tbuckley/cabot-search huggingface dataset:
Perforin and granzyme B may contribute to skin inflammation in atopic dermatitis and psoriasis
Authors: N. Yawalkar, S. Schmid, L.R. Braathen, W.J. Pichler
Journal: British Journal of Dermatology (2001)

Background Infiltration of the skin by pathogenic T cells is regarded as a key factor in the development of inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. Objectives To investigate whether T cells containing cytotoxic proteins may contribute to the generation of skin inflammation in these skin diseases. Methods Skin biopsy specimens were obtained from non‐lesional and lesional skin of patients with chronic AD (n = 8) and psoriasis (n = 6), and from non‐atopic controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by immunohistochemistry. Results A significant enhancement of perforin and granzyme B expression was observed in lesional AD skin as compared with normal skin, non‐lesional AD skin and psoriasis. Expression of these cytotoxic proteins was also increased in psoriasis as compared with normal skin and non‐lesional psoriatic skin. Immunoreactivity for perforin and granzyme B was mainly found in the cytoplasm of lymphocytic cells located in the perivascular infiltrate. In AD increased numbers of positive cells were also observed focally at sites of spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and CD8+ T cells are capable of expressing perforin and granzyme B. Conclusions Our data suggest that cytotoxic CD4+ and CD8+ T cells containing perforin and granzyme B may play an integral part in eliciting cutaneous inflammation in AD.
Antioxidant Supplements and Cardiovascular Disease in Men—Reply
Authors: Howard D. Sesso
Journal: JAMA (2009)

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
Pharmacologic characterization of endothelin receptor responses in the isolated perfused rat lung.
Authors: S Uhlig, A N von Bethmann, R L Featherstone, A Wendel
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Endothelin receptor subtypes were characterized in isolated perfused rat lungs using the peptide ETA-receptor antagonists BQ 610 and BQ 123, the nonpeptide mixed ETA-/ETB-receptor antagonist bosentan, and the ETB-receptor agonist IRL 1620. Intra-arterial injection of 1 nmol IRL 1620 caused an enhanced reduction in pulmonary conductance compared with 1 nmol endothelin (ET-1) or 0.33 nmol IRL 1620. Pretreatment of lungs with BQ 610, BQ 123, or bosentan aggravated the bronchoconstriction induced by 1 nmol ET-1 so that it was comparable to that induced by 1 nmol IRL 1620. Although perfusion with 1 nmol IRL 1620 had only minor effects on vascular conductance, 1 nmol ET-1 caused a marked decrease in this parameter. This vasonconstriction was prevented by BQ 610, BQ 123, or bosentan. High concentrations of the stable prostacyclin metabolite, 6-keto-PGF1 alpha, were found in the perfusate of lungs treated with 1 nmol IRL 1620 or 1 nmol ET-1. The ET-1-induced release of 6-keto-PGF1 alpha was blocked by bosentan, but not by BQ 610. ET-1, but not IRL 1620, provoked the release of thromboxane B2. The main effect of ETA-receptor stimulation is vasoconstriction, whereas ETB-receptor stimulation causes bronchoconstriction. Both actions, however, are attenuated by the other receptor, i.e., the ETA-induced vasoconstriction is attenuated by ETB-receptor-induced release of vasodilators such as prostacyclin, whereas the ETB-receptor-induced bronchoconstriction is attenuated by an unknown ETA-receptor-dependent bronchodilatory mechanism.
Medicare's new prescription drug plan causes confusion
Authors: Fred Charatan
Journal: BMJ (2005)

More than 43 million US senior citizens have started choosing a new prescription drug plan under the biggest change to the country's Medicare scheme since 1965. But many are finding the choice of different schemes bewildering.

Senior citizens can join without penalty as late as 15 May 2006, but for coverage to begin by 1 January 2006, they must select by the end of this year. The drug benefit is going to cost an estimated $724bn (£421bn; €615bn) over 10 years, as senior citizens have on average six prescriptions each. Some say it is President Bush's biggest domestic achievement. Up to now, …
Myocardial Infarction Due to Percutaneous Coronary Intervention
Authors: Abhiram Prasad, Joerg Herrmann
Journal: New England Journal of Medicine (2011)

At least 5% of patients who undergo percutaneous coronary intervention have evidence of a periprocedural myocardial infarction. This review examines the clinical, diagnostic, and therapeutic implications of this diagnosis, as well as its implications for clinical trials.
A PLEA FOR EARLY LAPAROTOMY IN INTESTINAL OBSTRUCTION.Read in the Section of Surgery at the Forty-first Annual Meeting of the American Medical Association, held at Nashville, Tenn., May, 1890.
Authors: J. G. CARPENTER
Journal: JAMA (1890)

Bantock, of England, and Joseph Price, of Philadelphia, have written most beautifully, eloquently and forcibly upon this subject, "A Plea for Early Ovariotomy," and have conclusively demonstrated that the best and most favorable time for ovariotomy, is when the diagnosis is made, and before complications and structural lesions have taken place in adjacent and remote organs, and when the patient is in the best possible condition for operation. How true and applicable these remarks are to the subject of intestinal obstruction, is only correctly appreciated by the abdominal surgeon. Surgery has made giant strides, and in no special field has there been more advance than in intestinal surgery. In every medical society there should be read a paper written on my subject, viz,: "A Plea for Early Laparotomy in Intestinal Obstruction." The mortality from delay, incorrect diagnosis, timidity, ignorance and prejudice in the past, has
THE EFFECTS ON RENAL ACTIVITY OF THE ORAL ADMINISTRATION OF PHLORIZIN IN MAN
Authors: William Goldring, Catherine Welsh
Journal: Journal of Clinical Investigation (1934)

Chasis, Jolliffe and Smith (1) have shown that phlorizin administered intravenously to man, raises the level of the glucose clearance to that of the simultaneous xylose and sucrose clearances, the duration of this effect depending upon the size of the dose.In the largest doses given, the cre- atinine clearance was not significantly affected with respect to the clearances of the non-metabolized sugars.It appeared desirable to investigate the effects of phlorizin when administered by mouth.It seemed possible that, if the phlorizin were well ab- sorbed, complete glycuresis might be maintained for considerable periods of time by the repeated administration of small doses and that under these conditions the clearances of creatinine, glucose and xylose might be brought together, as happens in the dog after larger doses of phlorizin (2).Cha- sis, Jolliffe and Smith (1) have reviewed the literature on the oral admin- istration of phlorizin in man, but in none of this previous work have the recorded observations made it possible to evaluate the effects upon the glu- cose clearance.Volunteers for this study were obtained from the Third (New York University) Medical Division of Bellevue Hospital.During the period of observation they were segregated and under the care of a special nurse.The subjects were maintained on the regular ward diet and the phlorizin tests were performed before breakfast, with the subject recumbent in bed.Blood was drawn from the antecubital vein, heparin being used as an anti- coagulant.The blood was centrifuged and the plasma precipitated im- mediately.All urine discards and observation specimens were removed by catheter and collected in flasks containing a few benzoic acid crystals.Appropriate dilutions were made subsequently, and plasma and urine were
Interaction of BARD1 and HP1 Is Required for BRCA1 Retention at Sites of DNA Damage
Authors: Wenwen Wu, Hiroyuki Nishikawa, Takayo Fukuda, Vinayak Vittal, Masahide Asano, Yasuo Miyoshi, Rachel E. Klevit, Tomohiko Ohta
Journal: Cancer Research (2015)

Stable retention of BRCA1/BARD1 complexes at sites of DNA damage is required for the proper response to DNA double-strand breaks (DSB). Here, we demonstrate that the BRCT domain of BARD1 is crucial for its retention through interaction with HP1. In response to DNA damage, BARD1 interacts with Lys9-dimethylated histone H3 (H3K9me2) in an ATM-dependent but RNF168-independent manner. This interaction is mediated primarily by HP1γ. A conserved HP1-binding motif in the BARD1 BRCT domain directly interacted with the chromoshadow domain of HP1 in vitro. Mutations in this motif (or simultaneous depletion of all three HP1 isoforms) disrupted retention of BARD1, BRCA1, and CtIP at DSB sites and allowed ectopic accumulation of RIF1, an effector of nonhomologous end-joining, at damaged loci in S-phase. UNC0638, a small-molecule inhibitor of histone lysine methyltransferase (HKMT), abolished retention and cooperated with the PARP inhibitor olaparib to block cancer cell growth. Taken together, our findings show how BARD1 promotes retention of the BRCA1/BARD1 complex at damaged DNA sites and suggest the use of HKMT inhibitors to leverage the application of PARP inhibitors to treat breast cancer.
Real-time assessment of inflammation and treatment response in a mouse model of allergic airway inflammation
Authors: Virna Cortez-Retamozo, Filip K. Swirski, Peter Waterman, Hushan Yuan, Jose Luiz Figueiredo, Andita P. Newton, Rabi Upadhyay, Claudio Vinegoni, Rainer Kohler, Joseph Blois, Adam Smith, Matthias Nahrendorf, Lee Josephson, Ralph Weissleder, Mikael J. Pittet
Journal: Journal of Clinical Investigation (2008)

Eosinophils are multifunctional leukocytes that degrade and remodel tissue extracellular matrix through production of proteolytic enzymes, release of proinflammatory factors to initiate and propagate inflammatory responses, and direct activation of mucus secretion and smooth muscle cell constriction. Thus, eosinophils are central effector cells during allergic airway inflammation and an important clinical therapeutic target. Here we describe the use of an injectable MMP-targeted optical sensor that specifically and quantitatively resolves eosinophil activity in the lungs of mice with experimental allergic airway inflammation. Through the use of real-time molecular imaging methods, we report the visualization of eosinophil responses in vivo and at different scales. Eosinophil responses were seen at single-cell resolution in conducting airways using near-infrared fluorescence fiberoptic bronchoscopy, in lung parenchyma using intravital microscopy, and in the whole body using fluorescence-mediated molecular tomography. Using these real-time imaging methods, we confirmed the immunosuppressive effects of the glucocorticoid drug dexamethasone in the mouse model of allergic airway inflammation and identified a viridin-derived prodrug that potently inhibited the accumulation and enzyme activity of eosinophils in the lungs. The combination of sensitive enzyme-targeted sensors with noninvasive molecular imaging approaches permitted evaluation of airway inflammation severity and was used as a model to rapidly screen for new drug effects. Both fluorescence-mediated tomography and fiberoptic bronchoscopy techniques have the potential to be translated into the clinic.
H pylori testing and endoscopy for dyspepsia in primary care
Authors: V. Heatley, B. C Delaney, S. Wilson, A. Roalfe, L. Roberts, A. Wearn, F D R. Hobbs, M J L. Smith
Journal: BMJ (2001)

Editor—Delaney et al's trial of Helicobacter pylori testing and endoscopy for dyspepsia in primary care surely misses the point of medical consultations for dyspepsia.1 Most doctors would view the purpose of a consultation as primarily to make a diagnosis before starting treatment. If the purpose is to initiate empirical prescribing—these authors seem to advocate this as they conclude that this “is . . . the best treatment”— the patients might as well go to a pharmacist and treat themselves.

This study is flawed. It uses a screening test for H pylori (Helisal) that has been reported to have sensitivities of only 67-88%, with a specificity of 78-91%.2,3 The test is therefore not an accurate means of detecting H pylori, which presumably explains why so many ulcers were found in the control patients who were H pylori negative (four out of 48 endoscopies carried out).

Conclusions have been drawn on symptomatic follow up and quality of life data that were recorded for only just over half the patients studied. Costs were greater in patients in the study group, who all had endoscopy. We are not told whether these costs were significantly higher, but certainly some of this was due to the cost of H pylori testing, which, for some reason, was significantly higher (P<0.0001) in the study group.

As the authors acknowledge, endoscopic investigation showed significantly more peptic ulcers than did standard management. Presumably the patients themselves would be interested in knowing this, since subsequent successful H pylori eradication treatment should produce cure of their ulcers rather than them having to continue with empirical acid suppressant treatment long term. The National Institute for Clinical Excellence has produced guidance on the use of proton pump inhibitors in the treatment of dyspepsia. It concluded that patients with non-ulcer dyspepsia—whom Delaney et al accept make up most of their patients—may have symptoms caused by different aetiologies and should not be routinely treated with [proton pump inhibitors].”4

Time has left these authors behind. Colleagues and I have shown that adding serum recognition of the CagA protein and serum pepsinogen I levels to simple but reliable H pylori serology further refines diagnostic accuracy and could reduce the endoscopy workload for patients with dyspepsia by about half.5 What patients with dyspepsia need is improved diagnostic accuracy and specifically tailored treatment, not further encouragement to take empirical treatment for life without any clear idea of why, apart from amelioration of symptoms.
Allergy symptoms and IgE immune response to rose: an occupational and an environmental disease
Authors: A. U. Demir, Gül Karakaya, A. F. Kalyoncu
Journal: Allergy (2002)

Background: Turkey is one of the four major producers of rose. Cultivation of rose is the main economic activity of many villagers in the Lakes region. Rose allergy has not been reported before. We investigated the prevalence of allergy symptoms and specific‐IgE immune response due to rose in villagers who had been cultivating rose in Güneykent village in the Lakes region. Methods: A screening questionnaire including respiratory and allergic symptoms was administered to 290 villagers. The investigation team visited and studied 75 randomly selected villagers with an interviewer‐administered questionnaire, pulmonary function testing, skin prick testing and serum total IgE. Specific IgE against Rosa rugosa was measured in 41 villagers. Results: Villagers reported asthma/allergy symptoms outside the rose season (17.6%), during the rose season (6.2%), and both during the rose season and outside the rose season (whole the year) (17.6%). Atopy and specific IgE against Rosa rugosa were detected in 12 (19%), and 8 (19.5%) of the villagers tested. Villagers who had symptoms whole the year reported wheeze more frequently than those who reported symptoms only outside the rose season (41.2% vs 11.1%). Conclusions: IgE‐mediated allergy could occur due to rose and/or its pollen. Symptoms mainly affect the upper airways. Further studies in the rose handlers, florists and workers of the rose industry would help elucidate the occurrence of rose allergy.
A Microelectrophoretic Technique
Authors: Lodewyk J. Denis
Journal: JAMA (1961)

SINCE the advent of electrophoresis in a supporting medium for the separation of proteins, many new techniques have been developed to produce constant, better fractionation to enhance the quantitative results. In spite of the multiplicity of techniques, no single one has been demonstrated to combine simplicity, reproducibility, high resolving power, and reduction of sample amount without direct or indirect interactions with the medium.  Many of the technical difficulties encountered can be traced to the supporting medium. Therefore, agar gel merits special consideration because of its virtually nonexistent adsorption of proteins, its homogeneity, its good optical properties in a wet or dry state, and its qualities which allow for easy preparation. Electrophoretic protein separation in an agar medium was first utilized by Gordon1and subsequently modified for immunoelectrophoresis by Grabar and Williams.2Recently Wieme3-5has described a new electrophoretic technique in agar gel that provides higher resolving
SHO training. Medical unit struggles with proposals.
Authors: C Davidson
Journal: BMJ (1993)

We hope that this extension ofour assessment of the senior house officers in our department proves to be both useful and acceptable to them.The main drawback to this form of assessment is that it is labour intensive, requiring the synchronous participation of both the junior and senior doctors of the department.This programme of assessment is being extended to include other hospitals in our region.Towards the end of this year we hope to report our experiences after assessing the training of further groups of senior house officers working in our department.
Use of Samples From Endoscopic Ultrasound–Guided 19-Gauge Fine-Needle Aspiration in Diagnosis of Autoimmune Pancreatitis
Authors: Takuji Iwashita, Ichiro Yasuda, Shinpei Doi, Nobuhiro Ando, Masanori Nakashima, Seiji Adachi, Yoshinobu Hirose, Tsuyoshi Mukai, Keisuke Iwata, Eiichi Tomita, Takao Itoi, Hisataka Moriwaki
Journal: Clinical Gastroenterology and Hepatology (2011)
Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans
Authors: Sharlene Murdoch, Ugljesa Djuric, Batool Mazhar, Muheiddine Seoud, Rabia Khan, Rork Kuick, Rashmi Bagga, Renate Kircheisen, Asangla Ao, Bhawna Ratti, Samir Hanash, Guy A Rouleau, Rima Slim
Journal: Nature Genetics (2006)
VASCULAR CLOSURE DEVICE VERSUS MECHANICAL COMPRESSION FOR PREVENTION OF COMPLICATIONS: A PROPENSITY SCORE ADJUSTED ANALYSES OF 28487 PATIENTS UNDERGOING CORONARY DIAGNOSTIC AND INTERVENTIONAL PROCEDURES
Authors: Sripal Bangalore, Venkatesan Vidi, Pinak B. Shah, Federick G. Welt, Suwada Hinds, Frederic Resnic
Journal: Journal of the American College of Cardiology (2010)
Differential CD4+ and CD8+ T-cell responsiveness in hepatitis C virus infection
Authors: Kyong-Mi Chang, Robert Thimme, Jacqueline J. Melpolder, David Oldach, Janell Pemberton, Jacquelyn Moorhead-Loudis, John G. McHutchison, Harvey J. Alter, Francis V. Chisari
Journal: Hepatology (2001)

This study was performed to compare the vigor and phenotype of virus–specific CD4 + and CD8 + T–cell responses in patients with different virologic and clinical outcomes after hepatitis C virus (HCV) infection. The results show that a vigorous and multispecific CD4 + proliferative T–cell response is maintained indefinitely after recovery from HCV infection whereas it is weak and focused in persistently infected patients. In contrast, the HCV–specific CD8 + T–cell response was quantitatively low in both groups despite the use of sensitive direct ex vivo intracellular interferon gamma (IFN–γ) staining. Furthermore, although HCV–specific cytolytic CD8 + memory T cells were undetectable ex vivo , they were readily expanded from the peripheral blood of chronically HCV–infected patients but not from recovered subjects after in vitro stimulation, suggesting that ongoing viremia is required to maintain the HCV–specific memory CD8 + T–cell response. HCV–specific CD8 + T cells displayed a type 1 cytokine profile characterized by production of IFN–γ despite persistent HCV viremia. The paradoxical observation that HCV–specific CD4 + T cells survive and CD8 + T cells are lost after viral clearance while the opposite occurs when HCV persists suggests the existence of differential requirements for the maintenance of CD4 + and CD8 + T–cell memory during HCV infection. Furthermore, the relative rarity of circulating CD8 + effector T cells in chronically infected patients may explain the chronic insidious nature of the liver inflammation and also why they fail to eliminate the virus.
A New Treatment for Ocular Neovascularization
Authors: Frederick L. Ferris
Journal: New England Journal of Medicine (2004)

Neovascularization leads to blindness in a large number of ocular disorders, most notably age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, and other vascular occlusive diseases. Various versions of scatter-photocoagulation (laser) treatment in the peripheral retina have been shown to reduce the loss of vision that results from retinal vascular diseases but not from age-related macular degeneration.13 For example, scatter photocoagulation, along with vitrectomy when necessary, can reduce the risk of blindness in eyes with retinal neovascularization from diabetic retinopathy by 90 percent.4 Current treatments for the neovascular complications of age-related macular degeneration are nowhere near this effective, with . . .
The Breast Reconstruction Patient and Her Health Insurance Carrier
Authors: Richard V. Dowden
Journal: JAMA (1979)

To determine policies of health insurance companies regarding payment for breast reconstruction following mastectomy, we polled 50 companies selected at random, as well as every Blue Cross-Blue Shield company. To verify that insurance carriers' replies represented their practices, we polled 96 plastic and reconstructive surgeons in 47 states. Although most health insurance carriers claim to fully cover breast reconstruction following mastectomy for cancer, practices vary widely; many postmastectomy patients receive incomplete or no coverage for reconstruction. Two major reasons for discrepancies appear to be (1) inadequate coverage prompted by unrealistic conception of reconstruction on the part of carriers and (2) specific contractual exclusion. We suggest (1) educating lay and professional persons about breast reconstruction, (2) encouraging more realistic coverage from insurance companies, and (3) if necessary, legislative protection for the postmastectomy patient.