tbuckley/cabot-search huggingface dataset:
Differentiation, Survival, and Function of Embryonic Stem Cell–Derived Endothelial Cells for Ischemic Heart Disease
Authors: Zongjin Li, Jenny C. Wu, Ahmad Y. Sheikh, Daniel Kraft, Feng Cao, Xiaoyan Xie, Manishkumar Patel, Sanjiv S. Gambhir, Robert C. Robbins, John P. Cooke, Joseph C. Wu
Journal: Circulation (2007)

Background— Embryonic stem (ES) cells are distinguished by their capacity for self-renewal and pluripotency. Here we characterize the differentiation of ES cell–derived endothelial cells (ESC-ECs), use molecular imaging techniques to examine their survival in vivo, and determine the therapeutic efficacy of ESC-ECs for restoration of cardiac function after ischemic injury. Methods and Results— Murine ES cells were transfected with a construct composed of a vascular endothelial cadherin promoter driving enhanced green fluorescence protein (pVE-cadherin-eGFP). Differentiation of ES cells to ECs was detected by FACS analysis using Flk-1 (early EC marker at day 4) and VE-cadherin (late EC marker at day 8). After isolation, these ESC-ECs express endothelial cell markers similar to adult mouse lung endothelial cells, form vascular-like channels, and incorporate DiI-labeled acetylated low-density lipoprotein (DiI-Ac-LDL). For in vivo imaging, ES cells were transduced with an ubiquitin promoter driving firefly luciferase and monomeric red fluorescence protein (pUb-Fluc-mRFP). A robust correlation exists between Fluc signals and cell numbers by ex vivo imaging analysis ( R 2 =0.98) and by in vitro enzyme assay ( R 2 =0.94). Afterward, 5×10 5 ESC-ECs or PBS (as control) was injected into the hearts of mice undergoing LAD ligation (n=15 per group). Bioluminescence imaging showed longitudinal survival of transplanted ESC-ECs for ≈8 weeks. Echocardiogram demonstrated significant functional improvement in the ESC-EC group compared with control ( P =0.04). Finally, postmortem analysis confirmed increased presence of small capillaries and venules in the infarcted zones by CD31 staining. Conclusions— This is the first study to track the fate and function of transplanted ESC-ECs in the heart. With further validation, these ESC-ECs could become a valuable source of cell therapy for induction of angiogenesis in the treatment of myocardial ischemia.
A key cytokine unlocks the door
Authors: H SHIRIN, S F MOSS
Journal: Gut (1999)

<h3>ABSTRACT</h3> Mitochondria are essential organelles in eukaryotic cells that provide critical support for energetic and metabolic homeostasis. Mutations that accumulate in mitochondrial DNA (mtDNA) in somatic cells have been implicated in cancer, degenerative diseases, and the aging process. However, the mechanisms used by somatic cells to maintain proper functions despite their mtDNA mutation load are poorly understood. Here, we analyzed somatic mtDNA mutations in more than 30,000 human single peripheral and bone marrow mononuclear cells and observed a significant overrepresentation of homoplastic mtDNA mutations in B, T and NK lymphocytes despite their lower mutational burden than other hematopoietic cells. The characteristic mutational landscape of mtDNA in lymphocytes were validated with data from multiple platforms and individuals. Single-cell RNA-seq and computational modeling demonstrated a stringent mitochondrial bottleneck during lymphocyte development likely caused by lagging mtDNA replication relative to cell proliferation. These results illuminate a potential mechanism used by highly metabolically active immune cells for quality control of their mitochondrial genomes.
STUDIES ON THE BIOCHEMICAL DEFECT OF PERNICIOUS ANEMIA. I. IN VITRO OBSERVATIONS ON OXYGEN CONSUMPTION, HEME SYNTHESIS AND DEOXYRIBONUCLEIC ACID SYNTHESIS BY PERNICIOUS ANEMIA BONE MARROW12
Authors: E. Donnall Thomas, Harry L. Lochte
Journal: Journal of Clinical Investigation (1958)

In microbiological systems, folic acid and vita- min B12 appear to be important in the synthesis of purines and pyrimidines, in the synthesis of methyl groups, and possibly in the synthesis of deoxyribose (1-3).Studies at the clinical level, summarized by Mueller and Will (4), indicate that similar biochemical processes may be involved in patients with pernicious anemia (P.A.). Be- cause such studies on patients are difficult to carry out and interpret, precise methods of in vitro as- sessment of the biochemical activity of P. A. mar- row cells are needed.Direct studies on P. A. marrow have been con- fined, for the most part, to observations of morphologic changes and cell counts in tissue culture(5-12).In attempting to avoid the difficulties inherent in evaluating these changes in tissue cul- ture and in an effort to secure more direct biochemical information, P. A. marrow has been studied in our laboratory by the following techniques: 1) oxygen consumption, 2) heme synthesis as measured by the rate of incorporation of C14- glycine into heme, and 3) deoxyribonucleic acid (DNA) synthesis by measurement of the rate of incorporation of C14-formate into thymine.With these techniques, which permit measure- ments of biochemical activity over short periods of time and with small amounts of bone marrow, we have attempted to answer the following ques- tions: 1) Does vitamin B12 have a direct effect on P. A. marrow cells?2) Why has the liquid cul- ture-vaccine vial technique failed to demonstrate an
Epigenetics, DNA Methylation, and Chromatin Modifying Drugs
Authors: Moshe Szyf
Journal: The Annual Review of Pharmacology and Toxicology (2008)

Evidence is emerging that several diseases and behavioral pathologies result from defects in gene function. The best-studied example is cancer, but other diseases such as autoimmune disease, asthma, type 2 diabetes, metabolic disorders, and autism display aberrant gene expression. Gene function may be altered by either a change in the sequence of the DNA or a change in epigenetic programming of a gene in the absence of a sequence change. With epigenetic drugs, it is possible to reverse aberrant gene expression profiles associated with different disease states. Several epigenetic drugs targeting DNA methylation and histone deacetylation enzymes have been tested in clinical trials. Understanding the epigenetic machinery and the differential roles of its components in specific disease states is essential for developing targeted epigenetic therapy.
THE COLONY MORPHOLOGY OF TUBERCLE BACILLI
Authors: Kenneth C. Smithburn
Journal: The Journal of Experimental Medicine (1935)

All the strains of human tubercle bacilli described in this report as recently isolated from clinical cases proved to be virulent and showed but slight differences in pathogenic properties. Neither did they show extreme variation in virulence when compared with Strain H-37, isolated many years ago. Between twelve bovine strains cultivated in vitro for varying periods, there was a much wider range in virulence, some being so attenuated as to give regressive lesions in both rabbits and guinea pigs, while other strains were highly pathogenic. In general, the more recently isolated strains were the more virulent. Attenuation occurs with prolonged in vitro cultivation, but the rate of attenuation is apparently not the same for all strains. Studies of cultures recovered from inoculated animals demonstrated that in the case of bovine tubercle bacilli virulence is correlated with three phenomena: the number of bacilli which can be stained in tissues of inoculated animals, the number of organisms recoverable in cultures from the tissues, and the proportion of smooth colonies in these cultures. All cultures of either human or bovine type recovered from animals showed either two or three types of colonies. In general the percentage of the smooth form varied directly with virulence. However, some smooth colonies were present in strains having little or no pathogenicity. One example was cited of an avian strain which had lost its virulence while retaining the smooth colony form-indicating that, although pathogenicity is usually correlated with smooth colony form, it is not necessarily so. And smooth variants devoid of virulence do occur. In the comparison of the effect of the same human strain on rabbits and guinea pigs, it was shown that native resistance (of the rabbit) was associated with a power to dissociate the inoculated bacilli into a greater proportion of rough forms, and then to destroy them. This power is not possessed by the naturally susceptible animal (guinea pig).
Combined treatment with low-dose methotrexate and initial short-term superpotent topical steroids in bullous pemphigoid: an open, multicentre, retrospective study
Authors: A. Du-Thanh, S. Merlet, H. Maillard, P. Bernard, P. Joly, E. Estève, M.A. Richard, C. Pauwels, S. Ingen-Housz-Oro, B. Guillot, O. Dereure
Journal: British Journal of Dermatology (2011)

The interest of long-term superpotent topical steroids (STS) in bullous pemphigoid (BP) has been supported by randomized controlled trials. However, inadequate compliance, poor cutaneous tolerance and nursing difficulties are potential drawbacks. Open-label studies on limited series of patients suggested that low-dose methotrexate (MTX) may be useful, permitting long-term maintenance of a clinical remission obtained by initial, short-term STS.Open, clinical records-based retrospective analysis of a multicentre series of patients receiving a combined regimen of initial, short-term STS and MTX followed by long-term MTX alone. The primary objective was evaluation of the clinical efficiency of this strategy based on initial clinical remission and subsequent clinical maintenance. The secondary objective was evaluation of the tolerance (type and rating of adverse events) of this combined regimen.Seventy patients with BP (mean age 82·7 years) were included. Treatment consisted of an initial combination of STS and MTX for a mean duration of 12·3 weeks followed by long-term MTX alone for a mean duration of 8·48 months with a mean and median MTX dosage of 10 mg per week.One hundred per cent of the patients showed an initial, complete clinical remission after a mean time interval of 21·9 days. The overall rate of long-term disease control was 76%, whereas 24% of patients experienced at least one relapse during subsequent treatment with MTX alone. Drug-related adverse effects were mainly haematological and gastrointestinal and resulted in treatment discontinuation in 11 patients (16%). Six patients (9%) died during the follow-up period with one death (1%) most likely to be related to treatment.Long-term low-dose MTX combined with short-term STS may result in protracted control of BP in carefully selected patients. These results should prompt randomized controlled trials comparing this treatment with the more usual regimen of long-term STS alone.
Bacteriological and endotoxin studies in cases of ulcerative colitis submitted to surgery.
Authors: K R Palmer, B I Duerden, C D Holdsworth
Journal: Gut (1980)

Culture for bacteria and assays for endotoxin were performed on specimens of mesenteric and peripheral venous blood from eight patients with ulcerative colitis who underwent surgery for severe uncontrolled disease. No significant bacteraemia occurred in either portal or systemic blood. Systemic endotoxaemia developed in three patients during surgery but occurred before bowel mobilisation only in the one patient whose colitis was complicated by hyposplenism. Mesenteric endotoxaemia occurred in only three patients before bowel mobilisation, but was detected during surgery in two of the three patients who developed systemic endotoxaemia. We conclude that, contrary to earlier reports, portal bacteraemia must be infrequent in ulcerative colitis. Systemic endotoxaemia does, however, occur in a significant proportion of cases during colectomy. Although in the patients studied this led to no clinical problems, it is likely to have been the precipitating factor for the syndrome of disseminated intravascular coagulation (DIC) that we have previously observed after colectomy in some of our patients with hyposplenism secondary to inflammatory bowel disease.
Settling Short on Tobacco
Authors: A M Brandt, J B Richmond
Journal: JAMA (1997)

IN THE LAST MONTH, since the announcement of a proposed comprehensive tobacco settlement, many critics have raised serious objections. In particular, they have properly focused on the proposed weakening of the Food and Drug Administration's recently acquired authority to regulate nicotine, as well as limitations on future class-action litigation and punitive damages. Little attention, however, has been focused on the potential public health benefits associated with a wide range of antitobacco litigation that inevitably would at tract intense media coverage. The settlement of major tobacco suits and the limitations on other antitobacco litigation would mark the decline of intense tobacco media attention that has, over the last quarter-century, transformed the meaning of cigarette use in American society. Above all else, the proposed settlement would spare the tobacco industry years of devastating publicity. If the attorneys general's cases, as well as others, are litigated, they will bring into the open
Impact of a Clinical Decision Rule on Hospital Triage of Patients With Suspected Acute Cardiac Ischemia in the Emergency Department
Authors: Brendan M. Reilly
Journal: JAMA (2002)

from the emergency department (ED) with possible acute cardiac ischemia, only one quarter are diagnosed with unstable angina or acute myocardial infarction (MI), and less than 5% experience a life-threatening complication. 1,2any of these patients are admitted unnecessarily to cardiac care units.At the same time, 2% to 5% of patients with acute cardiac ischemia are improperly diagnosed in the ED and not triaged to cardiac care units. 3-8Some of these patients experience life-threatening complications, raising concerns about the safety of physicians' decisions.0][11][12][13][14][15][16][17] However, no study has addressed whether accurate risk stratification can improve physicians' decisions in triaging patients to these different levels of care.In 1996, Goldman and colleagues 1 published their prediction rule for complications in ED patients with suspected acute cardiac ischemia.Although these investigators derived and validated their prediction rule in more
Mast cells are one major source of interleukin-4 in atopic dermatitis
Authors: L. HORSMANHETMO, I.T. HARVIMA, A. JARVIKALLIO, R.J. HARVIMA, A. NAUKKARINEN, M. HORSMANHEIMO
Journal: British Journal of Dermatology (1994)

Several reports have shown the presence of T-helper lymphocytes with Th2 characteristics in the skin lesions of atopic dermatitis (AD). However. Th2 cells themselves require an exogenous pulse of IL-4 to initiate their differentiation and synthesis of IL-4. As mast cells have recently been shown to contain IL-4, this finding prompted us to investigate IL-4 in mast cells of AD lesions, to determine if they might provide the IL-4 pulse needed by the Th2 cells. In this study, we measured IL-4 immunoreactivity in mast cells of non-lesional and lesional skin sections from 20 patients with AD. Ten patients with nummular eczema (NE) without any atopic features or background, and five healthy subjects, served as the control groups. Mast cells were first identified using an enzyme-histochemical staining method for tryptase. Subsequently, the sections were photographed, the tryptase stain was removed, and IL-4 was demonstrated with a polyclonal antibody. The sections were photographed again, and the percentage of IL-4-positive mast cells was calculated. The percentage of mast cells exhibiting IL-4 immunoreactivity in the upper dermis in lesional vs, non-lesional skin was 66±18% vs. 37±18% in AD (P<0.0001, paired t-test), but only 46±19% vs. 31±22% in NE. In the skin of healthy controls, only 23±25% of the mast cells were positive for IL-4. In addition, a significant difference was found between lesional skin of AD vs. NE patients (P<0.008, unpaired t-test). Moreover, the staining intensity of IL-4 in mast cells was clearly increased in the lesional compared with the non-lesional AD skin. Mast cells appeared to be the main cell type containing IL-4 in 40% of the lesional AD skin specimens, whereas in the remaining 60% prominent IL-4-positive mononuclear cell infiltrates were also present. In the non-lesional skin, mast cells appeared to be the main cell type containing IL-4 in all specimens. These results indicate that mast cells are one major source of IL-4 in lesional and non-lesional AD skin, and they could contribute significantly to the development of AD.
Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial
Authors: Otto Metzger Filho, Anita Giobbie-Hurder, Elizabeth Mallon, Barry Gusterson, Giuseppe Viale, Eric P. Winer, Beat Thürlimann, Richard D. Gelber, Marco Colleoni, Bent Ejlertsen, Marc Debled, Karen N. Price, Meredith M. Regan, Alan S. Coates, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2015)

To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma.
Increased Ras Expression and Caspase-Independent Neuroblastoma Cell Death: Possible Mechanism of Spontaneous Neuroblastoma Regression
Authors: C. Kitanaka
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Neuroblastoma undergoes spontaneous regression frequently during its natural course. Although programmed cell death (PCD) has been implicated in this process, accumulating evidence suggests that apoptosis, a form of PCD that is regulated by caspases, may not play a major role. We examined the mechanism(s) of spontaneous regression of neuroblastoma, focusing on the role of Ras, a favorable prognostic marker of neuroblastoma. Methods: Tumor tissues were analyzed by light microscopy, electron microscopy, and immunohistochemistry to examine cell degeneration and expression of Ras and several indicators of PCD. Cell degeneration was also studied in vitro in neuroblastoma cells transfected with the H-ras gene. All statistical tests were two-sided. Results: Immunohistochemical analyses revealed that Ras expression was increased in areas of cellular degeneration lacking apoptotic characteristics. The degenerating cells were fragmented without nuclear condensation and, essentially, lacked caspase-3 activation and apoptotic DNA fragmentation. These cells had ultrastructural features of autophagic degeneration, another form of PCD that is distinct from apoptosis. Focal areas of degeneration associated with Ras expression were seen more frequently in tumors from patients detected in a mass-screening program (53 [60.9%] of 87) than in tumors from clinically detected, advanced-stage patients over 1 year of age (7 [29.2%] of 24) (P = .006; chi-square test), suggesting a positive relationship between Ras-associated degeneration and probability of spontaneous regression/favorable prognosis. The characteristic features of Ras-associated nonapoptotic degeneration observed in tumor samples were recapitulated in vitro by transfection-mediated Ras expression, and Ras-mediated degeneration was augmented by TrkA, another favorable prognostic marker. Conclusions: High-level expression of H-Ras in neuroblastoma cells is associated with caspase cascade-independent, nonapoptotic PCD. This Ras-mediated nonapoptotic tumor cell death may play a key role in spontaneous regression of neuroblastoma.
Sexual Intercourse: You, Me, and the Microbe Makes Three
Authors: Piet C. de Groen
Journal: JAMA (1987)

To the Editor.—  In a recent article by Ellison and McGregor,1the recurrence of lower-extremity streptococcal erythroderma in women was found to be related to intercourse. We have observed postcoital urinary tract symptoms in two men with prostatitis.  Report of Cases.—Case 1.—  A 26-year-old man was admitted to the hospital for shaking chills and 40.1°C temperature. In the previous six months he had experienced four flares of chronic prostatitis for which he was being treated with sulfamethoxazole and trimethoprim, 160/800 mg twice daily. Cultures were never taken. The night of admission he had had intercourse with his wife, during which he experienced bilateral inguinal pain. Within minutes after ejaculation, fever and chills developed. He noticed dysuria and cloudy urine. However, during hospitalization all cultures (blood for bacteria and fungi [four]; urine for bacteria [one]; and urethra for bacteria [one],Neisseriagonorrhoeae[two],Chlamydia[one], andUreaplasma[one])
Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis
Authors: Lara Jehi, Ruta Yardi, Kevin Chagin, Laura Tassi, Giorgio Lo Russo, Gregory Worrell, Wei Hu, Fernando Cendes, Marcia Morita, Fabrice Bartolomei, Patrick Chauvel, Imad Najm, Jorge Gonzalez-Martinez, William Bingaman, Michael W Kattan
Journal: The Lancet Neurology (2015)
Oncolysis of Prostate Cancers Induced by Vesicular Stomatitis Virus in PTEN Knockout Mice
Authors: Maryam Moussavi, Ladan Fazli, Howard Tearle, Yubin Guo, Michael Cox, John Bell, Christopher Ong, William Jia, Paul S. Rennie
Journal: Cancer Research (2010)

Vesicular stomatitis virus (VSV) is an oncolytic virus which selectively infects and kills cancer cells. The goal of the present study was to determine the safety and efficacy of VSV treatment of prostate tumors that arise in situ in immunocompetent, transgenic prostate-specific PTEN-null (PTEN(-/-)) mice. Interferon-sensitive VSV(AV3 strain), which expresses luciferase, was injected intraprostatically into tumor-bearing PTEN(-/-) and control mice and then monitored for tissue bioluminescence over 96 hours. Virus readily dispersed throughout the bodies of mice after only 3 hours; however, it persisted at high levels for >72 hours in PTEN(-/-) mice, but at relatively low levels and for only approximately 48 hours in controls. Plaque assays provided a similar pattern, with much higher concentrations of replicating virus in prostates of PTEN(-/-) mice than in controls. Transient, low levels of virus were detected in the spleens of both groups. Apoptotic analyses by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that VSV(AV3) is able to selectively infect and kill prostate cells in PTEN(-/-) mice, while sparing normal cells in control mice. The primary mechanism for cell kill is apparently apoptotic oncolysis as opposed to neutrophil invasion as has been reported using xenograft models. These results suggest that control of locally advanced human prostate cancer may be achievable through intraprostatic injection and amplification of a safe oncolytic virus, such as VSV(AV3).
Response to Letter Regarding Article, “Impact of Pretreatment With Clopidogrel on Initial Patency and Outcome in Patients Treated With Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: A Systematic Review
Authors: Pieter J. Vlaar, Tone Svilaas, Kevin Damman, Bart J.G.L. de Smet, Hans L. Hillege, Felix Zijlstra, Jan G.P. Tijssen
Journal: Circulation (2009)