tbuckley/cabot-search huggingface dataset:
Histone deacetylase inhibitors preferentially augment transient transgene expression in human dermal fibroblasts
Authors: K. Yasukawa, D. Sawamura, M. Goto, H. Nakamura, H. Shimizu
Journal: British Journal of Dermatology (2007)

Skin is an attractive target for gene therapy. However, low efficiency of gene transfection has been a major problem. Histone deacetylase (HDAC) inhibitors have been reported to increase transgene expression in malignant cells.We have estimated how much HDAC inhibitors might increase transgene expression in HaCaT cells, normal human epidermal keratinocyte (NHEK) cells, normal human dermal fibroblast (NHDF) cells and also in stratified cultured epidermal sheets that mimic the structure of the skin.After treatment with each HDAC inhibitor [trichostatin A, FK228 and cyclic hydroxamic acid-containing peptide 31 (CHAP31)], transient transgene expression in HaCaT, NHEK and NHDF cells and stratified cultured epidermal sheets was compared with that of respective controls without treatment. Reactivation of transgene expression using HDAC inhibitors in HaCaT cells stably expressing the transgene was also studied.All HDAC inhibitors equally increased transient transgene expression by 2-fold in NHEK cells, 20-fold in NHDF cells and 6-fold in HaCaT cells when compared with untreated cells. This augmented expression continued for 72 h in all cell lines maintained under each HDAC inhibitor. In cells stably expressing the transgene, only CHAP31 reactivated transgene expression. In stratified cultured epidermal sheets, CHAP31 most effectively improved transient transgene expression.HDAC inhibitors are most efficient at amplifying transient transgene expression in NHDF cells. This suggests that NHDF cells may be most suitable as transgene targets for transient gene transfection using HDAC inhibitors. Specific HDAC inhibitors may not prove so useful for treating genetic dermatoses requiring cells stably expressing the correct gene, but may be advantageous in treating nonhealing cutaneous wounds or cancer.
Lung Scanning and Age
Authors: AVIR KAGAN
Journal: Annals of Internal Medicine (1972)

Letters, Comments, and Corrections1 September 1972Lung Scanning and AgeAVIR KAGAN, M.D., SANDOR A. FRIEDMAN, M.D.AVIR KAGAN, M.D.Search for more papers by this author, SANDOR A. FRIEDMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-77-3-483 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The recent article by Kronenberg and associates (1) in theAnnals of Internal Medicineis a significant contribution to the diagnostic art of lung scanning. The experience at Coney Island Hospital, both before and after publication of the recent paper by Friedman and colleagues (2), does appear to differ with their findings. Indeed the differences are owing to the choice of subjects. Themeanage of the Coney Island Hospital group is the upper age limit of the Kronenberg group, so thatallof his patients are younger than our average patient. Inclusion of a 47-year-old in...References1. KRONENBERGL'HEUREXPONTO RPR: The effect of aging on lung perfusion, Ann Intern Med 76:413-421, 1972 LinkGoogle Scholar2. FRIEDMANSCHUBSMITH SHE: Perfusion defects in the aging lung. Am Heart J 79:160-166, 1970 CrossrefMedlineGoogle Scholar3. TETALMANHOFFERHECK MPL: Appearance of the lung scan in normal individuals. J Nucl Med 12:401, 1971 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Coney Island Hospital Brooklyn, N.Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1972Volume 77, Issue 3Page: 483-483KeywordsDiagnostic medicineLungs Issue Published: 1 September 1972 PDF DownloadLoading ...
Rosuvastatin added to standard heart failure therapy improves cardiac remodelling in heart failure rats with preserved ejection fraction
Authors: Dulcenombre Gómez‐Garre, Ma Luisa González‐Rubio, Paloma Muñoz‐Pacheco, Alicia Caro‐Vadillo, Paloma Aragoncillo, Arturo Fernández‐Cruz
Journal: European Journal of Heart Failure (2010)
A Comparison Between Diagnostic I-123 and Posttherapy I-131 Scans in the Detection of Remnant and Locoregional Thyroid Disease
Authors: Damita L. Thomas, Yusuf Menda, David Bushnell
Journal: Clinical Nuclear Medicine (2009)

The aim of this study was to compare pretherapy diagnostic I-123 scans with 7-day posttherapy I-131 scans days in detecting remnant thyroid disease as well as locoregional metastases in patients who had undergone thyroidectomy for differentiated thyroid cancer.The I-123 and I-131 scans from 53 patients were reviewed. The number of lesions identified on each scan was compared as well as the relative intensity of each lesion on the I-123 and I-131 scans using region-of-interest-derived lesion to background ratios. For the I-123 diagnostic scans, 1.0 to 1.6 mCi of activity was administered orally 24 hours before scan acquisition. Patients received therapeutic doses of I-131 ranging from 30.7 to 362.2 mCi orally, on the same day but after acquisition of the I-123 scan. All posttherapy I-131 scans were performed 7 days after radioablative therapy with I-131.Of the 53 patients, 14 had concordant scans, with an equal number of lesions detected by both scans. Thirty-nine I-123/I-131 scan pairs showed discordance, with 27 patients demonstrating more lesions on the I-123 scans. Of the 142 total lesions, 35% were detected only by I-123 pretherapy images compared with 15% detected only on posttherapy images. In a subgroup of 42 patients I-123 scans showed 56 lesions (out of a total of 116) that demonstrated either a better lesion to background ratio than I-131 or were seen exclusively by I-123.The use of diagnostic I-123 pretherapy scintigraphy seems to be superior in many patients to posttherapy I-131 imaging obtained at 7 days in detecting locoregional metastases or remnant in postsurgical patients. This is likely due to the fact that 1 week is too long to wait to perform posttherapy imaging.
SIRT1 Limits the Function and Fate of Myeloid-Derived Suppressor Cells in Tumors by Orchestrating HIF-1<b>α</b>–Dependent Glycolysis
Authors: Guangwei Liu, Yujing Bi, Bo Shen, Hui Yang, Yan Zhang, Xiao Wang, Huanrong Liu, Yun Lu, Jiongbo Liao, Xi Chen, Yiwei Chu
Journal: Cancer Research (2013)

Myeloid-derived suppressor cells (MDSC) display an immature phenotype that may assume a classically activated (M1) or alternatively activated phenotype (M2) in tumors. In this study, we investigated metabolic mechanisms underlying the differentiation of MDSCs into M1 or M2 myeloid lineage and their effect on cancer pathophysiology. We found that SIRT1 deficiency in MDSCs directs a specific switch to M1 lineage when cells enter the periphery from bone marrow, decreasing the suppressive function in favor of a proinflammatory M1 phenotype associated with tumor cell attack. Glycolytic activation through the mTOR-hypoxia-inducible factor-1α (HIF-1α) pathway was required for differentiation to the M1 phenotype, which conferred protection against tumors. Our results define the essential nature of a SIRT1-mTOR/HIF-1α glycolytic pathway in determining MDSC differentiation, with implications for metabolic reprogramming as a cancer therapeutic approach.
Projections of the Cost of Cancer Care in the United States: 2010-2020
Authors: A. B. Mariotto, K. Robin Yabroff, Y. Shao, E. J. Feuer, M. L. Brown
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundCurrent estimates of the costs of cancer care in the United States are based on data from 2003 and earlier. However, incidence, survival, and practice patterns have been changing for the majority of cancers.
It's Peacetime, but War Against Disease Continues
Authors: Charles Marwick
Journal: JAMA (1990)

MILITARY COMMANDERS with a sense of history are aware that disease can decimate their troops far more efficiently than virtually any enemy weapon. That specter, epidemic disease raging uncontrolled, became the springboard for the formation, in 1940, of what is known today as the Armed Forces Epidemiological Board. This year, as the board celebrates its 50th birthday, it is evident that the results achieved by these civilian advisers have extended far beyond the uniformed services. "The impact of some research that the board recommended and the military implemented is beyond measure," says Theodore E. Woodward, MD, University of Maryland, Baltimore, the current president. The board's founders, BG James S. Simmons, MC, USA, and COL Stanhope Bayne-Jones, MC, USA, were aware of the millions of deaths caused by influenza and pneumonia during World War I, Woodward says. They created the Board for the Control of Influenza and Epidemic Diseases. The seven
A key pathogenic role for the STAT1/T-bet signaling pathway in T-cell-mediated liver inflammation
Authors: Jürgen Siebler, Stefan Wirtz, Sonja Klein, Martina Protschka, Manfred Blessing, Peter R. Galle, Markus F. Neurath
Journal: Hepatology (2003)

TH1 cytokines have been suggested to contribute to the pathogenesis of T-cell-mediated liver injury and inflammation. However, the molecular signaling pathways involved in such injury are still poorly understood. In the present study, we investigated the role of the STAT1/T-bet signaling pathway in a murine model of T-cell-mediated liver inflammation induced by the application of concanavalin A (Con A) using newly created STAT1 transgenic mice as well as STAT1- and T-bet-deficient mice. Liver injury induced by Con A was associated with an increase of both pSTAT1 and T-bet levels in the liver. Furthermore, functional studies suggested a pathogenic role for STAT1 in Con A-induced liver injury, because transgenic mice overexpressing STAT1 under the control of the CD2 promoter/enhancer construct showed elevated interferon gamma (IFN-gamma) and IRF-1 levels as well as significantly augmented liver injury following administration of Con A. Consistently, we observed that both STAT1-deficient and T-bet-deficient mice were protected from such T-cell-dependent liver injury. In conclusion, these findings suggest a key pathogenic role for the STAT1/T-bet signaling pathway for T-cell activation in the Con A model of T-cell-mediated liver pathology.
The ability of several short-term measures of RR variability to predict mortality after myocardial infarction.
Authors: J T Bigger, J L Fleiss, L M Rolnitzky, R C Steinman
Journal: Circulation (1993)

We studied 715 patients 2 weeks after myocardial infarction to test the hypothesis that short-term power spectral measures of RR variability (calculated from 2 to 15 minutes of normal RR interval data) will predict all-cause mortality or arrhythmic death.We performed power spectral analyses on the entire 24-hour RR interval time series. To compare with the 24-hour analyses, we selected short segments of ECG recordings from two time periods for analysis: 8 AM to 4 PM and midnight to 5 AM. The former corresponds to the time interval during which short-term measures of RR variability would most likely be obtained. The latter, during sleep, represent a period of increased vagal tone, which may simulate the conditions that exist when patients have a signal-averaged ECG recorded, ie, lying quietly in the laboratory. Four frequency domain measures were calculated from spectral analysis of heart period data over a 24-hour interval. We computed the 24-hour power spectral density and calculated the power within three frequency bands: (1) 0.0033 to < 0.04 Hz, very low frequency power, (2) 0.04 to < 0.15 Hz, low frequency power, and (3) 0.15 to 0.40 Hz, high frequency power. In addition, we calculated the ratio of low to high frequency power. These measures were calculated for 15-, 10-, 5-, and 2-minute segments during the day and at night. Mean power spectral values from short periods during the day and night were similar to 24-hour values, and the correlations between short segment values and 24-hour values were strong (many correlations were > or = 0.75). Using the optimal cutpoints determined previously for the 24-hour power spectral values, we compared the survival experience of patients with low values for RR variability in short segments of ECG recordings to those with high values. We found that power spectral measures of RR variability were excellent predictors of all-cause, cardiac, and arrhythmic mortality and sudden death. Patients with low values were 2 to 4 times as likely to die over an average follow-up of 31 months as were patients with high values. The power spectral measures of RR variability did not predict arrhythmic or sudden deaths substantially better than all-cause mortality.Power spectral measures of RR variability calculated from short (2 to 15 minutes) ECG recordings are remarkably similar to those calculated over 24 hours. The power spectral measures of RR variability are excellent predictors of all-cause mortality and sudden cardiac death.
Subdural haematoma as a complication of spinal anaesthetic
Authors: D B Scott
Journal: BMJ (1982)

pressures than those studied in the non-drug studies.The blood pressures before treatment of patients in the drug and non-drug studies were not significantly different (systolic blood pressure, t=0 69, df 98; diastolic blood pressure, t=0 43, df 109).In conclusion, we suggest that rather than see the outcome of our analysis primarily in terms of non-pharmacological treatments being shown to be less effective than drug treatments, the most important outcome is that several non-drug treatment modalities can be seen to have produced substantial and lasting reduction in blood pressure.These benefits are perhaps overall not as great as those of the drug studies, but are significantly greater than those of the placebo studies and are of appreciable clinical importance.We would certainly agree that many mildly hypertensive patients might be treated effec- tively by non-drug techniques, and indeed have concluded that: "Weight loss, progressive muscle relaxation, and yoga could provide competitive alternatives to step 1 drug treat- ment," and should be considered by the doctor.
Utility of needle aspiration of tumours.
Authors: P A Trott
Journal: BMJ (1978)

Association on Mental Deficiency (AAMD).The concept of mild retardation is quantitative and embraces, using conventional standards, some 2 20, of the population in addition to the 0 4%' who are even less gifted.Not all of this considerable population is in receipt of special services, even at school age; but prospects for training for skilled employment and independent social adaptation tend to be limited.Fortunately, the AAMD has omitted from the revised classification of mental handicap' the term "borderline mental retardation," but this is still in common use and embraces much of the "dull normal" stream.It seems contrary to the general sense of the leading article thus arbitrarily to exclude any causal role in mental retardation to mal- nutrition when this can admittedly cause some deficiency in the developing brain.It would seem more reasonable in the present state of science to keep an open mind on this question and to view it as one of the many possible modes of operation of the impact of adverse social and economic factors among under- privileged groups and disadvantaged classes.
Hyperammonemia following allogeneic bone marrow transplantation
Authors: Nielson Tse, Stephen Cederbaum, John A. Glaspy
Journal: American Journal of Hematology (1991)

Hyperammonemia is a rare and serious complication of intensive cytotoxic chemotherapy. We report the case of a patient who developed profound idiopathic hyperammonemia following bone marrow transplantation for chronic myelogenous leukemia. Despite rapid institution of hemodialysis, sodium benzoate, and the experimental agent sodium phenylacetate, the patient ultimately succumbed to complications of this metabolic derangement. The literature is reviewed, and recommendations for an approach to this complication of marrow transplantation are proposed.
Treatment of Ischemic Heart Disease
Authors: Dennis M. Davidson
Journal: JAMA (1983)

To the Editor.—  In Effects of Stress Management Training and Dietary Changes in Treating Ischemic Heart Disease (1983;249:54), Ornish and colleagues randomly assigned 48 persons with evidence of coronary artery disease to experimental and control groups of equal size. Despite the exclusion of aerobic exercise training from their intervention, they found significant improvement in duration of exercise and amount of total work performed, without alteration of maximum heart rate-systolic BP product attained. The experimental group had lower exercise tolerance than their controls before the intervention period, but their final level was significantly higher. The authors frankly admit their lack of a clear mechanism for this improvement, although they propose several possibilities. I wish to add one more, namely, the possible dissimilarity of intervention and control groups.  Despite the investigators' randomization efforts, their two groups were remarkably dissimilar regarding plasma triglyceride and high-density lipoprotein (HDL) levels before the intervention period. The
The Case of Samuel Golubchuk and the Right to be Spared an Excruciating Death
Authors: Tracey M. Bailey, Brendan Leier
Journal: The American Journal of Bioethics (2010)

The right to life has been raised as the central issue in a wide variety of health care debates. However, the assertions advanced by Jotkowitz and colleagues (2010) have little to do with such a ri...
Efficiently Killing a Sugar-Coated Yeast
Authors: John R. Perfect
Journal: New England Journal of Medicine (2013)

With the inclusion in this issue of the Journal of the study by Day et al. on the treatment of cryptococcal meningitis,1 the Journal has provided the medical community with a trilogy of studies for the understanding of combination therapy with amphotericin B and flucytosine for cryptococcal meningitis. In 1979, Bennett et al. provided the first results showing the value of this combination regimen, as compared with amphotericin B monotherapy, and validated its fungicidal properties.2 In 1997, van der Horst et al. described the success of 2-week induction therapy with amphotericin B plus flucytosine for cryptococcal meningitis in persons with . . .
The Unhappy Fat Man
Authors: Max Wishnofsky
Journal: JAMA (1961)

To the Editor:—  InThe Journal, Sept. 10, page 199, Dr. M. A. Goldzieher criticizes an editorial on obesity which appeared inThe Journal, July 9, page 1141. He states: It is a commonly ignored fact that not all obese people are hyperphagic; quite a few are euphagic or even hypophagic. Obviously, psychotherapy directed at restricting food intake would be of no benefit to the hypophagic who maintains his excessive weight by economies established in the field of intermediary metabolism (M. A. Goldzieher and J. W. Goldzieher, Amer J Dig Dis  19 :69, 1952). Does the author equate euphagics and hypophagics with subjects who are in caloric equilibrium or even in negative caloric balance? An increase in tissue (adipose or protein) would in these cases be a complete contravention of the law of the conservation of energy, which Rubner and Atwater, independently, proved conclusively to be applicable to human energy
Tamoxifen and Thromboembolism
Authors: Alex Hendrick
Journal: JAMA (1980)

<h3>To the Editor.—</h3> We question the safety of using tamoxifen citrate for patients with a known predisposition to thrombosis. This antiestrogen has been shown to be an effective hormonal agent in metastatic breast cancer, and so far, few serious side effects have been associated with its use. However, deep-vein thrombosis and pulmonary emboli have occurred in patients taking tamoxifen,<sup>1-3</sup>and it is possible that this could be related to its paradoxical estrogenic effects. <h3>Report of a Case.—</h3> A 72-year-old woman with metastatic pleural effusion and bone disease from breast cancer showed development of occlusion of the right brachial and ulnar arteries while she was receiving chemotherapy. A successful thromboembolectomy was performed. There was no obvious cardiac cause of embolism. A year later her disease progressed despite changes in chemotherapy. Estrogen receptor status was unknown. Tamoxifen citrate therapy, 10 mg twice daily, was started but was discontinued after a month
Changes in the Status of Neurotransmitter Receptors in a Rabbit Model of Hepatic Encephalopathy
Authors: Peter Ferenci, Chris S. Pappas, Peter J. Munson, Ken Henson, Anthony E. Jones
Journal: Hepatology (1984)

It has previously been shown in an animal model of hepatic encephalopathy (HE) that the number of receptors for the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), increases and that the number of receptors for the excitatory neurotransmitter, glutamate, decreases. To determine the functional status of other neurotransmitter systems in HE, measurements were made of the specific binding of other neurotransmitters to synaptic membranes prepared from the brains of normal rabbits and rabbits in HE due to galactosamine-induced acute liver failure. The development of HE was associated with: (i) a decrease in the density (B max ) of receptors for the two excitatory amino acid neurotransmitters, aspartate and kainic acid; (ii) an increase in the B max of both the low and high affinity binding site for strychnine, a marker for the inhibitory neurotransmitter glycine; (iii) a decrease in the affinity (K d ) of receptors for dopamine, and (iv) no appreciable change in either the specific binding of [ 3 H]D-ala 2 -methionine enkephalinamide or [ 3 H]naloxone, markers for opiate receptors, or in the B max or the K d of receptors for acetylcholine. If it is assumed that the sensitivity of the brain to neurotransmitters varies directly with the density of neurotransmitter receptors, HE may be associated with increased sensitivity to inhibitory amino acid neurotransmitters and decreased sensitivity to excitatory amino acid neurotransmitters. Thus, the observed changes in neurotransmitter receptors in HE afford a feasible pathophysiological basis for the mediation of the neural inhibition of HE.
Endoscopic Diagnosis of Gastric Lymphomas
Authors: P. Spinelli, C. Lo Gullo, P. Pizzetti
Journal: Endoscopy (1980)

From January 1970 to June 1979, 180 gastroscopies were performed in patients affected by lymphoma (168 in patients with non-Hodgkin lymphoma and 12 in patients with Hodgkin's disease). A gastric localization was evidenced in 48 patients with non-Hodgkin lymphoma (15 primaries and 33 secondaries), and no lesions were found in patients with Hodgkin's disease. The gastroscopies were accompanied by histological samples in all the cases and by cytological samples in most of them. The examination allowed a histological classification in 96 % of the cases. The endoscopic aspect most frequently observed (48 %) was vegetation, which was often associated with multiple ulcerations. The most frequent site (67 %) was the vertical portion of the stomach. Gastroscopy was also utilized in the follow-up of 22 of the 48 patients affected by gastric lymphoma: in two of these, gastric localizations missed at other examinations were found.