tbuckley/cabot-search huggingface dataset:
Engraftment and long-term expression of human fetal hemopoietic stem cells in sheep following transplantation in utero.
Authors: E D Zanjani, M G Pallavicini, J L Ascensao, A W Flake, R G Langlois, M Reitsma, F R MacKintosh, D Stutes, M R Harrison, M Tavassoli
Journal: Journal of Clinical Investigation (1992)

Hemopoietic stem cells from human fetal liver were transplanted in utero into preimmune fetal sheep (48-54 days of gestation). The fate of donor cells was followed using karyotype analysis, by immunofluorescence labeling with anti-CD antibodies, and by fluorescent in situ hybridization using human-specific DNA probes. Engraftment occurred in 13 of 33 recipients. Of five live born sheep that exhibited chimerism, all expressed human cells in the marrow, whereas three expressed them in blood as well. Engraftment was multilineage (erythroid, myeloid, and lymphoid) and human hemopoietic progenitors (multipotent colony-forming units, colony-forming units-granulocyte, macrophage, and erythroid burst-forming units) capable of forming colonies in vitro were detected in all five lambs for greater than 2 yr. These progenitors responded to human-specific growth factors both in vitro and in vivo. Thus the administration of recombinant human IL-3 and granulocyte macrophage-colony-stimulating factor to chimeric sheep resulted in a 2.1-3.4-fold increase in the relative expression of donor (human) cells. These results demonstrate that the permissive environment of the preimmune fetal sheep provides suitable conditions for the engraftment and long-term multilineage expression of human hemopoietic stem cells in a large animal model. In this model, donor human cells appear to retain certain phenotypic and functional characteristics that can be used to manipulate the size of donor cell pool.
Condoms and the Prevention of AIDS-Reply
Authors: Marcus A. Conant
Journal: JAMA (1986)

<h3>In Reply.—</h3> I agree fully with Drs Henry and Crossley that sexually active adults and teenagers do not know how to use condoms properly. Unfortunately, major newspapers and networks will not accept condom advertisements; an open discussion of condom use is considered "bad taste." George Schweitzer, the vice president of communications for the CBS broadcasting group, has recently stated, "Contraceptive ads would be an intrusion on the moral and religious beliefs of many members of our audience" (<i>New York Times</i>, Jan 5,1986, p F-10). A 1985 study by McKusick and Coates clearly demonstrated that gay men are no better motivated to use condoms than is the general population. Eighty percent knew that the use of a condom would prevent AIDS transmission; however, only 6% of the same sample actually used condoms.<sup>1</sup> We have an effective way of substantially reducing the transmission of the AIDS retrovirus. Our failure to educate
Serial In Vivo MRI Documents Arterial Remodeling in Experimental Atherosclerosis
Authors: Stephen G. Worthley, Gérard Helft, Valentin Fuster, Azfar G. Zaman, Zahi A. Fayad, John T. Fallon, Juan J. Badimon
Journal: Circulation (2000)

Background —Arterial remodeling in response to atherosclerosis may be outward (positive) or inward (negative) and is an important mechanism in the clinical manifestations of atherosclerosis and restenosis after percutaneous coronary interventions. Postmortem and intravascular ultrasound studies of arterial remodeling do not allow serial and noninvasive data to be obtained. In a rabbit model of atherosclerosis, we sought to validate MRI as a new tool for documentation of arterial remodeling. Methods and Results —Watanabe heritable hyperlipidemic rabbits underwent serial MRI at baseline and 6 months after aortic balloon denudation. The lumen area had a small but significant ( P =0.006) increase, from 4.36±0.16 to 4.89±0.12 mm 2 . There was a large, significant ( P &lt;0.0001) increase in the outer wall area, from 7.96±0.19 to 10.46±0.19 mm 2 . The vessel wall area (a marker of atherosclerotic burden) increased significantly ( P &lt;0.0001), from 3.61±0.07 to 5.57±0.09 mm 2 . Thus, the increase in atherosclerotic burden over time was completely accounted for by positive arterial remodeling. The subgroup used for histopathological validation confirmed a significant ( P &lt;0.0001) agreement between histopathology and MRI for assessment of all 3 parameters. Conclusions —MRI can provide serial and noninvasive data about the arterial wall, allowing assessment of arterial remodeling in this rabbit model. Thus, MRI appears to be a useful tool for the investigation of arterial remodeling both in native atherosclerosis and after percutaneous coronary intervention.
Brigid Gray Leventhal, MD
Authors: Victoria Forlini
Journal: JAMA (1994)

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
Metallothionein messenger RNA regulation in the mottled mouse and Menkes kinky hair syndrome.
Authors: S Packman, R D Palmiter, M Karin, C O'Toole
Journal: Journal of Clinical Investigation (1987)

Menkes kinky hair syndrome is an X-linked neurodegenerative disorder, causing tissue-specific increases in copper and metallothionein content. A mouse model is provided by hemizygotes for mutant alleles at the X-linked mottled locus. Herein we test the possibility that the primary defect in both species is in metallothionein gene regulation. We show that metallothionein-I messenger RNA (mRNA) (mouse) and metallothionein-II mRNA (human) are elevated in mutant fibroblasts. However, comparable dose-response curves in mutant and control cells are generated when mouse metallothionein-I mRNA concentrations are measured in cells exposed to varying concentrations of cadmium or copper (metallothionein inducers). Furthermore, when mutant and control cells are grown to achieve overlapping intracellular copper concentrations in the two cell types, metallothionein-I (mouse) and metallothionein-II (human) mRNA levels are proportional to the intracellular copper concentrations. Finally, in paired determinations in blotchy hemizygote and littermate kidneys containing comparable copper levels, metallothionein-I mRNA contents are very similar. The observations suggest that elevated intracellular copper in these mutants induces metallothionein synthesis by normal regulatory mechanisms.
THREE-DIMENSIONAL ACTIVATION IMAGING ECHOCARDIOGRAHY: A NOVEL ASSESSMENT OF RIGHT VENTRICULAR MECHANICS IN PATIENTS WITH PULMONARY HYPERTENSION
Authors: Akiko Goda, Keiko Ryo, Antonia Delgado-Montero, Bhupendar Tayal, Hunter Champion, John Gorcsan
Journal: Journal of the American College of Cardiology (2014)
Myocsrdial uptake of technetium-99m stannous pyrophosphate following direct current transthoracic countershock.
Authors: V C DiCola, G S Freedman, S E Downing, B L Zaret
Journal: Circulation (1976)

The effect of direct current (DC) countershock upon myocardial technetium-99m stannous pyrophosphate (PYP) uptake was studied in 22 dogs. All eight dogs imaged had positive abnormal PYP scintigrams that were usually indistinguishable from experimental infarction. In three animals, additional areas of radionuclide uptake were seen in overlying noncardiac tissue. Left and right ventricular myocardial PYP uptake averaged (+/- SEM) 23 +/- 5 times control and 24 +/- 6 times control, respectively. These activity ratios occurred without reduction in regional myocardial blood flow (RMBF), and were associated with histologic evidence of necrosis. The necrosis was usually epicardial, corresponding to the transmural site of greatest PYP uptake. The magnitude of PYP accumulation and the weight of damaged tissue increased with increasing applied energy. Thus, PYP uptake following DC countershock could result in false-positive interpretation of acute ischemic myocardial infarction. Since RMBF is normal in regions of PYP uptake, the major determinant of radionuclide accumulation is the extent of cellular damage.
SILICON DIOXIDE CONTENT OF LUNGS IN HEALTH AND DISEASE
Authors: WILLIAM D. McNALLY
Journal: JAMA (1933)

Henke and Lubarsch1found reference to dust as a cause for disease of the lung as early as 1556. Ursinius in 1652 reported two forms of mountain sickness caused by the inhalation of dust. The study of the presence of carbonaceous material within the lungs and its association with pulmonary disease progressed slowly but steadily from that time to the present. The names of Ramazzini2(1717), Bubbe (1721), Leblanc (1795) and Johnstone (1799) are closely allied to the early history and development of pneumonoconiosis. Pearson,3in 1813, applied the term anthracosis to lungs containing carbon particles. The greatest advances in the diagnosis, treatment and prevention of silicosis have been made in the last thirty years. The first report with a microscopic demonstration of silica was made by Peacock4in 1860. In his article, wood cuts were used to demonstrate the presence of carbon and silica in
996. Direct Comparison of Adeno-Associated Virus (AAV) Serotypes for Muscle Expression of Soluble Anti-Angiogenic Proteins
Authors: Mayu Isotani, Koichi Miyake, Noriko Miyake, Yukihiko Hirai, Takashi Shimada
Journal: Molecular Therapy (2006)

Skeletal muscle has been considered an attractive target for gene delivery because of its large size, good capacity for protein synthesis, and easy accessibility for intramuscular injection. Direct injection of viral vectors into muscles was widely used not only for the treatment of muscular disorders but also for expression of secreted proteins to treat variety of diseases such as hemophilia, lysosomal storage disorders, and cancer. Adeno-associated viral (AAV) vectors have been successfully used for long-term expression of transgene products in skeletal muscle. Recently, a number of novel AAV serotypes were isolated from nonhuman primates. In the present work, we attempted to determine which AAV serotype is suitable for muscle expression of anti-angiogenic proteins for systemic cancer gene therapy. We constructed AAV vectors (AAV2/1, AAV2/2, AAV2/ 7, and AAV2/8) expressing secretable murine endostatin (mEnd) or human soluble Flk-1 (hsFlk-1) and examined the secreted therapeutic protein levels in vitro and in vivo. High level of secreted proteins was observed in supernatant of AAV transduced murine myoblast cell line (C2C12) by ELISA analysis. The highest protein level of both mEnd and hsFlk-1 was obtained from AAV2/1 transduced C2C12 cells (1>>8>7>2). On the other hand, when these vectors (5x1010 particle each) were injected into a quadriceps muscle of immunocompetent C57BL/6 mice, the highest serum level of therapeutic protein was observed in AAV2/8 injected mice (8>7>1>2) one week after injection. Sustained expression of mEnd was detected at least for four months. In contrast, the serum level of hsFlk-1 was rapidly decreased to the background level two weeks after injection, although ELISA analysis demonstrated continuous expression of hsFLK-1 in the muscle. There is an apparent discrepancy between the transduction efficiency (1>7>8>2) and the serum levels of secreted protein (8>7>1>2). When we injected AAV vector expressing hsFlk-1 into muscle of immunodeficient mice (CB17scid), sustained expression of serum hsFlk-1 was detected for four months, indicating that secreted hsFlk-1 protein may elicit a strong immune response in immunocompetent mice with rapid elimination of secreted proteins by neutralizing antibody against hsFlk-1. AAV mediated expression of secreted protein seems to be influenced by various factors. AAV2/8 vector is the most efficient for expression of anti-angiogenic proteins. Control of antigenicity of secreted protein is the key element for achiving long-term secretion from muscle of immunocompetent animals
Blood: Gift or Merchandise—Towards an International Blood Policy
Authors: Edgar H. Pierce
Journal: JAMA (1983)

This carefully written text has a conversational style and fluently covers the topic of world utilization of blood and blood products. The book is decidedly philosophic but includes a strong vein of scientific data. The text openly looks at the problems of commercial<i>v</i>volunteer blood donation and considers the viewpoint of the donor, the patient, the medical profession, and the pharmaceutical industry, as well as the organizations that make their livelihood with blood products. Those persons involved in the industrial aspect of blood procurement may be interested in the detail and philosophic comments as well as the worldwide overview of this text. The content would also be enlightening to those persons more peripheral to the blood-processing industry. The author mentions how large the industry is in terms of dollar production, which in some instances is staggering. One definitely gets the impression that no matter how "nonprofit" an involvement is
Induction of differentiation in the human leukemia cell line SPI‐802: Morphological, immunological, and isoenzymatic changes
Authors: Hans Guenter Drexler, Gerhard Gaedicke, Atsushi Komiyama, Jun Minowada
Journal: American Journal of Hematology (1986)

Abstract The phorbolester 12‐0‐tetradecanoylphorbol 13‐acetate (TPA) was used for the induction of differentiation in cells of the human leukemia cell line SPI‐802. The cellular morphology, surface marker antigen expression, and isoenzyme profiles of four enzymes (carboxylic esterase, acid phosphatase, hexosaminidase, and lactate dehydrogenase) served as parameters for monitoring the induced phenotypical changes. TPA led to distinct alterations of the morphology and significantly affected the growth rate with cessation of cell proliferation. No major increase in the number of nitro blue tetrazolium‐positive cells or aggregation of cells, phagocytosis of latex beads, adherence to plastic surface, or development of pseudopodia were observed. As TPAtreated SPI‐802 cells remained negative for these markers of the monocyte‐macrophage complex, it can be concluded that the cells did not differentiate into monocytes and macrophages. The immunological marker profile based on testing of 55 monoclonal antibodies, terminal deoxynucleotidyl transferase and two erythrocyte rosette tests indicated a differentiation of SPI‐802 cells along the granulocytic cell lineage. This was confirmed by isoenzyme analysis, especially that of carboxylic esterase. An isoenzyme specific for monocytes and macrophages was not detected. In earlier studies it was found that SPI‐802 cells produce hemoglobin upon exposure to TPA or hemin. This latter observation and the present results suggested a comparison with the two erythroleukemia cell lines K‐562 and HEL. SPI‐802 cells appear to have the potential to differentiate along several cell lineages.
Safety profile and clinical activity of sifalimumab, a fully human anti-interferon monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study
Authors: J. T. Merrill, D. J. Wallace, M. Petri, K. A. Kirou, Y. Yao, W. I. White, G. Robbie, R. Levin, S. M. Berney, V. Chindalore, N. Olsen, L. Richman, C. Le, B. Jallal, B. White
Journal: Annals of the Rheumatic Diseases (2011)

Type I interferons (IFNs) appear to play a central role in disease pathogenesis in systemic lupus erythematosus (SLE), making them potential therapeutic targets.Safety profile, pharmacokinetics, immunogenicity, pharmacodynamics and clinical activity of sifalimumab, an anti-IFNα monoclonal antibody, were assessed in a phase I, multicentre, randomised, double-blind, dose-escalation study with an open-label extension in adults with moderately active SLE.received one intravenous dose of sifalimumab (n=33 blinded phase, 0.3, 1, 3, 10 or 30 mg/kg; n=17 open-label, 1, 3, 10 or 30 mg/kg) or placebo (n=17). Each phase lasted 84 days.Adverse events (AEs) were similar between groups; about 97% of AEs were grade 1 or 2. All grade 3 and 4 AEs and all serious AEs (2 placebo, 1 sifalimumab) were deemed unrelated to the study drug. No increase in viral infections or reactivation was observed. Sifalimumab caused dose-dependent inhibition of type I IFN-induced mRNAs (type I IFN signature) in whole blood and corresponding changes in related proteins in affected skin. Exploratory analyses showed consistent trends toward improvement in disease activity in sifalimumab-treated versus placebo-treated subjects. A lower proportion of sifalimumab-treated subjects required new or increased immunosuppressive treatments (12% vs 41%; p=0.03) and had fewer Systemic Lupus Erythematosus Disease Activity Index flares (3% vs 29%; p=0.014).Sifalimumab had a safety profile that supports further clinical development. This trial demonstrated that overexpression of type I IFN signature in SLE is at least partly driven by IFNα, and exploratory analyses suggest that IFNα inhibition may be associated with clinical benefit in SLE. Trial registration number NCT00299819.
HLA antibodies—the cause of platelet alloimmunization in chinese
Authors: Mo‐Ping Chow, Chien‐Hui Yung, Hui‐Yu Hu, Jaw‐Lin Tzeng, Jeong‐Shi Lin, Wen‐Mei Lin, Chung‐King Lin
Journal: American Journal of Hematology (1992)

Abstract Lymphocytotoxicity test (LCT) and platelet suspension immunofluorescence test (PSIFT) were used together to screen platelet‐associated antibodies in patients who received long‐term platelet transfusion. Twenty‐four of 53 patients (45.3%) were immunized subsequently. Since the concordence of LCT and PSIFT was 100%, most of the platelet associated antibodies were of HLA specificity, and platelet specific antibody alone (in absence of HLA) was not detected. The identified antibodies were anti‐A2, A11, A24, B5, B46, B57, B60, and B62. The majority of them were against the high frequency HLA antigens in the Chinese population. The development of antibody could not be correlated with the number of platelet‐donors exposed, the time interval after the initiation of platelet transfusion, or the percentage of reactive lymphocytotoxic panels. HLA antibody was the major factor in causing platelet alloimmunization in the Chinese patients. However, some other unknown factors should be looked for. In addition, ABO incompatibility did not affect the posttransfusional increment while the platelet was compatible with LCT crossmatching.
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy
Authors: Bhaswati Pandit, Anna Sarkozy, Len A Pennacchio, Claudio Carta, Kimihiko Oishi, Simone Martinelli, Edgar A Pogna, Wendy Schackwitz, Anna Ustaszewska, Andrew Landstrom, J Martijn Bos, Steve R Ommen, Giorgia Esposito, Francesca Lepri, Christian Faul, Peter Mundel, Juan P López Siguero, Romano Tenconi, Angelo Selicorni, Cesare Rossi, Laura Mazzanti, Isabella Torrente, Bruno Marino, Maria C Digilio, Giuseppe Zampino, Michael J Ackerman, Bruno Dallapiccola, Marco Tartaglia, Bruce D Gelb
Journal: Nature Genetics (2007)
Hospital Delays in Reperfusion for ST-Elevation Myocardial Infarction
Authors: Duane S. Pinto, Ajay J. Kirtane, Brahmajee K. Nallamothu, Sabina A. Murphy, David J. Cohen, Roger J. Laham, Donald E. Cutlip, Eric R. Bates, Paul D. Frederick, Dave P. Miller, Joseph P. Carrozza, Elliott M. Antman, Christopher P. Cannon, C. Michael Gibson
Journal: Circulation (2006)

It has been suggested that the survival benefit associated with primary percutaneous coronary intervention (PPCI) in ST-segment elevation myocardial infarction may be attenuated if door-to-balloon (DB) time is delayed by >1 hour beyond door-to-needle (DN) times for fibrinolytic therapy. Whereas DB times are rapid in randomized trials, they are often prolonged in routine practice. We hypothesized that in clinical practice, longer DB-DN times would be associated with higher mortality rates and reduced PPCI survival advantage. We also hypothesized that in addition to PPCI delays, patient risk factors would significantly modulate the relative survival advantage of PPCI over fibrinolysis.DB-DN times were calculated by subtracting median DN time from median DB time at a hospital using data from 192,509 patients at 645 National Registry of Myocardial Infarction hospitals. Hierarchical models that adjusted simultaneously for both patient-level risk factors and hospital-level covariates were used to evaluate the relationship between PCI-related delay, patient risk factors, and in-hospital mortality. Longer DB-DN times were associated with increased mortality (P<0.0001). The DB-DN time at which mortality rates with PPCI were no better than that of fibrinolysis varied considerably depending on patient age, symptom duration, and infarct location.As DB-DN times increase, the mortality advantage of PPCI over fibrinolysis declines, and this advantage varies considerably depending on patient characteristics. As indicated in the American College of Cardiology/American Heart Association guidelines, both the hospital-based PPCI-related delay (DB-DN time) and patient characteristics should be considered when a reperfusion strategy is selected.
Diuretic treatment in decompensated cirrhosis and congestive heart failure.
Authors: A L Gerbes, R M Arendt
Journal: BMJ (1986)

SIR,-Dr Helmer Ring-Larsen and others (24 May, p 1351) suggest that the blunted renal response to a diuretic agent in the upright as compared with the supine position is due to the activation of several hormonal mechanisms. They found evidence for increased activity of the sympathetic nervous system and of the reninaldosterone axis and mention vasopressin as another important homoeostatic measure. However, they do not consider the possible role of the atrial natriuretic factor. Several observations indicate that this novel diuretic and natriuretic peptide' has a substantial role in volume homoeostasis. We and others have shown that patients with hypertension or congestive heart failure show greatly increased plasma concentrations of atrial natriuretic factor, which are well correlated with right atrial pressures.23 In patients with cirrhosis we showed that discontinuation of diuretic treatment could increase circulating concentrations of atrial natriuretic factor.4 Values in children with renal, insufficiency are greatly increased and correlate well with the degree ofvolume expansion; they are significantly reduced after volume reduction by haemodialysis.5 Changes in posture influence plasma atrial natriuretic factor values.6 In the supine position central venous and right atrial pressure increase due to volume shifting. Such an increase, induced by head out water immersion, has been shown to stimulate release of atrial natriureticfactorinhealthy subjects7andin patients with cirrhosis.' These findings support the contention that atrial natriuretic factor is an important factor in volume regulation in health as well as disease. Determination of atrial natriuretic factor concentrations might be useful in studies ofvolume regulation and might elucidate the still unresolved complex of posture dependent diuresis. ALEXANDER L GERBES RAINERM ARENDT