tbuckley/cabot-search huggingface dataset:
Global Food Safety
Authors: Joan Stephenson
Journal: JAMA (2001)

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
ABC of complementary medicine: Complementary medicine and the patient
Authors: C. Zollman, A. Vickers
Journal: BMJ (1999)

In surveys of users of complementary medicine, about 80% are satisfied with the treatment they received. Interestingly, this is not always dependent on an improvement in their presenting complaint. For example, in one UK survey of cancer patients, changes attributed to complementary medicine included being emotionally stronger, less anxious, and more hopeful about the future even if the cancer remained unchanged. Satisfaction may influence further use of complementary medicine: a Community Health Council survey found that over two thirds of complementary medicine users returned for further courses of treatment and that over 90% thought that they might use complementary medicine in the future. What is it that patients find worth while and what does this tell us about their expectations of healthcare services in general? The specific effects of particular therapies obviously account for a proportion of patient satisfaction, but surveys and qualitative research show that many patients also value some of the general attributes of complementary medicine. These may include the relationship with their practitioner, the ways in which illness is explained, and the environment in which they receive treatment. When these augment the therapeutic outcome of treatment, they contribute to what is sometimes called "the placebo effect." None of these is unique to complementary medicine, but many are facilitated by the private, non-institutional settings in which most complementary practitioners work. The relative therapeutic importance of specific and non-specific attributes obviously depends on individual patients and practitioners, but some complementary practitioners may be better than their conventional colleagues at using and maximising "the placebo effect."
Fibrogenic signalling in hepatic stellate cells
Authors: Derek A. Mann, Fabio Marra
Journal: Journal of Hepatology (2010)

(1) Upon liver damage, hepatic stellate cells undergo a process defined as activation (Fig. 1), that enables them to acquire a myofibroblastic phenotype. The biological actions of myofibroblasts are pivotal for liver tissue repair and fibrogenesis [1]. (2) Activation of TGFb-dependent fibrogenic signalling in hepatic stellate cells. The source of TGFb is initially paracrine including hepatocytes, Kupffer cells, and platelets activated in response to hepatic injury [2]. (3) At the same time TLR4 signalling in hepatic stellate cells is required for down-regulation of TGFb pseudoreceptor (and inhibitor) BAMBI in order to render hepatic stellate cells sensitive to TGFb signalling. Bacterial-derived LPS is currently considered to be the key fibrogenic TLR4 ligand; however, additional endogenous ligands from damaged and dying hepatocytes cannot yet be ruled out as playing a role [3]. (4) TGFb signals generate transcriptional active pro-fibrogenic Smad2 and Smad3 complexes [2], but also stimulates collagen transcription in hepatic stellate cells via hydrogen peroxide and C/EBPb. (5) Transcription factors Sp1 and KLF6 stimulate TGFb gene transcription in hepatic stellate cells to provide autocrine fibrogenic signalling. (6) Accumulation of fibrillar matrix is facilitated by increased expression of tissue inhibitors of metalloproteinases (TIMPs). (7) Agonists of the nuclear receptor PPARc oppose TGFb signalling by inhibiting activation of hepatic stellate cells and collagen expression. PPARc expression is diminished during activation of hepatic stellate cells by an epigenetic mechanism involving the methylCpG binding protein MeCP2. Ongoing clinical trials with PPARc agonists will determine their efficacy as anti-fibrotics [4]. (8) Kupffer cells and damaged hepatocytes generate reactive oxygen species (ROS) [5] which stimulate hepatic stellate cell expression of chemokines and amplification of inflammation by an NF-jB-dependent pathway. (9) Paracrine and autocrine PDGF signalling [1,5] via PI3 Kinase and ERK serves to perpetuate hepatic stellate cell activa-
Serotype-specific Binding Properties and Nanoparticle Characteristics Contribute to the Immunogenicity of rAAV1 Vectors
Authors: Maxime Ferrand, Sylvie Da Rocha, Guillaume Corre, Anne Galy, Florence Boisgerault
Journal: Molecular Therapy (2015)

The immunogenic properties of recombinant adeno-associated virus (rAAV) gene transfer vectors remain incompletely characterized in spite of their usage as gene therapy vectors or as vaccines. Molecular interactions between rAAV and various types of antigen-presenting cells (APCs), as well as the impact of these interactions on transgene or capsid-specific immunization remain unclear. We herein show that binding motifs recognized by the capsid and which determine the vector tissue tropism are also critical for key immune activation processes. Using rAAV capsid serotype 1 (rAAV1) vectors which primary receptors on target cells are α2,3 and α2,6 N-linked sialic acids, we show that sialic acid-dependent binding of rAAV1 on APCs is essential to trigger CD4(+) T-cell responses by increasing rAAV1 uptake and contributing to antigenic presentation of both the capsid and transgene product although this involves different APCs. In addition, the nanoparticulate structure of the vector in itself appears to be sufficient to trigger mobilization and activation of some APCs. Therefore, combinations of structural and of serotype-specific cell-targeting properties of rAAV1 determine its complex immunogenicity. These findings may be useful to guide a selection of rAAV variants depending on the intended level of immunogenicity for either gene therapy or vaccination applications.
Liver Fluke in Common Bile Duct
Authors: F. D. Murphy, K. G. Pascall
Journal: BMJ (1950)

Liver-fluke infestation in man has been recorded in fewer than 50 cases in Europe (Stitt, Clough, and Clough, 1939), and in only two reported cases has a liver fluke been surgically removed from a common bile duct.We have therefore thought it worth while to report three cases in which the liver fluke was found in the common bile duct at operation.Two of these occurred in Bath and one in Plymouth, and all within the last decade.Case Reports Case 1.-A married woman aged 50 was admitted to the Royal United Hospital on May 12, 1939.She complained of flatulence and attacks of epigastric pain for over ten years.A few weeks before admission she had a typical attack of gallbladder colic followed by jaundice which lasted for two weeks.Laparotomy was carried out on May 15.The gall-bladder was
Variation in gastroscopy rate in English general practice and outcome for oesophagogastric cancer: retrospective analysis of Hospital Episode Statistics
Authors: Mustafa Shawihdi, Elizabeth Thompson, Neil Kapoor, Geraint Powell, Richard P Sturgess, Nick Stern, Michael Roughton, Michael G Pearson, Keith Bodger
Journal: Gut (2013)

<h3>Objective</h3> To determine whether variation in gastroscopy rates in English general practice populations is associated with inequality in oesophagogastric (OG) cancer outcome. <h3>Design</h3> Retrospective observational study of the Hospital Episode Statistics (HES) dataset for England (2006–2008) linked to death registration. <h3>Methods</h3> were validated using independent local and national data. General practices with new cases of OG cancer were included. Practices were grouped into tertiles according to standardised elective gastroscopy rate per capita (low, medium or high). Outcome measures for cancer cases were: emergency admission during diagnostic pathway, major surgical resection and mortality at 1 year. Covariates were: age group, gender, comorbidity, general practice average deprivation and patient deprivation. <h3>Results</h3> 22 488 incident cases of OG cancer from 6513 general practices were identified. Patients registered with the low tertile group of practices had the lowest rate of major surgery, highest rate of emergency admission and highest mortality. The inequality was widest for the most socioeconomically deprived cases. After adjustment for covariates in logistic regression, the gastroscopy rate (low, medium or high) at the patient9s general practice was an independent predictor of emergency admission, major surgery and mortality. <h3>Conclusions</h3> There is wide variation in the rate of gastroscopy among general practice populations in England. On average, OG cancer patients belonging to practices with the lowest rates of gastroscopy are at greater risk of poor outcome. These findings suggest that initiatives or current guidelines aimed at limiting the use of gastroscopy may adversely affect cancer outcomes.
Abstract 472: Nek3 kinase in breast cancer pathogenesis: The role of paxillin phosphorylation
Authors: Katherine Harrington, Charles Clevenger
Journal: Cancer Research (2012)

Abstract Breast cancer progression to metastatic disease is responsible for the majority of breast cancer related deaths. The acquisition of a motile and invasive phenotype is a critical step in the metastatic process. The hormone prolactin (PRL) is increasingly recognized as contributing to the development and progression of human breast cancer. In particular, data from our laboratory has shown that PRL serves as a chemoattractant for breast cancer cells and can stimulate the formation of the focal-adhesion complex that is necessary for cell motility. PRL mediates its biological effects through binding to the PRL receptor (PRLr) and initiates several downstream signaling cascades, including activation of the serine/threonine kinase, Nek3. Nek3 regulates breast cancer cell survival, motility and invasion and has been shown to interact with the focal-adhesion adaptor protein, paxillin, in a PRL-dependent manner. Interestingly, we have determined that knockdown of Nek3 by siRNA significantly decreases the phosphorylation of paxillin, which suggests that paxillin may represent a novel substrate of Nek3. Given these findings, we sought to further elucidate the role of Nek3 in the regulation of paxillin phosphorylation and function in breast cancer. Co-immunoprecipitation analysis using mutant truncated proteins demonstrated that Nek3 interacts with the C-terminal region of paxillin, which contains 4 tandem LIM domains. Additionally, to determine the specific site(s) of phosphorylation an in vitro kinase assay was performed and it was determined that Nek3 directly phosphorylates paxillin at T401 located in the LIM2 domain. It is known that LIM2 and LIM3 comprise the focal adhesion targeting motif of paxillin and phosphorylation in this region plays an important role in modulating its activity. Ongoing studies will determine the biological effects of Nek3-mediated phosphorylation at paxillin T401 by examining the effect on breast cancer cell motility and invasion as well as the effect on paxillin localization and function in the focal adhesion complex. These studies will provide novel mechanistic insight into how Nek3-mediated phosphorylation of paxillin contributes to the pathogenesis of breast cancer. We propose that Nek3 is a potential novel therapeutic target for the treatment of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 472. doi:1538-7445.AM2012-472
Role of smooth muscle cell death in advanced coronary primary lesions: implications for plaque instability
Authors: Gerhard Bauriedel, Randolph Hutter, Ulrich Welsch, Roland Bach, Horst Sievert, Berndt Lüderitz
Journal: Cardiovascular Research (1999)

Objective: Instability of coronary atheroma leads to the onset of acute coronary syndromes including myocardial infarction and death, as well as to the progression of the arteriosclerotic disease. As yet, the underlying factors and mechanisms causing plaque rupture are not completely understood. Since a low content of smooth muscle cells (SMCs) apparently plays a key role, the question points to the events leading to the loss of intimal SMCs. Methods: We compared coronary atherectomy specimens from 25 patients with unstable angina to those from 25 patients with stable angina. Transmission electron microscopy was used to identify intimal cell population, to detect stage and cell type of apoptosis, and to differentiate between apoptosis and necrosis. Results: Plaques associated with unstable angina contained more macrophages/lymphocytes and significantly less SMCs (P=0.01), compared with stable angina plaques. Specific cell death forms, apoptosis and necrosis, were present in all coronary atheroma. As key findings, both the proportion of SMCs undergoing apoptosis and the frequency of cytoplasmic remnants of apoptotic SMCs (matrix vesicles) were significantly increased in unstable versus stable angina lesions (P=0.002 and P=0.002). In addition, cellular necrosis was more frequent in the first coronary atheroma group (P=0.02). Positive correlations were found between the frequency of apoptotic cells and necrosis (r=0.41, P=0.04), and that of matrix vesicles and necrosis (r=0.63, P=0.001) only in plaques with unstable angina, but not in those with stable angina. Conclusions: Our data demonstrate that high cell death due to apoptosis and necrosis is a basic in situ feature found in advanced coronary primary lesions associated with unstable angina, possibly explaining their low density of (viable) SMCs. Thus, antagonization of intimal cell death should be considered in order to stabilize the intimal plaque texture of coronary atheroma with the ultimate goal to prevent plaque rupture.
Avascular Necrosis and Corticosteroids
Authors: STEVEN SNYDER
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 May 1984Avascular Necrosis and CorticosteroidsSTEVEN SNYDER, M.D.STEVEN SNYDER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-100-5-770_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I read with interest the letter from Dr. Parker (1) in the December issue. I write to describe the cases of two patients who developed aseptic necrosis of the hips while they were taking physiologic or slightly supraphysiologic doses of hydrocortisone.A 36-year-old man had a craniotomy in 1974 for removal of a large chromophobe adenoma. Surgery was followed by radiation therapy. A preoperative thyroxine level was 3.4 ng/L, and the free thyroxine index was 90 (normal range, 150 to 350). Postoperatively, the patient was empirically placed on 60 mg/d of hydrocortisone in divided doses, as well...Reference1. PARKER L. Corticosteroid therapy and aseptic necrosis [Letter]. Ann Intern Med. 1983;99:882. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Permanente Medical Group, Inc. Hayward, CA 94545 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByGlucocorticoid-Induced Bone DiseaseSteroid induced osteonecrosis: An analysis of steroid dosing riskCase report 554Corticotrophins and corticosteroids 1 May 1984Volume 100, Issue 5Page: 770-770KeywordsAdenomasHipNecrosisRadiation therapySurgeryThyroxine Issue Published: 1 May 1984 PDF DownloadLoading ...
Teratogenic effects of waste anaesthetic gases
Authors: D I Rushton
Journal: BMJ (1978)

<h3>Abstract</h3> There is increasing evidence that level of consciousness can be captured by neural informational complexity: for instance, complexity, as measured by the Lempel Ziv (LZ) compression algorithm, decreases during anesthesia and non-rapid eye movement (NREM) sleep in humans and rats, when compared to LZ in awake and REM sleep. In contrast, LZ is higher in humans under the effect of psychedelics, including subanesthetic doses of ketamine. However, it is both unclear how this result would be modulated by varying ketamine doses, and whether it would extend to other species. Here we studied LZ with and without auditory stimulation during wakefulness and different sleep stages in 5 cats implanted with intracranial electrodes, as well as under subanesthetic doses of ketamine (5, 10, and 15 mg/kg i.m.). In line with previous results, LZ was lowest in NREM sleep, but similar in REM and wakefulness. Furthermore, we found an inverted U-shaped curve following different levels of ketamine doses in a subset of electrodes, primarily in prefrontal cortex. However, it is worth noting that the variability in the ketamine dose-response curve across cats and cortices was larger than that in the sleep-stage data, highlighting the differential local dynamics created by two different ways of modulating conscious state. These results replicate previous findings, both in humans and other species, demonstrating that neural complexity is highly sensitive to capture state changes between wake and sleep stages while adding a local cortical description. Finally, this study describes the differential effects of ketamine doses, replicating a rise in complexity for low doses, and further fall as doses approach anesthetic levels in a differential manner depending on the cortex. <h3>In brief</h3> Previous studies have shown that Lempel Ziv complexity (LZ) decreases during anesthesia and non-rapid eyes movement (NREM) sleep in humans and rats whereas it increases in REM sleep and under the effect of psychedelics. In this work we show that in the cat, LZ is lowest in NREM sleep, but similar in REM and wakefulness. We also found a ketamine inverted U-shape dose-response curve only in the auditory and prefrontal cortex, with a much larger variability in the ketamine across cats and cortices when compared to the sleep cycle.
ACTINIC RETICULOID WITH LYMPHOMA
Authors: N. E. JENSEN, I. B. SNEDDON
Journal: British Journal of Dermatology (1970)

Journal Article ACTINIC RETICULOID WITH LYMPHOMA Get access N. E. JENSEN, N. E. JENSEN Rupert Hallam Department of Dermatology, Royal Infirmary, Sheffield Search for other works by this author on: Oxford Academic Google Scholar I. B. SNEDDON I. B. SNEDDON Rupert Hallam Department of Dermatology, Royal Infirmary, Sheffield Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 82, Issue 3, 1 March 1970, Pages 287–291, https://doi.org/10.1111/j.1365-2133.1970.tb12439.x Published: 01 March 1970 Article history Accepted: 26 September 1969 Published: 01 March 1970
Enhanced neuronal excitability in the absence of neurodegeneration induces cerebellar ataxia
Authors: Vikram G. Shakkottai, Chin-hua Chou, Salvatore Oddo, Claudia A. Sailer, Hans-Günther Knaus, George A. Gutman, Michael E. Barish, Frank M. LaFerla, K. George Chandy
Journal: Journal of Clinical Investigation (2004)

Cerebellar ataxia, a devastating neurological disease, may be initiated by hyperexcitability of deep cerebellar nuclei (DCN) secondary to loss of inhibitory input from Purkinje neurons that frequently degenerate in this disease. This mechanism predicts that intrinsic DCN hyperexcitability would cause ataxia in the absence of upstream Purkinje degeneration. We report the generation of a transgenic (Tg) model that supports this mechanism of disease initiation. Small-conductance calcium-activated potassium (SK) channels, regulators of firing frequency, were silenced in the CNS of Tg mice with the dominant-inhibitory construct SK3-1B-GFP. Transgene expression was restricted to the DCN within the cerebellum and was detectable beginning on postnatal day 10, concomitant with the onset of cerebellar ataxia. Neurodegeneration was not evident up to the sixth month of age. Recordings from Tg DCN neurons revealed loss of the apamin-sensitive after-hyperpolarization current (IAHP) and increased spontaneous firing through SK channel suppression, indicative of DCN hyperexcitability. Spike duration and other electrogenic conductance were unaffected. Thus, a purely electrical alteration is sufficient to cause cerebellar ataxia, and SK openers such as the neuroprotective agent riluzole may reduce neuronal hyperexcitability and have therapeutic value. This dominant-inhibitory strategy may help define the in vivo role of SK channels in other neuronal pathways.
Synergistic effect of nitric oxide and vasoactive intestinal peptide on bronchoprotection against histamine in anesthetized guinea pigs.
Authors: H Kanazawa, T Kawaguchi, S Shoji, T Fujii, S Kudoh, K Hirata, N Kurihara, J Yoshikawa
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are considered to be nonadrenergic, noncholinergic (NANC) inhibitory neurostransmitters in the airways. It seems likely that these neurotransmitters may be coreleased and act as functional antagonists against bronchoconstrictor stimuli. In the present study, we examined the synergistic effect of NO and VIP on bronchoprotection against histamine in anesthetized guinea pigs. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP) significantly inhibited histamine-induced bronchoconstriction in a dose-dependent manner. VIP also inhibited histamine-induced bronchoconstriction in a dose-dependent manner, but this bronchoprotective effect was short-lived. Additionally, VIP (10(-9) M) had no significant bronchoprotective effect, but a subthreshold dose of SNAP (10(-7) M) significantly potentiated VIP (10(-9) M)-induced bronchoprotection against histamine. Moreover, SNAP (10(-7) M) significantly enhanced VIP (10(-7) M)-induced bronchoprotection for a longer period of time. On the other hand, VIP (10(-9) M) also significantly potentiated SNAP-induced bronchoprotection against histamine. In conclusion, combination therapy with NO donor and VIP receptor agonist may have important advantages in the treatment of bronchial asthma, and both NO and VIP may contribute in complementary fashion to the NANC-induced relaxant response in guinea pig airways.