tbuckley/cabot-search huggingface dataset:
Evidence for Excessive Bronchial Inflammation during an Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Patients with α<sub>1</sub>-Antitrypsin Deficiency (PiZ)
Authors: ADAM T. HILL, EDWARD J. CAMPBELL, DARREN L. BAYLEY, SUSAN L. HILL, ROBERT A. STOCKLEY
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Patients with homozygous (PiZ) α1-antitrypsin (AAT) deficiency have not only low baseline serum AAT levels (approximately 10 to 15% normal) but also an attenuated acute phase response. They are susceptible to the development of premature emphysema but may also be particularly susceptible to lung damage during bacterial exacerbations when there will be a significant neutrophil influx. The purposes of the present study were to assess the inflammatory nature of acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) in subjects with AAT deficiency, to compare this with COPD patients without deficiency, and to monitor the inflammatory process and its resolution following appropriate antibacterial therapy. At the start of the exacerbation, patients with AAT deficiency had lower sputum AAT (p < 0.001) and secretory leukoprotease inhibitor (SLPI; p = 0.02) with higher elastase activity (p = 0.02) compared with COPD patients without deficiency. Both groups had a comparable acute phase response as assessed by C-reactive protein (CRP) but the AAT-deficient patients had a minimal rise in serum AAT (to < 6 μ M). After treatment with antibiotics, in patients with AAT deficiency, there were significant changes in many sputum proteins including a rise in SLPI levels, and a reduction in myeloperoxidase (MPO) and elastase activity (p < 0.005 for all measures); the sputum chemoattractants interleukin-8 (IL-8) and leukotriene B4 (LTB4) fell (p < 0.01), and protein leak (sputum/serum albumin ratio) became lower (p < 0.01). The changes were rapid and within 3 d of the commencement of antibiotic therapy the biochemical markers had decreased significantly, but took a variable time thereafter to return to baseline values. In conclusion, patients with AAT deficiency had evidence of increased elastase activity at the start of the exacerbation when compared with nondeficient COPD patients which probably reflects a deficient antiproteinase screen (lower sputum AAT and SLPI). The increased bronchial inflammation at presentation resolved rapidly with 14 d of antibiotic therapy. Hill AT, Campbell EJ, Bayley DL, Hill SL, Stockley RA. Evidence for excessive bronchial inflammation during an acute exacerbation of chronic obstructive pulmonary disease in patients with α1-antitrypsin deficiency (PiZ).
Bortezomib Primes Glioblastoma, Including Glioblastoma Stem Cells, for TRAIL by Increasing tBid Stability and Mitochondrial Apoptosis
Authors: Thomas Unterkircher, Silvia Cristofanon, Sri Hari Krishna Vellanki, Lisa Nonnenmacher, Georg Karpel-Massler, Christian Rainer Wirtz, Klaus-Michael Debatin, Simone Fulda
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Searching for novel approaches to sensitize glioblastoma for cell death, we investigated the proteasome inhibitor bortezomib. Experimental Design: The effect of bortezomib on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)–induced apoptosis signaling pathways was analyzed in glioblastoma cell lines, primary glioblastoma cultures, and in an in vivo model. Results: Bortezomib and TRAIL synergistically trigger cell death and reduce colony formation of glioblastoma cells (combination index &amp;lt; 0.1). Investigations into the underlying molecular mechanisms reveal that bortezomib and TRAIL act in concert to cause accumulation of tBid, the active cleavage product of Bid. Also, the stability of TRAIL-derived tBid markedly increases on proteasome inhibition. Notably, knockdown of Bid significantly decreases bortezomib- and TRAIL-mediated cell death. By comparison, silencing of Noxa, which is also upregulated by bortezomib, does not confer protection. Coinciding with tBid accumulation, the activation of Bax/Bak and loss of mitochondrial membrane potential are strongly increased in cotreated cells. Overexpression of Bcl-2 significantly reduces mitochondrial perturbations and cell death, underscoring the functional relevance of the mitochondrial pathway. In addition, bortezomib cooperates with TRAIL to reduce colony formation of glioblastoma cells, showing an effect on long-term survival. Of note, bortezomib profoundly enhances TRAIL-triggered cell death in primary cultured glioblastoma cells and in patient-derived glioblastoma stem cells, underlining the clinical relevance. Importantly, bortezomib cooperates with TRAIL to suppress tumor growth in an in vivo glioblastoma model. Conclusion: These findings provide compelling evidence that the combination of bortezomib and TRAIL presents a promising novel strategy to trigger cell death in glioblastoma, including glioblastoma stem cells, which warrants further investigation. Clin Cancer Res; 17(12); 4019–30. ©2011 AACR.
CONTINUED FOLLOW-UP RESULTS IN INSULIN-SHOCK THERAPY AND IN CONTROL CASES
Authors: EARL D. BOND
Journal: American Journal of Psychiatry (1941)

This is a study of one hospital working out for itself answers to questions raised by the use of insulin-shock in schizophrenia. At the Pennsylvania Hospital there have been immediate and important gains in one-half of all patients, and in two-thirds of acute cases (less than 18 months in duration). After two years these gains remained in only one-fourth of all patients, but in one-half of the acute cases. Control cases in the same hospital were found to show similar gains, two years from the time of admission, in one-sixth of all cases. These gains were without important relation to the previous duration of illness. The experience of one hospital indicates that insulin-shock is a strikingly effective agent in schizophrenia. It also indicates a need for supportive measures to hold more firmly the gains that come quickly but which often tend to disappear.
Abstract 2290: Rational targeting of inhibitor of apoptosis proteins (IAPs) for effective therapy of colorectal cancer
Authors: Nyree T. Crawford, Philip D. Dunne, Patrick G. Johnston, David J. Waugh, Daniel B. Longley
Journal: Cancer Research (2014)

Abstract Background Inhibitor of Apoptosis Proteins (IAPs) are anti-apoptotic proteins which suppress the activation of caspases. IAP proteins have been shown to be overexpressed in several cancers, including colorectal cancer and correlate with poor prognosis. SMAC mimetics are a class of apoptosis inducing drugs that target IAPs by mimicking the N-terminal IAP-binding motif of SMAC. Colorectal cancer has a pro-inflammatory microenvironment with high levels of TNFα. The aims of this study were to assess the efficacy of SMAC mimetic treatment in colorectal cancer. Methods Colorectal cell lines were treated with SMAC mimetics and cell viability was determined using MTT assays. Apoptosis was assessed by Western blotting for caspase activation and PARP cleavage and Flow Cytometry using Annexin V/PI staining. Protein-protein interactions were assessed using co-immunoprecipitation experiments. The pro-inflammatory microenvironment was modelled by addition of exogenous TNFα and also media transfer from and direct co-cultures with macrophages (THP-1, monocytic cell line). Results Colorectal cell lines were resistant to SMAC mimetic treatment alone unless co-cultured with TNFα. Pretreatment of colorectal cancer cells with 5-FU and oxaliplatin sensitised the cells to SMAC mimetic treatment. THP-1 cells were found to secrete soluble TNFα and media transfer experiments and also co-culture with colorectal cell lines, sensitised the cancer cells to SMAC mimetic mediated cell death. Cell death under these conditions was found to be dependent on soluble TNFα through the utilisation of neutralising antibodies. Conclusion Our results to date suggest that the pro-inflammatory microenvironment of colorectal cancer could be exploited to target overexpressed IAP proteins leading to cell death. Citation Format: Nyree T. Crawford, Philip D. Dunne, Patrick G. Johnston, David J. Waugh, Daniel B. Longley. Rational targeting of inhibitor of apoptosis proteins (IAPs) for effective therapy of colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2290. doi:10.1158/1538-7445.AM2014-2290
Reduction of enzyme levels by propranolol after acute myocardial infarction.
Authors: T Peter, R M Norris, E D Clarke, M K Heng, B N Singh, B Williams, D R Howell, P K Ambler
Journal: Circulation (1978)

The effect of propranolol (0.1 mg/kg intravenously followed by 320 mg given over 27 hour orally) on serum levels of creatine kinase enzyme was studied in a randomized trial involving 95 patients seen within 12 hours of onset of symptoms of uncomplicated myocardial infarction. In 15 patients who were treated with propranolol within 4 hours of onset, and who eventually developed pathological Q waves, peak measured enzyme levels were 27% (P less than 0.0125) lower than in 19 control patients who were also seen within 4 hours of the onset but had no specific treatment. Total calculated enzyme appearance was also lower in the treated patients (reduced 25%, P less than 0.05) as was the calculated rate of the appearance (33%, P less than 0.005). No significant difference was found for treated compared with control patients entering the trial more than 4 hours after the onset of chest pain. This evidence suggests that propranolol may reduce the size of uncomplicated infarctions if it is given intravenously within 4 hours of the onset.
WEIGHT LOSS, SALINE LOADING, AND THE NATRIURETIC PEPTIDE SYSTEM
Authors: Pankaj Arora, Jason Reingold, Aaron Baggish, Derek Guanaga, Connie Wu, Anahita Ghorbani, Annabel Chen-Tournoux, Abigail Khan, Laurel Tainsh, Emmanuel Buys, Jonathan Williams, Marielle Scherrer-Crosbie, Christopher Newton-Cheh, Lee Kaplan, Thomas Wang
Journal: Journal of the American College of Cardiology (2014)
Abstract 234: Transcription factor LSF is a novel oncogene for hepatocellular carcinoma (HCC)
Authors: Byoung Kwon Yoo, Luni Emdad, Rachel Gredler, Dong Chen, Zhao-zhong Su, Paul B. Fisher, Devanand Sarkar
Journal: Cancer Research (2010)

Abstract While the incidence of overall cancers is decreasing, Hepatocellular Carcinoma (HCC) is one of the few cancers the incidence of which is on an increase. The mortality rate of HCC parallels that of incidence since HCC is a highly aggressive cancer with extremely limited currently available therapeutic strategies. Understanding the molecular mechanism of hepatocarcinogenesis will help develop novel, targeted and more effective therapeutic regimen to counteract this fatal disease. Here, we demonstrate that the cellular transcriptional factor Late SV40 Factor (LSF) functions as an oncogene in HCC. The level of LSF expression is significantly increased in human HCC patients compared to matched non-neoplastic controls and normal liver and LSF expression significantly correlates with the stages and grades of HCC. Ectopic overexpression of LSF in nontumorigenic human HCC cells leads to highly aggressive, multi-organ metastatic tumors while inhibition of LSF in aggressive human HCC cells profoundly inhibits tumorigenic and metastatic properties in athymic nude mice. Affymetrix microarray studies identified novel LSF-downstream genes that are associated with cell growth, angiogenesis, invasion, metastasis, chemoresistance, and senescence. Osteopontin, a key molecule mediating tumor progression, especially metastasis, was identified as a downstream target gene of LSF. Promoter-reporter and chromatin immunoprecipitation analyses confirmed that LSF transcriptionally upregulates OPN by binding to its promoter. Knockdown of OPN gene in LSF-overexpressing HCC cells markedly inhibits LSF-mediated tumor progression including metastasis. This is the first report on the novel function of LSF as an oncogene in any cancer indication. Since LSF expression correlates with the advanced stages of the disease, it might be employed as a diagnostic/prognostic marker for HCC. The DNA binding domain of LSF might be targeted with small molecule inhibitors that might be developed as potential HCC therapeutic. Our findings thus have significant translational implications. 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 234.
Dioxins and Cardiovascular Disease Mortality
Authors: Olivier Humblet, Linda Birnbaum, Eric Rimm, Murray A. Mittleman, Russ Hauser
Journal: Environmental Health Perspectives (2008)

ObjectiveIn this systematic review we evaluated the evidence on the association between dioxin exposure and cardiovascular disease (CVD) mortality in humans.Data sources and extractionWe conducted a PubMed search in December 2007 and considered all English-language epidemiologic studies and their citations regarding dioxin exposure and CVD mortality. To focus on dioxins, we excluded cohorts that were either primarily exposed to polychlorinated biphenyls or from the leather and perfume industries, which include other cardiotoxic coexposures.Data synthesisWe included results from 12 cohorts in the review. Ten cohorts were occupationally exposed. We divided analyses according to two well-recognized criteria of epidemiologic study quality: the accuracy of the exposure assessment, and whether the exposed population was compared with an internal or an external (e.g., general population) reference group. Analyses using internal comparisons with accurate exposure assessments are the highest quality because they minimize both exposure misclassification and confounding due to workers being healthier than the general population ("healthy worker effect"). The studies in the highest-quality group found consistent and significant dose-related increases in ischemic heart disease (IHD) mortality and more modest associations with all-CVD mortality. Their primary limitation was a lack of adjustment for potential confounding by the major risk factors for CVD.ConclusionsThe results of this systematic review suggest that dioxin exposure is associated with mortality from both IHD and all CVD, although more strongly with the former. However, it is not possible to determine the potential bias, if any, from confounding by other risk factors for CVD.
Temporal Relationship and Predictive Value of Urinary Acute Kidney Injury Biomarkers After Pediatric Cardiopulmonary Bypass
Authors: Catherine D. Krawczeski, Stuart L. Goldstein, Jessica G. Woo, Yu Wang, Nuntawan Piyaphanee, Qing Ma, Michael Bennett, Prasad Devarajan
Journal: Journal of the American College of Cardiology (2011)
Cerebral Hypermetabolism Demonstrated by FDG PET in Familial Creutzfeldt-Jakob Disease
Authors: Takamura Nagasaka, Kaori Nagasaka, Emiko Ohta, Kazumasa Shindo, Yoshihisa Takiyama, Zenji Shiozawa, Nobuyuki Miyazawa, Naomi Yamasaki, Nobuhiko Mori, Hideaki Onda, Toyoaki Shinohara
Journal: Clinical Nuclear Medicine (2011)

Right cerebral and contralateral cerebellar hypermetabolism were observed on FDG PET in a 68-year-old woman with familial Creutzfeldt-Jakob disease (CJD) at an early stage before seizures occurred. The disease progressed with frequent seizures, myoclonus, and a startle reaction. In all past reports, FDG PET studies demonstrated hypometabolism in the cerebrum, cerebellum, and thalamus in patients with CJD. Focal hypermetabolism corresponding with epileptic foci is a common finding in ictal epilepsy patients, and hypometabolism is common in patients with myoclonus or the startle reaction. This finding may reflect a prodromal pathophysiology of epilepsy. Attention should be paid to the diagnosis of CJD while using FDG PET.
Glucose Turnover and Disposal in Maturity-Onset Diabetes
Authors: H. F. Bowen, J. A. Moorhouse
Journal: Journal of Clinical Investigation (1973)

The glucose turnover rate in maturity-onset diabetes in man has been variously reported as increased, normal, and decreased. The present experiments suggest that these discrepancies may have been due to methodology, and to nonrecognition of a circadian cycle in the glucose turnover rate that is present in health, and marked in diabetes. During the early morning hours the glucose turnover rate in maturity-onset diabetes is increased in proportion to the fasting blood glucose level. It may reach three to four times the rate found in health. During the evening hours the increments are about one-half as great. The glucose outflow rate constant, k, lower in diabetes than in health, is also lower in both groups in the evening than in the morning. An analysis of the relative contributions of glucose overproduction and underutilization to the development of hyperglycemia in maturity-onset diabetes indicates that overproduction is the greater factor. The relative role of underutilization appears to increase as the fasting blood glucose level increases. The circulating glucose oxidation rate in maturity-onset diabetes is only slightly lower than in health, but the fraction oxidized is markedly lower, and only a small fraction is excreted. The principal conclusion is that in maturity-onset diabetes there is a hypertrophied flux of endogenous glucose, most of which is neither oxidized nor excreted. The precursors and the qualitative and quantitative metabolic fates of this excess glucose are unknown.
Duplication of the Stomach Simulating Pyloric Stenosis
Authors: M. E. R. Stoneman
Journal: BMJ (1958)

Special Investigations.-Thespecific gravity of the urine varied from 1000 to, on one occasion, 1012.More usually it was between 1004 and 1008.It was not possible to carry out a urine concentration test, as the patient could not be deprived of water for a sufficient length of time.M.S.U.: reaction acid; protein nil; reducing substances nil; deposit N.A.D.; cultures sterile.The blood urea was 32 mg./ 100 ml.Serum electrolytes were within normal limits.X-ray films of the chest and skull were normal.The Wassermann, Kahn, and Price precipitation reaction were negative.At first twice-weekly injections of 5 units of pitressin in oil were given intramuscularly.This, however, had a negligible effect in reducing the polyuria.The patient did feel that pitressin snuff administered four or five times daily reduced his frequency slightly, but this was not enough to render its continued use worth while.It can be concluded, in this case, that pitressin by the intramuscular or nasal route had no appreciable effect in reducing diuresis.COMMENT This case is of interest in that females appear to have ex- hibited the fully developed clinical syndrome.This feature is unusual.Recent published work has shown that symp- tomless female carriers of the disease show an impairment of urine-concentrating power and a lowered response to pitressin (Garrod, 1956).Carter and Simpkiss (1956) in- vestigated four families and showed that the female carriers were unable to concentrate urine beyond 1018.They suggested that this test be used as a means of " carrier state" detection.My thanks are due to Lieutenant-Colonel R.
Lung Abscess as a Complication of Shock Therapies
Authors: P. Wayl, J. Rakower
Journal: Thorax (1954)

Shock therapy has been accepted today as one of the most successful methods for the treatment of the affective psychoses.The shock may be induced by insulin coma or by convulsions produced either electrically or by leptazol (" cardiazol ").Pul- monary suppuration has been a major complication of insulin coma therapy and, except for vertebral compression fractures, the most frequent sequel of convulsion therapy.i.e., 1%.Many more cases of lung abscess have been reported in the French and Italian literature.Lalanne (1944) from Algiers reported 46 cases of lung abscess following electrical shock, 40 of them among Arabs.The incidence of pulmonary abscesses among on July 15, 2023 by guest.
Units of management in reorganised NHS: what choice for senior medical staff?
Authors: D. M Wayte
Journal: BMJ (1982)

epidemiological data since the answers being given are worthless for this.One must conclude therefore that this must be a further attempt at restricting abortion by attempting to dissuade doctors from performing abortions for anything other than strict medical con- ditions.This is against the repeated wishes of Parliament, the medical profession, and opinion polls and is an attempt to limit the clinical freedom of a doctor.This new form needs to be abandoned and any new one introduced only after consideration of the existing law and the views of people knowledgeable about the subject and with a clear idea of its intentions.
The Predictive Value of Gensini Score in the Clinical Outcomes in Patients with Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Authors: Aycan Esen Zencirci, Ertuğrul Zencirci, Aleks Değirmencioğlu, Gültekin Karakuş, Ahmet Ekmekçi, Kıvılcım Ozden, Aysun Erdem, Uğur Fındıkçıoğlu, Servet Altay, Dilaver Öz, Hatice Betül Erer, Ahmet Akyol, Mehmet Eren
Journal: Journal of the American College of Cardiology (2013)
A new agenda for AIDS research
Authors: B. D Walker
Journal: BMJ (1995)

surgeons or chiropractors incurred much greater costs than those who consulted primary care practitioners, but the outcomes of treatment in terms of functional recovery and return to work were similar in the three groups.'0The development of group practice health maintenance organisations, many of which incorporate a primary care gatekeeping role, has achieved appreciable cost reductions in the United States.It has also coincided with a resurgence of interest in general practice among American medical students."IWe know too little about the relative cost effectiveness of providing care in different settings and by professionals with different types of training.We also need to develop a better understanding of patients' needs and attitudes.There is some evidence that patients' expectations of the benefits and availability of specialist care are rising.12Hospital closures are highly unpopular, and patients' perceptions of the need for specialist opinions can influence general practitioners' referral decisions.'3Primary care may not prove to be an acceptable substitute for secondary care in the popular imagination.There is a danger that consumer demand for increased access to specialists, coupled with commercial incentives for hospitals to induce demand for their services, will undermine the current trend towards primary care.If further shifts are to be secured, it will require a culture change among both professionals and the public.