tbuckley/cabot-search huggingface dataset:
Lady With Her Pets (Molly Wales Fobes)
Authors: M. Therese Southgate
Journal: JAMA (2004)

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
Tamoxifen-loaded liposomal topical formulation arrests hair growth in mice
Authors: A. Bhatia, B. Singh, B. Amarji, O.P. Katare
Journal: British Journal of Dermatology (2010)

Background For several decades, androgens have dominated endocrine research in the domain of hair growth control. However, it has long been known that oestrogens also tend to alter hair follicle (HF) growth and cycling significantly by binding to locally expressed high‐affinity oestrogen receptors (ORs). Tamoxifen (TAM) is a selective OR modulator. Objectives The current work aims to investigate the effect of topically applied TAM on the hair growth of mice. Methods Test formulations were applied once daily on the shaved back area of the mice for a period of 5 weeks. The effect of these formulations was studied by visual and histological examinations. Results Animals treated with saline and placebo gel formulation showed significant hair growth on the 20th day. The number and length of follicles were also found to be normal. In contrast, no hair growth was observed in the animals treated with TAM gel, even after the termination of treatment. The HFs were found to be arrested in telogen phase with clear signs of follicle dystrophy. Conclusions The hair growth‐retarding effect of TAM observed in the current study clearly demonstrates its OR agonistic effect on hair growth. This work also provides a distinct lead towards the possible potential of TAM liposomal gel in the treatment of hirsutism.
War Against Tropical Disease. Being Seven Sanitary Sermons Addressed to All Interested in Tropical Hygiene and Administration.
Authors: Andrew. Balfour
Journal: JAMA (1924)

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
The unique roles of murine granzymes (Gzm) A and B for NK-dependent tumor cell killing and regulatory T cell control of NK cells
Authors: Xuefang Cao, Todd A. Fehniger, Sheng F. Cai, Timothy J. Ley
Journal: Cancer Research (2006)

626   NK-dependent clearance of RMAS lymphoma and B16 melanoma has been demonstrated in NK cell-deficient mice ( Kim S et al, PNAS, 2000, 97:2731-6 ). To examine the roles of Gzm A and B in NK-mediated tumor clearance, RMAS and B16 cells were injected intravenously into WT mice and mice deficient for Gzm A, Gzm B, or Gzm AxB. The survival curves following RMAS injection are shown in Fig. 1; similar results were found with B16 cells. All Gzm AxB-deficient mice died within 6 weeks. Gzm A-deficient mice also displayed reduced survival. Surprisingly, Gzm B-deficient mice demonstrated significantly improved survival compared to WT mice. To understand the molecular and cellular basis, we examined the Gzm expression patterns at various times following tumor injection. Lymphocytes isolated from tumor-infiltrated organs, from spleens and lymph nodes were examined for Gzm A and B expression in NK cells and T cell subsets using 4-color flow cytometric analysis. Within NK compartment, Gzm A expression is constitutive and remains unchanged during the 1st 4 weeks. In contrast, very few Gzm B-expressing cells ( In vitro  killing assays indicated that resting NK cells enriched from spleens of Gzm A-deficient mice exhibited diminished killing of RMAS cells, while Gzm B-deficient resting NK cells killed RMAS cells as efficiently as WT resting NK cells. These data suggest that Gzm A is a major effector in NK cells in the early stages of tumor challenge, while Gzm B plays a more important role later. Importantly, Gzm B (but not Gzm A) was detected in 10-25% of CD4 + /FoxP3 +  regulatory T cells isolated from tumors, tumor-infiltrated lungs and livers between day 12 and 26, but Gzm B was not detected in regulatory T cells found in spleens or lymph nodes. Since Gzm B deficient mice clear RMAS and B16 more efficiently than WT mice, these data suggest that these tumors may somehow induce the expression of Gzm B in regulatory T cells that go on to kill tumor-specific NK cells. By recruiting and activating regulatory T cells that kill NK cells, these tumors could gain a survival advantage that would be lost in the setting of Gzm B deficiency.
Headaches
Authors: Geraint Fuller, Claire Kaye
Journal: BMJ (2007)

Headaches are one of the commonest reasons for attending a general practice or a neurology clinic.Some 15% of the UK adult population have migraine, and 80% have episodic tension-type headache from time to time.The lifetime prevalence of headache is 96%, being higher in women than in men.Every day more than 100 000 people are absent from school or work because of migraine, with a cost to the economy that may exceed £1.5bn (€2.3bn; $2.9bn) a year. 1 What should I already know about this condition?Most headaches are benign, with tension-type headaches and migraines being the main sorts.Tension-type headaches are the most common type of headache, with the lifetime prevalence ranging between 30% and 78% according to different studies.Migraine can occur with or without an aura.A typical aura lasts from five to 60 minutes before the headache starts.It consists of transient visual, sensory, and speech disturbances.Visual symptoms are the most common manifestation of an aura and consist of flickering lights, spots or lines, or blind spots.Cluster headaches are unilateral severe headaches that occur in clusters over six to 12 weeks.They are more common in men, people who smoke, and adults older than 20 years.They tend to occur daily and wake the patient if they occur within a few hours of falling asleep.The pain of cluster headaches is severe, sometimes compared to the pain from renal colic.They are associated with ipsilateral watering of the eye, conjunctival redness, rhinorrhoea, nasal blockage, and ptosis.Their prevalence in the UK adult population is 69/100 000, so they are much less common than migraine.Dangerous headaches-A small proportion of patients have headaches that are dangerous (such as subarachnoid haemorrhage, meningitis, temporal arteritis, and raised intracranial pressure for whatever reason).Fewer than 1% of patients referred to outpatient clinics with headaches have an intercranial lesion.Dangerous headaches tend to be "first and worst," single and of sudden onset, progressive, and with onset later in life.Consider temporal arteritis in any patient older than 50 who has a headache of new onset. 1Only a minority of patients with temporal arteritis have temporal pain, but jaw claudication (pain in the jaw during talking or chewing) is virtually diagnostic.Arrange for a patient to have a temporal artery biopsy to confirm the diagnosis. What new evidence do I need to know about? features of medication overuse headacheThis study 2 found that
Hepatocellular cancer risk in diabetes: Not all diabetics are the same
Authors: Siddharth Singh, Preet Paul Singh
Journal: Hepatology (2013)

We read with great interest the recent article titled “Effect of Type 2 Diabetes on Risk for Malignancies Includes Hepatocellular Carcinoma in Chronic Hepatitis C” by Arase et al.1 published in the March issue of Hepatology. In this Japanese cohort of 4,302 interferon-treated patients with hepatitis C, the authors observed that diabetes mellitus (DM) was associated with a 1.7-fold higher risk of hepatocellular carcinoma (HCC) as compared to patients without DM. Interestingly, they also observed that the risk of HCC was reduced by 44% in diabetics with mean HbA1c <7.0% during follow-up compared with those with mean HbA1c ≥7.0%. The authors concluded that “stringent control of DM is important for protecting against the development of HCC.” However, before drawing this inference the potential cancer-modifying effect of antidiabetic medications must be considered. In a recent meta-analysis, we have shown that metformin use was associated with a 50% reduction in risk of developing HCC, whereas sulfonylurea or insulin use was associated with a 62% and 161% increase in the risk of HCC, respectively.2 Metformin may exert its antineoplastic effect by activation of adenosine monophosphate (AMP)-kinase and a consequent inhibition of the mammalian target of rapamycin (mTOR) pathway.3 On the other hand, sulfonylureas, by increasing insulin secretion, and exogenous insulin itself, can promote carcinogenesis by increasing insulin-like growth factor 1 activity, resulting in abnormal stimulation of multiple cellular proliferation cascades.4 Lack of information about antidiabetic medications is a crucial limitation of this study. It is likely that patients with good glycemic control are treated with metformin, whereas patients with poor glycemic control require aggressive polypharmacy and the use of insulin. This selective use of antidiabetic medications driven by glycemic control may explain the apparent lower risk of HCC observed in well-controlled diabetics. Multiple observational studies and meta-analysis have failed to demonstrate an association between intensive glycemic control and risk of cancer, including gastrointestinal cancer.5-7 The variable effects of different antidiabetic medications on cancer risk modification may explain why intensive glucose lowering with combination therapy is not associated with lower cancer risk. Siddharth Singh, M.D.1 Preet Paul Singh, M.D.2 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 2Department of Medical Oncology, Mayo Clinic, Rochester, MN
Morphological and immunohistochemical assessment of in vitro cell proliferation of fresh human tumor tissues in an agarose based assay.
Authors: Weidong Huang, Yen Huynh, Linda Hiroshima, Dennis Bansil, Ing-Ru Yu, Lilian Tee
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5432 

The Oncotech Extreme Drug Resistance (EDR) assay is a soft agarose-based cell culture assay that accurately determines a tumor’s resistance to chemotherapeutic agents. Previous observations on agarose based assays have suggested that agarose supports proliferation of tumor cells while suppressing proliferation of normal tissue components, such as epithelium, fibroblasts, endothelium and lymphocytes. Thus, the presence of normal tissue elements in the tumor samples does not significantly interfere with the incorporation of tritiated thymidine into DNA in the assay. To validate and extend the diagnostic potential of the agarose based assay, we have developed a method to isolate cells from the EDR assay to examine tumor and normal proliferating cells morphologically and immunohistochemically. Methods: We examined 39 tumor tissues, which included 1 breast, 3 colon, 1 cervical, 1 kidney, 6 lung, 11 ovarian, and 5 uterine carcinomas, 10 sarcomas, and 1 melanoma. Fresh viable tumor tissues were minced and enzymed to disaggregate the cells. Cell preparations with 20% to 80% tumor cells were selected for analysis. The cells were plated in the 0.3% agarose and incubated at 37oC, 5% CO2 for 5 to 6 days, depending on tumor type, according to the standard EDR assay protocol; no [3H] thymidine was added. The culture plates were harvested by melting the agarose in 75-80oC water bath until the agarose was completely dissolve. Cells were then isolated by centrifugation and embedded in paraffin after routine formalin fixation. Sections were cut and stained for Hematoxylin and Eosin (H&E) and analyzed immunohistochemically (IHC). IHC markers, cytokeratin (AE1/AE3), vimentin, CD45, CD31, and S-100, were used to determine the phenotype of the cells. Results: Three-dimensional spheroid structures growing in agarose were observed using an inverted microscope. The H&E staining of cell blocks showed that the cells present as single cells and cellular spheroids with a maximum growth size of 10 cells from the center. The histological/cellular features of the cells were similar to those of the tumor cells in the original tumor tissue specimen. Carcinoma cases showed 92% of cells expressing AE1/AE3, sarcomas with 81% of cells expressing vimentin, and melanoma with 90% of cells expressing S-100. No lymphoid cells (CD45+) were present. Endothelial staining (CD31) was mostly negative, with rare positive staining seen in the center of cellular spheroids. Conclusion: Our morphologic and IHC analyses directly demonstrated that the EDR assay promotes tumor cell proliferation while suppressing proliferation of normal tissue components in various types of solid tumors, and, therefore, is an effective in vitro technique to analyze tumor-drug interactions.
Role of PD-L1 and PD-L2 in allergic diseases and asthma
Authors: A. K. Singh, P. Stock, O. Akbari
Journal: Allergy (2010)

To cite this article: Singh AK, Stock P, Akbari O. Role of PD-L1 and PD-L2 in allergic diseases and asthma. Allergy 2011; 66: 155–162. Asthma is the result of chronic airway inflammation associated predominantly with CD4+ cells, eosinophils, mast cells, and basophils. Several T-cells subsets, including NKT cells, play a critical role in orchestrating the inflammation in the airways predominantly, by secreting interleukin-4 and interleukin-13. Recently, programmed death-1 (PD-1) with its ligands, programmed death ligand B7H1 (PD-L1) and B7DC (PD-L2), was shown to regulate T-cell activation and tolerance. PD-1 has been characterized as a negative regulator of conventional CD4+T cells. In addition, the relative roles of PD-L1 and PD-L2 in regulating the activation and function of T cells have recently been characterized. Recent studies have demonstrated that PD-L1 and PD-L2 have important but opposing roles in modulating and polarizing T-cell functions in airway hyperreactivity. Whereas the severity of asthma is greatly enhanced in absence of PD-L2, PD-L1 deficiency resulted in reduced airway hyperresponsiveness and only minimal inflammation. This observation is partially because of the polarization of NKT cells in PD-L1- and PD-L2-deficient mice. This review will discuss the recent literature regarding the role of PD-L1 and PD-L2 in allergic disease and asthma. Current understanding of the role of PD ligands in allergic asthma gives impetus to the development of novel therapeutic approaches.
Abstract 18516: Regional Dysfunction of Left Atrial Appendage and its Association with Stroke in Atrial Fibrillation
Authors: Abdullah A Alissa, Yuko Inoue, Jochen Cammin, Qiulin Tang, Elliot Fishman, Katsuyuki Taguchi, Hiroshi Ashikaga
Journal: Circulation (2014)

Background: Atrial Fibrillation (AF) is associated with an increased risk of cardioembolic stroke. Previous studies demonstrate that the Left atrial appendage (LAA) is the most common site of intracardiac thrombus, and the LAA morphology alone may determine the risk of stroke. We aimed to determine the association between LAA regional dysfunction using novel, noninvasive, image-based motion-estimation CT (iME) and prior history of stroke in patients with AF. Methods: Among the patients with history of AF referred for ablation who underwent pre-ablation CT with retrospective ECG gating, we identified 18 patients with a prior history of stroke or TIA, and 18 age- and gender-matched controls. The patients in AF at the time of CT were excluded. Four-dimensional motion vector field was estimated from reconstructed CT images using iME at every 5% RR interval. To assess myocardial deformation, area change ratio and area change rate were calculated over the endocardial surface of the LA and LAA. Univariate and multivariate comparisons were made by using binary logistic regression model. Results: A total of 36 patients (mean age 67.6 ± 8.1 years, 66.7% male, 16.7% persistent AF) were included in the study. Univariate analysis showed that the LA pre-atrial contraction area change ratio and LAA maximum area change ratio were significantly lower (P= 0.02 and 0.04, respectively) in the stroke/TIA group compared to the control group. These changes remained statistically significant in multivariate analysis (P=0.03 and 0.04, respectively) after adjusting for age, sex, body mass index, LV ejection fraction, type of AF, and CHADS score. Conclusions: LAA regional dysfunction is associated with stroke/TIA in patients with AF. LAA regional dysfunction detected by iME could represent a marker for stroke and a possible therapeutic target.
Which components of heart failure programmes are effective? A systematic review and meta‐analysis of the outcomes of structured telephone support or telemonitoring as the primary component of chronic heart failure management in 8323 patients: Abridged Cochrane Review
Authors: Sally C. Inglis, Robyn A. Clark, Finlay A. McAlister, Simon Stewart, John G.F. Cleland
Journal: European Journal of Heart Failure (2011)
Abstract 2816: Immune-tolerant elastin-like polypeptide (iTEP) particles promote peptide vaccine presentation by dendritic cells
Authors: Mingnan Chen, Shuyun Dong, Scott Cho
Journal: Cancer Research (2014)

Abstract T cell epitope-based peptide vaccines are promising experimental therapeutics for cancer and infection due to their unparalleled specificity, yet their presentations by dendritic cells (DCs) are hindered by their intrinsic limitations: short half-lives, non-typical antigen sizes for DCs to take in and process, lack of intrinsic adjuvants, and poor cross-presentation efficiencies. We aimed to boost the presentation by fabricating an immune-tolerant elastin-like polypeptide (iTEP) nanoparticle (NP) to resolve the limitations. The properties of iTEPs that render them as ideal vaccine carriers include their non-immunogenic and non-inflammatory natures, their simple purification method through phase transition, and their ability to fuse the vaccines and peptide adjuvants together. We first fused a cytotoxic T lymphocyte (CTL) epitope vaccine, SIINFEKL, from ovalbumin to an iTEP amphiphilie and found the fusion is able to self-assemble into NPs. The NP was turned into a size similar to virus-like particles by modulating the iTEP sequences. The NP enhanced the presentation of SIINFEKL with H2b on the surface of DC2.4 cells in comparison with free peptide, ovalbumin, or soluble vaccine-iTEP fusions. Interestingly, another iTEP-vaccine fusion which forms larger, micrometer-sized aggregates led to even stronger vaccine presentation, an observation still under investigation. Moreover, our preliminary data showed that co-delivering the vaccines and an adjuvant peptide from flagellin by iTEPs also augmented the peptide vaccine presentation. Lastly, the iTEP NPs that deliver tumor antigen Kras- and hTERT-derived peptide vaccines were also generated and are currently under study with a hope to improve the efficacy of these vaccines. In summary, iTEP particles enhanced peptide vaccine presentation. The underlying mechanisms of the enhancing effects of iTEP particles on the vaccine presentation will be studied next. Supported by the University of Utah Start-up fund and the University of Utah SEED grant Citation Format: Mingnan Chen, Shuyun Dong, Scott Cho. Immune-tolerant elastin-like polypeptide (iTEP) particles promote peptide vaccine presentation by dendritic cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2816. doi:10.1158/1538-7445.AM2014-2816
Abstract 8949: Intermittent Systolic Overload induces Rapid Ventricular Hypertrophy and Promotes Better Ventricular Function in Young Goats
Authors: Gustavo A Favaro, Renato S Assad, Maria C Abduch, Gustavo Justo, Guilherme Gomes, José L Andrade, José E Krieger, Noedir A Stolf
Journal: Circulation (2011)

Introduction: Anatomical repair of transposition of the great vessels beyond the neonatal period requires preparation of the left ventricle for the 2-stage Jatene operation. Previous studies have demonstrated myocardial edema and necrosis in hearts that experience abrupt systolic overload, followed by late ventricular failure. Hypothesis: Subpulmonary ventricle retraining with intermittent systolic overload could minimize the inadequacy of conventional pulmonary artery banding and promote better LV function under pharmacologic stress testing. Methods: Nineteen young goats were divided into 3 groups: Sham (n=7; no systolic pressure overload), Continuous (n=6; systolic overload maintained for 96 hours) and Intermittent (n=6; 4 periods of 12-hour systolic overload, paired with a 12-hour resting period). Echocardiographic and hemodynamic evaluations were performed every day. Myocardial performance index and ejection fraction were evaluated at rest and during dobutamine stress. The animals were then killed for morphologic evaluation. Results: Systolic overload area of Intermittent group, measured by RV to PA pressure gradient over time, was significantly smaller than Continuous group (p&lt;0.05). Nevertheless, both groups had increased RV and septal masses, as compared to Sham (p&lt;0.0002). Echocardiography revealed a major increase in the RV wall thickness of the Intermittent group (+64.8% ± 23.37%), when compared to Continuous group (+43.9% ± 19.26%; p=0.015). RV dilation and dysfunction was observed in both study groups after starting systolic overload (p&lt;0.002). However, only Continuous group remained with significant RV dilation throughout the protocol (p &lt;0.006). Intermittent group presented a significantly better myocardial performance index at the end of protocol, under resting and dobutamine infusion, when compared to Continuous group (p&lt;0.012). Conclusions: Both systolic overload protocols have induced a rapid RV hypertrophy. However, only Intermittent group had a better preservation of RV function, at the end of the protocol, both at rest and under dobutamine infusion. This study suggests that intermittent systolic overload may favorably affect the results for 2-stage Jatene operation.