tbuckley/cabot-search huggingface dataset:
Abstract 3352: miR-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma
Authors: Zhi Xu, Angela Liu, Nikki Lee, Jinfei Chen, John M. Luk
Journal: Cancer Research (2014)

Abstract In contrast to normal differentiated cells that depend on mitochondrial oxidative phosphorylation for energy production, cancer cells have evolved to utilize aerobic glycolysis (Warburg's effect), with benefit of providing intermediates for biomass production. MicroRNA-122 (miR-122) is highly expressed in normal liver tissue regulating a wide variety of biological processes including cellular metabolism, but is reduced in hepatocellular carcinoma (HCC). Overexpression of miR-122 was shown to inhibit cancer cell proliferation, metastasis, and increase chemosensitivity, but its functions in cancer metabolism remains unknown. The present study aims to identify the miR-122 targeted genes and to investigate the associated regulatory mechanisms in HCC metabolism. We found the ectopic overexpression of miR-122 affected metabolic activities of HCC cells, evidenced by the reduced lactate production and increased oxygen consumption. Integrated gene expression analysis in a cohort of 94 HCC tissues revealed miR-122 level tightly associated with a battery of glycolytic genes, in which pyruvate kinase (PK) gene showed the strongest anti-correlation coefficient (Pearson r = -0.6938, p = &amp;lt;0.0001). In addition, reduced PK level was significantly associated with poor clinical outcomes of HCC patients. We found isoform M2 (PKM2) is the dominant form highly expressed in HCC and is a direct target of miR-122, as overexpression of miR-122 reduced both the mRNA and protein levels of PKM2, whereas PKM2 re-expression abrogated the miR-122-mediated glycolytic activities. The present study demonstrated the regulatory role of miR-122 on PKM2 in HCC, having an implication of therapeutic intervention targeting cancer metabolic pathways. Citation Format: Zhi Xu, Angela Liu, Nikki Lee, Jinfei Chen, John M. Luk. miR-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma. [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 3352. doi:10.1158/1538-7445.AM2014-3352
Infected Puncture Wounds in Diabetic and Nondiabetic Adults
Authors: Lawrence A Lavery, Steven C Walker, Lawrence B Harkless, Kim Felder-Johnson
Journal: Diabetes Care (1995)

To evaluate bone and soft tissue pathogens resulting from puncture wounds among diabetic and nondiabetic adults.We used a case-control design to compare bacterial pathogens in diabetic and nondiabetic subjects with foot infections precipitated by puncture injuries. We used ICD-9-CM code E920.8 to identify 77 diabetic and 69 nondiabetic patients admitted to the hospital for infected puncture wounds. We identified surgical bone and soft tissue cultures and number and type of organisms per culture.Nondiabetic subjects had significantly less osteomyelitis (13 vs. 35%, P < 0.01) than diabetic subjects and were infected by fewer organisms. Pseudomonas was the most common cause of osteomyelitis among nondiabetic subjects (P < 0.001). Staphylococcus aureus was more common in diabetic bone (P < 0.001) and soft tissue (P < 0.001) infections. Polymicrobial osteomyelitis was more common in diabetic subjects. There was a longer delay until diabetic subjects received medical treatment compared with nondiabetic subjects (8.7 vs. 5.3 days, P < 0.002). Diabetic subjects were more likely to have neuropathy (P < 0.001) and to have sustained their injuries while barefoot (P < 0.006).Puncture wounds in diabetic subjects were commonly associated with polymicrobial infections. Pseudomonas was the most common cause of nondiabetic osteomyelitis. These results have implications for differential emergent and chronic treatment of puncture wounds in diabetic versus nondiabetic subjects.
More on switching statins: Authors' reply
Authors: James C Moon, Richard G Bogle
Journal: BMJ (2006)

Editor-Last year Hern et al published an editorial on knife crime and clearly the problem has not gone away. 1 A quick search of the Times website finds 90 hits on the single search term "stabbing" in the past three months alone.Several recent deaths have fuelled the perception that forensic knife injuries have become an epidemic, resulting in a knife amnesty and government discussion of new punitive measures.An increase in such injuries is supported by data from regional police forces and the Home Office, with 1200 reported attacks in London last year and 30% of homicides caused by knife injury. 2 Crimes defined as "more serious wounding or other act endangering life" almost doubled nationally from 1995 to 2005. 3 We audited forensic knife injuries at this hospital, one of Europe's busiest emergency departments, to establish the size of this problem in a representative urban area (east London).We extracted data on forensic knife injuries (excluding deliberate self harm) from a detailed prospectively recorded database of all trauma calls from July 2004 to June 2006 (these reflecting more severe injuries).Overall there were 309 forensic knife injuries; 259 patients were admitted, 184 were operated on, and eight died.The chest was the most common area injured (183/309 patients, 6/8 deaths).Most patients were men (297/309), and mean age was 28 (range 15-74).To give a measure of changing incidence over a longer time of a greater range of severity of injury, we also performed an audit of all cases coded as "stabbing" on the patient administration system during the 10 year period from July 1997 to June 2006 (figure).Over both periods, the data show an increase in the overall incidence of stabbings.Furthermore, increased need for surgical intervention in the prospective study may reflect increasing severity of injury.These data therefore seem to support the general perception that knife injuries are increasing.
Modified Supine versus Prone Position in Percutaneous Nephrolithotomy for Renal Stones Treatable with a Single Percutaneous Access: A Prospective Randomized Trial
Authors: Marco De Sio, Riccardo Autorino, Giuseppe Quarto, Francesco Calabrò, Rocco Damiano, Francesco Giugliano, Salvatore Mordente, Massimo D'Armiento
Journal: European Urology (2008)
The use or uselessness of annual public health reports
Authors: G. Scally
Journal: BMJ (1997)

In the mid 1980s an inquiry into the development of the public health function was established in response to two major outbreaks of communicable disease. The report of the inquiry, chaired by the then Chief Medical Officer of England, Sir Donald Acheson, recommended, among other things, that “community medicine” should be renamed “public health medicine” and that each health authority should appoint a director of public health, who should produce a report on the health of the authority's population each year.1 After almost 10 years of annual reports from directors of public health the Institute for Public Policy Research has published a review of their purpose and form.2

Anne Davies's review is timely because of the huge amount of public health activity taking place nationally. Not only has England its first ever …
Mesenchymal stem cell–mediated ectopic hematopoiesis alleviates aging-related phenotype in immunocompromised mice
Authors: Takayoshi Yamaza, Yasuo Miura, Kentaro Akiyama, Yanming Bi, Wataru Sonoyama, Stan Gronthos, WanJun Chen, Anh Le, Songtao Shi
Journal: Blood (2008)
Lipid peptide nanocomplexes for gene delivery and magnetic resonance imaging in the brain
Authors: Michele J. Writer, Panagiotis G. Kyrtatos, Alison S. Bienemann, John A. Pugh, Andrew S. Lowe, Claudio Villegas-Llerena, Gavin D. Kenny, Edward A. White, Steven S. Gill, Cameron W. McLeod, Mark F. Lythgoe, Stephen L. Hart
Journal: Journal of Controlled Release (2012)

Gadolinium-labelled nanocomplexes offer prospects for the development of real-time, non-invasive imaging strategies to visualise the location of gene delivery by MRI. In this study, targeted nanoparticle formulations were prepared comprising a cationic liposome (L) containing a Gd-chelated lipid at 10, 15 and 20% by weight of total lipid, a receptor-targeted, DNA-binding peptide (P) and plasmid DNA (D), which electrostatically self-assembled into LPD nanocomplexes. The LPD formulation containing the liposome with 15% Gd-chelated lipid displayed optimal peptide-targeted, transfection efficiency. MRI conspicuity peaked at 4 h after incubation of the nanocomplexes with cells, suggesting enhancement by cellular uptake and trafficking. This was supported by time course confocal microscopy analysis of transfections with fluorescently-labelled LPD nanocomplexes. Gd-LPD nanocomplexes delivered to rat brains by convection-enhanced delivery were visible by MRI at 6 h, 24 h and 48 h after administration. Histological brain sections analysed by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) confirmed that the MRI signal was associated with the distribution of Gd3 + moieties and differentiated MRI signals due to haemorrhage. The transfected brain cells near the injection site appeared to be mostly microglial. This study shows the potential of Gd-LPD nanocomplexes for simultaneous delivery of contrast agents and genes for real-time monitoring of gene therapy in the brain.
Withdrawing artificial feeding from children with brain damage
Authors: R. E Cranford
Journal: BMJ (1995)

lives."'As for the errors that do occur and that could or do lead to harm, these need to be made known, examined, and acted on.A formal reporting system, in which all hospital staff report suspected or near miss errors confidentially to a named member of the medical, pharmaceutical, or audit staff, allows this to happen."Critical incident reporting" in intensive care units provides an example of data gathering that uses mistakes constructively, without threatening individual reporters.We should take note of the conclusions of the Boston study:
PLASMA IMIPRAMINE LEVEL IN SYNDROMES OF DEPRESSION
Authors: GEORGE G. HAYDU, ANDREAS DHRYMIOTIS, GERTRUDE P. QUINN
Journal: American Journal of Psychiatry (1962)

Imipramine plasma level was determined after a single oral dose. Patients who responded to subsequent imipramine therapy showed low plasma levels, refractory cases showed high levels. The low plasma levels of responders continued during therapy. Their imipramine stool and urine excretions were also low. A differential binding of the drug according to psychopathology was discussed.
Unsupervised junior surgeons carry out operations
Authors: K. Abbasi
Journal: BMJ (1997)

In 1995–6 a fifth of operations during weekday evenings and 7% during the daytime on weekdays were performed by apparently unsupervised senior house officers, according to the national confidential inquiry into peri-operative deaths.

In the report, Who Operates When? , the pattern of surgical activity during 1995–6 in 355 British hospitals is described, with data from 51 000 cases. Only 6.1% of …
Try out the paperless NHS when doctors change jobs in the NHS
Authors: J. M. Roycroft
Journal: BMJ (2013)

Every August, thousands of junior doctors rotate jobs. For some of us it occurs even more often. Usually, it involves a change of hospital, colleagues, job description, commute, and even accommodation, all of which is stressful. It also brings a mountain of paperwork, which is sent out 7-10 days before starting …
Effect of Telecare Management on Pain and Depression in Patients With Cancer
Authors: Kurt Kroenke, Dale Theobald, Jingwei Wu, Kelli Norton, Gwendolyn Morrison, Janet Carpenter, Wanzhu Tu
Journal: JAMA (2010)

Pain and depression are 2 of the most prevalent and treatable cancer-related symptoms, yet they frequently go unrecognized, undertreated, or both.
The Initiation of Ventricular Tachycardia and Fibrillation in Isolated Hearts by Potassium Chloride
Authors: L. GRUMBACH
Journal: Circulation Research (1956)

An accelerating tachycardia ending in fibrillation can be initiated in isolated hearts by injections of KCl after the administration of epinephrine, but not in untreated hearts. KCl acts in two ways to do this. First, it causes an A-V block that enables epinephrine to cause a paroxysmal ventricular tachycardia. Secondly, it causes the latter to accelerate by delaying the recovery of excitability so that at least one premature systole can fall into the recovery phase of a preceding impulse. This event is necessary and sufficient for the initiation of a self-sustaining accelerating tachycardia that can end in fibrillation.
In-Stent Restenosis and Remote Coronary Lesion Progression Are Coupled in Cardiac Transplant Vasculopathy But Not in Native Coronary Artery Disease
Authors: Michael Jonas, James C. Fang, John C. Wang, Satyendra Giri, Dan Elian, Yedael Har-Zahav, Hung Ly, Philip A. Seifert, Jeffrey J. Popma, Campbell Rogers
Journal: Journal of the American College of Cardiology (2006)
Health-related quality-of-life and psychological distress of postmenopausal breast cancer patients after surgery during the randomized trial, N-SAS BC 03, comparing further tamoxifen with switching to anastrozole after adjuvant tamoxifen for 1 to 4 years: the final results.
Authors: S Ohsumi, K Shimozuma, Y Ohashi, Y Nomura, T Aihara, Y Takatsuka
Journal: Cancer Research (2009)

Abstract Abstract #1136 Backgroud: Three years ago, we reported the interim results regarding heath-related quality of life (HRQOL) outcomes of the patients who switched their adjuvant endocrine therapy from several years of tamoxifen (TAM) to anastrozole (ANA) and those who had TAM for a total of 5 years in the randomized trial, National Surgical Adjuvant Study of Breast Cancer (NSAS BC) 03. We present the final results of HRQOL and psychological distress in the NSAS BC 03.&amp;#x2028; Patients and Methods: Recurrence-free postmenopausal breast cancer patients who had received definitive surgery for hormone receptor positive breast cancer, and had been taking TAM for 1 to 4 years after the surgery were enrolled in the randomized trial: N-SAS BC 03. They were randomly assigned to continue TAM for the remaining periods of a total of 5 years or to switch from TAM to ANA and take the latter for the remaining periods. Primary endpoints of the N-SAS BC 03 trial were disease-free survival and adverse events. HRQOL and psychological distress were evaluated as secondary endpoints. They were asked to answer patient-administered instruments to assess HRQOL (FACT-B [breast cancer scale] and FACT-ES [endocrine symptom scale]) and psychological distress (CES-D: Center for Epidemiologic Studies Depression scale) at the randomization (baseline), 3 months, 1 and 2 years after the randomization. HRQOL and psychological distress scores during this period were compared using t-test and the general linear model with correlated errors.&amp;#x2028; Results: There was no difference in demographic and medical characteristics between the two treatment groups. The response rates of the questionnaires were 98.6%, 97.2%, 90.9% and 78.5% at baseline, 3 months, 1 and 2 years after the randomization, respectively. At baseline 694 patients (346 in the TAM group and 348 in the ANA group) answered them. The total scores of FACT-G, and FACT-ES and the scores of FACT-G physical well-being (PWB) subscale were statistically significantly better in the TAM group than in the ANA group (P = 0.042, 0.038, and 0.005, respectively) after the randomization, while those of FACT-B in the former were marginally better than those in the latter (P= 0.066). However, there were no statistically significant differences between the two treatment groups for the scores of CES-D, and subscales other than PWB of FACT-G, FACT-B, and FACT-ES.&amp;#x2028; Conclusions: Further TAM treatment after adjuvant TAM for 1 to 4 years may provide postmenopausal breast cancer patients with slightly better HRQOL comparing with switching to ANA. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1136.
Glycemic Status and Development of Kidney Disease
Authors: Caroline S. Fox, Martin G. Larson, Eric P. Leip, James B. Meigs, Peter W.F. Wilson, Daniel Levy
Journal: Diabetes Care (2005)

OBJECTIVE—Diabetes is a major risk factor for the development of kidney disease and is the leading cause of end-stage renal disease in the U.S. Whether pre-diabetes is associated with the development of kidney disease is unclear. RESEARCH DESIGN AND METHODS—Subjects free of chronic kidney disease (CKD) were drawn from the Framingham Heart Study offspring cohort (1991–1995), given an oral glucose tolerance test, and followed for an average of 7 years for development of CKD (glomerular filtration rate [GFR] of &amp;lt;59 ml/min per 1.73 m2 in women and &amp;lt;64 ml/min per 1.73 m2 in men). Multivariable logistic regression models, adjusted for cardiovascular disease risk factors including age, sex, hypertension, smoking, BMI, total and HDL cholesterol levels, and prevalent myocardial infarction or congestive heart failure, were used to estimate the odds of patients developing kidney disease among glycemic categories. RESULTS—Of 2,398 subjects (53% women; mean age 54 years), 63% were normoglycemic, 29% had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), 3.4% were newly diabetic, and 4.6% had known diabetes. By glycemic category, mean GFR at follow-up was 87, 85, 82, and 78 ml/min per 1.73 m2, respectively. The fully adjusted odds of developing CKD were 0.98 (95% CI 0.67–1.45), 1.71 (95% CI 0.83–3.55), and 1.93 (95% CI 1.06–3.49) among those with IFG or IGT, newly diagnosed diabetes, or known diabetes, respectively, compared with those who were normoglycemic at baseline. Among participants without diabetes, metabolic syndrome was not associated with kidney disease at follow-up (odds ratio 1.46, P = 0.06). CONCLUSIONS—Cardiovascular disease risk factors explain much of the relationship between prediabetes and the development of chronic kidney disease. Clinical trials are warranted to determine whether vascular risk factor modification can slow the decline of kidney function among those with pre-diabetes.
Growth Factor Stimulation Reduces Residual Quiescent Chronic Myelogenous Leukemia Progenitors Remaining after Imatinib Treatment
Authors: Melissa Holtz, Stephen J. Forman, Ravi Bhatia
Journal: Cancer Research (2007)

Abstract The BCR/ABL tyrosine kinase inhibitor imatinib mesylate is highly effective in the treatment of chronic myelogenous leukemia (CML) but fails to eliminate all leukemia cells. Residual leukemia stem and progenitor cells persist in imatinib-responsive patients and may be a potential source of relapse. Previous studies indicate that imatinib preferentially targets dividing cells, and nondividing progenitor cells are resistant to imatinib-mediated apoptosis. We investigated whether growth factor stimulation of progenitor proliferation could reduce the number of residual nondividing cells remaining after imatinib treatment. CML and normal CD34+ cells were labeled with 5-(and 6-)-carboxyfluorescein diacetate succinimidyl ester (CFSE) to track cell division and cultured in low or high concentrations of growth factor to determine effects of growth factor stimulation on nondividing cells. High growth factor concentrations significantly enhanced CML proliferation with or without imatinib treatment and significantly reduced the number of viable, nondividing CFSE bright cells remaining after imatinib exposure. Stimulation with high growth factor before imatinib treatment further reduced the number of residual nondividing CML CD34+ cells. Importantly, clinically achievable concentrations of granulocyte macrophage colony-stimulating factor alone or in combination with granulocyte colony-stimulating factor also significantly reduced nondividing CML CD34+ cells. These results support the potential efficacy of growth factor stimulation in reducing the residual leukemia progenitor population in imatinib-treated patients. [Cancer Res 2007;67(3):1113–20]
THE LYMPHOID TISSUES AND IMMUNE RESPONSES OF NEONATALLY THYMECTOMIZED MICE BEARING THYMUS TISSUE IN MILLIPORE DIFFUSION CHAMBERS
Authors: David Osoba, J. F. A. P. Miller
Journal: The Journal of Experimental Medicine (1964)

Neonatally thymectomized mice were implanted intraperitoneally at 7 days of age with Millipore diffusion chambers containing either embryonic or neonatal thymus tissue. Mice which received either empty diffusion chambers or no further treatment following neonatal thymectomy served as controls. In contrast to these controls, most of the mice implanted with thymus-filled chambers gained weight satisfactorily, did not develop a wasting syndrome, and had the capacity to produce serum antibodies in response to sheep erythrocytes and to reject allogeneic skin grafts. Lymphoid follicles were present in the lymph nodes, spleen, and intestinal tract of the implanted mice but most still showed some diminution in the population of lymphocytes in both blood and tissues. Control thymectomized mice had markedly depleted lymphoid tissues and low peripheral blood lymphocyte levels. The tissue recovered after 1 to 2 months from the diffusion chambers showed only epithelial-reticular cells but no lymphoid cells. It is suggested that a humoral factor produced by the thymus epithelial-reticular complex may be responsible for endowing lymphoid cells with immunological competence.
Week 1 of the Senate Debate — Amending the Reform Bill
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2009)

The Democrats' ambitious health care reform measure escaped its first week of Senate debate unscathed, with the defeat of Republican amendments that would have eliminated Medicare spending cuts and killed a new program for long-term care championed by the late Senator Edward Kennedy (D-MA). The only amendment that both attracted bipartisan support and won approval was one that would provide free mammograms and other preventive services to women.Reversing their stance on Medicare growth — which, with the exception of their 2003 prescription-drug benefit, Republicans have traditionally aimed to cut — GOP senators positioned themselves as staunch defenders of the . . .
Macular Dystrophy Associated with Mutations at Codon 172 in the Human Retinal Degeneration Slow Gene
Authors: John J. Wroblewski, John A. Wells, Anja Eckstein, Fred Fitzke, Chris Jubb, T. Jeffrey Keen, Chris Inglehearn, Shomi Bhattacharya, Geoffrey B. Arden, Marcelle Jay, Alan C. Bird
Journal: Ophthalmology (1994)
A case of red‐cell adenosine deaminase overproduction associated with hereditary hemolytic anemia found in Japan
Authors: Shiro Miwa, Hisaichi Fujii, Noboru Matsumoto, Tadako Nakatsuji, Susumu Oda, Yukari Miura, Hiroyuki Asano, Seiichi Asano
Journal: American Journal of Hematology (1978)

Abstract A case of red cell adenosine deaminase (ADA) overproduction associated with hereditary hemolytic anemia is reported here. This appears to be the second report. Proband is a 38‐year‐old Japanese male who had hemoglobin, 15.8 g/100 ml; reticulocyte count, 4.5%; serum indirect bilirubin, 4.9 mg/100 ml; 51 Cr‐labeled red cell half‐life, 12 days; red cells showed moderate stomatocytosis. His red cell ADA activity showed 40‐fold increase while that of the mother showed 4‐fold increase. The mother was hematologically normal. The father had a normal enzyme activity. The proband and the mother showed slightly high serum uric acid levels. The proband's red cell showed: ATP, 628 nmoles/ml (normal, 1,010‐1,550); adenine nucleotide pool, 46% of the normal mean; 2,3‐diphosphoglycerate content, 3,782 nmoles/ml (normal 4,170‐5,300); increased oxygen affinity of hemoglobin, P 50 of intact crythrocytes being 21.8 mmHg (normal, 24.1‐26.1). Red cell glycolytic intermediates in the proband were low in general, and the rate of lactate production was low. Kinetic studies using crude hemolysate revealed a normal Km for adenosine, normal electrophoretic mobility but slightly abnormal pH curve and slightly low utilization of 2‐deoxyadenosine. The ADA activity of lymphocytes was nearly normal.