tbuckley/cabot-search huggingface dataset:
Muscarinic inhibitory autoreceptors in different generations of human airways.
Authors: R E ten Berge, J Zaagsma, A F Roffel
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The present study was undertaken to investigate the functional presence of inhibitory muscarinic M2 autoreceptors on postganglionic cholinergic nerve endings in different generations of human airways. To this end, the effects of the M2-selective muscarinic receptor antagonists AQ-RA 741 and gallamine were studied on electrical field stimulation-induced twitch contractions of preparations from trachea and from bronchial airways of varying diameter. Furthermore, electrically evoked release of endogenous acetylcholine from human bronchial preparations, and the effect of the muscarinic receptor antagonist atropine thereon, was measured by high-performance liquid chromatography. On average, twitch contractions were significantly but only slightly (11 to 15%) potentiated by M2-selective concentrations of AQ-RA 741 and gallamine, despite approximately half of the preparations showing no potentiation at all. A subdivision into airway generations showed that M2 autoreceptor function was not readily detectable in bronchioles and subsegmental bronchi. By contrast, both with AQ-RA 741 and gallamine a clear potentiation (26 to 36%) of the twitch contractions was observed in approximately half of the terminal bronchi and in all central airway preparations. Moreover, the evoked release of endogenous acetylcholine in terminal and subsegmental bronchi was significantly facilitated by atropine, to 162 to 189% of controls. These results provide strong and partly direct evidence for the existence of inhibitory muscarinic M2 receptors on postganglionic cholinergic nerve endings in human central airways and subsegmental and terminal bronchi, but not in bronchioli. It remains to be established, however, why these M2 receptors exhibit a rather variable functionality in regulating cholinergic nerve-mediated contraction in different airway generations.
The effect of flow on Doppler estimates of bioprosthetic mitral valve function in vitro
Authors: J. B CHAMBERS, T. COCHRANE, M. M BLACK, G. JACKSON
Journal: Cardiovascular Research (1989)

Journal Article The effect of flow on Doppler estimates of bioprosthetic mitral valve function in vitro Get access JOHN B CHAMBERS, JOHN B CHAMBERS **From the Cardiac Department, Guy's Hospital, London SE1, UK Address for correspondence and reprints: Dr JB Chambers, Cardiac Dept, Guy's Hospital, London SE1 9RT, UK. Search for other works by this author on: Oxford Academic PubMed Google Scholar THOMAS COCHRANE, THOMAS COCHRANE †From the Department of Medical Physics and Clinical Engineering, Royal Hallamshire Hospital, Sheffield S102JF, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar MARTIN M BLACK, MARTIN M BLACK †From the Department of Medical Physics and Clinical Engineering, Royal Hallamshire Hospital, Sheffield S102JF, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar GRAHAM JACKSON GRAHAM JACKSON **From the Cardiac Department, Guy's Hospital, London SE1, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 23, Issue 12, December 1989, Pages 1007–1014, https://doi.org/10.1093/cvr/23.12.1007 Published: 01 December 1989 Article history Accepted: 03 June 1989 Published: 01 December 1989
Clinical Recognition of Innocent Cardiac Murmurs in Children
Authors: Robert F. Castle
Journal: JAMA (1961)

The author has presented a classification comprising 5 major innocent murmurs which have been described on the basis of their own positive features. These include the vibratory, pulmonic ejection, and cardiorespiratory murmurs, the venous hum, and the carotid bruit. Each type may simulate the murmur of one or more organic cardiac lesions. Simultaneous phonocardiograms and electrocardiograms, taken from 5 patients between 6 and 8 years of age, are reproduced to illustrate these points. A clinical approach is discussed which should enable the physician to establish a positive diagnosis of the specific innocent murmur or organic lesion without recourse to expensive or hazardous diagnostic procedures.
New treatment improves symptoms of Parkinson's disease
Authors: S. Mayor
Journal: BMJ (2002)

Patients with advanced Parkinson's disease have shown dramatic improvements in the preliminary results of a small pilot study of a technique whereby a growth factor is pumped directly into dopamine deficient areas of the brain.

Neurologists working at the Frenchay Hospital in Bristol implanted catheters in the brains of five patients with Parkinson's disease (unilaterally affected, Hoehn and Yahr stage III; age range 46-62 years). The catheters were situated in the dorsal putamen—the region of the brain controlling movement that becomes deficient in the neurotransmitter dopamine in …
Should treatment recommendations for lipid lowering drugs be based on absolute coronary risk or risk reduction?
Authors: S Ramachandran
Journal: BMJ (2000)

P < 0.0001).When individual variables were subjected to logistic regression, male sex, age, blood pressure, smoking status, and cholesterol concentrations were all significant predictors of heart disease but when corrected for the Framingham risk score no single factor remained predictive on its own.The figure shows the number of coronary events predicted by the Framingham model and the number observed during follow up.The agreement is good at a predicted event rate above 30% (1.5% per year), with no significant difference between the observed and expected event rates (P = 0.85).However, at lower event rates the predictive model significantly underestimates the number of observed events (P < 0.01).The wide confidence intervals indicate that there is significant overlap between risk scores in those participants who developed heart disease and those who did not.
Abstract 3967: ErbB2/HER2-specific natural killer cells for adoptive immunotherapy of glioblastoma.
Authors: Concong Zhang, Kurt Schönfeld, Michael Burger, Sabrina Genßler, Christiane Sahm, Christian Brendel, Sonja Naundorf, Marcus Odendahl, Ulrike Köhl, Torsten Tonn, Manuel Grez, Joachim P. Steinbach, Winfried S. Wels
Journal: Cancer Research (2013)

Abstract In addition to primary natural killer (NK) cells, continuously growing cytotoxic cell lines such as NK-92 are being considered for adoptive cancer immunotherapy. High cytotoxicity of NK-92 has been shown against malignant cells of hematologic origin in preclinical studies, and general safety of infusion of NK-92 cells has been established in phase I clinical trials. To enhance their therapeutic utility, we genetically modified NK-92 cells to express chimeric antigen receptors (CAR) specific for different tumor-associated surface antigens including ErbB2 (HER2). Such CAR were composed of a tumor-specific scFv antibody fragment fused via hinge and transmembrane domains to intracellular signaling proteins such as CD3 zeta chain or a composite CD28-CD3 zeta fusion molecule. Glioblastoma multiforme (GBM) is the most common and severe intracranial malignant tumor in humans. Despite aggressive therapy, recurrence of GBM is very frequent, and the median survival of GBM patients is only 12 to 15 months. Since enhanced ErbB2 expression was found in up to 80% of GBM cases, adoptive ErbB2-targeted immunotherapy may represent a more efficient alternative to standard therapy. For development towards clinical applications, here we generated a lentiviral second generation CAR construct (5.28.z) specific for the ErbB2 antigen, and established GMP-compliant protocols for transduction and expansion of NK-92 cells. An ErbB2-specific single cell clone (NK-92/5.28.z) was isolated, which showed high and selective cytotoxicity towards different established ErbB2-expressing glioblastoma cells and tumor cells of various other origins in vitro, as well as specific tumor homing in murine in vivo models. Treatment with NK-92/5.28.z cells also resulted in marked inhibition of the growth of subcutaneous glioblastoma xenografts in NOD/SCID γc KO mice. Ongoing work now focuses on evaluating the feasibility and efficacy of intracranial application of NK-92/5.28.z cells in orthotopic xenograft models of ErbB2-positive glioblastoma cells as a basis for further development of these cells as an adoptive immunotherapy for glioblastoma patients. Citation Format: Concong Zhang, Kurt Schönfeld, Michael Burger, Sabrina Genßler, Christiane Sahm, Christian Brendel, Sonja Naundorf, Marcus Odendahl, Ulrike Köhl, Torsten Tonn, Manuel Grez, Joachim P. Steinbach, Winfried S. Wels. ErbB2/HER2-specific natural killer cells for adoptive immunotherapy of glioblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3967. doi:10.1158/1538-7445.AM2013-3967
Localization of the gene for familial dysautonomia on chromosome 9 and definition of DNA markers for genetic diagnosis
Authors: Anat Blumenfeld, Susan A. Slaugenhaupt, Felicia B. Axelrod, Diane E. Lucente, Channa Maayan, Christopher B. Liebert, Laurie J. Ozelius, James A. Trofatter, Jonathan L. Haines, Xandra O. Breakefield, James F. Gusella
Journal: Nature Genetics (1993)
Grass tablet sublingual immunotherapy downregulates the TH2 cytokine response followed by regulatory T-cell generation
Authors: Abel Suárez-Fueyo, Tania Ramos, Agustín Galán, Lucia Jimeno, Peter A Wurtzen, Alicia Marin, Consolación de Frutos, Carlos Blanco, Ana C Carrera, Domingo Barber, Rosa Varona
Journal: Journal of Allergy and Clinical Immunology (2013)
Treatment of Depression-Reply
Authors: E. H. Uhlenhuth
Journal: JAMA (1983)

In Reply.—  These letters suggest the need for explicit clarification of certain issues implicit in my editorial entitled Depressives, Doctors, and Antidepressants.  Doubtless there would be general agreement that chlordiazepoxide is [not] preferentially indicated compared with imipramine in patients who have been depressed for at least three months, with a Hamilton test score of 25 or higher, probable or definite endogenous syndrome, and required admission as inpatients. The question is how faithfully this description, the sample studied by Keller et al, and the patients seen by investigators in tertiary-care centers generally represent depressed persons in the community who do not contact the medical care system or who are seen by primary care physicians.  Systematic information about this point apparently is not yet available. Conversations with research psychiatrists who have long experience in working with family physicians suggest that depressed persons seen in primary care settings tend to be less severely
Fundamentals of Cancer Prevention
Authors: James R. Egner
Journal: JAMA (2009)

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 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
Herpes Zoster with Postherpetic Neuralgia -- Persisting Pain and Frustration
Authors: Donald H. Gilden
Journal: New England Journal of Medicine (1994)

Herpes zoster (shingles) is an acute infection of the dorsal-root ganglia and skin caused by a reactivation of varicella-zoster virus, the cause of chickenpox. It is characterized by pain and vesicles on an erythematous base limited to one to three dermatomes. In immunocompromised persons, widespread viral infection of skin (disseminated zoster) and viscera may lead to fatal pneumonitis, hepatitis, or encephalitis.Zoster is common. The annual incidence in the United States is 4 per 1000 population1. After the age of 50 years, the rate of zoster increases to 5.1 per 1000 patients, and among octogenarians it is 10.1 per . . .
Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group.
Authors: M Marre, X Jeunemaitre, Y Gallois, M Rodier, G Chatellier, C Sert, L Dusselier, Z Kahal, L Chaillous, S Halimi, A Muller, H Sackmann, B Bauduceau, F Bled, P Passa, F Alhenc-Gelas
Journal: Journal of Clinical Investigation (1997)

Diabetic nephropathy is a glomerular disease due to uncontrolled diabetes and genetic factors. It can be caused by glomerular hypertension produced by capillary vasodilation, due to diabetes, against constitutional glomerular resistance. As angiotensin II increases glomerular pressure, we studied the relationship between genetic polymorphisms in the renin-angiotensin system-angiotensin I converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II, subtype 1, receptor-and the renal involvement of insulin-dependent diabetic subjects with proliferative retinopathy: those exposed to the risk of nephropathy due to diabetes. Of 494 subjects recruited in 17 centers in France and Belgium (GENEDIAB Study), 157 (32%) had no nephropathy, 104 (21%) incipient (microalbuminuria), 126 (25 %) established (proteinuria), and 107 (22%) advanced (plasma creatinine > or = 150 micromol/liter or renal replacement therapy) nephropathy. The severity of renal involvement was associated with ACE insertion/deletion (I/D) polymorphism: chi2 for trend 5.135, P = 0.023; adjusted odds ratio attributable to the D allele 1.889 (95% CI 1.209-2.952, P = 0.0052). Renal involvement was not directly linked to other polymorphisms. However, ACE I-D and AGT M235T polymorphisms interacted significantly (P = 0.0166): in subjects with ACE ID and DD genotypes, renal involvement increased from the AGT MM to TT genotypes. Thus, genetic determinants that affect renal angiotensin II and kinin productions are risk factors for the progression of glomerular disease in uncontrolled insulin-dependent diabetic patients.
Tempo and Mode of Human and Simian T-Lymphotropic Virus (HTLV/STLV) Evolution Revealed by Analyses of Full-Genome Sequences
Authors: M. Salemi, J. Desmyter, A.-M. Vandamme
Journal: Molecular Biology and Evolution (2000)

We investigated the tempo and mode of evolution of the primate T-lymphotropic viruses (PTLVs). Several different models of nucleotide substitution were tested on a general phylogenetic tree obtained using the 20 full-genome HTLV/STLV sequences available. The likelihood ratio test showed that the Tamura and Nei model with discrete γ-distributed rates among sites is the best-fitting substitution model. The heterogeneity of nucleotide substitution rates along the PTLV genome was further investigated for different genes and at different codon positions (cdp's). Tests of rate constancy showed that different PTLV lineages evolve at different rates when first and second cdp's are considered, but the molecular-clock hypothesis holds for some PTLV lineages when the third cdp is used. Negative selection was evident throughout the genome. However, in the gp46 region, a small fragment subjected to positive selection was identified using a Monte Carlo simulation based on a likelihood method. Employing correlations of the virus divergence times with anthropologically documented migrations of their host, a possible timescale was estimated for each important node of the PTLV tree. The obtained results on these slow-evolving viruses could be used to fill gaps in the historical records of some of the host species. In particular, the HTLV-I/STLV-I history might suggest a simian migration from Asia to Africa not much earlier than 19,500–60,000 years ago.
Highlighting the Role of FDG PET Scan in Early Response Assessment of Gastrointestinal Stromal Tumor Treated With Imatinib Mesylate
Authors: Suman A. Abhyankar, Narendra Nair
Journal: Clinical Nuclear Medicine (2008)

A 55-year-old man presented with a progressively increasing mass in the abdomen. The biopsy on debulking surgery demonstrated a gastrointestinal stromal tumor (GIST) with immunopositivity for c-kit. A CT scan done before the initiation of imatinib mesylate therapy demonstrated a generalized solid heterogeneous mass occupying the entire omentum and paracolic gutters and peritoneal spaces with encasement of the entire liver and spleen with peritoneal deposits. An F-18 FDG PET scan was done before the initiation of therapy. The scan demonstrated intense and nonhomogeneous uptake involving almost the entire abdomen. The maximum standardized uptake value (SUVmax) of the mass was 9.59. The FDG PET scan was repeated 24 hours after a single dose of 400 mg of imatinib (approximately 48 hours after the baseline scan), which demonstrated significant reduction in the metabolic activity, observed in the preimatinib scan. The SUVmax was now 2.47. The present case highlights the role of FDG PET scan in assessment of tumor response to imatinib as early as 24 hours.
Destabilized Adhesion in the Gastric Proliferative Zone and c-Src Kinase Activation Mark the Development of Early Diffuse Gastric Cancer
Authors: Bostjan Humar, Ryuji Fukuzawa, Vanessa Blair, Anita Dunbier, Helen More, Amanda Charlton, Han Kwang Yang, Woo Ho Kim, Anthony E. Reeve, Iain Martin, Parry Guilford
Journal: Cancer Research (2007)

Abstract The initial development of diffuse gastric cancer (DGC) is poorly understood. The study of E-cadherin (CDH1) germ line mutation carriers predisposed to DGC provides a rare opportunity to elucidate the genetic and biological events surrounding disease initiation. Samples from various stages of hereditary and sporadic DGC were investigated to determine general mechanisms underlying early DGC development. Paraffin-embedded tissues from 13 CDH1 mutation carriers and from 10 sporadic early DGC cases were analyzed. Immunofluorescence and immunohistochemistry using differentiation, proliferation, and adhesion markers showed that DGC initiation seems to occur at the proliferative zone (the upper neck) of the gastric epithelium and correlates with absent or reduced expression of junctional proteins (β-actin, p120, Lin-7). Slow proliferation of neoplastic cells at the upper gastric neck leads to the formation of intramucosal signet-ring cell carcinoma (SRCC) displaying differentiated features. As shown by immunolabeling, invasion from SRCC lesions beyond the gastric mucosa is associated with poor differentiation, increased proliferation, activation of the c-Src system, and an epithelial-mesenchymal transition. Our results provide a molecular description of the early development of DGC and explain the relationship between the two main DGC types, poorly differentiated carcinoma and SRCC: both share their origin, but SRCC develops following cancer cell differentiation and seems relatively indolent in its intramucosal stage. [Cancer Res 2007;67(6):2480–9]
GP dossier says patients getting "second rate" service
Authors: Z. Kmietowicz
Journal: BMJ (2001)

Intolerable working conditions in general practice mean that many patients are receiving a “second rate—or worse” health service, and unless extra resources are pumped into the system patient care will continue to be compromised, warned the BMA this week.

The experiences of more than 100 doctors from across the United Kingdom have been assembled in a snapshot survey to highlight the strains under which family doctors are working.

Among the stories is one from a Cardiff GP whose patients have to wait six years for a hip replacement operation and one from a GP in Bolton who complained that a patient with suspected ovarian cancer had to wait 23 weeks before being …
Sir Francis Darwin and Sir William Osler
Authors: Maurice B. Strauss
Journal: JAMA (1966)

<h3>To the Editor:—</h3> "But in science the credit goes to the man who convinces the world, not to the man to whom the idea first occurs" (EDITORIALS<b>194</b>:1006, 1965; and W. S. Atkinson,LETTERS<b>195</b>:970, 1966) may be found in Sir Francis Darwin's first Galton lecture, published in<i>Eugenics Review</i><b>6</b>:1, 1914 (p 9, paragraph 5). Sir William Osler, in his remarks made on presenting the original papers of W. T. G. Morton to the Royal Society of Medicine on May 15, 1918 (<i>Proc Roy Soc Med</i>11: 65, 1917-1918, p 66, paragraph 2) credits Darwin properly. Harvey Cushing is ambiguous in his Osler biography and Bartlett is incorrect.
Rapid Autolysis of Pulmonary Emboli: A Potential Cause for Apparent False-Positive V/Q Scintigraphy on Non-Contemporaneous CTPA Findings
Authors: Ian Jong, Kim Taubman, Stephen Schlicht
Journal: Clinical Nuclear Medicine (2005)

Pulmonary embolism (PE) is a not uncommon and potentially fatal condition if left untreated. The mortality rate of undiagnosed PE, and therefore, untreated PE is reported as high as 35%. However, if appropriately diagnosed and treated early, the mortality rate decreases to 2.5%, as 75 to 90% of patients who die of PE do so within the first few hours of the primary event. Therefore, accurate and rapid diagnosis is essential. The natural history of pulmonary embolus is an evolving process. In animal models, such as dogs, the in vivo fibrinolytic process begins within hours of embolism. In humans, particularly those who have sufficient cardiopulmonary reserve and right ventricular strength to survive the initial few hours, autolysis of emboli occurs over the next few days and weeks. On average, approximately 20% of the clot disappears by 7 days and complete resolution may occur by 14 days. For many patients, up to 30 days are needed to dissolve emboli.4–6 These observations were made from the evidence drawn from a number of studies utilizing sequential pulmonary angiography and by radio-isotopic lung scintigraphy.7–10 We report a potential cause for apparent false-positive V/Q scintigraphy on noncontemporaneous CTPA findings, because of rapid autolysis of pulmonary emboli.