tbuckley/cabot-search huggingface dataset:
Role of Peptide Growth Factors in Development of Macrovascular Complications of Diabetes
Authors: David R Clemmons
Journal: Diabetes Care (1991)

Peptide growth factors provide an important means of coordinating the growth of cells within tissues and organs. Although their role in controlling cell growth is not well understood, they have been implicated in derangements of cellular proliferation that occur in diabetes, e.g., mesangial cell hyperplasia and atherosclerosis. Because several growth factors have been structurally characterized and the cell types on which they act identified, research is focusing on developing model systems to determine whether they are involved in the pathogenesis of specific disease states. New techniques, i.e., in situ hybridization, gene transfection, and detailed structural analysis of proteins, have made it possible to define both changes in the relative abundance of specific growth factors and potential changes in their actions in specific disease states. These techniques are being applied in diabetes research and will make it possible to determine the alterations that have occurred in growth factor synthesis and growth factor-matrix protein interaction and cell-type-specific alterations in cell growth that occur after loss of normal glucose homeostasis. The findings from these types of analyses should lead to a better understanding of how the complications of diabetes develop and rational strategies to control their effects.
Using clinicopathological analysis of general practitioner skin surgery to determine educational requirements and guidelines.
Authors: N. H. Cox, R. Wagstaff, A. W. Popple
Journal: BMJ (1992)

To study the impact of skin surgery in general practice on the workload of a pathology laboratory and to identify what further training might be helpful.Analysis of skin biopsy specimens from general practitioners before and after their new contract to determine numbers of specimens, changes in diagnoses, adequacy of treatment of malignant tumours, and areas of low diagnostic accuracy.District general hospital.All 1017 skin biopsy specimens from general practice for 15 months before and 12 months after the new general practitioner contract.The number of pathology specimens received increased from 16 to 65 per month (median = 6 submitted by each general practitioner in the post-contract year). The proportion of the more common pathological diagnoses was unchanged between the two periods, but the proportion of correctly diagnosed naevi, cysts, and seborrhoeic keratoses increased in the second. Although few diagnoses were overtly incorrect, accurate diagnosis of dermatofibromas and malignancies decreased after the contract, and the overall correct diagnosis rate for seborrhoeic keratoses, dermatofibromas, rashes, and malignancies was below 30%. Only nine out of 21 squamous cell carcinomas were adequately excised with tumour free margins, and follow up of malignant tumours may have been inadequate.Skin surgery in general practice has advantages but matters of concern are the increase in laboratory workload, the excision of some benign lesions, and the inappropriateness of biopsy of rashes. Squamous cell carcinoma and other malignant tumours submitted for pathological examination were often unsuspected and inadequately excised, and heightened suspicion is recommended. Pathology request forms may need redesigning to encourage provision of clinical details.
Study Finds Tdap Vaccine Is Safe for Older Adults
Authors: Rebecca Voelker
Journal: JAMA (2012)

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
Electrophysiological changes in animal model of chronic cardiac failure
Authors: J. D Doherty, S. M Cobbe
Journal: Cardiovascular Research (1990)

Journal Article Electrophysiological changes in animal model of chronic cardiac failure Get access John D Doherty, John D Doherty Department of Medical Cardiology, Queen Elizabeth Building, Royal Infirmary, Glasgow G31 2ER, Scotland Search for other works by this author on: Oxford Academic PubMed Google Scholar Stuart M Cobbe Stuart M Cobbe Department of Medical Cardiology, Queen Elizabeth Building, Royal Infirmary, Glasgow G31 2ER, Scotland Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 24, Issue 4, April 1990, Pages 309–316, https://doi.org/10.1093/cvr/24.4.309 Published: 01 April 1990 Article history Received: 19 June 1989 Accepted: 27 November 1989 Published: 01 April 1990
What do young doctors think of their training and themselves?
Authors: J Parkhouse, M G Campbell
Journal: BMJ (1984)

Of the British qualified doctors whose career preferences and progress we have been surveying, our first group has been in medical practice for 10 years.We thought that this would be a good stage to ask for views about medical training and its effects.Some tentative questions were therefore added to the latest questionnaire, which we sent in 1983 to those who qualified in 1974.We wanted to see if our respondents were interested in a qualitative study of their medical education and, further, if they were willing to engage in a frank self assessment exercise about their own competencies and deficiencies. MethodsWe wrote to 2348 doctors who were known to have qualified in 1974 from medical schools in England, Scotland, and Wales, obtaining addresses and using the methods described for our previous career preference surveys.1-3The general findings, about choices and career progress, will be reported separately.A covering letter gave a brief idea of our thoughts about assessment of training, and self evaluation.We took five major elements of medical practice, which we thought would be relevant to the work of all doctors: clinical skills, teaching ability, research, administration and management, and communication with patients and colleagues.For each of these elements, qualifiers were asked to grade: (a) its importance for their career, using the responses "not important,""minor importance," and "major im- portance"; (b) how well their undergraduate and postgraduate training had met their requirements-as "not at all," "adequately," or "very well"; and (c) their need for further competence or training, or both-as "no need," "some need," or "great need.
PKR negatively regulates leukemia progression in association with PP2A activation, Bcl-2 inhibition and increased apoptosis
Authors: X Cheng, R L Bennett, X Liu, M Byrne, W Stratford May
Journal: Blood Cancer Journal (2013)

Reduced expression and activity of the proapoptotic, double-stranded RNA-dependent protein kinase, PKR (protein kinase R) is observed in breast, lung and various leukemias, suggesting that loss of PKR potentiates transformation. Now we report that decreased PKR activity inhibits chemotherapy-induced apoptosis of leukemia cells both in vitro and in vivo. Inhibition of PKR expression or activity reduces protein phosphatase 2A (PP2A) activity, a B-cell lymphoma 2 (Bcl-2) phosphatase, resulting in enhanced Bcl-2 phosphorylation. Thus, inhibition of PKR activity leads to hyperphosphorylation of Bcl-2, stabilization of Bcl-2/Bax interaction and decreased Bax insertion into the outer mitochondrial membrane. Treatment with the PP2A activator, FTY720, restores Bcl-2 dephosphorylation and apoptosis in cells with reduced PKR expression following stress. Significantly, xenografts of REH leukemic cells with reduced PKR display significantly increased tumor volume, increased resistance to doxorubicin treatment and shorter survival. Importantly, FTY720 treatment restores sensitivity to chemotherapy and prolongs overall survival of these mice. Collectively, these findings suggest that PP2A activation is a downstream target of PKR and the PKR/PP2A signaling axis is required for rapid and potent stress-induced apoptosis. Importantly, loss of PKR promotes leukemia progression and may serve as a biomarker for predicting chemosensitivity.
Small changes to diet could bring substantial health and environmental benefits, say researchers
Authors: J. Wise
Journal: BMJ (2015)

Making even relatively small changes to current UK diets could have a substantial effect on the environment and the population’s health, two research papers have claimed.1 2

The United Kingdom has committed to reducing greenhouse gas emissions by 80% from their 1990 levels by 2050, and some say that this should include a 70% reduction in emissions from the food industry.

Research published in the journal Climatic Change estimated the greenhouse gas emissions associated …
967. Targeted Delivery of Antisense Oligonucleotides to Human T-Leukemia Cells Mediated by Novel Liposomal Formulations: Evaluation of In Vitro and In Vivo Anti-Tumoral Activity
Authors: Cristina Fonseca, Liliana Mendonça, João Nuno Moreira, António Cabrita, Artur Paiva, Maria Teresa Lopes, Maria C. Pedroso de lima, Sérgio Simões
Journal: Molecular Therapy (2006)

Acute Lymphoblastic Leukemia (ALL) is the most prevalent type of cancer, as well as the most common form of leukemia in children. In general, contemporary treatment protocols achieve overall long- term survival rates of 70% to 80%. Nevertheless, patients with T- cell lineage ALL (T-ALL), an aggressive form of the disease, require intensive chemotherapy regimens and often remain refractory to treatment. Therefore, it has already been recognized that alternative therapies are urgently needed for this sub-group of patients. Antisense oligonucleotides (asODNs) have been considered promising tools for the treatment of a variety of malignant diseases due to their ability to specifically inhibit gene expression. However, the successful application of antisense therapy, strongly relies on the development of formulations capable of protecting the genetic material from premature degradation, promoting its specific delivery to target cells or tissues and enhancing its intracellular delivery. In this study, we investigated the efficacy of novel liposome- based strategies to inhibit leukemia cell proliferation in vitro. Formulations consisted of sterically stabilized pH-sensitive liposomes bearing coupled transferrin (Trf) and encapsulating asODNs against mRNA of dihidrofolate reductase (DHFR). In addition, an appropriate animal model of human T-ALL was developed using severe combined immune deficient (SCID) mice and used to evaluate the in vivo anti-tumoral activity mediated by the developed formulations. Significant levels of cytotoxicity were observed upon treatment of HSB-2 cells with targeted liposomes encapsulating asODNs as compared to free drug or a control formulation. Accordingly, a significant reduction on the levels of mRNA and of DHFR activity was observed. Human HSB-2 leukemia cells were successfully engrafted into SCID mice and disseminated in a pattern analogous to human disease, with the presence of malignant cells in blood, bone marrow and infiltration of peripheral organs. Animals treated with asODNs encapsulated in targeted liposomes had significantly less percentage of tumor cells at the sites most frequently manifesting leukemic cell infiltration (such as bone marrow and spleen) as compared to animals treated with free asODNs. Overall, these formulations can be considered promising delivery systems for in vivo targeting of asODNs to leukemia cells and may constitute a novel strategy for the treatment of human leukemias.
Cux1 and Cux2 Regulate Dendritic Branching, Spine Morphology, and Synapses of the Upper Layer Neurons of the Cortex
Authors: Beatriz Cubelos, Alvaro Sebastián-Serrano, Leonardo Beccari, Maria Elisa Calcagnotto, Elsa Cisneros, Seonhee Kim, Ana Dopazo, Manuel Alvarez-Dolado, Juan Miguel Redondo, Paola Bovolenta, Christopher A. Walsh, Marta Nieto
Journal: Neuron (2010)
Impairment of Alveolar Macrophage Transcription in Idiopathic Pulmonary Fibrosis
Authors: Ping Ren, Ivan O. Rosas, Sandra D. MacDonald, Hai-Ping Wu, Eric M. Billings, Bernadette R. Gochuico
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Alveolar macrophages are inflammatory cells that may contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF), which is characterized by excessive alveolar aggregation of cells and extracellular matrix proteins.Objectives: To identify potential molecular mechanisms of IPF.Methods: To examine large-scale gene expression, messenger RNA isolated from alveolar macrophages and peripheral blood mononuclear cells from subjects with IPF and normal volunteers was hybridized to cDNA filters.Measurements and Main Results: We showed that in IPF there is global down-regulation of gene expression in alveolar macrophages but not in blood monocytes. Nuclear run-on and pulse-chase studies showed that alveolar macrophages had significantly reduced transcription (p < 0.01). No significant difference in RNA degradation was found between subjects with IPF and normal volunteers. Western blot analyses revealed that concentrations of transcription factor II-H, a general transcription factor, were significantly lower in alveolar macrophages from subjects with IPF than in those from normal volunteers (p = 0.012).Conclusions: Impaired transcription in IPF is associated with decreased concentrations of transcription factor II-H in alveolar macrophages and may alter the intraalveolar milieu in IPF.
Diagnostic criteria for metabolic syndrome: a comparative analysis in an unselected sample of adult male population
Authors: Pasquale Strazzullo, Antonio Barbato, Alfonso Siani, Francesco P. Cappuccio, Marco Versiero, Pierluigi Schiattarella, Ornella Russo, Sonia Avallone, Elisabetta della Valle, Eduardo Farinaro
Journal: Metabolism (2008)
The 'I' and the 'Not-I': A Study in the Development of Consciousness
Authors: Marjorie C. Meehan
Journal: JAMA (1965)

Although the late C. G. Jung is generally regarded (except by orthodox Freudians) as an important contributor to an understanding of the mind, he has relatively few disciples. Perhaps the difficulty of understanding his writing is one reason for the relative neglect of his work. Therefore, a clearly written interpretation of some of his ideas would be welcome. Dr. Harding, who studied with him in 1922 and since then has practiced "analytical psychology" (the Jungian variety of psychotherapy), here attempts to provide such a contribution, based on a series of lectures to educators and clergymen. The book, intended for lay readers as well as physicians, does not presuppose much knowledge of psychiatry but does demand intelligence and attention of the reader, since it is by no means popularly written. The first chapter attempts to define consciousness and the remainder of the book deals with the development and the role of
mi<scp>RNA</scp>‐155 controls mast cell activation by regulating the <scp>PI</scp>3Kγ pathway and anaphylaxis in a mouse model
Authors: K. Biethahn, Z. Orinska, E. Vigorito, D. A. Goyeneche‐Patino, F. Mirghomizadeh, N. Föger, S. Bulfone‐Paus
Journal: Allergy (2014)

Abstract Background Mast cells ( MC s) play a central role in allergic and inflammatory disorders by rapid degranulation and release of inflammatory mediators upon antigen‐driven engagement of the Fcε RI . Receptor‐mediated MC responses are controlled by the activation of different isoforms of phosphoinositide‐3‐kinase ( PI 3K) and the downstream signaling processes. Recent evidence suggests that mi RNA s are important molecular players regulating the PI 3 K / A kt pathway. Methods The role of miR‐155 in the regulation of MC functions in vivo was studied in the passive cutaneous anaphylaxis ( PCA ) MC ‐dependent model. WT and miR‐155 −/− mice were injected intradermally with anti‐ DNP ‐IgE and intravenously with the antigen DNP ‐ HSA . Ear swelling was assessed to evaluate the anaphylactic response. All investigations, to characterize miR‐155 specific activities in MC s, were conducted comparing WT and miR‐155 −/− bone marrow‐derived MC s ( BMMC s). Results We report that miR‐155 −/− mice display enhanced anaphylaxis reactions. Although miR‐155 −/− BMMC s show normal development, proliferation, and survival, miR‐155 deficiency enhances Fcε RI ‐mediated degranulation and release of TNF ‐α, IL ‐13, and IL ‐6. Interestingly, the level of A kt phosphorylation on both of its regulatory residues Thr308 and Ser473 was increased in miR‐155 −/− compared to WT BMMC s. Gene expression profiling showed that miR‐155 −/− BMMC s exhibited significantly increased expression of the adapter PI 3Kγ subunits Pik3r5 ( p101 ) and Pik3r6 ( p84, p87 PIKAP ). Furthermore, selective blockade of the PI 3Kγ pathway inhibited degranulation in miR‐155 −/− BMMC s. Conclusions Thus, we suggest that miR‐155 plays a critical role in Fcε RI ‐mediated MC responses by modulating components of the PI 3Kγ pathway. This newly identified mechanism of mi RNA ‐controlled MC activation may affect the initiation and maintenance of allergic disorders.
Two Cases of Imperforate Anus
Authors: I. A. J. McCready
Journal: BMJ (1944)

JOUJRNALpresent on gums and palate.The chest was normal.The spleen was palpable and tender.Pathological examination of the stools showed no evidence of dysentery.In four days the stools were repeatedly normal and the blood count was: R.B.C., 2,900,000; Hb, 57%; C.I., 1.0; W.B.C., 13,000.Intensive iron therapy and liver- diet for 16 days produced no beneficial effects-in fact, there was a diminution of 490,000 in the red cell count and 8% in the Hb estimation.His temperature remained normal, his spleen was palpable, and no malaria parasites were found in the blood films.Since neither symptoms nor anaemia had been improved by iron therapy and liver diet this was stopped, and replaced by a full couirse of antimalarial treatment.The response was immediate.By the end of the course he w3,s symptom-free; the spleen was not palpable; and the blood count was: R.
Maturation of fetal hepatocytes in vitro by extracellular matrices and oncostatin M: Induction of tryptophan oxygenase
Authors: Akihide Kamiya, Nobuhiko Kojima, Taisei Kinoshita, Yasuyuki Sakai, Atsushi Miyaijma
Journal: Hepatology (2002)

Previously, we described that embryonic day 14.5 (E14.5) mouse fetal hepatocytes differentiate to express tyrosine amino transferase (TAT) and glucose-6-phosphatase, which are expressed in the perinatal liver, in response to oncostatin M (OSM) or in high-cell-density culture. However, under such conditions, fetal hepatic cells failed to express genes for adult liver-specific enzymes, such as tryptophan oxygenase (TO). Although phenobarbital (PB) and dimethylsulfoxide (DMSO) have been known to maintain the functions of adult hepatocytes in vitro, they failed to induce TO expression in fetal hepatic cells. Thus far, no system has been developed that reproduces terminal differentiation of fetal hepatocytes in vitro. Here, we describe that extracellular matrices derived from Engelbreth-Holm-Swarm sarcoma (EHS) in combination with OSM or high-cell-density culture induced expression of TO as well as cytochrome P450 genes that are involved in detoxification. However, EHS alone was insufficient to induce expression of TO, although it induced TAT expression in fetal hepatocytes. In addition, high-density culture further augmented differentiation. In conclusion, the combination of signals by cytokines, cell-cell contact, and cell-matrix interaction is required for induction of adult liver functions in fetal hepatocytes in vitro. This primary culture system will be useful for studying the mechanism of liver development.
Childhood factors that predict asthma in young adulthood
Authors: B.G. Toelle, W. Xuan, J.K. Peat, G.B. Marks
Journal: European Respiratory Journal (2003)

Predicting adult asthma, using childhood characteristics, is important for advising on prognosis and, potentially, for secondary prevention. A novel use of multivariate likelihood ratios (LRs) to quantify prognosis is described here. Of 718 subjects of a community-based cohort, 575 (80%) members were recruited at age 8–10 yrs and were re-assessed 15–17 yrs later. At baseline, information about symptoms, spirometry, histamine challenge and skin-prick tests were collected. At follow-up “asthma symptoms” were defined as wheeze, sleep disturbance from asthma or inhaled steroid use within the previous year. LRs were calculated for significant predictors of this outcome. Shinkage factors were applied to yield multivariate LRs. Childhood characteristics that independently predicted asthma symptoms in adulthood were obstructive spirometry (adjusted (adj)LR 2.9, 95% confidence interval (CI) 1.3–6.5), airway hyperresponsiveness (adjLR 2.6, 95% CI 1.8–3.7), atopy (adjLR 2.0, 95% CI 1.5–2.7), recent wheeze (adjLR 1.9, 95% CI 1.5–2.5) and being female (adjLR 1.29, 95% CI 0.8–2.1). Children with all five characteristics had a cumulative LR of 36.9 for asthma symptoms in adulthood. Most adults who had asthma symptoms did not have manifestations of asthma as children. However, the presence of obstructive spirometry, airway hyperresponsiveness and atopy in childhood identifies individuals with increased likelihood of having asthma in adulthood. Cumulative likelihood ratios are more valuable than odds ratios for quantifying risk in individuals and for identifying people with most to gain from preventive interventions.
The Argon Laser for Cutaneous Lesions
Authors: L. F. Safer
Journal: JAMA (1982)

To the Editor.—   review article entitled The Argon Laser for Cutaneous Lesions by Apfelburg et al (1981;245:2073) was most timely. However, one might question the practicality of treating seborrheic keratoses with the argon laser. After all, these stuck-on nevoid excrescences are typically amenable to superficial curettage.  Moreover, the authors' description of granuloma faciale as a  dermal inflammatory fibrosis is incorrect. Clinically, this lesion appears as an enlarging, brownish-red plaque of the face that may occasionally manifest follicular dilation.  histopathological pattern is characteristic. 1 Salient features include the presence of a Grenz zone, polymorphous inflammatory infiltrate consisting of histiocytes, lymphocytes, plasma cells, and eosinophils with evidence of leukocytoclasia, and connective tissue trabeculations adjacent to the dermal blood vessels. Therefore, granuloma faciale is a type of leukocytoclastic vasculitis and quite the antithesis of a nonspecific dermatopathic entity.