tbuckley/cabot-search huggingface dataset:
Cytokines, including stem cell factor alone, enhance lentiviral transduction in nondividing human LTCIC and NOD/SCID repopulating cells
Authors: Steven P Zielske, Stanton L Gerson
Journal: Molecular Therapy (2003)

Hematopoietic stem cells (HSC) require extensive cytokine-mediated stimulation and proliferation for efficient transduction by oncoretroviral vectors. Since lentiviral vectors can transduce nondividing cells, the need for cytokine stimulation has been questioned. We studied HIV-based lentiviral transduction of human early hematopoietic progenitors from umbilical cord blood in the presence or absence of IL-3, IL-6, stem cell factor (SCF), and Flt-3L (36SF) or SCF alone and characterized the effects of these conditions on the stem cell phenotype. Gene transfer was significantly higher in the presence of 36SF in mass culture cells, CFC, LTCIC, and NOD/SCID repopulating cells (SRC). Transduction of primitive progenitor/stem cells was poor without cytokines, with only 12% LTCIC and 23% SRC transduced, compared to 59% in LTCIC and 81% in SRC with 36SF. SCF alone matched transduction rates of multiple cytokines with 70% in CFC. Cytokines prevented apoptosis, expanded CD34+ cell number, and maintained CFC and LTCIC frequencies. Cytokine stimulation increased transduction of nondividing Ara-C-resistant and aphidicolin-inhibited cells similar to dividing cells. These data suggest that cytokines enhance lentiviral transduction of HSC, without requiring cell division, and maintain the stem cell phenotype. SCF stimulation alone was sufficient for high level transduction.
Review of interventions should help to reduce inequalities in health
Authors: V. Entwistle, I. Watt
Journal: BMJ (1996)

and one shows all forms of alcohol to be harmful.Of 10 cohort studies, only one shows a consistent significant benefit for all forms of alcohol.Ecological studies are least prone to confounding by sick non-drinkers and are the least supportive of the theory that alcohol may protect against heart disease.We question the wisdom of publishing these papers without giving any form of public health advice.They will be perceived by the public as giving a signal to consume more alcohol.
Chloramphenicol Combined with Ampicillin in Treatment of Typhoid
Authors: F. De Ritis, G. Giammanco, G. Manzillo
Journal: BMJ (1972)

Fifty out of 100 patients with typhoid fever, matched for age, stage of illness, and degree of fever, were treated with chloramphenicol and the other 50 were treated with chloramphenicol combined with ampicillin. The febrile period was shortened by up to 29% in patients treated with the combined drugs compared with those given only chloramphenicol. Moreover, no patient on combined therapy had a febrile relapse, whereas two relapses occurred among patients treated with chloramphenicol only. We conclude that chloramphenicol and ampicillin together are better than chloramphenicol alone in the treatment of typhoid fever.
Clinical significance of bile ducts injury (Poulsen's Lesions) in chronic hepatitis C (CHC)
Authors: M. Fernández Bermejo, L. García Buey, A. Moreno Borque, A. García Sánchez, J.A. Moreno Monteagudo, C. García-Monzón, R. Moreno-Otero
Journal: Journal of Hepatology (2000)
Estrogen Replacement Therapy and Endometrial Hyperplasia
Authors: Patricia Tsang
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The PEPI trial group<sup>1</sup>recently demonstrated that in 94% (34/36) of postmenopausal women who developed endometrial hyperplasia in association with estrogen-only replacement, progestin therapy was effective in reversing the hyperplastic changes, while the remaining patients were refractory to progestin therapy. The next natural question that should be considered is whether there are any factors that can reliably predict response to progestin therapy in patients with endometrial hyperplasia. The importance of predicting response to progestin therapy is obvious, considering that the alternative for many patients is hysterectomy. It is reasonable to conjecture that immunohistochemical or molecular markers exist in hyperplastic endometrial tissues, such as estrogen and progesterone receptors (ER/PRs) and proliferative index, which can be exploited to predict response prior to a trial of progestin therapy. In breast cancers, ER/PR status has been shown to reliably predict response to hormonal therapy, and together with a panel of
Activation of skeletal muscle casein kinase II by insulin is not diminished in subjects with insulin resistance.
Authors: R Maeda, I Raz, F Zurlo, J Sommercorn
Journal: Journal of Clinical Investigation (1991)

Insulin resistance, which may precede the development of non-insulin-dependent diabetes mellitus in Pima Indians, appears to result from a postreceptor defect in signal transduction in skeletal muscle. To identify the putative postreceptor lesion responsible for insulin resistance in Pima Indians, we investigated the influence of insulin on the activity of casein kinase II (CKII) in skeletal muscle of seven insulin-sensitive, four insulin-resistant, nondiabetic, and five insulin-resistant diabetic Pima Indians during a 2 h hyperinsulinemic, euglycemic clamp. In sensitive subjects, CKII was transiently activated reaching a maximum over basal activity (42%) at 45 min before declining. CKII was also stimulated in resistant (19%) and diabetic (34%) subjects. Basal CKII activity in resistant subjects was 40% higher than in either sensitive or diabetic subjects, although the concentration of CKII protein, as determined by Western blotting, was equal among the three groups. Basal CKII activity was correlated with fasting plasma insulin concentrations, suggesting that the higher activity in resistant subjects resulted from insulin action. Extracts of muscle obtained from all three groups either before or after insulin administration were treated with immobilized alkaline phosphatase, which reduced and equalized CKII activity. These results suggest that insulin stimulates CKII activity in human skeletal muscle by a mechanism involving phosphorylation of either CKII or of an effector molecule, and support the idea that elevated basal activity in resistant subjects results from insulin action. It appears that the ability of insulin to activate CKII in skeletal muscle is not impaired in insulin-resistant Pima Indians, and that the biochemical lesion responsible for insulin resistance occurs either downstream from CKII or in a different pathway of insulin action.
Isometric Contraction Period of the Left Ventricle in Acute Myocardial Infarction
Authors: KIYOSHI INOUE, GEORGE M. YOUNG, ARCHIBALD L. GRIERSON, HAROLD SMULYAN, ROBERT H. EICH
Journal: Circulation (1970)

The usefulness of nontraumatic methods for measuring the left ventricular isometric contraction period (ICP) in myocardial infarction (MI) has been evaluated. The ICP was measured in 13 normal men and 38 patients admitted to a coronary care unit with chest pain, including 18 with acute MI, 12 with old MI, and nine with chest pain of miscellaneous origin; one of these nine was also included in the group with acute myocardial infarction. ICP was determined by three different methods: (1) time between the onset of systolic wave (A) of apexcardiogram (ACG) and the beginning of upstroke (C) of carotid pulse tracing (CPT); (2) time between A and ejection crest (E) of the ACG; and (3) time between the initial low frequency, low amplitude vibration of the first heart sound, and the C of CPT. Statistically significant differences of ICP between the normal group and the three groups of patients were demonstrated only by method 1. Likewise, acute coronary ligation in seven dogs produced characteristic changes in ICP by method 1, which were associated with a reduction in the left ventricular (LV) stroke volume, LV dp/dt, and the aortic flow velocity. The ICP obtained by method 1 appears to be of value in the bedside evaluation of acute myocardial infarction.
Transcriptional Gene Silencing Promotes DNA Hypermethylation through a Sequential Change in Chromatin Modifications in Cancer Cells
Authors: Clare Stirzaker, Jenny Z. Song, Ben Davidson, Susan J. Clark
Journal: Cancer Research (2004)

Abstract It is well established that DNA hypermethylation of tumor suppressor and tumor-related genes can occur in cancer cells and that each cancer subtype has specific gene sets that are commonly susceptible to methylation and silencing. Glutathione S-transferase (GSTP1) is one example of a gene that is hypermethylated and inactivated in the majority of prostate cancers. We previously reported that hypermethylation of the GSTP1 CpG island promoter in prostate cancer cells is initiated by a combination of transcriptional gene silencing (by removal of the Sp1 sites) and seeds of methylation that, instead of being constantly removed because of demethylation associated with transcription, acts as a catalyst for the spread of methylation across the CpG island. In this study, we now demonstrate that the seeds of DNA methylation also play an important role in initiating chromatin modification. Our results address a number of central questions about the temporal relationship between gene expression, DNA hypermethylation, and chromatin modification in cancer cells. We find that for the GSTP1 gene, (a) histone acetylation is independent of gene expression, (b) histone deacetylation is triggered by seeds of DNA methylation, (c) the spread of DNA hypermethylation across the island is linked to MBD2 and not MeCP2 binding, and (d) histone methylation occurs after histone deacetylation and is associated with extensive DNA methylation of the CpG island. These findings have important implications for understanding the biochemical events underlying the mechanisms responsible for abnormal hypermethylation of CpG island-associated genes in cancer cells.
Adenoviral Gene Transfer Corrects the Ion Transport Defect in the Sinus Epithelia of a Porcine CF Model
Authors: Andrea E Potash, Tanner J Wallen, Philip H Karp, Sarah Ernst, Thomas O Moninger, Nicholas D Gansemer, David A Stoltz, Joseph Zabner, Eugene H Chang
Journal: Molecular Therapy (2013)

Cystic fibrosis (CF) pigs spontaneously develop sinus and lung disease resembling human CF. The CF pig presents a unique opportunity to use gene transfer to test hypotheses to further understand the pathogenesis of CF sinus disease. In this study, we investigated the ion transport defect in the CF sinus and found that CF porcine sinus epithelia lack cyclic AMP (cAMP)-stimulated anion transport. We asked whether we could restore CF transmembrane conductance regulator gene (CFTR) current in the porcine CF sinus epithelia by gene transfer. We quantified CFTR transduction using an adenovirus expressing CFTR and green fluorescent protein (GFP). We found that as little as 7% of transduced cells restored 6% of CFTR current with 17-28% of transduced cells increasing CFTR current to 50% of non-CF levels. We also found that we could overcorrect cAMP-mediated current in non-CF epithelia. Our findings indicate that CF porcine sinus epithelia lack anion transport, and a relatively small number of cells expressing CFTR are required to rescue the ion transport phenotype. These studies support the use of the CF pig as a preclinical model for future gene therapy trials in CF sinusitis.
Genome-wide Association Study of Genetic Loci and Alzheimer Disease—Reply
Authors: Abraham M. Brown, Stephen J. Finch, Derek Gordon
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Megestrol for AIDS-Related Anorexia
Authors: Martin H. Cohen
Journal: Annals of Internal Medicine (1995)

Letters1 June 1995Megestrol for AIDS-Related AnorexiaMartin H. CohenMartin H. CohenSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-122-11-199506010-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Two recent double-blind, randomized trials suggest that megestrol is effective for AIDS-related cachexia [1, 2]. Von Roenn and colleagues [1] concluded that megestrol should be considered for all patients with AIDS and a persistent weight loss of 5% or more of ideal body weight. This conclusion raises several concerns. The first centers on the persistence of objective and subjective improvement. Both studies were of 12 weeks' duration. In one [2], 52% of patients receiving megestrol discontinued treatment during the 12-week period. Comparable data were not provided by the other study. Neither study stated how many patients continued ...References1. Von Roenn JH, Armstrong D, Kotler DP, Cohn DL, Klimas NG, Tchekmedyian NS, et al. Megestrol acetate in patients with AIDS-related cachexia. Ann Intern Med. 1994; 121:393-9. Google Scholar2. Oster MH, Enders SR, Samuels SJ, Cohn LA, Hooton TM, Browder HP, et al. Megestrol acetate in patients with AIDS and cachexia. Ann Intern Med. 1994; 121:400-8. Google Scholar3. Shike M, Russel DM, Detsky AS, Harrison JE, McNeill KG, Sheperd FA, et al. Changes in body composition in patients with small-cell lung cancer. The effect of total parenteral nutrition as an adjunct to chemotherapy. Ann Intern Med. 1984; 101:303-9. Google Scholar4. Kotler DP, Tierney AR, Wand J, Pierson RN Jr. Magnitude of body-cell-mass depletion and the timing of death from wasting in AIDS. Am J Clin Nutr. 1989; 50:444-7. Google Scholar5. Murray MJ, Murray MB. Starvation suppression and refeeding activation of infection. An ecological necessity? Lancet. 1977; 1:123-5. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1995Volume 122, Issue 11Page: 879-881KeywordsAIDSEatingFatsMortalityNutritionQuality of lifeRandomized trialsStarvationWeight gainWeight loss ePublished: 15 August 2000 Issue Published: 1 June 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Targeted Delivery of Antiprotease to the Epithelial Surface of Human Tracheal Xenografts
Authors: Thomas Ferkol, Leah A. Cohn, Thomas E. Phillips, Arnold Smith, Pamela B. Davis
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The cystic fibrosis (CF) lung is uniquely susceptible to Pseudomonas aeruginosa, and infection with this organism incites an intense, compartmentalized inflammatory response that leads to chronic airway obstruction and bronchiectasis. Neutrophils migrate into the airway, and released neutrophil elastase contributes to the progression of the lung disease characteristic of CF. We have developed a strategy that permits the delivery of antiproteases to the inaccessible CF airways by targeting the respiratory epithelium via the human polymeric immunoglobulin receptor (hpIgR). A fusion protein consisting of a single-chain Fv directed against secretory component, the extracellular portion of the pIgR, linked to human alpha1-antitrypsin is effectively ferried across human tracheal xenografts and delivers the antiprotease to the apical surface to a much greater extent than occurs by passive diffusion of human alpha1-antitrypsin alone. Targeted antiprotease delivery paralleled hpIgR expression in the respiratory epithelium in vivo and was not increased by escalating dose, so airway penetration was receptor-dependent, not dose-dependent. Thus, this approach provides us with the ability to deliver therapeutics, like antiproteases, specifically to the lumenal surface of the respiratory epithelium, within the airway surface fluid, where it will be in highest concentration at this site.
Glucose Control and Renal and Retinal Complications of Diabetes Mellitus
Authors: Alex M. Saunders
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Chase et al<sup>1</sup>were forced into a working definition of glucose control by the limitation of current technology, so they set arbitrary thresholds on individual glycohemoglobin (Hb A<sub>1c</sub>) readings. A newly developing technology may provide another definition.<sup>2</sup> To deal first with a minor point, the therapeutic definition of "good control" changed during the study. The "poor control" group became better controlled. Maybe the threshold for poor control should be set higher, because the damage was done at a time when the mean Hb A<sub>1c</sub>was well above 12.3%, perhaps closer to 14%. Glucose control is a daily or hourly matter. Yet Hb A<sub>1c</sub>of a whole-blood hemolysate measures the integrated mean of control for 120 days. The contribution of reticulocytes to this mean should be almost zero, while the contribution from the most senescent circulating erythrocytes should be considerably above the mean.
Die Bronchoskopie bei Kindern und Jugendlichen
Authors: H. Doesel
Journal: Endoscopy (1970)

The bronchoscopy is an important tool in diagnosis, treatment and prognosis of broncho-pulmonary diseases of child and adolescent. Since 1955 the author has performed about 7000 bronchoscopies in childhood and adolescence using barbiturate- or Ketanest®-Succinyl-analgesia. Indications may be divided into three main groups: 1. foreign body aspiration, 2. tuberculosis, 3. bronchopulmonary and endothoracic diseases of other origin.
Carcinoma of the Prostate
Authors: George J. Bulkley
Journal: JAMA (1960)

Radioactive gold (Au198) was used with little success in the treatment of 42 patients with carcinoma of the prostate gland. Experiments with dogs injected with Au198, P32, and Y90had shown that these radioactive elements can destroy carcinomatous prostatic tissue and adjacent lymphatic tissue without excessive danger to other tissue nearby. Au198was injected into the patients first in the prostate through an open retropubic (Cherny) operative incision and later as a simple perineal injection with multiple needles. Of the 42 patients, 19 died of prostatic carcinoma, the autopsies showing shrinkage of the tumor in only 3 cases. Seventeen of the 20 living have improved, with noticeable softening of the mass and with temporary arrest of the carcinoma in 10, and complete arrest in 7. Best results were shown in well localized prostatic carcinoma, while large cancerous areas did not respond markedly. Au198does not appear to prolong survival of these patients in most cases but seems more advisable in patients refusing total protato-vesiculectomy.
ELSI Priorities for Brain Imaging
Authors: Judy Illes, Raymond De Vries, Mildred K. Cho, Pam Schraedley-Desmond
Journal: The American Journal of Bioethics (2006)

As one of the most compelling technologies for imaging the brain, functional MRI (fMRI) produces measurements and persuasive pictures of research subjects making cognitive judgments and even reasoning through difficult moral decisions. Even after centuries of studying the link between brain and behavior, this capability presents a number of novel significant questions. For example, what are the implications of biologizing human experience? How might neuroimaging disrupt the mysteries of human nature, spirituality, and personal identity? Rather than waiting for an ethical agenda to emerge from some unpredictable combination of the concerns of ethicists and researchers, the attention of journalists, or after controversy is sparked by research that cannot be retracted, we queried key figures in bioethics and the humanities, neuroscience, media, industry, and patient advocacy in focus groups and interviews. We identified specific ethical, legal and social issues (ELSI) that highlight researcher obligations and the nonclinical impact of the technology at this new frontier. Keywords: neuroethicsneuroimagingpolicy ACKNOWLEDGMENTS We are deeply grateful to all who took part in our focus groups and interviews. This research was supported by The Greenwall Foundation and NIH/NINDS #NS045831. Thanks also to Kim Karetsky, Marisa Gallo, and Doniel Drazin for help with this project, Drs. Thomas A. Raffin and Scott W. Atlas for invaluable scientific advice, and reviewers for thoughtful comments.
Renal Tubular Dysfunction Secondary to Jejunoileal Bypass
Authors: Milton Vainder
Journal: JAMA (1976)

HYPEROXALURIA as a sequel of jejunoileal bypass operation has been reported previously. We were, however, unable to find any reports of renal parenchymal deposition of oxalate with resultant tubular dysfunction. The following report describes such a case. <h3>Report of a Case</h3> A 51-year-old woman gave a long history of obesity characterized by multiple abortive attempts at weight reduction over the preceding 20 years. On Sept 11, 1966, a 61-and 25-cm jejunoileal shunt operation was performed. Her weight at that time was 140.5 kg. No biochemical abnormalities were noted, and the only incidental pathological finding was the presence of cholelithiasis. The patient was given various supplements including vitamins, calcium, and potassium postoperatively. She lost approximately 50 kg over the next year, and for five additional years stabilized at 90.5 kg. In November 1972, an elective cholecystectomy was performed for the relief of recurrent episodes of right-upper-quadrant pain. A revision of the
Keratoacanthoma in a smallpox vaccination site
Authors: S. HAIDER
Journal: British Journal of Dermatology (1974)

Tumours arising at the site of smallpox vaccination are rare. A case of keratoacanthoma developing within 2 months at the site of vaccination is described and a likely role of vaecinia virus in the causation of such a tumour is discussed. Complications of varying type and severity may follow smallpox vaccination. Except for encephalitis, these are not officially notifiable diseases, and thus available statistics on their incidence are often un-reliable; however, a primary tumour developing in the site of vaccination is certainly rare. Lane et al. (1970) in 1,648,000 vaccinations against smallpox described one patient who developed melanoma. We describe here a case of keratoacanthoma developing within 2 months at the site of a successful primary vaccination.
MMC inquiry chairman asks doctors to take part in online survey
Authors: Kaushal Pandey
Journal: BMJ (2007)

The chairman of the inquiry into the government's Modernising Medical Careers (MMC) initiative, John Tooke, has urged doctors to fill in an online questionnaire that has been set up to assist the inquiry.

Professor Tooke was speaking at a conference on the future of postgraduate medical training organised by the Postgraduate Medical Education and Training Board, held last week at the Institute of Directors in London.

The inquiry will gather evidence from questionnaires completed by doctors and interested members of the …