tbuckley/cabot-search huggingface dataset:
Target organ localization of memory CD4+ T cells in patients with chronic beryllium disease
Authors: Andrew P. Fontenot, Scott J. Canavera, Laia Gharavi, Lee S. Newman, Brian L. Kotzin
Journal: Journal of Clinical Investigation (2002)

Chronic beryllium disease (CBD) is caused by exposure to beryllium in the workplace, and it remains an important public health concern. Evidence suggests that CD4+ T cells play a critical role in the development of this disease. Using intracellular cytokine staining, we found that the frequency of beryllium-specific CD4+ T cells in the lungs (bronchoalveolar lavage) of 12 CBD patients ranged from 1.4% to 29% (mean 17.8%), and these T cells expressed a Th1-type phenotype in response to beryllium sulfate (BeSO4). Few, if any, beryllium-specific CD8+ T cells were identified. In contrast, the frequency of beryllium-responsive CD4+ T cells in the blood of these subjects ranged from undetectable to 1 in 500. No correlation was observed between the frequency of beryllium-responsive bronchoalveolar lavage (BAL) CD4+ T cells as detected by intracellular staining and lymphocyte proliferation in culture after BeSO4 exposure. Staining for surface marker expression showed that nearly all BAL T cells exhibit an effector memory cell phenotype. These results demonstrate a dramatically high frequency and compartmentalization of antigen-specific effector memory CD4+ cells in the lungs of CBD patients. These studies provide insight into the phenotypic and functional characteristics of antigen-specific T cells invading other inaccessible target organs in human disease.
Book: A Few Months to Live: Different Paths to Life's End Physician's Guide to End-of-Life Care
Authors: M. L. Williams
Journal: BMJ (2002)

Jan Staton, Roger Shuy, Ira Byock Georgetown University Press, £19.50, pp 384 ISBN 0 87840 841 X Eds Lois Snyder, Timothy E Quill American College of Physicians, £27, pp 267 ISBN 1 930513 28 3 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>; ![Graphic][4]</img>![Graphic][5]</img>![Graphic][6]</img> Five years ago, one of my dearest friends was diagnosed with leukaemia. Three years later she died. The close involvement with her and her outgoing, fun loving family during that time taught me more about palliative care than any number of years of specialist training could. Hospital appointments governed their lives. They were swamped by seemingly dozens of professionals—all no doubt by now identified in the cancer pathway—but they still managed to share laughter until the end. It is difficult to imagine what it must be … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif [5]: /embed/inline-graphic-5.gif [6]: /embed/inline-graphic-6.gif
THE ANNALS AND CONTROVERSY
Authors: WILLIAM E. CONNOR
Journal: Annals of Internal Medicine (1969)

Letters and Comments1 June 1969THE ANNALS AND CONTROVERSYWILLIAM E. CONNOR, M.D.WILLIAM E. CONNOR, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-6-1282_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:Reading some of the correspondence in the March 1969 issue of the ANNALS, I was struck with its liveliness. I believe that it is lively and interesting because it is controversial. I urge that the ANNALScontinue this bent of presenting several sides to a subject, including the side of the underdog and the side of the student activist. The medical profession certainly needs to become aware of the real issues in life which ferment dissent in the young. Medicine and medical care by their very nature are also social disciplines and have at times radical implications... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1969Volume 70, Issue 6Page: 1282-1282 Issue Published: 1 June 1969 PDF downloadLoading ...
Comparison of Metabolic Effects of White Beans Processed Into Two Different Physical Forms
Authors: Alain Golay, Ann M Coulston, Clarie B Hollenbeck, Lucia L Kaiser, Pierre Würsch, Gerald M Reaven
Journal: Diabetes Care (1986)

In the present study eight control subjects and eight patients with non-insulin-dependent diabetes mellitus (NIDDM) consumed single portions of processed beans equivalent to 50 g of carbohydrate. The beans were processed by different methods into two physical forms; one maintained the integrity of the bean cells (undamaged bean cells, UC) and the other ruptured the bean cells (damaged bean cells, DC). Incremental glucose response areas after ingestion of either UC or DC were not significantly different in control subjects, while incremental insulin response areas (49 ± 7 vs. 26 ± 4 μU · ml−1 · h−1 P &amp;lt; .05) were significantly lower after eating UC-processed beans. In patients with NIDDM both incremental glucose (150 ± 14 vs. 73 ± 25 mg · dl−1 · h - 1 ,P &amp;lt; .001) and insulin (67 ± 16 vs. 46 ± 11 μU · ml−1 · h−1 P &amp;lt; .05) response areas were significantly lower after UC administration. To test the effectiveness of the UC-processed bean when incorporated into mixed meals, nine patients with NIDDM consumed mixed meals containing either DC or UC on two separate mornings. The test meals represented a typical Mexican American use of pureed beans wrapped in a flour tortilla topped with melted cheese. Incremental glucose responses were significantly lower after the UC meal (171 ± 42 mg · dl−1 · h−1 P &amp;lt; .05) when compared with the DC meal (212 ± 34 mg · dl−1 · h−1). Incremental insulin areas were also lower after the UC (91 ± 19 μU · ml−1 · h−1) when compared with the DC meal (120 ± 22 μU · ml−1 · h−1). Our study demonstrates that consumption of white beans prepared in a manner that maintains the integrity of the cells profoundly modified the ensuing plasma glucose and insulin response in patients with NIDDM as compared with white beans milled in a more conventional fashion. Moreover, the lower glucose and insulin response to UC beans occurred when the beans were consumed alone or in a mixed meal and suggests that the practice of processing carbohydrate-rich foods in a manner that leaves the food form intact may be of significant clinical importance.
Abstract 2200: Identification of GLI1 binding partners that regulate transactivation or cell transformation
Authors: Joon Won Yoon, Nicole Higashiyama, Marilyn Lamm, Philip M. Iannaccone, David O. Walterhouse
Journal: Cancer Research (2012)

Abstract Activation of the GLI1 transcription factor and oncogene appears to play a role in the genesis of desmoplastic medulloblastomas, basal cell carcinomas, and some rhabdomyosarcomas. We identified interactions between GLI1 and proteins that enhance the transactivating or cell transforming function of GLI1. Such protein-protein interactions could potentially be targeted in the treatment of some GLI1-related malignancies. We focused on proteins interacting with GLI1 transactivation domains, believing these would be essential for transactivation and cell transformation. Previously, we identified an acidic alpha-helical transcription activation domain (TAD1; aa 1020-1091) at the carboxyl terminus of the GLI1 protein. We show that TAD1 physically interacts with the coactivator TAF9 in vitro by pull down assays and in rhabdomyosarcoma cells in vivo by proximity ligation assays and co-immunoprecipitation. Inhibition of this interaction reduces transactivation by GLI1 and the ability of GLI1 to transform RK3E cells. We identify a second GLI1 transactivation domain (TAD2; aa 635-740), which activates reporter gene transcription and accounts for the TAD1-independent cell transforming ability of GLI1. TAD2 contains conserved sequences among GLI1 family proteins, including a CBP binding domain identified in GLI3. However, consistent with in vitro data from others, we could not demonstrate interaction of TAD2 and CBP in rhabdomyosarcoma cells in vivo by proximity ligation assay. To identify TAD2 binding proteins, we performed yeast 2 hybrid screening and identified other transcription factors (Y-Box1, HSF2, RBMX2, and ZMYM2), cytoskeleton-associated proteins and membrane-associated proteins. Based on a previously described GLI1-p53 inhibitory loop that controls stem cell and tumor cell numbers, we demonstrate that p53 down-regulates TAD1 but not TAD2 function. Understanding the mechanism of transactivation and cell transformation by GLI1 can provide novel targeted approaches to inhibit the GLI1 transcription factor in cancer. 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 2200. doi:1538-7445.AM2012-2200
Occurrence of <i>Aspergillus umbrosus</i> Antibodies in Danish Farmers
Authors: C. Hjort, P. Andersen, H. Schønheyder, A. Stenderup
Journal: Allergy (1986)

Antibodies to Aspergillus umbrosus were investigated in 181 Danish farmers, 137 farmers spouses and a control group of 104 male blood donors with no relation to farming. By enzyme‐linked immunosorbent assay (ELISA) higher levels of IgG antibodies were found in farmers than in their spouses and in non‐farming controls ( P &lt; 0.0001). By double immunodiffusion precipitating antibodies occurred in 11 farmers, in none of farmers' spouses and in one control subject. Farmers and farmers' spouses who were non‐smokers had higher IgG antibody levels than smokers in the same groups ( P &lt; 0.04). Farmers more than 30 years of age had higher IgG antibody levels than younger farmers ( P &lt; 0.04). Farmers rearing cattle tended to have higher IgG antibody levels than farmers without cattle. No correlation between antibody levels and respiratory symptoms or lung function parameters (FEV 1 or FVC) could be demonstrated.
Conservative vs. Endoscopic Closure of Colocutaneous Fistulas after Percutaneous Endoscopic Gastrostomy Complications
Authors: T. Gyökeres, M. Burai, J. Hamvas, M. Varsányi, M. Mácsai, L. Paput, Á. Köveskuti, C. Fekete, Á. Pap
Journal: Endoscopy (2003)

We read with interest the paper by Kim et al. [1], presenting an ingenious idea for using a metallic clip to close a colocutaneous fistula after placement of a percutaneous endoscopic gastrostomy (PEG) tube. We would query whether it was really necessary to close the fistula interventionally. In the case reported, early dislodgment of the PEG tube occurred at 2 weeks. The time at which the colonoscopy was carried out is not clear from the paper. Evidently, a 10-day period with total parenteral nutrition and systemic antibiotic treatment elapsed after the patient had vomited the feculent material. It can be assumed that endoscopic removal of the PEG tube and endoscopic closure of the fistula were carried out after that period. Was it really necessary to use a sophisticated endoscopic technique after a 10-day delay, instead of the familiar conservative solution?
Rheumatoid arthritis associated with ulcerative colitis
Authors: J A MOSQUERA-MARTINEZ
Journal: Annals of the Rheumatic Diseases (2001)

I was interested to read the letter on “Rheumatoid arthritis associated with ulcerative colitis” by Boyer et al published recently in the Annals ,1 and would like to make the following comments. Studies in patients with established Crohn's disease (CD) have generally supported the predominance of Th1 responses.2 3 In ulcerative colitis, although enhanced humoral immunity has been described, evidence for classical Th2 predominance remains to be demonstrated. On the other hand, it has …
Dual Therapeutic Efficacy of Vinblastine as a Unique Chemotherapeutic Agent Capable of Inducing Dendritic Cell Maturation
Authors: Hiroaki Tanaka, Hironori Matsushima, Akiko Nishibu, Björn E. Clausen, Akira Takashima
Journal: Cancer Research (2009)

Abstract Our recent unbiased functional screen of 54 chemotherapeutic drugs unveiled striking heterogeneity in their effects on dendritic cells (DC). Most notably, vinblastine (VBL) was found to induce phenotypic and functional maturation of DCs in vitro. Here, we sought to determine whether VBL exhibits “dual” therapeutic efficacy in living animals by directly killing tumor cells and by boosting host immunity via DC maturation. Local injection of VBL in a low dose into the skin of C57BL/6 mice induced in situ maturation of epidermal Langerhans cells. When coinjected with a model antigen, ovalbumin (OVA), VBL enhanced OVA-specific cellular and humoral immune responses. When injected directly into the OVA cDNA–transduced E.G7 tumors, VBL augmented clonal expansion of OVA-reactive CD8 T cells and CTL activities. In B16 melanoma model, intratumor VBL injection induced apoptosis of melanoma cells, phenotypic maturation of tumor-infiltrating DCs, and significant CTL activities. Although complete clearance was never achieved, growth kinetic of B16 melanoma was markedly reduced in C57BL/6 mice by intratumor VBL injection. Importantly, the same treatment was far less efficacious in immunocompromised severe combined immunodeficient mice, indicating the requirement of intact host immunity. Our results introduce a new concept that VBL may be used to design “immunostimulatory” chemotherapy regimens. [Cancer Res 2009;69(17):6987–94]
Absorption and metabolism of oral progesterone.
Authors: M I Whitehead, P T Townsend, D K Gill, W P Collins, S Campbell
Journal: BMJ (1980)

The absorption, metabolism, and clearance of progesterone from the peripheral circulation were investigated in five postmenopausal women after oral administration of 100 mg daily for five consecutive days. Maximal plasma concentrations of progesterone were observed within four hours after ingestion of the last dose, when the range (22.11-34.18 nmol/l; 696-1077 ng/100 ml) was comparable with that observed during the mid-luteal phase of the ovarian cycle. The surge in values lasted six hours, and progesterone concentrations remained raised for at least 96 hours. Of the three metabolites studied, the plasma concentrations of pregnanediol-3 alpha-glucuronide were most raised by treatment, the peak values ranging from 1097 nmol/l (54.9 microgram/100 ml) to over 2000 nmol/l (100 microgram/100 ml), which was the upper limit of the assay used. Concentrations of 17-hydroxyprogesterone were least raised, and the peak values ranged from 4.32 to 9.68 nmol/l (143-319 ng/100 ml). The plasma profile of 20 alpha-dihydroprogesterone most closely approximated that of progesterone, although the range of maximal values was lower (7.11-16.06 nmol/l; 228-514 ng/100 ml). Plasma concentrations of oestradiol were unchanged by giving progesterone. It is concluded that the increases in circulating concentrations of progesterone and the biologically active metabolite 20 alpha-dihydroprogesterone, and the duration of these increases, were sufficient to modulate the biochemistry of responsive tissues. Oral progesterone may thus have a therapeutic role, and this route of administration merits further investigation.
Controlled Trial Comparing Effect of Two and Six Weeks' Treatment in Recurrent Urinary Tract Infection
Authors: P. Kincaid-Smith, K. F. Fairley
Journal: BMJ (1969)

Patients with recurrent urinary tract infection were allocated at random to two weeks9 or six weeks9 treatment with an appropriate antibacterial drug. There was no difference in the results achieved by the two different periods of treatment as judged by the presence of infection in the urine one week and six weeks after treatment was stopped. The urine was clear of infection in a higher percentage of patients following a course of nitrofurantoin than following a course of ampicillin, but the difference was not significant.
Urinary NMP22&lt;sup&gt;TM&lt;/sup&gt; and Karyometry in the Diagnosis and Follow-Up of Patients with Superficial Bladder Cancer
Authors: J.A. Witjes, H.G. van der Poel, M.R. van Balken, F.M.J. Debruyne, J.A. Schalken
Journal: European Urology (1998)
Renal-Clip Hypertension in Rabbits Immunized Against Angiotensin II
Authors: GRAHAM J. MACDONALD, WILLIAM J. LOUIS, VINCENZO RENZINI, GRAHAM W. BOYD, W. STANLEY PEART
Journal: Circulation Research (1970)

The rabbit immunized against angiotensin II was shown to be a valid model for the study of renal-clip hypertension. In particular, there was a specific and complete blockade of the pressor effect of high doses of intravenous renin and angiotensin in vivo, even at angiotensin II production rates which far exceeded those associated with renal-clip hypertension. Despite this, four immunized rabbits developed hypertension after renal-artery clipping with contralateral nephrectomy, and in three of these the hypertension was severe. In four other rabbits, there was no evidence of modification of an established hypertension after immunization against angiotensin II. In both groups, the specific absence of pressor response to high doses of renin and angiotensin II after immunization was confirmed. These studies provide strong evidence that angiotensin is not the sole or even the major factor in either the initiation or maintenance of this form of hypertension.
<i>TMPRSS2</i>:<i>ERG</i> Fusion Identifies a Subgroup of Prostate Cancers with a Favorable Prognosis
Authors: Outi R. Saramäki, Anna E. Harjula, Paula M. Martikainen, Robert L. Vessella, Teuvo L.J. Tammela, Tapio Visakorpi
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Our aim was to assess the frequency of ERG overexpression and TMPRSS2:ERG rearrangement in prostate cancer and their association with clinicopathologic variables and outcome. Experimental Design: The presence of the TMPRSS2:ERG rearrangement was studied by reverse transcription-PCR and fluorescence in situ hybridization in 19 prostate cancer xenografts and 7 prostate cancer cell lines. The expression of ERG was studied in the xenografts and cell lines and in 49 freshly frozen clinical prostate samples by quantitative reverse transcription-PCR. The frequency of the TMPRSS2:ERG fusion in clinical prostate cancer (n = 253) on tissue microarrays was assessed by three-color fluorescence in situ hybridization. Results: Seven of 19 (37%) of the xenografts overexpressed ERG and had TMPRSS2:ERG rearrangement. Two xenografts, representing small cell carcinomas, also contained the fusion but did not express ERG. In clinical tumor specimens, the overexpression of ERG was associated with the rearrangement (P = 0.0019). Fifty of 150 (33%) of the prostatectomy specimens and 28 of 76 (37%) of the hormone-refractory prostate cancers on the tissue microarrays carried the TMPRSS2:ERG rearrangement. It was associated with longer progression-free survival in patients treated by prostatectomy (P = 0.019), and according to multivariate analysis, it was an independent predictor of favorable outcome (relative risk, 0.54; 95% confidence interval, 0.30-0.98). The fusion was not associated with Gleason score, pT stage, diagnostic prostate-specific antigen, or cell proliferation activity in prostatectomy specimens nor with the AR gene amplification in hormone-refractory tumors. Conclusions: The TMPRSS2:ERG rearrangement can be found in about one third of prostate cancers. A subgroup of prostate cancer patients with a good prognosis may be identified by the rearrangement.
Uninsured Children
Authors: Stephen Berman
Journal: JAMA (1995)

How well does our current health care system care for children? The article by Kogan et al<sup>1</sup>in this issue ofTHE JOURNALprovides information needed to answer this critical question. The article increases our understanding of three key issues related to health care system reform for children: first, the health impact of gaps in insurance coverage for young children; second, the extent of the problem with respect to the number of children affected and the duration of their gap in coverage; and third, the sociodemographic characteristics of children and families most likely to experience gaps in coverage. <h3>Understanding the Health Impact of Gaps in Insurance Coverage</h3> Having a gap in coverage affects access to and quality of needed medical care through two pathways: first, it requires financially strapped families to pay out-of-pocket for services; and second, it makes maintaining a continuous relationship with a primary care physician much
Randomized Double-Blind Comparison of Two Doses of Hirulog With Heparin as Adjunctive Therapy to Streptokinase to Promote Early Patency of the Infarct-Related Artery in Acute Myocardial Infarction
Authors: Pierre Théroux, Félix Pérez-Villa, David Waters, Jacques Lespérance, Faryala Shabani, Raoul Bonan
Journal: Circulation (1995)

Background An improved survival rate is a consequence of successful reperfusion of the infarct-related artery. This double- blind, randomized trial investigated the potential of Hirulog, a direct thrombin inhibitor, to improve the early patency rates obtained with streptokinase and aspirin. Methods and Results Angiographic patency of the culprit coronary artery lesion was assessed 90 and 120 minutes after the initiation of streptokinase and aspirin and again after 4±2 days in 68 patients with acute myocardial infarction. Patients were randomized to Hirulog 0.5 mg/kg per hour for 12 hours followed by 0.1 mg/kg per hour (low dose), Hirulog 1.0 mg/kg per hour for 12 hours followed by placebo (high dose), or to heparin 5000 U bolus followed by 1000 U/h titrated to an activated partial thromboplastin time (aPTT) 2 to 2.5 times control after 12 hours. At 90 minutes, TIMI flow grade 2 or 3 was observed in 96% of patients treated with the low dose of Hirulog, in 79% with the high dose, and in 46% with heparin ( P =.006) and TIMI flow grade 3 was observed in 85%, 61%, and 31% of patients, respectively ( P =.008). At 120 minutes, these figures were 100%, 82%, and 62% for TIMI flow grades 2 and 3 ( P =.046) and 92%, 68%, and 46% for TIMI flow grade 3 ( P =.014). At 90 minutes, the relative risk for restoring TIMI flow grade 3 was 2.77 with Hirulog 0.5 mg/kg per hour compared with heparin (95% confidence limits, 1.21 to 6.35; P &lt;.001) and 1.4 compared with Hirulog 1.0 mg/kg per minute (95% confidence limits, 1.00 to 1.51; P =.04). Patients who received a placebo infusion after 12 hours experienced more clinical events and reocclusion during the following 4 days than patients in the other two groups. Conclusion Hirulog yields higher early patency rates in the culprit coronary artery than heparin when used as adjunctive therapy to streptokinase and aspirin in the early phase of acute myocardial infarction. High doses are not required and may be less effective than lower doses, which suggests that too much thrombin inhibition may be harmful.
Excessive hospital and one-year mortality in diabetics compared to nondiabetics with non-ST elevation myocardial infarction in clinical practice: Results of the ACOS-registry
Authors: Anselm K. Gritt, Rudolf Schiele, Harm Wienbergen, Steffen Schneider, Tobias Heer, Martin G. Gottwik, Jochen Senges
Journal: Journal of the American College of Cardiology (2003)