tbuckley/cabot-search huggingface dataset:
Interleukin-10 promotes activation-induced cell death of SLE lymphocytes mediated by Fas ligand.
Authors: L Georgescu, R K Vakkalanka, K B Elkon, M K Crow
Journal: Journal of Clinical Investigation (1997)

Immune function in SLE is paradoxically characterized by active T cell help for autoantibody production, along with impaired T cell proliferative and cytokine responses in vitro. To reconcile these observations, we investigated the possibility that the accelerated spontaneous cell death of SLE lymphocytes in vitro is caused by an activation-induced cell death process initiated in vivo. 27 SLE patients, three patients with systemic vasculitis, seven patients with arthritis, and 14 healthy subjects were studied. Patients with clinically active SLE or systemic vasculitis had accelerated spontaneous death of PBMC with features of apoptosis at day 5 of culture. A prominent role for IL-10 in the induction of apoptosis was observed, as neutralizing anti-IL-10 mAb markedly reduced cell death in the active SLE patients by 50%, from 22.3 +/- 5.2% to 11.2 +/- 2.8%, and the addition of IL-10 decreased viability in the active SLE group, but not in the control group, by 38%. In addition, apoptosis was shown to be actively induced through the Fas pathway. The potential clinical relevance of T cell apoptosis in active SLE is supported by the correlation of increased apoptosis and IL-10 levels in vitro with low lymphocyte counts in vivo. We conclude that the spontaneous cell death observed in vitro in lymphocytes from patients with SLE and other systemic autoimmune disorders results from in vivo T cell activation, is actively induced by IL-10 and Fas ligand, and reflects pathophysiologically important events in vivo. Activation-induced cell death in vivo provides a pathogenic link between the aberrant T helper cell activation and impaired T cell function that are characteristic features of the immune system of patients with SLE.
Abstract PD01-02: Increased expression of phosporylated mTOR in metastatic breast tumors compared to primary tumors in patients who received adjuvant endocrine therapy
Authors: LDC Hoefnagel, KJ Beelen, M Opdam, A Vincent, SC Linn, PJ van Diest
Journal: Cancer Research (2012)

Abstract BACKGROUND: Activation of the PI3K pathway as an adaptive change in response to estrogen depletion results in acquired endocrine therapy resistance in vitro. Metastatic breast cancer patients with previous exposure to endocrine therapy do derive substantial benefit from the addition of an mTOR inhibitor to endocrine therapy compared to endocrine therapy alone. This suggests that compensatory PI3K pathway activation might play a role in the development of clinical resistance to endocrine therapy. We evaluated the activation of the downstream PI3K pathway protein mTOR in primary breast tumors and matched metastatic lesions. METHODS: From a previously described series of breast cancer patients from whom both primary tumor tissue as well as metastatic tumor tissue was collected, we selected estrogen receptor α (ERα) positive patients who had received endocrine therapy (N = 34) and who did not receive endocrine therapy (N = 37). The difference in expression of phosphorylated mTOR (p-mTOR) between primary and metastatic tumor was assessed by immunohistochemistry, which was scored by using the proportion of tumor cells with sub-membranous p-mTOR expression. We assessed whether this p-mTOR difference between primary and metastatic tumor was associated with clinico-pathological factors (location of metastasis, lymph node status, T-stage, grade, progesterone receptor status) or varied between patients who did and did not receive endocrine therapy, using Mann-Whitney tests. In addition we performed a linear regression model including the same clinico-pathological factors. RESULTS: In patients who had received endocrine therapy we observed an increase in p-mTOR expression in metastatic tumor lesions compared to the primary tumor (median difference 45%). This was significantly different from the mTOR changes observed in patients who did not receive endocrine therapy (median difference between metastatic and primary lesion 0 %) (p = 0.003). The difference remained significant in the multivariate regression model (p = 0.001). None of the other factors was significantly associated with a differential p-mTOR change. CONCLUSION: In patients who received previous adjuvant endocrine therapy, the increase in p-mTOR expression in metastatic tumor lesions compared to the primary tumor is significantly higher than in patients who did not receive endocrine therapy. Compensatory activation of the PI3K pathway might therefore be a clinically relevant resistance mechanism resulting in secondary endocrine therapy resistance. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD01-02.
“After a long battle”
Authors: Risa Denenberg
Journal: Annals of Internal Medicine (2012)

Ad Libitum6 March 2012“After a long battle”Risa Denenberg, NP, MSNRisa Denenberg, NP, MSNFrom Tacoma, WA 98405.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-156-5-201203060-00006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I heard of his death on the radio. And now,and now, I wonder how I will die. Days shrinkwith darkness and chilblain rain. We slideon black ice, car slams into car, love's gone mad.We have sung, beating out prayers on chestand thighs, but such words are vain.Why listen to imitations of hope? I'm stuckinside a corpse inside a situation inside an accident.I look for crevices where I can hide without brushingagainst this bruise. I wait with good cheer to makemy escape. There are no more tests to take.In my story, I will not be losing a long battle.... Author, Article, and Disclosure InformationAffiliations: From Tacoma, WA 98405.Current Author Address: Risa Denenberg, NP, MSN; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 March 2012Volume 156, Issue 5Page: 349KeywordsThorax ePublished: 6 March 2012 Issue Published: 6 March 2012 Copyright & PermissionsCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A British Medical Association Lecture on MINOR ORTHOPAEDICS OF THE FEET IN GENERAL PRACTICE
Authors: J. Fraser
Journal: BMJ (1929)

TuIis address ilncludes the consideration of a inumber of conditionis apparently so simiple that some milay feel that there is nothing new to be said about themll'; but I have Poticed that miiinor orthopaeedic disabilities are remarkably collmmoll, that amonog the work of a young consultant they form a considerable proportion of his material, and sinceC they come to the institutioni and the consultant, I infer that they are a souroe of trouble and anxietv to the man in general practice.When I add that mlialny of these coll- ditions are among the most difficult to treat and to cure, I have justified, I hope, the choice of mny subject.I propose to illustrate wvhat I hiave to say by short abstracts from case notes, and, so far as possible, to demonstrate the conditions to which I refer.INGROWING TOENAIL.
Abstract 547: Mapping of estrogen receptor-dependent and independent signaling pathways for xeno- and phytoestrogens
Authors: Anne C. Katchy, Caroline Pinto, Maria Bondesson, Cecilia Williams
Journal: Cancer Research (2012)

Abstract Xenoestrogens (e.g. bisphenol A) and phytoestrogens (isoflavones) are endocrine disrupting chemicals (EDC) that are capable of disrupting hormonal signaling in mammary and reproductive systems. These compounds are similar in structure to estrogen and bind to the estrogen receptors (ER). Estrogen receptors are involved in the regulation of cell cycle, proliferation, and apoptosis. It is likely that these compounds could affect the same biological processes or have their own subsets of target pathways. Here, we extensively identify target genes and signaling pathways for selected xeno- and phytoestrogens. Dose response curves for these compounds were measured using real-time PCR (RT-PCR) and transactivation assays of known estrogen target genes. Gene expression profilings for each EDC were performed on MCF-7 breast cancer cell lines using dual-color comparative array. Validations of array results were carried out using RT-PCR. Gene ontology and gene network mapping studies were done to identify the mechanism of action of these compounds. Non-ER mediated targets and the kinetics of each EDC were investigated in detail. Results show that many target genes regulated by bisphenol A and Genistein were involved in biological processes including cell cycle and proliferation, similar to that of estrogen. This contributes to an increased understanding of the mechanisms of EDC action, which may be implicated in development of diseases such as breast cancer and reproductive disorders, and would contribute to a more reliable risk assessment of different EDC compounds. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 547. doi:1538-7445.AM2012-547
Molecular Interrelations of Nutrition and Cancer
Authors: John H. Weisburger
Journal: JAMA (1982)

This volume continues the long tradition of recording the presentations of the annual Symposia on Fundamental Cancer Research at the M. D. Anderson Hospital and Tumor Institute, University of Texas. The relationship between nutrition and cancer has been the subject of research for many years. Recently, however, there has been a resurgence of interest, especially with respect to nutritional elements in cancer causation. The current symposium proceedings deal with an examination at the molecular level of the effect of macronutrients, particularly lipids and carbohydrates, and especially micronutrients such as vitamins and minerals. The topics discussed can be divided further as to nutritional elements studied in vivo in humans and in animals with regard to physiological effects in cancer-bearing hosts, the question of nutritional elements at the level of normal and tumor cell growth and development, and the effect of such factors on cell transformation and on the development of cancer.
<b> The Natural Estrogenic Compound Diarylheptanoid (D3): <i>In Vitro</i> Mechanisms of Action and <i>in Vivo</i> Uterine Responses via Estrogen Receptor </b> α
Authors: Wipawee Winuthayanon, Pawinee Piyachaturawat, Apichart Suksamrarn, Katherine A. Burns, Yukitomo Arao, Sylvia C. Hewitt, Lars C. Pedersen, Kenneth S. Korach
Journal: Environmental Health Perspectives (2013)

Diarylheptanoid (D3) isolated from the medicinal plant, Curcuma comosa, has estrogenic activity.We aimed to elucidate the mechanism(s) of D3 action and compare it with that of 17β-estradiol (E2) using both in vitro and in vivo uterine models.We used human uterine (Ishikawa) cells to determine the estrogenic action of D3 on the activation and nuclear translocation of estrogen receptor α (ERα). In addition, we further characterized the uterine response to D3 treatment in vivo.D3 activated an estrogen responsive element (ERE) luciferase reporter through ERα, and molecular modeling suggested that D3 could be accommodated in the ERα binding pocket. Using modified ERα to assay ligand-dependent nuclear translocation, we observed D3-dependent ERα interaction and translocation. In mouse uteri, early- and late-phase estrogen-regulated gene responses were increased in D3-treated ovariectomized wild-type animals, in a manner similar to that of E2; no response was seen in ERα knockout animals. We observed a divergence in estrogen responses after D3 treatment: D3 induced robust DNA synthesis in uterine epithelial cells, linked to an increase in cell-cycle-related genes; however, no increase in uterine weight was observed 24 hr after treatment. D3 also affected uterine progesterone receptor expression patterns similar to E2. When D3 and E2 were administered together, we observed no additive or antagonistic effects of D3 on E2. Our findings suggest that D3 is a weak estrogenic agonist compound.D3 is a weakly acting phytoestrogen that mimics the mitogenic responses produced by E2 in an ERα-dependent manner, but it is unable to increase uterine weight or enhance or antagonize the effects of estrogen.
Insights Into Medical Care Public Assistance Expenditures
Authors: Robert W. Hammel
Journal: JAMA (1972)

Public assistance medical care expenditure data supplied to the US Department of Health, Education, and Welfare by nine Western and ten Southern state were analyzed. For comparison purposes, data from states without a drug formulary or with an open or unrestricted formulary were compared with those from states maintaining a closed formulary. Contrary to popular expectation, no relationship was found between formulary status and expenditures. Broadly based peer review and utilization control programs are suggested as a sounder approach to the efficient provision of medical care.
Omeprazole in H2 blocker non-responders.
Authors: V Savarino, G Mela, A Sumberaz, G Celle
Journal: Gut (1990)

SIR, -The comments of Drs Colombel, Janin, and Torpier are of interest.We agree that the immune processes which may contribute to the mucosal lesion of coeliac disease may be multifactorial.The eosinophil is a major com- ponent of the inflammatory infiltrate in coeliac disease, although this is frequently not emphasised in descriptions of the lesion.We have recently produced additional evidence that eosinophils and polymorphs are present in increased numbers in the coeliac mucosa: using monoclonal antibodies to Fc receptors (for the gamma chain of IgG) types II and III, which are found on eosinophils and polymorphs, a marked increase in reactive cells was found.The evidence of Dr Colombel and colleagues that many of these eosinophils have degranulated and the associated finding of increased release of granule components points to mech- anisms whereby eosinophils might mediate damage.The possibility that IgA, produced in large quantities in the damaged intestine, may be involved in eosinophil degranulation through interaction with IgA Fc receptors should also be considered.The finding that many coeliac patients react rapidly to gluten challenge (both symptomatically and histologically) is in keeping with more immediate mechanisms of damage also participating in the development of the lesion.Eosinophils are good candidates for such a mechanism.
Sorry John--try again next year.
Authors: B J Rowlands
Journal: BMJ (1978)

The new legislation affecting foreign medical graduates has placed several obstacles in the path of potential visitors and immigrants to the United States. Now that there is no longer a shortage of doctors in the USA the need for these new laws is clear, but their implementation has been hasty and has allowed no time for planned transition. If further modifications are made, which may well happen, every effort should be made to disseminate information about new requirements as widely and rapidly as possible.
Risks of Postmenopausal Hormone Replacement
Authors: Houston H. Stokes
Journal: JAMA (2002)

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 Empty Sella Syndrome
Authors: Ronald N. Shore
Journal: JAMA (1974)

A woman with diabetes mellitus, hypertension, obesity, and prominent virilization was discovered to have an enlarged sella turcica. A pneumoencephalogram with tomographic views demonstrated the sella turcica was empty except for a thin layer of tissue on the sellar floor. Studies of the patient's pituitary and androgenic hormones showed that they were normal. For reasons unclear, empty sellae occur predominantly in obese adult women, many of whom have hypertension and diabetes. Hirsutism is occasionally present, but actual virilization has not been noted previously.
Reversibility of Cardiac Wall-Motion Abnormalities Predicted by Positron Tomography
Authors: Jan Tillisch, Richard Brunken, Robert Marshall, Markus Schwaiger, Mark Mandelkern, Michael Phelps, Heinrich Schelbert
Journal: New England Journal of Medicine (1986)

Positron emission tomography (PET) can be used with nitrogen-13–ammonia (13NH3) to estimate regional myocardial blood flow, and with fluorine-18–deoxyglucose (18FDG) to measure exogenous glucose uptake by the myocardium. We used PET to predict whether preoperative abnormalities in left ventricular wall motion in 17 patients who underwent coronary-artery bypass surgery were reversible. The abnormalities were quantified by radionuclide or contrast angiography or both, before and after grafting. PET images were obtained preoperatively. Abnormal wall motion in regions in which PET images showed preserved glucose uptake was predicted to be reversible, whereas abnormal motion in regions with depressed glucose uptake was predicted to be irreversible. According to these criteria, abnormal contraction in 35 of 41 segments was correctly predicted to be reversible (85 percent predictive accuracy), and abnormal contraction in 24 of 26 regions was correctly predicted to be irreversible (92 percent predictive accuracy). In contrast, electrocardiograms showing pathological Q waves in the region of asynergy predicted irreversibility in only 43 percent of regions. We conclude that PET imaging with 13NH3 to assess blood flow and 18FDG to assess the metabolic viability of the myocardium is an accurate method of predicting potential reversibility of wall-motion abnormalities after surgical revascularization. (N Engl J Med 1986; 314:884–8.)
The Journal of Men's Health and Gender
Authors: Tom O'Dowd
Journal: BMJ (2005)

P eople are worried about men and their health. Inequalities in male health are staggering. Nine out of 10 prisoners are poorly educated young males from our urban blackspots. Half are on short term sentences of six months or so and many will return to prison.

In the deprived urban areas of Europe you will see many young girls pushing buggies with young babies. They usually travel in groups and you seldom see a male with them. They don't know it …
NHS "good news unit" to be wound up
Authors: J. Jones
Journal: BMJ (1997)

The NHS intelligence unit that helps ministers put a positive gloss on politically damaging “horror stories” is set to be wound up as part of an efficiency drive.

The Corporate Affairs Intelligence Unit of the NHS Executive, otherwise known as the “good news unit,” was set up in 1993. In four years the unit has given ministers early warning of a range of …
Acute generalized pustular bacterid AN UNUSUAL MANIFESTATION OF LEUKOCYTOCLASTIC VASCULITIS
Authors: R.S.-H. TAN
Journal: British Journal of Dermatology (1974)

A woman, aged 58 years, suddenly developed a widespread sterile pustular and purpuric eruption after a streptococcal infection. The eruption resolved spontaneously within a few weeks. Histopathology showed an intra-epidermal pustule with underlying leukocytoclastic vasoilitis. The cutaneous vasculitis in this patient presented as a true pustular bacterid.
Till death do us part
Authors: T. Dalrymple
Journal: BMJ (2011)

Perhaps the greatest, because unintended, tribute to the triumph of modern medicine is the number of detailed literary accounts now published of illness experienced by patients or witnessed by their relatives: for writers choose as subject matter what strikes them as out of the ordinary or worthy of note. Where illness rather than health is quotidian, therefore, accounts of it will not be frequent. Only where good health is assumed to be normal, the default setting of the human frame, as it were, will the experience of illness be thought worth writing about.

It is not surprising, then, that illness memoirs were less frequent in the 1950s than they are now. Among the most striking …
Clinical evaluation of group A and group C meningococcal polysaccharide vaccines in infants.
Authors: R Gold, M L Lepow, I Goldschneider, T L Draper, E C Gotschlich
Journal: Journal of Clinical Investigation (1975)

Group A and group C meningoccal polysaccharide vaccines were evaluated in infants. No significant local or systemic reactions were observed with 908 doses of vaccine given to 396 infants between 3 and 12 mo of age. The antibody response varied with the age of the infant, vaccine dose, molecular weight of vaccine, prior immunization with vaccine, and prior exposure to naturally occurring cross-reactive antigens. Only 7% of 3-mo-old infants had detectable antibody responses to primary immunization with 5-200 mug of A vaccine, presumably because of suppressive effects of high concentrations of maternal anti-A. More than 90% of 7- and 12-mo-old infants responded to A vaccine, achieving geometric mean anti-A concentrations of 0.38 and 0.98 mug/ml, respectively. The dose-response curve was flat between 10 and 200 mug of A vaccine. Geometric mean anti-A concentrations of 2.51 and 4.00 mug/ml were induced in 7- and 12-mo-old infants by booster injections of A vaccine. Approximately 90% of 3-mo-old infants had detectable antibody responses to primary immunization with C vaccine. The 100-mug dose appeared to be optimal, resulting in geometric mean anti-C concentrations of 0.49, 1.55, and 2.64 mug/ml in 3-, 7-, and 12-mo-old infants, respectively. Significant booster responses were not observed with C vaccine. Indeed, except for the 10-mug dose, booster injections of C vaccine in 7- and 12-mo-old infants resulted in lower anti-C concentrations than did primary immunizations.