tbuckley/cabot-search huggingface dataset:
Spatiotemporal trafficking of HIV in human plasmacytoid dendritic cells defines a persistently IFN-α–producing and partially matured phenotype
Authors: Meagan O’Brien, Olivier Manches, Rachel Lubong Sabado, Sonia Jimenez Baranda, Yaming Wang, Isabelle Marie, Linda Rolnitzky, Martin Markowitz, David M. Margolis, David Levy, Nina Bhardwaj
Journal: Journal of Clinical Investigation (2011)

Plasmacytoid DCs (pDCs) are innate immune cells that are specialized to produce IFN-α and to activate adaptive immune responses. Although IFN-α inhibits HIV-1 replication in vitro, the production of IFN-α by HIV-activated pDCs in vivo may contribute more to HIV pathogenesis than to protection. We have now shown that HIV-stimulated human pDCs allow for persistent IFN-α production upon repeated stimulation, express low levels of maturation molecules, and stimulate weak T cell responses. Persistent IFN-α production by HIV-stimulated pDCs correlated with increased levels of IRF7 and was dependent upon the autocrine IFN-α/β receptor feedback loop. Because it has been shown that early endosomal trafficking of TLR9 agonists causes strong activation of the IFN-α pathway but weak activation of the NF-κB pathway, we sought to investigate whether early endosomal trafficking of HIV, a TLR7 agonist, leads to the IFN-α–producing phenotype we observed. We demonstrated that HIV preferentially traffics to the early endosome in human pDCs and therefore skews pDCs toward a partially matured, persistently IFN-α–secreting phenotype.
Subcapsular Splenic Hematoma vs Intrasplenic Pancreatic Pseudocyst
Authors: ROBERT J. WALLNER, BRUNO E. BASARA, SIMIN DADPARVAR, MILLARD N. CROLL, LUTHER W. BRADY
Journal: Clinical Nuclear Medicine (1984)

An intrasplenic pancreatic pseudocyst may mimic a subcapsular splenic hematoma. Misdiagnosis of this entity may have serious consequences. Particular care should be taken when a patient presents with a cystic mass in the region of the spleen and a history of chronic alcohol abuse, regardless of the presence or absence of a history of a traumatic episode. Thin-needle aspiration is the current diagnostic modality of choice. A high fluid amylase level establishes the diagnosis of an intrasplenic pancreatic pseudocyst.
Radiation Therapy Plus Tamoxifen Versus Tamoxifen Alone After Breast-Conserving Surgery in Postmenopausal Women With Stage I Breast Cancer: A Decision Analysis
Authors: Rinaa S. Punglia, Karen M. Kuntz, Jason H. Lee, Abram Recht
Journal: Journal of Clinical Oncology (2003)

Purpose: To compare outcomes for hypothetical cohorts of postmenopausal patients with estrogen receptor–positive tumors that are ≤ 2 cm in size, with pathologically uninvolved axillary nodes, treated with radiation therapy plus tamoxifen versus tamoxifen alone after breast-conserving surgery. Methods: A Markov model was used to simulate patients’ clinical course and estimate overall survival, recurrence-free survival, time with an intact breast, and death from breast cancer. Probabilities were derived from randomized trials and retrospective studies. Analyses were performed separately by age of diagnosis in 5-year increments from 50 to 80 years. Sensitivity analyses tested the stability of radiation benefit. Results: The modeled recurrence-free survival benefit of giving radiation therapy was 3.35 years for women who were 50 years of age at diagnosis, versus 0.61 years for women who were 80 years of age. In the 50-year-old cohort, radiation therapy resulted in additional 0.60 years survival, compared with 0.04 years among 80-year-olds. A 50-year-old woman who received radiation therapy plus tamoxifen was less likely to die from breast cancer than if she received tamoxifen alone (2.43% v 5.29%; relative-risk reduction, 54%). An 80-year-old woman had a 1.17% chance of dying from breast cancer if she received radiation therapy plus tamoxifen, versus 2.02% with tamoxifen alone (relative-risk reduction, 42%). Sensitivity analyses showed that the magnitude of benefit was strongly influenced by including unequal rates of developing distant disease after breast recurrence between the treatment arms and varying rates of local recurrence. Conclusion: The absolute and relative benefits of radiation therapy and individual patient preferences for different health states should be considered when selecting treatment.
Treatment of Gonorrhea — Is Penicillin Passé?
Authors: William M. McCormack
Journal: New England Journal of Medicine (1977)

The penicillin era of the treatment of infections due to Neisseria gonorrhoeae began in 1943, when Mahoney et al.1 demonstrated that penicillin was effective in the treatment of gonococcal urethritis in men. They gave their patients a total of 160,000 units of penicillin sodium in divided doses. Penicillin, when it became generally available in the late 1940's, rapidly became the drug of choice for the treatment of gonorrhea.Over the ensuing three decades, clinical isolates of N. gonorrhoeae gradually became more resistant to the action of penicillin.2 There are two basic mechanisms by which a micro-organism may become resistant to . . .
Abstract 4764: Vaccination of tumor-bearing mice with irradiated tumor cells and depot-formulated IL-2, IL-12, IL-4, GM-CSF and IFN-a eradicates the tumor cells and induces lasting immunity to the tumor
Authors: Frank W. Falkenberg, Dirk Pendzialek
Journal: Cancer Research (2010)

Abstract In order to overcome the complex tumor-host interactions equally complex biological countermeasures have to be taken. By applying several cytokines in the vaccine the cytokine network is activated more efficiently then by using a single cytokine. To render the approach mote feasible, the cytokines were applied in depot Form. This allows formulation following pharmaceutical rules, and, at the same time, leads to steady release and keeps the inflammatory process active over a long period of time. Applying this concept, vaccines were designed that contained, besides irradiated tumor cells, a bouquet of cytokines in depot formulation. Due to their different biological activities IL-2, IL-4, IL-12, GM-CSF and IFNα were chosen. The sequential steps of vaccine action: The release of a multiplicity of cytokines accelerates the influx of inflammatory cells of the innate immune system. Under the influence of IL-4. GM-CSF and IL-12 released from the depot, Dendritic cells are recruited, maturated and activated under physiological conditions in situ, at the inoculation site, circumventing tedious ex vivo procedures. Tumor cell fragments generated by cells of the innate immune system are taken up by the locally generated CD86+ mature Dendritic Cells and transported to the lymph nodes where they are presented to T cells. In addition, cytokine-loaded depot particles are carried to the lymph nodes where they become involved in activation processes that are not understood yet. Due to its angiogenic activity, depot-released GM-CSF induces the sprouting of capillaries into the inoculum, thus opening the way for recirculation of activated CD4+ and CD8+ T cells into the inoculum. Depot-released IL-2 and IFNα further activate cells of the NK/NK-T cell lineage. Applying Multi-Cytokine-Depot Tumor Vaccines, we have been able to cure mice from tumors induced by injection of a lethal dose of vital tumor cells. Although the set-up of the vaccine is complex, its preparation is easy and relies on formulation following pharmaceutical principles rather than on trial and error. For each cytokine as well as for the tumor cells a specific Dose-Response-relations has been determined. We are currently preparing for the application of this concept in clinical trials. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4764.
Too Many Physicians Trained in Spain
Authors: Xavier Bosch
Journal: JAMA (1999)

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
Platelet count is independently associated with insulin resistance in non-obese Japanese type 2 diabetic patients
Authors: Ataru Taniguchi, Mitsuo Fukushima, Yutaka Seino, Masahiko Sakai, Satoru Yoshii, Shoichiro Nagasaka, Ichizoh Yamauchi, Takahide Okumura, Kazuko Nin, Kunpei Tokuyama, Noriko Yamadori, Masahito Ogura, Akira Kuroe, Yoshikatsu Nakai
Journal: Metabolism (2003)
Practical Psychiatry for the Internist
Authors: Z. J. Lipowski
Journal: JAMA (1969)

In their preface the authors state their purpose, "to improve the practitioner's sense of security in dealing with emotional and psychologic manifestations, overt and covert, while maintaining the integrity of his own particular interests." Is the book likely to achieve its purpose? In my opinion it is most unlikely to do so. The best thing about this volume is its brevity—168 pages. The nine chapters encompass "human biology," psychiatric aspects of surgery, psychosomatics, psychiatric disorders and methods of treatment, psychopharmacology, and the uses of hypnosis in general practice. The authors keep to their promise to avoid "all psychiatric jargon." This is laudable, but unfortunately the jargon is replaced by platitudes and verbiage which fail to ensure useful communication. A foretaste of what is to come can be found in the preface, in which the authors announce, "Human biology, which probably ranks with physical and psychiatric illness as a source of
Knockout of ERK1 MAP Kinase Enhances Synaptic Plasticity in the Striatum and Facilitates Striatal-Mediated Learning and Memory
Authors: Cristina Mazzucchelli, Chiara Vantaggiato, Alessandro Ciamei, Stefania Fasano, Pavel Pakhotin, Wojciech Krezel, Hans Welzl, David P Wolfer, Gilles Pagès, Olga Valverde, Anne Marowsky, Annamaria Porrazzo, Paul C Orban, Rafael Maldonado, Markus U Ehrengruber, Vincenzo Cestari, Hans-Peter Lipp, Paul F Chapman, Jacques Pouysségur, Riccardo Brambilla
Journal: Neuron (2002)
Endoscopic Choledochoduodenostomy for Choledocholithiasis through Choledochoduodenal Fistula
Authors: M. Osnes, T. Kahrs
Journal: Endoscopy (1977)

A new endoscopic method for treatment of choledocholithiasis in patients with choledochoduodenal fistula is described. In 2 patients with common bile duct stones a choledochoduodenostomy was performed by means of a diathermy snare. In both patients the calculi passed into the duodenum within some days. No complications occurred. It is concluded that the described technique may be helpful when surgery is contra-indicated and when endoscopic papillotomy is difficult to perform.
Topics of the Day
Authors: H. W. Sharpin
Journal: BMJ (1876)

exertion.It happened, from circumstances not necessary to be detailed, that efforts were made to evoke some intelligent action from her and to train her somewhat in the same way as idiots are trained.The experi- ment went on well, and the patient seemed to be making progress in employing herself by needlework and in other ways.But the effort was too much; a paroxysm of excitement supervened, clearly due to over-exertion of an enfeebled incapacitated brain.WVhen the paroxysm subsided, she relapsed into her usual torpid state, but was rather more demented than-before.The second example is a case of mania, ac-
Cumulative Incidence of Childhood-Onset IDDM is Unaffected by Pertussis Immunization
Authors: Harald Heijbel, Robert T Chen, Gisela Dahlquist
Journal: Diabetes Care (1997)

OBJECTIVE To identify a possible effect of pertussis vaccination in infancy on the risk for developing human IDDM. RESEARCH DESIGN AND METHODS A comparison was made of the cumulative incidence of IDDM in children age 0–12 years between two birth cohorts born before pertussis vaccination and two birth cohorts born after pertussis vaccination had been excluded from the Swedish national immunization program. The Swedish Childhood Diabetes registry was used to identify cases of IDDM. Yearly nurse reports on administered vaccines were used to determine coverage for diphtheria/tetanus/pertussis (DTP) and diphtheria/tetanus (DT) vaccines. Pertussis vaccine coverage was estimated based on number of doses of vaccine made available on license. RESULTS No difference in cumulative incidence rate of IDDM up to the age of 12 years was found when the birth cohorts for 1978 and 1979 with high DTP vaccination coverage were compared with the cohorts of 1980 and 1981 with low pertussis vaccination coverage. CONCLUSIONS The comparison of the cumulative incidence of IDDM, up to the age of 12 years, in birth cohorts with high and low exposure to pertussis vaccine does not support the hypothesis that pertussis could induce autoimmunity to the β-cell that may lead to IDDM.
Glutamate dehydrogenase: a reliable marker of liver cell necrosis in the alcoholic.
Authors: L Van Waes, C S Lieber
Journal: BMJ (1977)

The usefulness of blood enzyme determinations as markers of liver necrosis was tested in 100 alcoholics who underwent biopsy during clinical investigation. Mean values of glutamate dehydrogenase (GDH), serum aspartate and alanine transferase (SGOT and SGPT), ornithine carbamoyltransferase (OCT), and gamma-glutamyltranspeptidase (gamma-GTP) tended to rise with increasing liver cell necrosis, though values of SGOT, SGPT, OCT, and gamma-GTP showed considerable overlap between the 32 patients with histologically proved hepatitis and the 68 without. By contrast, GDH values showed virtually no overlap between patients with and without hepatitis, and a value of two and a half times the normal value discriminated between the two groups. Because of its easy determination and its reliable reflection of liver cell necrosis the GDH concentration should be estimated routinely in alcoholic patients.
Portopulmonary Hypertension
Authors: Jérôme Le Pavec, Rogério Souza, Philippe Herve, Didier Lebrec, Laurent Savale, Colas Tcherakian, Xavier Jaïs, Azzedine Yaïci, Marc Humbert, Gérald Simonneau, Olivier Sitbon
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Portopulmonary hypertension (PoPH) can be defined as elevation of pulmonary arterial pressure and pulmonary vascular resistance in the setting of portal hypertension. Survival results in PoPH are contrasting, and prognostic factors need to be identified.To analyze long-term survival in a large cohort of patients with PoPH with the aim of determining the independent variables affecting survival.We retrospectively analyzed charts of all patients referred to the French Referral Center for pulmonary arterial hypertension with the diagnosis of PoPH between 1984 and 2004.The study population comprised 154 patients; 57% male. Mean age at diagnosis was 49 +/- 11 years, 60% of patients were in New York Heart Association functional class III-IV, and mean 6-minute walk distance was 326 +/- 116 m. Hemodynamic measurements showed a mean pulmonary arterial pressure of 53 +/- 13 mm Hg, cardiac index of 2.9 +/- 0.9 L/min/m(2), and pulmonary vascular resistance of 752 +/- 377 dyn/s/cm(5). Portal hypertension was related to cirrhosis in 136 patients, with a severity assessed as follows: Child-Pugh class A 51%, Child-Pugh class B 38%, Child-Pugh class C 11%. Overall survival rates at 1, 3, and 5 yr were 88, 75, and 68%, respectively. Multivariate regression analysis individualized the presence and severity of cirrhosis and cardiac index as major independent prognostic factors.Prognosis in PoPH is mainly related to the presence and severity of cirrhosis and to cardiac function. The place of pulmonary arterial hypertension-specific therapies remains to be determined in the setting of PoPH.
SAP regulates T cell–mediated help for humoral immunity by a mechanism distinct from cytokine regulation
Authors: Jennifer L. Cannons, Li J. Yu, Dragana Jankovic, Shane Crotty, Reiko Horai, Martha Kirby, Stacie Anderson, Allen W. Cheever, Alan Sher, Pamela L. Schwartzberg
Journal: The Journal of Experimental Medicine (2006)

X-linked lymphoproliferative disease is caused by mutations affecting SH2D1A/SAP, an adaptor that recruits Fyn to signal lymphocyte activation molecule (SLAM)-related receptors. After infection, SLAM-associated protein (SAP)−/− mice show increased T cell activation and impaired humoral responses. Although SAP−/− mice can respond to T-independent immunization, we find impaired primary and secondary T-dependent responses, with defective B cell proliferation, germinal center formation, and antibody production. Nonetheless, transfer of wild-type but not SAP-deficient CD4 cells rescued humoral responses in reconstituted recombination activating gene 2−/− and SAP−/− mice. To investigate these T cell defects, we examined CD4 cell function in vitro and in vivo. Although SAP-deficient CD4 cells have impaired T cell receptor–mediated T helper (Th)2 cytokine production in vitro, we demonstrate that the humoral defects can be uncoupled from cytokine expression defects in vivo. Instead, SAP-deficient T cells exhibit decreased and delayed inducible costimulator (ICOS) induction and heightened CD40L expression. Notably, in contrast to Th2 cytokine defects, humoral responses, ICOS expression, and CD40L down-regulation were rescued by retroviral reconstitution with SAP-R78A, a SAP mutant that impairs Fyn binding. We further demonstrate a role for SLAM/SAP signaling in the regulation of early surface CD40L expression. Thus, SAP affects expression of key molecules required for T–B cell collaboration by mechanisms that are distinct from its role in cytokine regulation.
The Nature of Charles Darwin's Lifelong Ill-Health
Authors: Walter C. Alvarez
Journal: New England Journal of Medicine (1959)

ONE of the most interesting and instructive stories of lifelong ill-health is that of the eminent Charles Darwin. It can be read with great profit by anyone interested in medicine, and especially anyone in whose family a strain of melancholia runs. For fifty years I have been reading everything I could find on the ill-health of the Darwin family. Why was I so interested in this matter? Because I kept seeing in my practice some intelligent and interesting and likable patients who had exactly Darwin's strange lack of strength to stand up to any happening out of the ordinary routine. . . .
BMA rejects proposal that GPs should pay cost of patients’ unnecessary visits to emergency departments
Authors: Lynn Eaton
Journal: BMJ (2008)

GPs’ leaders have criticised the suggestion that primary care trusts should be able to recoup from general practices the costs of any unnecessary visits made by their patients to emergency departments or walk-in clinics.

The proposals, apparently passed to the government for consideration in the review being carried out by the health minister Ara Darzi, suggest that charges are imposed if a patient uses emergency services because they cannot see their own doctor in normal surgery hours.

Laurence Buckman, chairman of the BMA’s General Practitioners Committee, said that the proposal, from the NHS Confederation and NHS Employers, could mean that many general practices would lose all their funds. Those in areas where there was a culture of patients tending to go to emergency departments would be the hardest …
Dermatitis Herpetiformis: The Skin and the Gut
Authors: STEPHEN I. KATZ
Journal: Annals of Internal Medicine (1980)

Dermatitis herpetiformis is an intensely itchy, chronic, papulovesicular eruption that is usually symmetrically distributed on extensor surfaces. Histologically, it is characterized by dermal papillary collections of neutrophils and subepidermal vesicle formation. The skin has IgA deposits in areas corresponding to the earliest histopathologic change; that is, at the epidermal-dermal junction. Most patients have an associated asymptomatic gluten-sensitive enteropathy that mimics ordinary glutensensitive enteropathy (celiac disease) both morphologically and in its response to gluten protein. There is a marked increase in the prevalence of the major histocompatibility antigens, HLA-B8 and HLA-Dw3, and in certain B cell antigens in these patients. Although the sulfones or sulfapyridine have been the mainstay of treatment, it is now clear that the skin disease responds to strict adherence to a gluten-free diet. These findings are reviewed and from them are drawn certain conclusions as to possible pathophysiologic mechanisms involved in dermatitis herpetiformis.
HEMARTHROSIS AND ANTICOAGULANTS
Authors: GEORGE E. MCLAUGHLIN
Journal: Annals of Internal Medicine (1969)

Letters and Comments1 October 1969HEMARTHROSIS AND ANTICOAGULANTSGEORGE E. MCLAUGHLIN, M.D.GEORGE E. MCLAUGHLIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-71-4-867_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: Dr. Normal O. Rothermich, in the June issue of the ANNALS, criticized Question No. 92 which had appeared the previous December. This question concerned hemarthrosis after anticoagulant therapy in a man with acute myocardial infarction.The basic purpose of this question was to point out the synergestic effect of phenylbutazone on Coumadin⌖-type anticoagulants. I agree that hemarthrosis after routine anticoagulation is quite rare, but enhancement of the anticoagulant effect with certain drugs (such as phenylbutazone) make this complication much more likely.The value of synovianalysis is again emphasized by this question. The three most likely diagnoses in... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Germantown Hospital Phila., Pa. 19144 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPyrazolone Derivatives (Antipyrine, Aminopyrine, Phenylbutazone, Oxyphenbutazone) 1 October 1969Volume 71, Issue 4Page: 867-867KeywordsAcute myocardial infarctionAnticoagulant therapyAnticoagulantsDrugsHemarthrosis ePublished: 1 December 2008 Issue Published: 1 October 1969 PDF downloadLoading ...