tbuckley/cabot-search huggingface dataset:
Mash1 and Neurogenin 2 Enhance Survival and Differentiation of Neural Precursor Cells After Transplantation to Rat Brains via Distinct Modes of Action
Authors: Sang-Hoon Yi, A-Young Jo, Chang-Hwan Park, Hyun-Chul Koh, Rae-Hee Park, Haeyoung Suh-Kim, Incheol Shin, Yong-Sung Lee, Jaesang Kim, Sang-Hun Lee
Journal: Molecular Therapy (2008)

Neural precursor cells (NPCs) are regarded as a promising source of donor cells in transplantation-based therapies for neurodegenerative disorders. However, poor survival and limited neuronal differentiation of the transplanted NPCs remain critical limitations for developing therapeutic strategies. In this study, we investigated the effects of the proneural basic helix-loop-helix (bHLH) transcription factors Mash1 and Neurogenin 2 (Ngn2) in neuronal differentiation and survival of NPCs. Induction of Mash1 or Ngn2 expression strikingly enhanced neuronal differentiation of cultured NPCs in vitro. Ngn2-transduced NPCs underwent a rapid cell cycle arrest, which often accompanies differentiation. In contrast, cells continuously expanded upon Mash1 expression during NPC differentiation. Notably, sonic hedgehog (SHH) was upregulated by Mash1 and mediated the proliferative and survival effects of Mash1 on NPCs. Upon transplantation into adult rat brains, Mash1-expressing NPCs yielded large grafts enriched with neurons compared to control LacZ-transduced NPCs. Interestingly, enhancements in neuronal yield, as well as in donor cell survival, were also achieved by transplanting Ngn2-transduced NPCs. We show that a differentiation stage- and cell density-dependent survival effect of Ngn2 involves neurotrophin3 (NT3)/TrkC-mediated signaling. Together, these findings suggest potential benefits of bHLH gene manipulation to develop successful transplantation strategies for brain disorders.
Iron-Deficiency Pruritus
Authors: John R. T. Reeves
Journal: JAMA (1977)

<h3>To the Editor.—</h3> Lewiecki and Rahman recently reported what they described as the first report of pruritus as a manifestation of iron deficiency (236:2319, 1976). This is an association that has been studied for several years by C. F. H. Vickers, and he has presented findings at numerous scientific meetings. I am aware of only one published report from his findings; it is a summary of 14 years of experience<sup>1</sup>in which 59 patients with iron deficiency and itching are described. Of particular importance are the following: (1) in many of the patients there was no anemia, but serum iron levels were low, (2) in men with low iron levels, anemia, and pruritus, 12 of 13 were subsequently found to have underlying neoplasia or reticulosis. His number of cases has doubled since that report, and the findings are holding up. I have examined serum iron levels in several patients with
The sickening of medical research
Authors: N Moore
Journal: BMJ (1988)

Another factor that contributes to the development and especially the severity of the infection is deficiency of the comiiplement component properdin.Meningococcal infections associated with properdin deficiency have a fatality rate approaching 75"!0I.Propcrdin stabilises the in- herentlv labile (3 and C5 convertases."The severe meningococcal infCctions in people with properdin deficiencv contrast with the mild disease in people with deficiencies of the terminal components of complement.'Several factors mav influence the outcome in patients with properdin deficiencv.Opsonisation is unimpaired in terminal deficiencies, but pro- perdin deficiency is associated with impaired serum opsonisation and bactcricidal rcactions.The abilitv to dissolve immunocomplexes in vivo is absent in serum dcficicnt in properdin."The ability to opsonisc cndotoxin coatcd oil drops is also absent., and inability to clear endotoxin could influence the progression of the diseasc.
International response risks undermining Haiti's health system, warns relief agency
Authors: P. Moszynski
Journal: BMJ (2011)

<b>Summary</b> <b>Background and objectives</b> Low physical activity (PA) is a risk factor for mortality in the general population. This is largely unexplored in renal transplant recipients (RTRs). We studied whether PA is associated with cardiovascular and all-cause mortality in a prospective cohort of RTR. <b>Design, setting, participants, &amp; measurements</b> Between 2001 and 2003, 540 RTRs were studied (age, 51 ± 12 years; 54% male). PA was assessed using validated questionnaires (Tecumseh Occupational Activity Questionnaire and the Minnesota Leisure Time Physical Activity Questionnaire). Cardiovascular and all-cause mortality were recorded until August 2007. <b>Results</b> Independent of age, PA was inversely associated with metabolic syndrome, history of cardiovascular disease, fasting insulin, and triglyceride concentration, and positively associated with kidney function and 24-hour urinary creatinine excretion (<i>i.e.,</i> muscle mass). During follow-up for 5.3 years (range, 4.7 to 5.7 years), 81 RTRs died, with 37 cardiovascular deaths. Cardiovascular mortality was 11.7, 7.2, and 1.7%, respectively, according to gender-stratified tertiles of PA (<i>P</i> = 0.001). All-cause mortality was 24.4, 15.0, and 5.6% according to these tertiles (<i>P</i> &lt; 0.001). In Cox regression analyses, adjustment for potential confounders including history of cardiovascular disease, muscle mass, and traditional risk factors for cardiovascular disease did not materially change these associations. <b>Conclusions</b> Low PA is strongly associated with increased risk for cardiovascular and all-cause mortality in RTRs. Intervention studies are necessary to investigate whether PA improves long-term survival after renal transplantation.
Psychosocial Aspects of HIV Treatment
Authors: Kristin Brousseau
Journal: JAMA (2007)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 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
Physicians show strong leadership in US accountable care organizations but surgeons are largely left out
Authors: M. McCarthy
Journal: BMJ (2014)

Physicians are assuming strong leadership roles in the new accountable care organizations (ACOs), but the organizations appear to be paying little attention to surgical care, two new studies in the journal Health Affairs have said.1 2

ACOs are groups of providers who enter a contract to care for a set group of patients and, in return for containing costs and meeting specific quality goals, receive financial rewards such as bonuses or a share in the savings that they generate. Proponents of the ACOs have said that the organizations create an alternative to the highly fragmented, fee for service model that currently dominates the US healthcare delivery system and will provide more cost effective, comprehensive, coordinated care.

The 2010 Affordable Care Act created a voluntary ACO program for Medicare, the US health insurance plan for elderly and disabled people, but many private insurers have also adopted the model. More than 600 ACOs operate in the United States.

In the first study Carrie H Colla, of the Dartmouth Institute for Health Policy and Clinical Practice …
The Changing Base Line of Complex Ventricular Arrhythmias
Authors: Craig M. Pratt, George Delclos, Ann M. Wierman, Sara A. Mahler, A. Allen Seals, Carlos A. Leon, James B. Young, Miguel A. Quinones, Robert Roberts
Journal: New England Journal of Medicine (1985)

Initial base-line electrocardiograms are used to assess the efficacy of treatment for ventricular arrhythmias. This approach assumes that in the absence of treatment the frequency of arrhythmia would remain constant. To test the validity of this assumption, we studied 26 clinically stable patients with symptomatic but not life-threatening ventricular arrhythmias, during two periods of placebo treatment separated by a mean of 17 months. As compared with the initial placebo period, there were significant reductions in ventricular premature depolarizations (50 per cent), pairs (65 per cent), and ventricular tachycardia (83 per cent) during the second period of placebo administration (P≤0.05 for all comparisons). Over one third of the patients gave the appearance of receiving successful therapy during the second placebo period, even when the reported spontaneous variability of ventricular arrhythmia was taken into consideration. If unrecognized, these long-term spontaneous changes in the frequency of arrhythmia could result in continuation of unnecessary and potentially toxic therapy and lead to incorrect conclusions regarding the efficacy of antiarrhythmic drugs in clinical trials. We therefore recommend that the frequency of arrhythmia be reassessed annually in the absence of treatment in patients similar to those in our study. These recommendations should not be applied to patients with life-threatening ventricular arrhythmias. (N Engl J Med 1985; 313:1444–9.)
Community occupational therapy for older patients with dementia and their care givers: cost effectiveness study
Authors: Maud J L Graff, Eddy M M Adang, Myrra J M Vernooij-Dassen, Joost Dekker, L Jönsson, Marjolein Thijssen, Willibrord H L Hoefnagels, Marcel G M Olde Rikkert
Journal: BMJ (2008)

<b>Objective</b> To assess the cost effectiveness of community based occupational therapy compared with usual care in older patients with dementia and their care givers from a societal viewpoint. <b>Design</b> Cost effectiveness study alongside a single blind randomised controlled trial. <b>Setting</b> Memory clinic, day clinic of a geriatrics department, and participants' homes. <b>Patients</b> 135 patients aged ≥65 with mild to moderate dementia living in the community and their primary care givers. <b>Intervention</b> 10 sessions of occupational therapy over five weeks, including cognitive and behavioural interventions, to train patients in the use of aids to compensate for cognitive decline and care givers in coping behaviours and supervision. <b>Main outcome measures</b> Incremental cost effectiveness ratio expressed as the difference in mean total care costs per successful treatment (that is, a combined patient and care giver outcome measure of clinically relevant improvement on process, performance, and competence scales) at three months after randomisation. Bootstrap methods used to determine confidence intervals for these measures. <b>Results</b> The intervention cost €1183 (£848, $1738) (95% confidence interval €1128 (£808, $1657) to €1239 (£888, $1820)) per patient and primary care giver unit at three months. Visits to general practitioners and hospital doctors cost the same in both groups but total mean costs were €1748 (£1279, $2621) lower in the intervention group, with the main cost savings in informal care. There was a significant difference in proportions of successful treatments of 36% at three months. The number needed to treat for successful treatment at three months was 2.8 (2.7 to 2.9). <b>Conclusions</b> Community occupational therapy intervention for patients with dementia and their care givers is successful and cost effective, especially in terms of informal care giving.
THE RELATION OF THE MEDICAL PROFESSION TO WAR
Authors: V. Matthews
Journal: BMJ (1906)

<h3>Objective:</h3> To estimate the impact of caesarean delivery on the incidence of selected neonatal outcomes. <h3>Patients and methods:</h3> A 15-year, population-based, cohort study (1988–2002) using the Nova Scotia Atlee Perinatal Database compared neonatal outcomes in term newborns born by spontaneous and assisted vaginal delivery, with newborns born by caesarean delivery, with and without labour, using multiple logistic regression. <h3>Results:</h3> From a total of 142 929 deliveries, there were 27 263 caesarean deliveries, 61% of which were performed in labour. Relative risks were adjusted for year of birth, maternal age, parity, smoking, maternal weight at delivery, hypertensive diseases, diabetes, previous caesarean delivery, use of regional anaesthesia, induction of labour, gestational age at delivery and large and small for gestational age, where significant. Caesarean delivery in labour, but not caesarean delivery without labour, had increased risks for depression at birth and neonatal respiratory conditions compared with spontaneous or assisted vaginal delivery. Compared with spontaneous vaginal delivery and assisted vaginal delivery, the risk of major neonatal birth trauma was decreased for infants after caesarean delivery with labour (odds ratio (OR) = 0.34, 95% CI 0.21 to 0.56 and OR = 0.07, 95% CI 0.04 to 0.11, respectively) and caesarean delivery without labour (OR = 0.20, 95% CI 0.08 to 0.52 and OR = 0.04, 95% CI 0.02 to 0.10, respectively). <h3>Conclusion:</h3> Caesarean delivery in labour, compared with vaginal delivery, is more likely to be associated with an increased risk for respiratory conditions and depression at birth than caesarean delivery without labour. Caesarean delivery appears protective against neonatal birth trauma, especially when performed without labour.
Abstract 4399: EphA2-targeting antibody-gelonin conjugate specifically binds and kills target-expressing tumor cells, including multi-drug resistant (MDR) lines
Authors: John W. Marks, John Gooya, Nabendu Pore, Shenlan Mao, Dowdy Jackson, Michael G. Rosenblum
Journal: Cancer Research (2010)

Abstract The EphA2 receptor is over-expressed on the surface of many different human tumors, and has been shown to internalize upon ligand or antibody binding. The fully human monoclonal antibody anti-EphA2 antibody was developed by phage display methods and specifically binds both human and rodent EphA2 receptors. The type II ribosome-inactivating protein gelonin was genetically engineered with an extra cysteine residue to facilitate chemical cross-linking with targeting proteins. The fully human anti-EphA2 antibody, anti-EphA2 antibody, was conjugated to the recombinant gelonin (rGel) using the heterobifunctional cross-linker SPDP and partially reduced rGel. The conjugated antibody (anti-EphA2 antibody/rGel) was separated from free antibody and rGel by gel-permeation and affinity chromatography. The final material was composed of antibody+1 rGel (predominant) and antibody+2 rGel (minor) and was essentially free of contaminating rGel or unreacted anti-EphA2 antibody. The anti-EphA2 antibody/rGel conjugate was assessed for cell-free protein synthesis inhibitory activity and found to be similar to free rGel. The conjugate proved specifically cytotoxic to the EphA2 expressing PC-3, MDA-MB-231 and CT-26 cell lines, with IC50 values of 3.8, 6.1 and 11 ng/ml, respectively. The Targeting Index for the anti-EphA2 antibody/rGel conjugate (vs. rGel) was high, with values of 1909, 306 and 75 for PC-3, PC-3-MDR and MDA-MB-231, respectively. Confocal microscopy showed that the anti-EphA2 antibody/rGel conjugate was specifically and rapidly internalized. The maximal intracellular concentration was achieved 4 hours after exposure. Minimal contact time studies showed specific cytotoxicity with only 1 hour exposure while optimal cytotoxicity was achieved with an exposure time of 24 hours. Of special interest, the anti-EphA2 antibody/rGel conjugate demonstrated no significant loss in specific cytotoxicity against Dox-resistant (MDR expressing) cell lines derived from either MDA-MB-231 or PC-3 cells compared to their parental cell lines. These data suggest that the development of MDR-resistant phenotypes may not impair the successful utilization of rGel-based targeted therapeutics. These results support the continued evaluation of the rGel antibody conjugate technology. Research conducted, in part, by the Clayton Foundation for Research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4399.
Fungiform papillary glossitis: atopic disease in the mouth?
Authors: R. Marks, C.E. Scarff, L.M. Yap, V. Verlinden, D. Jolley, J. Campbell
Journal: British Journal of Dermatology (2005)

Asthma, eczema and hay fever are the classical manifestations of atopic disease. Geographic tongue (benign migratory glossitis) has also been reported to be a manifestation. Anecdotally, atopic people frequently report irritation of the tongue by heat and certain foods, which may be more common than realized.To determine whether atopic people have an increased likelihood of a sensitive tongue manifest as inflamed fungiform papillae and a history of irritation by certain foods.A descriptive classification of inflammation of the fungiform papillae on the tongue was developed using a 9-point analogue scale where 1 was considered normal and 9 was considered to be severely inflamed. An opportunistic sample of participants were classified as atopic or not on the basis of a personal history of asthma, eczema or hay fever. An examination of the tongue was performed using the classification and then a questionnaire was administered on whether they burnt their tongue easily with hot food and whether they were irritated by certain foods.There were 200 participants aged 20 years and over of whom 104 (52%) were classified as atopic on the basis of the personal history. There was a significant positive association between increasingly inflamed fungiform papillae and the likelihood of being atopic. There was also a positive association between increasing inflammation of the fungiform papillae and a history of both burning the tongue easily and irritation of the tongue by food. There was an increased likelihood of a history of irritation of the tongue with certain foods amongst atopic participants and they were also more likely to burn their tongue with hot food than those who were nonatopic.Atopic people are more likely than the normal community to have inflammation of the fungiform papillae of their tongue which correlates with a history of a sensitive tongue manifest as irritation by heat and certain foods. These data suggest that atopic disease may occur in the mouth as a common inflammatory change on the tongue-fungiform papillary glossitis.
Comparison of Four Chemotherapy Regimens for Advanced Non–Small-Cell Lung Cancer
Authors: Joan H. Schiller, David Harrington, Chandra P. Belani, Corey Langer, Alan Sandler, James Krook, Junming Zhu, David H. Johnson
Journal: New England Journal of Medicine (2002)

We conducted a randomized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non–small-cell lung cancer.
The effect of physical activity on serum total and low-density lipoprotein cholesterol concentrations varies with apolipoprotein E phenotype in male children and young adults: The cardiovascular risk in young finns study
Authors: Simo Taimela, Terho Lehtimäki, Kimmo V.K. Porkka, Leena Räsänen, Jorma S.A. Viikari
Journal: Metabolism (1996)
Interleukin 1 stimulates T lymphocytes to produce granulocyte-monocyte colony-stimulating factor.
Authors: F Herrmann, W Oster, S C Meuer, A Lindemann, R H Mertelsmann
Journal: Journal of Clinical Investigation (1988)

T lymphocytes are thought to cooperatively interact with monocytes to produce colony-stimulating factors (CSF). However, little is known about monocyte-mediated signals leading to CSF-secretion by T lymphocytes, although soluble monocyte products have been implicated. We have employed monoclonal antibody anti-T3B covalently coupled to CnBr-activated Sepharose 4B beads, to show that multimeric ligation of T cell antigen receptor leads to T cell receptiveness to interleukin 1 (IL-1), as indicated by T cell production of CSF, which induces growth of myeloid progenitor cells into neutrophil, eosinophil, and monocyte colonies. To investigate the molecular basis of these findings, total RNA was extracted from T3B Sepharose-primed and IL-1-stimulated T lymphocytes and probed for granulocyte-monocyte-CSF (GM-CSF), granulocyte-CSF (G-CSF), and monocyte-CSF (M-CSF) mRNA. GM-CSF, but not G-CSF or M-CSF, messages were detected. Nuclear "run on" assays revealed that IL-1 action is effective primarily at the level of GM-CSF gene transcription. These results suggest a previously unrecognized role of IL-1 in the regulation of GM-CSF secretion by T cells.
Endoplasmic reticulum-associated calcium regulates taxol-induced apoptosis in breast cancer cells.
Authors: Z Pan, L Gollahon
Journal: Cancer Research (2009)

Abstract Abstract #4163 Background: The body eliminates unhealthy cells through programmed cell-suicide called apoptosis. Calcium (Ca2+), one of the key regulators of cell survival, is also important in regulating apoptosis. Although the chemotherapeutic agent Taxol employs apoptosis to induce cell death in breast cancer treatment, the exact mechanism of how it induces apoptosis and the role of Ca2+ in this process remain unclear. The endoplasmic reticulum (ER), the main intracellular Ca2+ store, is newly-recognized as an important gateway in apoptosis, and possibly provides a target for Taxol.&amp;#x2028; Objective/Hypothesis: Putting these facts together, our hypothesis is that ER Ca2+ changes induced by Taxol determine breast cancer cell susceptibility to apoptosis and thus play a key role in ER-associated apoptosis. Therefore, this study investigated whether Ca2+ changes, especially associated with the ER, were generated and related to this apoptotic event.&amp;#x2028; Study Design and Methods: For this study, we used the MDA-MB-468 breast cancer cell line. The dynamic Ca2+ changes induced by Taxol were determined in living breast cancer cells by two methods: free cytosolic Ca2+ changes were measured using Fluo4-AM Ca2+ dye; and ER Ca2+ changes were measured by a novel Ca2+ cameleon, D1ER. After inducing and evaluating Taxol-induced apoptosis in this breast cancer cell line, the effects of different Ca2+ interfering agents on the apoptotic event were tested to determine whether Taxol-induced apoptosis is Ca2+ dependent.&amp;#x2028; Results: Taxol has a direct effect on Ca2+ homeostasis. Taxol induces a rapid ER Ca2+ release and results in a transient increase in cytosolic Ca2+ levels. A gradual ER Ca2+ depletion developed and contributed to the final sustained cytosolic Ca2+ increase. Interfering with these Ca2+ changes inhibited the Taxol-induced apoptosis, indicating that ER Ca2+ promotes Taxol-induced apoptosis.&amp;#x2028; Relevance: It is critical to understand the process through which the widely used anticancer agent Taxol induces apoptosis. This research addressed the question of whether intracellular Ca2+ changes play a critical or marginal role in mediating Taxol-induced apoptosis. Elucidating the role of calcium in this process will not only help to clarify the mechanism of Taxol, but also aid in more effective application of Taxol in breast cancer treatment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4163.