tbuckley/cabot-search huggingface dataset:
Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors
Authors: E. Gaffal, M. Cron, N. Glodde, T. Tüting
Journal: Allergy (2013)

Background ∆9-Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases. Here we investigated the mechanism of the anti-inflammatory activity of THC and the role of CB1 and CB2 receptors. Methods We evaluated the impact of topically applied THC on DNFB-mediated allergic contact dermatitis in wild-type and CB1/2 receptor-deficient mice. We performed immunohistochemical analyses for infiltrating immune cells and studied the influence of THC on the interaction between T cells, keratinocytes and myeloid immune cells in vitro. Results Topical THC application effectively decreased contact allergic ear swelling and myeloid immune cell infiltration not only in wild-type but also in CB1/2 receptor-deficient mice. We found that THC (1) inhibited the production of IFNγ by T cells, (2) decreased the production of CCL2 and of IFNγ-induced CCL8 and CXL10 by epidermal keratinocytes and (3) thereby limited the recruitment of myeloid immune cells in vitro in a CB1/2 receptor-independent manner. Conclusions Topically applied THC can effectively attenuate contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors. This has important implications for the future development of strategies to harness cannabinoids for the treatment of inflammatory skin diseases.
Inositol 1,4,5-trisphosphate-induced Ca2+ signalling is involved in estradiol-induced breast cancer epithelial cell growth
Authors: Cécilia Szatkowski, Jan B Parys, Halima Ouadid-Ahidouch, Fabrice Matifat
Journal: Molecular Cancer (2010)

Abstract Background Ca 2+ is a ubiquitous messenger that has been shown to be responsible for controlling numerous cellular processes including cell growth and cell death. Whereas the involvement of IP 3 -induced Ca 2+ signalling (IICS) in the physiological activity of numerous cell types is well documented, the role of IICS in cancer cells is still largely unknown. Our purpose was to characterize the role of IICS in the control of growth of the estrogen-dependent human breast cancer epithelial cell line MCF-7 and its potential regulation by 17β-estradiol (E 2 ). Results Our results show that the IP 3 receptor (IP 3 R) inhibitors caffeine, 2-APB and xestospongin C (XeC) inhibited the growth of MCF-7 stimulated by 5% foetal calf serum or 10 nM E 2 . Furthermore, Ca 2+ imaging experiments showed that serum and E 2 were able to trigger, in a Ca 2+ -free medium, an elevation of internal Ca 2+ in a 2-APB and XeC-sensitive manner. Moreover, the phospholipase C (PLC) inhibitor U-73122 was able to prevent intracellular Ca 2+ elevation in response to serum, whereas the inactive analogue U-73343 was ineffective. Western-blotting experiments revealed that the 3 types of IP 3 Rs are expressed in MCF-7 cells and that a 48 hours treatment with 10 nM E 2 elevated IP 3 R3 protein expression level in an ICI-182,780 (a specific estrogen receptor antagonist)-dependent manner. Furthermore, IP 3 R3 silencing by the use of specific small interfering RNA was responsible for a drastic modification of the temporal feature of IICS, independently of a modification of the sensitivity of the Ca 2+ release process and acted to counteract the proliferative effect of 10 nM E 2 . Conclusions Altogether, our results are in favour of a role of IICS in MCF-7 cell growth, and we hypothesize that the regulation of IP 3 R3 expression by E 2 is involved in this effect.
Fifth Phase of the Epidemiologic Transition
Authors: J. Michael Gaziano
Journal: JAMA (2010)

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
Presence of Intratumoral Neutrophils Is an Independent Prognostic Factor in Localized Renal Cell Carcinoma
Authors: Hanne Krogh Jensen, Frede Donskov, Niels Marcussen, Marianne Nordsmark, Finn Lundbeck, Hans von der Maase
Journal: Journal of Clinical Oncology (2009)

We have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC).The study comprised 121 consecutive patients who had a nephrectomy for localized RCC. Biomarkers (intratumoral CD8+, CD57+ immune cells, CD66b+ neutrophils, and carbonic anhydrase IX [CA IX]) were assessed by immunohistochemistry, and the relationship with clinical and histopathologic features and patient outcome was evaluated.The intratumoral neutrophils ranged from zero to 289 cells/mm(2) tumor tissue. The presence of intratumoral neutrophils was statistically significantly associated with increasing tumor size, low hemoglobin, high creatinine, and CA IX < or = 85%. In multivariate analysis, the presence of intratumoral neutrophils (hazard ratio [HR], 3.0; 95% CI, 1.7 to 5.4; P < .0001), pT stage T3b/T4 (HR, 2.1; 95% CI, 1.2 to 3.6; P = .007), and low hemoglobin (HR, 1.8; 95% CI, 1.0 to 3.1; P = .03) were independent prognostic factors significantly associated with short recurrence-free survival. The presence of intratumoral neutrophils was also an independent prognostic factor for cancer-specific survival (HR, 3.5; 95% CI, 1.9 to 6.4; P < .0001) and overall survival (HR, 3.1; 95% CI, 1.9 to 5.0; P < .0001). Applying the prognostic value of intratumoral neutrophils to the Leibovich low-/intermediate-risk group (n = 78) showed a 5-year recurrence-free survival of 53% (95% CI, 34.6% to 71.8%; presence of intratumoral neutrophils) versus 87% (95% CI, 77.8% to 96.8%; absence of intratumoral neutrophils). The estimated concordance index was 0.74 using the Leibovich risk score and 0.80 when intratumoral neutrophils were added.The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC.
NGAL Expression Is Elevated in Both Colorectal Adenoma–Carcinoma Sequence and Cancer Progression and Enhances Tumorigenesis in Xenograft Mouse Models
Authors: Yan Sun, Kenji Yokoi, Hui Li, Jun Gao, Limei Hu, Ben Liu, Kexin Chen, Stanley R. Hamilton, Dominic Fan, Baocun Sun, Wei Zhang
Journal: Clinical Cancer Research (2011)

There is growing evidence implicating that neutrophil gelatinase-associated lipocalin (NGAL) plays a role in the development and progression of cancers. However, the effect of NGAL in colorectal carcinoma (CRC) has not been clearly elucidated. In this study, we investigated the role of NGAL in the tumorigenesis and progression of CRC and evaluated the clinical value of NGAL expression.We examined NGAL expression in 526 colorectal tissue samples, including 53 sets of matched specimens (histologically normal mucosa, adenomas, and carcinomas) using immunohistochemical analysis. In CRCs, correlations between NGAL expression and clinicopathologic parameters were analyzed, and survival analysis was conducted. The role of NGAL was further tested using mouse xenograft models.NGAL expression was elevated during the colorectal adenoma-carcinoma sequence both among the 526 cases (r(s) = 0.66, P < 0.001) and in the 53 sets of matched specimens (r(s) = 0.60, P < 0.001). In CRCs, NGAL expression was associated with cancer stage (P = 0.041) and tumor recurrence in stage II patients (P = 0.037). Survival analysis revealed that NGAL expression was an independent prognostic factor for overall survival (HR = 1.84, P = 0.004) and for disease-free survival of stage II patients (HR = 5.88, P = 0.021). In mouse models, the xenografts in cecum and spleen were heavier and more numerous in the group injected with NGAL-overexpressing CRC cells (P < 0.05).NGAL overexpression may promote the tumorigenesis and progression of CRC. Detecting NGAL expression in tumor tissues may be useful for evaluating prognosis of patients with CRC.
Endoplasmic Reticulum Stress Triggers XBP-1–Mediated Up-regulation of an EBV Oncoprotein in Nasopharyngeal Carcinoma
Authors: Jenn-Ren Hsiao, Kung-Chao Chang, Chaio-Wei Chen, Shih-Yi Wu, Ih-Jen Su, Mei-Chi Hsu, Ying-Tai Jin, Sen-Tien Tsai, Kenzo Takada, Yao Chang
Journal: Cancer Research (2009)

Endoplasmic reticulum (ER) stress-activated unfolded protein response (UPR) plays multiple roles in cancer development, but its specific roles for virus-associated cancers have not been fully understood. It is still unknown whether ER stress/UPR occurs in and contributes to nasopharyngeal carcinoma (NPC), an epithelial malignancy closely associated with EBV. Here, we report that UPR proteins are frequently detected in NPC biopsies. In addition, we reveal that, in EBV-infected NPC cells, ER stress inducers up-regulate a potent EBV oncoprotein latent membrane protein 1 (LMP1), and the ER stress-induced LMP1 enhances production of interleukin-8. ER stress triggers LMP1 expression at a transcriptional level, activating a distal LMP1 promoter TR-L1. TR-L1 contains an ER stress-responsive element, which is targeted by an UPR protein XBP-1. Ectopic expression of XBP-1 induces LMP1 expression, and knockdown of XBP-1 blocks ER stress-triggered up-regulation of LMP1 in NPC cells. Furthermore, XBP-1 significantly correlates with LMP1 expression in NPC tumor biopsies. Therefore, this study not only provides a novel clue linking ER stress/UPR to EBV-associated NPC but also suggests that ER stress/UPR can promote virus-associated cancer in a unique way by driving expression of a viral oncogene.
Smallpox Manifestations and Survival during the Boston Epidemic of 1901 to 1903
Authors: Michael R. Albert
Journal: Annals of Internal Medicine (2002)

Clinical records of 243 patients with smallpox consecutively admitted to the Southampton Street smallpox hospital in Boston, Massachusetts, during the 1901–1903 epidemic were reviewed. Smallpox was divided into five categories of varying severity; 47% of patients had varioloid, a relatively mild form of the disease usually occurring in previously vaccinated individuals with incomplete immunity. Survival information is available for 206 patients, of whom 36 (17.5%) died. Vaccination status, disease severity, and age were associated with survival, whereas sex, birthplace, and race were not. While full recovery often took weeks, most deaths occurred 7 to 14 days after the onset of symptoms, and all deaths occurred within 18 days of symptom onset. Smallpox was eradicated worldwide in 1977, but knowledge of the disease is essential because its cause, variola virus, is considered a potential biological weapon.
Retinol-Binding Protein 4 and Insulin Resistance in Polycystic Ovary Syndrome
Authors: Samantha K. Hutchison, Cheryce Harrison, Nigel Stepto, Caroline Meyer, Helena J. Teede
Journal: Diabetes Care (2008)

OBJECTIVE—Polycystic ovary syndrome (PCOS) is an insulin-resistant state with insulin resistance being an established therapeutic target; however, measurement of insulin resistance remains challenging. We aimed to 1) determine serum retinol-binding protein 4 (RBP4) levels (purported to reflect insulin resistance) in women with PCOS and control subjects, 2) examine the relationship of RBP4 to conventional markers of insulin resistance, and 3) examine RBP4 changes with interventions modulating insulin resistance in overweight women with PCOS. RESEARCH DESIGN AND METHODS—At baseline, 38 overweight women (BMI &amp;gt;27 kg/m2) with PCOS and 17 weight-matched control subjects were compared. Women with PCOS were then randomly assigned to 6 months of a higher-dose oral contraceptive pill (OCP) (35 μg ethinyl estradiol/2 mg cyproterone acetate) or metformin (1 g b.i.d.). Outcome measures were insulin resistance (total insulin area under the curve) on an oral glucose tolerance test, RBP4, and metabolic/inflammatory markers. RESULTS—Overweight women with PCOS were more insulin resistant than control subjects, yet RBP4 levels were not different in women with PCOS versus those in control subjects (35.4 ± 4.3 vs. 28.9 ± 3.1 μg/ml, P = 0.36). RBP4 correlated with cholesterol and triglycerides but not with insulin resistance. Metformin improved insulin resistance by 35%, whereas the OCP worsened insulin resistance by 33%. However, RBP4 increased nonsignificantly in both groups (43.7 ± 6.3 vs. 42.6 ± 5.5 μg/ml, P = 0.92). CONCLUSIONS—Overweight women with PCOS were more insulin resistant than control subjects, but this finding was not reflected by RBP4 levels. RBP4 correlated with lipid levels but not with insulin resistance markers. RBP4 levels did not change when insulin resistance was reduced by metformin or increased by the OCP. These data suggest that RBP4 is not a useful marker of insulin resistance in PCOS but may reflect other metabolic features of this condition.
Neurocognitive Challenges in Brain Tumor Survivors: Is There Anything We Can Do?
Authors: Lawrence Kleinberg
Journal: Journal of Clinical Oncology (2015)

Neurocognitive and neuropsychological deficits after treatment of primary and metastatic tumors in the brain are significant, much feared survivorship challenges for a group of patients that is enlarging as treatment effectiveness for primary brain tumors and metastatic cancers improve. When reporting the initial phase II results1 that motivated the phase III trial that accompanies this editorial,2 Shaw et al framed this issue with a quotation from a survivor, Susan Sontag, 16 years after combined-modality therapy: “‘Everything I do is slow. I walk, talk, and think slowly… I still have no short-term memory… Much of the time I can’t even remember the names of relatives and close friends… I am always confused… Because I look normal and often sound normal, people assume I am normal. But I’m not… I get depressed a lot knowing that I will never have my competence back.’ (Sontag Foundation Distinguished Scientists Awards ceremony speech at the Society for Neuro-Oncology Meeting, Toronto, Canada, November 20, 2004.)”2(p1415) Have there been advances in the last decade to address this problem, and does the phase III trial now reported provide evidence that contributes to an appropriate strategy?
US Supreme Court says no to medical marijuana
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

The US Supreme Court voted six-three that medical use of marijuana was illegal in a vote last week, despite laws in 11 states that permit its use. The court ruling puts the federal government at odds with many in the scientific establishment and with public opinion. The decision is unlikely to affect people living in states that allow medical marijuana use, where state laws permitting this use are still in effect, however. Most people who are prosecuted for use or possession of marijuana are large scale drug dealers, not those using the drug under a doctor's supervision to …
Serum-Starved Adipose-Derived Stromal Cells Ameliorate Crescentic GN by Promoting Immunoregulatory Macrophages
Authors: Kazuhiro Furuhashi, Naotake Tsuboi, Asuka Shimizu, Takayuki Katsuno, Hangsoo Kim, Yosuke Saka, Takenori Ozaki, Yoshikazu Sado, Enyu Imai, Seiichi Matsuo, Shoichi Maruyama
Journal: Journal of the American Society of Nephrology (2013)

Mesenchymal stromal cells (MSCs) derived from adipose tissue have immunomodulatory effects, suggesting that they may have therapeutic potential for crescentic GN. Here, we systemically administered adipose-derived stromal cells (ASCs) in a rat model of anti-glomerular basement membrane (anti-GBM) disease and found that this treatment protected against renal injury and decreased proteinuria, crescent formation, and infiltration by glomerular leukocytes, including neutrophils, CD8+ T cells, and CD68+ macrophages. Interestingly, ASCs cultured under low-serum conditions (LASCs), but not bone marrow-derived MSCs (BM-MSCs), increased the number of immunoregulatory CD163+ macrophages in diseased glomeruli. Macrophages cocultured with ASCs, but not with BM-MSCs, adopted an immunoregulatory phenotype. Notably, LASCs polarized macrophages into CD163+ immunoregulatory cells associated with IL-10 production more efficiently than ASCs cultured under high-serum conditions. Pharmaceutical ablation of PGE2 production, blocking the EP4 receptor, or neutralizing IL-6 in the coculture medium all significantly reversed this LASC-induced conversion of macrophages. Furthermore, pretreating LASCs with aspirin or cyclooxygenase-2 inhibitors impaired the ability of LASCs to ameliorate nephritogenic IgG-mediated renal injury. Taken together, these results suggest that LASCs exert renoprotective effects in anti-GBM GN by promoting the phenotypic conversion of macrophages to immunoregulatory cells, suggesting that LASC transfer may represent a therapeutic strategy for crescentic GN.
Hematogenous dissemination of glioblastoma multiforme
Authors: Carolin Müller, Johannes Holtschmidt, Martina Auer, Ellen Heitzer, Katrin Lamszus, Alexander Schulte, Jakob Matschke, Sabine Langer-Freitag, Christin Gasch, Malgorzata Stoupiec, Oliver Mauermann, Sven Peine, Markus Glatzel, Michael R. Speicher, Jochen B. Geigl, Manfred Westphal, Klaus Pantel, Sabine Riethdorf
Journal: Science Translational Medicine (2014)

Hematogenous spread of glioblastoma multiforme (GBM) might be responsible for reported extracranial metastases and transmission of GBM by organ transplantation.
Do patients with unexplained physical symptoms pressurise general practitioners for somatic treatment? A qualitative study
Authors: Adele Ring, Christopher Dowrick, Gerry Humphris, Peter Salmon
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> To identify the ways in which patients with medically unexplained symptoms present their problems and needs to general practitioners and to identify the forms of presentation that might lead general practitioners to feel pressurised to deliver somatic interventions. <b>Design</b> Qualitative analysis of audiorecorded consultations between patients and general practitioners. <b>Setting</b> 7 general practices in Merseyside, England. <b>Participants</b> 36 patients selected consecutively from 21 general practices, in whom doctors considered that patients9 symptoms were medically unexplained. <b>Main outcome measures</b> Inductive qualitative analysis of ways in which patients presented their symptoms to general practitioners. <b>Results</b> Although 34 patients received somatic interventions (27 received drug prescriptions, 12 underwent investigations, and four were referred), only 10 requested them. However, patients presented in other ways that had the potential to pressurise general practitioners, including: graphic and emotional language; complex patterns of symptoms that resisted explanation; description of emotional and social effects of symptoms; reference to other individuals as authority for the severity of symptoms; and biomedical explanations. <b>Conclusions</b> Most patients with unexplained symptoms received somatic interventions from their general practitioners but had not requested them. Though such patients apparently seek to engage the general practitioner by conveying the reality of their suffering, general practitioners respond symptomatically.
Exercise prescription for the overweight and the obese: how to quantify and yet keep it simple
Authors: R Ehrsam, U Hoerler-Koerner, S Stoffel, T Melges, B Ainsworth
Journal: British Journal of Sports Medicine (2009)

An activity point system (APS) is presented that assists healthcare providers and health professionals with a way to prescribe exercise in a semiquantitative manner and to motivate their patients to begin an exercise programme. Activity points are specific to one's body weight, body mass index and activity intensity for 10-minute bouts of activity performed. With a goal of accumulating 100-300 activity points per week, the APS provides a simple yet quantitatively accurate way to prescribe exercise for overweight and obese adults.
Endosonographic Evaluation of the Patient with Achalasia
Authors: J. Van Dam
Journal: Endoscopy (1998)

Using endosonography, esophageal wall thickening is commonly observed in patients with achalasia. Imaging artifacts with the endosonographic appearance of an esophageal tumor in some patients with achalasia suggest that endosonographic images must be interpreted with caution. The endosonographer must be aware of anatomical peculiarities (dilated, tortuous, or "sigmoid" esophagus) and imaging techniques (tangential imaging) that may lead to artifactual imaging, and thereby avoid misinterpretation of results. Failure to recognize such imaging artifacts may lead to an erroneous diagnosis of pseudoachalasia, thereby subjecting patients to unnecessary surgery. Future applications of endoscopic ultrasonography for patients with achalasia may include endosonographically guided therapy. Prospective analyses of EUS-guided therapy are anticipated.