maarten J. Titulaer, Núria Gresa-Arribas, Josep Dalmau
Journal: JAMA Neurology (2013)

Patients with anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis often develop prominent psychiatric manifestations. The frequency and type of isolated psychiatric episodes (pure psychiatric symptoms without neurological involvement) either as initial presentation of the disease or as relapse are unknown.To determine the frequency, symptoms, and outcome of isolated psychiatric episodes in a cohort of patients with anti-NMDAR encephalitis.Observational cohort of patients diagnosed during a5-year period (median follow-up, 2 years). A total of 571 patients with IgG antibodies against the NR1 subunit of the NMDAR were included in the study. Antibody studies were performed at the University of Pennsylvania and the University of Barcelona, and clinical information was obtained by us or referring physicians.Frequency, type of symptoms, and outcome of patients with anti-NMDAR encephalitis and isolated psychiatric manifestations.Of 571 patients, 23 (4%) developed isolated psychiatric episodes, 5 at disease onset and 18 during relapse. For all 23 patients, age (median, 20 years), sex (91%female), and tumor association (43%; ovarian teratoma in all cases) were similar to the population at large.Predominant symptoms included delusional thinking (74%), mood disturbances (70%,usually manic), and aggression (57%). Brain magnetic resonance imaging findings were abnormal in 10 of 22 patients (45%) and cerebrospinal fluid analysis showed pleocytosis in 17 of 22 patients (77%). Eighty-three percent of the patients had full or substantial recovery after immunotherapy and tumor resection when appropriate. After relapse, 17 of 18 patients(94%) returned to a similar or better prerelapse functional level.Isolated psychiatric episodes are rare but can occur as initial onset or relapse of anti-NMDAR encephalitis. Recognition of these episodes is important because they respond to immunotherapy. In patients with new-onset psychosis, having a history of encephalitis, subtle neurological symptoms, and/or abnormal results on ancillary tests should prompt screening for NMDAR antibodies.
Endothelial cells modulate renin secretion from isolated mouse juxtaglomerular cells.
Authors: A Kurtz, B Kaissling, R Busse, W Baier
Journal: Journal of Clinical Investigation (1991)

Utilizing cocultures of mouse renal juxtaglomerular cells with bovine microvascular endothelial cells, we have examined whether endothelial cells exert direct influence on renin secretion from renal juxtaglomerular cells. In the presence of endothelial cells both spontaneous and forskolin (10 microM) or isoproterenol (10 microM) stimulated renin release were markedly attenuated. The stimulatory effect of the calmodulin antagonist calmidazolium (10 microM) on renin secretion was not altered by endothelial cells, whereas the stimulatory effect of ethylisopropylamiloride (50 microM) an inhibitor of sodium-proton exchange was enhanced in the presence of endothelial cells. Indomethacin (10 microM) and NG-monomethyl-l-arginine (NMMA) (1 mM) used to inhibit cyclooxygenase activity and production of endothelium-derived relaxing factor (EDRF) decreased spontaneous renin release in the presence of endothelial cells only, but had no effect on forskolin stimulated renin secretion. Endothelin (1 microM) inhibited cAMP stimulated renin release both in the absence and in the presence of endothelial cells. ATP (10 microM) which acts on both endothelial and juxtaglomerular cells via purinergic P2 receptors inhibited cAMP stimulated renin release only in the absence but not in the presence of endothelial cells. This modulatory effect of endothelial cells was no altered by indomethacin nor by NMMA. Taken together, our findings provide first evidence for a local control function of the endothelium on cAMP stimulated renin secretion from renal juxtaglomerular cells, which could in part be mediated by endothelin.
The low frequency of defective <i>TPMT</i> alleles in Turkish population: A study on pediatric patients with acute lymphoblastic leukemia
Authors: Tugba Boyunegmez Tumer, Gulen Ulusoy, Orhan Adali, Gurses Sahin, Sevgi Gozdasoglu, Emel Arinç
Journal: American Journal of Hematology (2007)

Abstract 6‐Mercaptopurine (6MP) is an essential anticancer drug used in the treatment of childhood acute lymphoblastic leukemia (ALL). Thiopurine methyltransferase (TPMT) polymorphisms are the major determinants of interindividual differences in the severe toxicity or efficacy of 6MP. Four variant alleles, TPMT*2 , TPMT*3A , TPMT*3B , and TPMT*3C , are responsible over the 80% of low or undetectable enzyme activity. The frequencies of these variants were investigated among 106 children with ALL in Turkish population. TPMT*3A and TPMT*3C were the only deficiency alleles detected in Turkish population with an allele frequency of 0.9% for both. While *3C allele frequency in Turkish population was found to be very similar to Asian and other Caucasian populations, * 3A allele frequency was significantly ( P &lt; 0.05) lower. So far, studies showed that the genetic polymorphisms of other drug metabolizing enzymes like CYP2E1 , CYP1A1 , GSTM1/ T1 in Turkish population were similar to Caucasian populations. However, we found that the distribution of TPMT polymorphisms in Turkish population was significantly lower than those in other Caucasians like British, French, and Italian whereas the distributions of TPMT variants were found to be very similar to Kazak population which is also Caucasian in ethnic origin. In this study, the clinical histories of the patients in the sample population were also examined, retrospectively. The patients with heterozygous or homozygous mutant genotypes had developed severe neutropenia and infection during 6MP therapy. The study provides the first data on the frequency of common TPMT variants in the Turkish population, based on analysis of pediatric patients with ALL. Am. J. Hematol. 82:906–910, 2007. © 2007 Wiley‐Liss, Inc.
A Growth-Related Oncogene/CXC Chemokine Receptor 2 Autocrine Loop Contributes to Cellular Proliferation in Esophageal Cancer
Authors: Bo Wang, Denver T. Hendricks, Fred Wamunyokoli, M. Iqbal Parker
Journal: Cancer Research (2006)

Abstract Growth-related oncogene (GRO), a member of the CXC chemokine subfamily, plays a major role in inflammation and wound healing. CXC chemokines have been found to be associated with tumorigenesis, angiogenesis, and metastasis. Although elevated expression of GRO has been reported in several human cancers, the expression and role of GRO and its receptor, CXCR2, in esophageal cancer are poorly understood. This study used real-time reverse transcription-PCR (RT-PCR) and immunohistochemical approaches to show that GROα, GROβ, and CXCR2 are up-regulated in esophageal tumor tissue. Furthermore, GROα, GROβ, and CXCR2 are constitutively expressed in WHCO1, an esophageal cancer cell line that was used as a model system here. GROβ enhances transcription of EGR-1, via the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, which can be blocked by a specific antagonist of CXCR2 (SB 225002) or specific antibody to GROβ. WHCO1 cells treated with SB 225002 exhibited a 40% reduction in cell proliferation. A stable WHCO1 GROα RNA interference (RNAi) clone displayed a 43% reduction in GROα mRNA levels as determined by real-time RT-PCR, reduced levels of GROα by fluorescence microscopy, and a 60% reduction in the levels of phosphorylated ERK1/2. A stable clone expressing GROβ RNAi displayed &amp;gt;95% reduction in GROβ mRNA levels, reduced levels of GROβ by fluorescence microscopy, and an 80% reduction in the levels of phosphorylated ERK1/2. Moreover, these GROα RNAi- and GROβ RNAi-expressing clones displayed a 20% and 50% decrease in cell proliferation, respectively. Our results suggest that GROα-CXCR2 and GROβ-CXCR2 signaling contributes significantly to esophageal cancer cell proliferation and that this autocrine signaling pathway may be involved in esophageal tumorigenesis. (Cancer Res 2006; 66(6): 3071-7)
Impact of Open-Access Endoscopy on Detection of Early Oesophageal and Gastric Cancer 1994 - 2003: Population-Based Study
Authors: H. Paterson, D. McCole, C. Auld
Journal: Endoscopy (2006)

There is conflicting evidence regarding the ability of open-access endoscopy to detect oesophageal and gastric cancers at an earlier stage. The aim of the study was to assess the impact, with regard to earlier diagnosis of oesophageal and gastric cancer, of the first 10 years of a regional open-access endoscopy service in the Dumfries and Galloway region of Scotland.Data were retrieved from prospectively compiled endoscopy and cancer registry databases. Route of referral (open-access vs. outpatient vs. inpatient), presenting symptoms (alarm vs. benign) and UICC disease stage in consecutive 5-year periods (1994 - 1998 and 1999 - 2003) were compared.386 oesophagogastric cancers were identified (179 during 1994 - 1998 and 207 in 1999 - 2003). The number of patients undergoing endoscopy increased from 500 per annum prior to the open-access service to 7359 during 1994 - 1998 and 9701 in 1999 - 2003. Patient age, route of referral and presenting symptoms were unchanged. There was no improvement in disease stage at diagnosis (stage I, 7 % vs. 7 %; stage II, 16 % vs. 17 %; stage III, 31 % vs. 28 %).Despite a 32 % increase in endoscopy workload, the provision, over 10 years, of a regional open-access endoscopy service was not associated with earlier detection of oesophageal or gastric cancer.
An Oncolytic Adenovirus Redirected with a Tumor-Specific T-Cell Receptor
Authors: Zsolt Sebestyen, Jeroen de Vrij, Maria Magnusson, Reno Debets, Ralph Willemsen
Journal: Cancer Research (2007)

Abstract To improve safety and specificity of oncolytic adenoviruses, we introduced T-cell receptors (TCR) specific for a unique class of truly tumor-specific antigens into the adenoviral fiber protein. The adenoviral fiber knob responsible for attachment to the coxsackie-adenoviral receptor (CAR) on target cells was replaced by a single-chain TCR (scTCR) molecule with specificity for the melanoma-associated cancer-testis antigen MAGE-A1, presented by HLA-A1, and an extrinsic trimerization motif in a replicating Ad5 vector (Ad5.R1-scTCR). The production of the recombinant virus was initiated in a novel producer cell line that expressed an antibody-based hexon-specific receptor (293T-AdR) in the cell membrane. This new production system allowed CAR-independent and target antigen–independent propagation of Ad5.R1-scTCR. Infection with adenovirus bearing the scTCR-based fiber resulted in an efficient killing of target tumor cells. The infection was cell type specific because only HLA-A1+/MAGE-A1+ melanoma cells were killed, and thus, this retargeting strategy provides a versatile tool for future clinical application. [Cancer Res 2007;67(23):11309–16]
OP39 * THE ROLE OF EARLY INTRA-OPERATIVE MRI IN SUBTOTAL RESECTION OF OPTIC-HYPOTHALAMIC GLIOMAS IN CHILDREN
Authors: C. P. Millward, J. R. Ellenbogen, S. Perez da Rosa, M. Didi, S. Avula, C. Mallucci
Journal: Neuro-Oncology (2014)

INTRODUCTION: Optic pathway/hypothalamic gliomas (OPHGs) are generally benign but situated in an exquisitely sensitive brain region. They follow an unpredictable course and are often impossible to completely resect. We describe a series of OPHGs in 11 patients who underwent surgical resection of their tumour with the aid of intra-operative MRI (iMRI) and discuss their post-surgical outcome. METHOD: All patients with OPHGs managed surgically utilising iMRI at Alder Hey Children's Hospital between 2010 and 2013 were prospectively identified. Demographic and relevant clinical data were obtained. MRI was used to estimate tumour volume pre-operatively and post-resection. If iMRI suggested that further resection was possible, second look surgery was performed followed by post-operative imaging to establish the final status of resection. Tumour volume was estimated for each MR image using the MRIcron software package. RESULTS: Control of tumour progression was achieved in all patients. 7 patients had second look surgery with significant tumour resection following iMRI without any surgically related morbidity. The mean additional quantity of tumour removed following second look surgery as a percentage of the initial total volume was 26.3% (range 11.2-59.2%). 1 patient developed permanent diabetes insipidius unrelated to gross tumour resection, and 3 patients developed a partial ACTH deficit that were easily managed. CONCLUSION: OPHG resection poses a technical difficulty due to their eloquent location. iMRI allows the surgeon to evaluate the tumour resection, and decide whether further resection can be achieved safely. We have demonstrated that utilising iMRI, significantly greater tumour resection can be safely achieved.
A piece of my mind. Mr Turner's toenails
Authors: R. M. Berlin
Journal: JAMA (1989)

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
HIV in injecting drug users in Asian countries: Authors' reply
Authors: Alex Wodak, Robert Ali, M Farrell
Journal: BMJ (2005)

EDITOR—Reece concedes the critical importance of controlling the epidemic of HIV among and from injecting drug users, especially in Asia. This is a useful start. However, his subsequent comments are less than helpful.

Reece argues that the high incidence of hepatitis C indicates that harm minimisation is ineffective. A recent study estimated that needle …
Distribution of mental health professionals working on site in English and Welsh general practices.
Authors: T Kendrick, B Sibbald, J Addington-Hall, D Brenneman, P Freeling
Journal: BMJ (1993)

OBJECTIVE--To describe the nature and distribution of mental health professionals working on site in general practices. DESIGN--Postal questionnaire and telephone interview survey. SETTING--English and Welsh general practices. SUBJECTS--1880 general practitioners, of whom 1542 (82%) responded. MAIN OUTCOME MEASURES--Prevalence, types, and distribution of mental health professionals working on site among general practices. Factors predicting the presence of mental health professionals on site. RESULTS--The number of practices reporting the presence on site of each type of professional were 528 for community psychiatric nurses; 266 for practice counsellors; 177 for clinical psychologists; 132 for psychiatrists; 96 for psychiatric social workers; and 45 for psychotherapists. Mental health professionals tended to cluster together in practices more often than expected by chance alone. Practice characteristics which independently predicted the presence of a mental health professional on site were having four or more partners; being a training practice; and running stress, bereavement, or other mental health clinics. The proportions of practices with mental health professionals on site varied significantly among health regions. There was no association between the presence of mental health professionals on site and the location of practices, the social class mix of patients, or the estimated percentage of elderly patients or patients of non-European origin. CONCLUSIONS--Mental health professionals tend to cluster together, with a preponderance in larger training practices. Specialist mental health care provision within general practices is unevenly distributed. Further research is needed to determine whether this uneven distribution reflects differences in need or inequalities in the provision of mental health services.
Lenalidomide — The Phoenix Rises
Authors: Alan F. List
Journal: New England Journal of Medicine (2007)

Perhaps the darkest memory in modern pharmaceutical history is that of the devastating effects of thalidomide exposure on fetal development. More than four decades later, thalidomide reemerged from the ashes as the prototype for a new proprietary class of drugs with broad pharmacologic effects and promising antineoplastic activity, referred to collectively as immunomodulatory drugs.Thalidomide was first marketed in Europe in the late 1950s as a hypnotic and antiemetic for the treatment of morning sickness during pregnancy. Between 1956 and 1962, approximately 10,000 children were born with severe physical deformities, or phocomelia, as a result of the drug's unrecognized teratogenic . . .
Forced expiratory time--its reliability as a lung function test.
Authors: J B Macdonald, T J Cole, A Seaton
Journal: Thorax (1975)

Three studies of factors affecting variability of forced expiratory time (FET) have been carried out. In the first, different observers or repeated measurements over a few minutes were shown to make no significant contribution to FET variability. Time of day was also relatively unimportant. In the second study, FET was shown to vary considerably more than peak flow rate, forced expiratory volumes, and mid expiratory flow rates over the course of five days. In the third study, FET was shown to correlate with other measurements of airways obstruction though the correlation coefficients were relatively low. The measurement of FET is thought to be too variable to be of practical use as a screening test for small airways disease, though its clinical value is not questioned.
Acute non-B hepatitis in the Israel defence forces: Comparison of some epidemiologic features before and after the usage of preexposure immune serum globulin prophylaxis
Authors: Haim Matzkin
Journal: Hepatology (1987)

Large-scale epidemics of non-B (HBsAg-negative) hepatitis have occurred in the Israel Defense Forces prior to post- and preexposure immune serum globulin administration. Presently, hepatitis morbidity rates have stabilized around 1 to 2 per 1,000. Several years after vaccine initiation, a comparison of epidemiological features was made in order to redefine risk groups. Seasonal morbidity, sex, ethnic origin and educational status (as a representative of socioeconomic level) were not different after the preexposure immunization compared to the preimmunization era. Therefore, a more selective immunization is proposed.
Increased Nitrotyrosine in Exhaled Breath Condensate of Patients with Asthma
Authors: TOYOYUKI HANAZAWA, SERGEI A. KHARITONOV, PETER J. BARNES
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The reaction of nitric oxide (NO) and superoxide anions (O(2)(-)) in the airway results in the formation of peroxynitrite, a highly reactive oxidant species. Peroxynitrite reacts with tyrosine residues in proteins to form the stable product nitrotyrosine. We investigated whether nitrotyrosine in exhaled breath condensates may be increased in patients with asthma. Four groups of nonsmoking subjects were studied. We measured exhaled NO, nitrotyrosine, and leukotrienes concentrations in breath condensate in healthy nonatopic subjects (n = 15) and in patients with mild asthma (steroid naive, n = 15), moderate asthma (inhaled steroid treatment, n = 12), and severe asthma (oral steroid treatment, n = 12). Exhaled NO was increased significantly in patients with mild (19.2 +/- 2.7 ppb, p < 0.01) and moderate asthma (14.0 +/- 1.53 ppb, p < 0.05), as compared with normal control (6.58 +/- 0.61 ppb). The levels of LTC(4)/D(4)/E(4) and LTB(4) were increased significantly in patients with moderate and severe asthma treated with steroids. Nitrotyrosine concentrations were detectable (6.3 +/- 0.8 ng/ml) in breath condensate of normal subjects, and were increased significantly in patients with mild asthma (15.3 +/- 2.0 ng/ml, p < 0.01). However, the levels of nitrotyrosine in exhaled condensate were lower in patients with moderate (5.0 +/- 0.6 ng/ml) and severe asthma (3.3 +/- 0.6 ng/ml, p < 0.05). There was a significant correlation between nitrotyrosine in breath condensate and exhaled NO in patients with mild asthma (r = 0.65, p < 0.05). We conclude that nitrotyrosine formation in exhaled breath condensates may be a marker of oxidative stress in airways of asthma.