tbuckley/cabot-search huggingface dataset:
Abstract 180: Suppressor of cytokine signaling 6 (SOCS6) induces apoptosis through promoting mitochondrial fragmentation and Bax activation
Authors: Huan-Yu Lin, Chung-Chih Lin, Hsin-Chen Lee, Fung-Fang Wang, Jeou-Yuan Chen
Journal: Cancer Research (2011)

Abstract Mitochondria are highly motile organelles that constantly undergo fission and fusion. Impairment of mitochondrial dynamics is associated with mitochondrial dysfunction and frequently linked to the pathogenesis of neurodegenerative diseases and cancer. We have previously shown that loss-of-function of suppressor of cytokine signaling 6 (SOCS6) is a frequent event in human gastric cancer. In this study, we recapitulated the event of loss of SOCS6 in cancer-derived cell lines where endogenous SOCS6 was expressed, and we showed that elimination of SOCS6 expression delays UV-induced apoptosis process. By contrast, overexpression of SOCS6 in cancer cell lines that express endogenous SOCS6 at minimal levels promotes apoptosis. SOCS6 induces intrinsic apoptotic process and facilitates cytochrome c release by enhancing Bax conformational change, mitochondrial targeting and oligomerization. We further demonstrated that SOCS6 is a novel mitochondrial protein that regulates mitochondrial dynamics. By confocal microscopy, we showed that ectopically expressed SOCS6 is predominantly localized in mitochondria, and the carboxyl-terminal SOCS box is important for its mitochondrial localization. Localization of SOCS6 in mitochondria is accompanied with concomitant mitochondrial fragmentation, both of which can be reversed by coexpression of mitochondrial fusion proteins (Mfn1 and Mfn2) or a dominant-negative form of Drp1. Ectopic expression of SOCS6 severely impairs the dynamics and function of mitochondria. Taken together, our data suggest that SOCS6 is a novel mitochondrial protein that induces intrinsic apoptosis pathway through perturbing mitochondrial dynamics and facilitating Bax activation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 180. doi:10.1158/1538-7445.AM2011-180
Natural history of bronchial asthma in childhood A prospective study from birth up to 12–14 years of age
Authors: S. Croner, N‐I. M. Kjellman
Journal: Allergy (1992)

In a cohort of 1654 consecutively born children followed from birth, the cumulated incidence of asthma up to 11 years was 5.3% and the prevalence 3% between 10 and 11 years of age. The asthma début was prior to 1.5 years in 1/3 and before 3 years in 1/2 of the children. Among 59 children examined at 11.5-14.5 years of age, 16 (27%) had no prevalent asthma. On the other hand, inadequate medication was found in 13, undiagnosed chest deformity in four, and wheezing in seven children. All 54 tested children including those with no prevalent asthma had a PC20 histamine less than 8 mg/ml. Tread mill test gave a significant reaction in 15 children. Animal danders and pollens were the most common allergens giving reactions at skin prick test. Compared to one earlier Swedish study an increase in mite sensitivity was found. Cord-blood IgE concentration and a positive immediate family history of atopic disease had no predictive value for the severity of asthma at this follow-up. A new total asthma score including number of days with functional impact of asthma during the last year and present medication was used for group comparisons. Children with a high score at 11.5-14.5 years had more exercise-induced asthma, more concomitant allergic diseases, earlier asthma start, more chest deformity, hyperreactivity both on tread mill and histamine challenge tests, elevated IgE, positive Phadiatop and more reactions at skin prick test, especially to animals and mites. Bronchial asthma was found more often in children born during August through October, possibly due to unsuitable indoor climate and more virus infections during their first 6 months of life. The severity of the asthma was, however, not influenced by the month of birth. No significant differences were found between boys and girls regarding the age at début, asthma severity at follow-up, or bronchial histamine threshold levels.
Program on Realities of Medicine
Authors: Constance C. Conrad
Journal: JAMA (1983)

<h3>To the Editor.—</h3> We were interested in reading " 'Realities of Medicine': A Week of the Future" (1982;248:2090) and delighted to hear of the success of the program described. In reviewing the course content, we discovered that much of the same material is offered in our community health course for freshmen medical students. Our course meets four hours a week for 15 weeks and is organized around a format of lectures, small-group discussions, and field experiences. The course outline is focused on four areas: The Health Care Delivery System, Social Support Structures in Health and Disease, Health Care and the Larger Society, and The Challenge of Prevention. Some of the subjects included in lectures include an overview of the US health care system, environmental and occupational health, health data, international comparisons of health care systems, and a session on the medical consequences of nuclear war. One of the most popular sessions
Diagnostic Decision
Authors: ALLAN S. TROUPIN
Journal: Annals of Internal Medicine (1984)

Monitoring levels of antiepileptic drugs is useful in formulating a therapeutic plan but not in making a diagnosis. Differences in assay methods are not important. Differences in therapeutic ranges do not reflect procedural differences but merely the source that is quoted. Therapeutic ranges are not absolute criteria for therapy, but guides to a clinical balance between dose and side effects. Because therapeutic ranges reflect trough (early morning) serum levels, clinical determinations should be done at this time. Serum drug determinations should be used to establish the successful drug level for a patient; assess compliance; identify the relative contributions of each drug to efficacy and to side effects in complex programs; identify bioavailability problems; and characterize idiosyncrasies in the rate of drug metabolism.
Theγ-Glutamyl Cycle
Authors: A. MEISTER
Journal: Annals of Internal Medicine (1974)

The γ-glutamyl cycle consists of six enzyme-catalyzed reactions that account for the synthesis and degradation of glutathione, a tripeptide that is found in virtually all living cells. It has been proposed that the γ-glutamyl cycle functions in the transport of amino acids across cell membranes. The status of research on the γ-glutamyl cycle is considered. There is evidence that the cycle functions in the kidney and in other tissues. Patients with diseases associated with a deficiency of a specific enzyme of the γ-glutamyl cycle have been found, and the nature of the biochemical defects has been explored.
Abstract B4: Elevated expression of c-FLIP in castrate-resistant prostate cancer antagonizes response to androgen receptor-targeted therapy
Authors: Clare McCourt, Pamela Maxwell, Roberta Mazzucchelli, Manuel Salto-Tellez, Joe O'Sullivan, Rodolfo Montironi, Marina Scarpelli, Daniel Longley, David Waugh
Journal: Cancer Research (2012)

Abstract Cellular Fas-associated death domain (FADD)-like interleukin 1β-converting enzyme (FLICE) inhibitory protein (c-FLIP) is a key inhibitor of caspase 8 (FLICE)-promoted apoptosis. We have previously shown c-FLIP to be a transcriptional target of the androgen receptor (AR) and NF-κB. Accordingly, we proposed that cells with elevated expression of c-FLIP may remain viable and withstand androgen-deprivation. Expression of c-FLIP was assessed in prostatectomy tissue while in vitro experiments were performed to determine its importance in regulating response to the androgen receptor (AR)-targeted therapeutic bicalutamide. c-FLIP expression was increased in pre-malignant prostatic intra-epithelial neoplasia (PIN) (P&amp;lt;0.001) and each of Gleason 3 and Gleason 4 prostate cancer (CaP) tissue (P&amp;lt;0.001) relative to normal prostate epithelium. Maximal expression of c-FLIP was detected in castrate-resistant prostate cancer (CRPC) (P&amp;lt;0.001 relative to Gleason 3/4 cancer. In vitro, siRNA-mediated silencing of c-FLIP in 22Rv1 and LNCaP cells induced spontaneous apoptosis and increased their response to bicalutamide, determined by flow cytometry, PARP cleavage and caspase activity assays. Two histone deacetylase inhibitors (HDACi), droxinostat and SAHA, were also shown to down-regulate c-FLIP expression, resulting in caspase-8 and caspase-3/7 mediated apoptosis. HDACi also potentiated the sensitivity of 22Rv1 cells to bicalutamide, while maximal apoptosis induction in LNCaP cells was not changed in the presence of bicalutamide. The combination of SAHA and bicalutamide promoted cell-specific inhibition of the AR or NF-κB signaling pathways consistent with decreased transcription of c-FLIP in these cells. Conversely, the elevated expression of c-FLIP and Bcl-2 was consistent with the insensitivity of the castrate-resistant VCaP cell line to SAHA in vitro, and the sub-optimal performance of this class of agents in castrate-resistant patients. Therefore, HDACi may prove more effective in enhancing androgen-deprivation therapy (ADT) in early-stage disease. Moreover, c-FLIP expression may serve as a predictive biomarker for androgen-deprivation strategies including bicalutamide. Citation Format: Clare McCourt, Pamela Maxwell, Roberta Mazzucchelli, Manuel Salto-Tellez, Joe O'Sullivan, Rodolfo Montironi, Marina Scarpelli, Daniel Longley, David Waugh. Elevated expression of c-FLIP in castrate-resistant prostate cancer antagonizes response to androgen receptor-targeted therapy [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B4.
Arthritis associated with hidradenitis suppurativa.
Authors: R Bhalla, W Sequeira
Journal: Annals of the Rheumatic Diseases (1994)

To review the presentation and clinical findings of arthritis associated with hidradenitis suppurativa.Medical records from the rheumatology clinics of two major teaching hospitals were reviewed for arthritis and hidradenitis suppurativa. The nine patient records fulfilling these criteria were reviewed and compared with 20 previous reports.The arthritis associated with hidradenitis suppurativa is rare and most commonly affects the peripheral joints. The axial skeleton is less frequently involved and is often asymptomatic.
Anaesthesia for Bronchoscopy
Authors: I. C. W. English, R. E. Loder, C. Parish
Journal: BMJ (1959)

symptoms became apparent, but this may have been due to the rapidity with which I have administered the drug.Macdonald and Watts and Madgwick1 have commented on the fact that the " build-up " must be gradual, and my rapid method of treatment probably predisposed to side-effects.Circumstances, however, did not permit waiting for any length of time before I was forced to transfer patients.It was possible to reduce the drug, after the initial good effects were obtained, to 5-10 mg. per day, but I have found that the patients must be maintained regularly on the drug or else symptoms recur.At this low level of dosage side-effects are negligible.Manic and paranoid patients have responded well, but no effect was seen in depressed cases.The agitated patient is rapidly controlled and the results have encouraged me to continue with this form of therapy.No difference was noted between the sexes, and I have observed no jaundice, dermatitis, or blood dyscrasias.I consider that trifluoperazine is extremely useful for agitated senile patients and that in all probability it will control effectively senile patients who become difficult and unmanageable, and thus relieve the pressure on the beds in mental institutions.-I am, etc.,
Asbestos, asbestosis, and lung cancer: observations in Quebec chrysotile workers.
Authors: B W Case, A Dufresne
Journal: Environmental Health Perspectives (1997)

One prospective epidemiologic study of asbestos cement workers with radiological small opacities has been cited as a rationale for attributing excess lung cancer to asbestosis. This approach could have considerable practical value for disease attribution in an era of decreasing exposure. However, a recent International Agency for Research on Cancer review concludes that the mechanism of production of asbestos-related lung cancer are unknown. Asbestosis, therefore, cannot be a biologically effective dose marker of lung cancer susceptibility. Asbestosis nonetheless would be useful in identifying asbestos-attributable lung cancer cases if it could be proven an infallible exposure indicator. In this study, we tested this hypothesis in the chrysotile miners and millers of Quebec, Canada. We examined exposure histories, autopsy records, and lung fiber content for 111 Quebec chrysotile miners and millers. If the hypothesis of an asbestosis requirement for lung cancer attribution were accurate, we would expect as asbestosis diagnosis to separate those with lung cancer and high levels of exposure from those with lower levels of exposure in a specific and sensitive manner. This is the first such study in which historical job-based individual estimates based on environmental measurements, lung fiber content, exposure timing, and complete pathology records including autopsies were available for review. We found significant excesses of lung tremolite and chrysotile and estimated cumulative exposure in those with lung cancer and asbestosis compared to those with lung cancer without asbestosis. However, when the latter were directly compared on a case-by-case basis, there was a marked overlap between lung cancer cases with and without asbestosis regardless of the measure of exposure. Smoking habits did not differ between lung cancer cases with and without asbestosis. In regression models, smoking pack-years discriminated between those with the without lung cancer, regardless of asbestosis status. Most seriously, the pathologic diagnosis of asbestosis itself seemed arbitrary in many cases. We conclude that although the presence of pathologically diagnosed asbestosis is a useful marker of exposure, the absence of this disease must be regarded as one of many factors in determining individual exposure status and disease causation.
Abstract 4184: Expression analysis of iPS inductive gene in gastrointestinal cancer by tissue microarray
Authors: Shinichi Sekine, Yutaka Shimada, Tomoyuki Okumura, Soshi Osawa, Makoto Moriyama, Koshi Matsui, Shigeaki Sawada, Takuya Nagata, Junya Fukuoka, Kazuhiro Tsukada
Journal: Cancer Research (2011)

Abstract Background: Recent progress is enabling us to induce iPS cells using somatic differentiated cells. We are now establishing iPS cells from normal gastrointestinal epithelial cells. However, the risks associated with transfection of iPS inductive genes (Sox2, Oct 3/4, klf4 and c-Myc) to somatic differentiated cells has not been well examined. Thus, in order to understand the role of iPS inductive genes in gastrointestinal cancer, we examined the expression of Sox2, Oct3/4, klf4, c-Myc and Nanog by cancer tissue microarray. Methods: We examined gene expression in 86 esophageal cancers, 50 gastric cancers, 80 colorectal cancers, 37 biliary tract cancers and 34 pancreatic cancers. Immunohistochemical expression levels of 5 genes were evaluated by the combination of their intensity and distribution. The expression level was compared to the clinico-pathological data of the patients. Results: Klf4 reduction was associated with lymph node metastasis of colorectal cancer which resulted in a poor prognosis for the patients (p=0.02). Klf4 reduction also tended to indicate a poor prognosis in esophageal cancer (P=0.06). Furthermore, Sox2 reduction was an independent prognostic factor in gastric cancer (p=0.03) and a high expression of OCT3/4 tended to indicate a poor prognosis in esophageal cancer (p=0.07). Nanog reduction was associated with poor prognosis in biliary tract and pancreatic cancer(p=0.02). On the other hand, c-Myc did not have any association with clinico-pathological factors of gastrointestinal cancer. Clustering analysis revealed that prognosis of the subgroup of simultaneous positive expressions of iPS inductive genes was better than that of other subgroups in colon cancer, however there was no difference among subtypes in esophageal cancer. Conclusions: The role of iPS inductive genes may differ in various gastroenterological cancer patients. However, further large-scale analysis is needed to elucidate this issue. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4184. doi:10.1158/1538-7445.AM2011-4184
Tissue-Engineered Bone Serves as a Target for Metastasis of Human Breast Cancer in a Mouse Model
Authors: Jodie E. Moreau, Kristen Anderson, Joshua R. Mauney, Trang Nguyen, David L. Kaplan, Michael Rosenblatt
Journal: Cancer Research (2007)

The high frequency and mortality associated with breast cancer metastasis to bone has motivated efforts to elucidate tumor-stroma interactions in the bone microenvironment contributing to invasion and proliferation of metastatic cells. The development of engineered tissues has prompted the integration of engineered bone scaffolds into animal models as potential targets for metastatic spread. Silk scaffolds were coupled with bone morphogenetic protein-2 (BMP-2), seeded with bone marrow stromal cells (BMSC), and maintained in culture for 7 weeks, 4 weeks, and 1 day before s.c. implant in a mouse model of human breast cancer metastasis from the orthotopic site. Following injection of SUM1315 cells into mouse mammary fat pads, tumor burden of implanted tissues was observed only in 1-day scaffolds. Scaffold development and implantation was then reinitiated to identify the elements of the engineered bone that contribute to metastatic spread. Untreated scaffolds were compared with BMP-2-coupled, BMSC-seeded, or BMP-2/BMSC-combined treatment. Migration of SUM1315 cells was detected in four of four mice bearing scaffolds with BMP-2 treatment and with BMSC treatment, respectively, whereas only one of six mice of the BMP-2/BMSC combination showed evidence of metastatic spread. Histology confirmed active matrix modeling and stromal cell/fibroblast infiltration in scaffolds positive for the presence of metastasis. These results show the first successful integration of engineered tissues in a model system of human breast cancer metastasis. This novel platform now can be used in continued investigation of the bone environment and stem cell contributions to the process of breast cancer metastasis.
Cancer of the urogenital tract: bladder cancer. Comment: the accuracy of staging for combined therapies
Authors: P. Rubin
Journal: JAMA (1969)

With the increasing trend toward combined therapies in clinical, oncologic, investigational protocols, there is a demand for greater accuracy in staging the true extent of the cancer at the initiation of treatment. The development of a clinical form of staging is often passed over in favor of the greater accuracy of surgical evaluation. The surgical evaluation is coupled with pathological examination, further refining the accuracy of anatomic staging. However, with the application of preoperative adjuvants such as irradiation therapy and chemical agents, an alteration of staging occurs and renders surgical staging meaningless unless it is compared to a pretreatment evaluation. The obstacles to an acceptable clinical staging relate to a few key points. First, a classification must be precise, simple, and meaningful so that it can be applied generally in practice and reporting. Second, the diagnostic procedures which are used in arriving at a clinical staging must be defined and
Breast cancer screening with mammography: overview of Swedish randomised trials
Authors: L. Nyström, S. Wall, L.E. Rutqvist, A. Lindgren, M. Lindqvist, S. Rydén, J. Andersson, N. Bjurstam, G. Fagerberg, J. Frisell, L. Tabár, L.-G. Larsson
Journal: The Lancet (1993)
Delayed Ischemic Preconditioning Activates Nuclear-Encoded Electron-Transfer-Chain Gene Expression in Parallel With Enhanced Postanoxic Mitochondrial Respiratory Recovery
Authors: Christopher J. McLeod, Anandhi P. Jeyabalan, Jan O. Minners, Randall Clevenger, Robert F. Hoyt, Michael N. Sack
Journal: Circulation (2004)

Delayed ischemic preconditioning promotes cardioprotection via genomic reprogramming. We hypothesize that molecular regulation of mitochondrial energetics is integral to this cardioprotective program.Preconditioning was induced by use of 3 episodes of 3-minute coronary artery occlusion separated by 5 minutes of reperfusion. Twenty-four hours later, infarct size was reduced by 58% after preconditioning compared with sham-operated controls (P<0.001). Cardiac mitochondria were isolated from sham and preconditioned rat hearts. Mitochondrial respiration and ATP production were similar between the groups; however, preconditioned mitochondria exhibit modest hyperpolarization of the inner mitochondrial membrane potential (> or =22% versus control, P<0.001). After 35-minute anoxia and reoxygenation, preconditioned mitochondria demonstrated a 191+/-12% improvement in ADP-sensitive respiration (P=0.002) with preservation of electron-transfer-chain (ETC) activity versus controls. This augmented mitochondrial recovery was eradicated when preconditioning was abolished by the antioxidant 2-mercaptopropionyl glycine (2-MPG). These biochemical modulations appear to be regulated at the genomic level in that the expression of genes encoding rate-controlling complexes in the ETC was significantly upregulated in preconditioned myocardium, with a concordant induction of steady-state protein levels of cytochrome oxidase, cytochrome c, and adenine nucleotide translocase-1. 2-MPG abolished preconditioning induction of these transcripts. Moreover, transcripts of nuclear regulatory peptides known to orchestrate mitochondrial biogenesis, nuclear respiratory factor-1 and peroxisome-proliferator-activated receptor gamma coactivator 1alpha, were significantly induced in preconditioned myocardium.Delayed preconditioned mitochondria display increased tolerance against anoxia-reoxygenation in association with modifications in mitochondrial bioenergetics, with concordant genomic induction of a mitochondrial energetic gene regulatory program. This program appears to be mediated by reactive oxygen species signaling.
Air in the Portal and Mesenteric Veins
Authors: Diego de Mendoza-Asensi, Kenneth Planas
Journal: New England Journal of Medicine (2009)

A 73-year-old man with history of smoking, hypertension, chronic obstructive pulmonary disease, and type 2 diabetes mellitus presented with respiratory distress. The trachea was intubated, and the patient was admitted to the intensive care unit. On the eighth day of hospitalization, atrial fibrillation developed, with associated hypotension, lactic acidosis, and mild elevation of liver enzymes (alanine aminotransferase, 190 U per liter; aspartate aminotransferase, 220 U per liter) and plasma amylase (140 mg per deciliter). The physical examination showed abdominal distention and regurgitation of enteral-tube nutrients. Computed tomography of the abdomen showed gas in the intrahepatic portal veins (Panel A, arrows), . . .