tbuckley/cabot-search huggingface dataset:
<i>Lpr</i> and <i>gld</i>: Single Gene Models of Systemic Autoimmunity and Lymphoproliferative Disease
Authors: Philip L. Cohen, Robert A. Eisenberg
Journal: Annual Review of Immunology (1991)

The autosomal recessive lpr and gld genes induce in mice multiple autoantibodies and the progressive accumulation of large numbers of non-malignant CD4 - CD8 - T lymphocytes. The clinical syndromes and immune abnormalities associated with these two nonallelic genes are nearly identical and are also highly dependent on background genes. MRL/lpr mice are particularly severely affected, and they develop a syndrome that is serologically and pathologically similar to human systemic lupus erythematosus (SLE). Abnormal cell marker expression in the aberrant lpr T lymphocytes includes surface antigens normally associated with activated T cells or even with B cells, and it occurs along with enhanced expression of certain oncogenes. The lpr gene results in intrinsic abnormalities of both T and B lymphocytes, yet its location and product are unknown. The gld gene is located on chromosome 1; its product is also unknown. Although many immunological abnormalities are known, the mechanism whereby these two genes induce autoimmunity and lymphoproliferation remains obscure. Further studies of mice bearing these mutant genes are certain to yield insights into systemic autoimmunity and the control of lymphocyte proliferation.
Treatment of Ventricular Extrasystoles and Tachyarrhythmias in Acute Myocardial Infarction
Authors: A Selzer, K E Cohn
Journal: Annual Review of Medicine (1970)

Two developments at the beginning of this decade exerted a profound influence upon clinical management of acute myocardial infarction: the in­ troduction of closed-chest resuscitation with electric shock therapy for ven­ tricular fibrillation, and the availability of continuous monitoring of the electrocardiogram by means of the cathode-ray oscilloscope. As a result of this, the coronary care unit has become a standard facility for the treatment of myocardial infarction. I t should be recognized that the concept of thera­ peutic centers for patients with myocardial infarction encompasses a broad range of facilities available in such units (1). On the one end of the spectrum, one can place the comprehensive cardiology center, equipped to treat all as­ pects and complications of myocardial infarction, including the use of emer­ gency surgery and artificial pump-support. On the other end, is the small area in a hospital in which nurses can observe the patient's rhythm displayed upon the monitoring oscilloscope. The great majority of coronary care units ap­ proach the latter end of the spectrum-based primarily on the availability of electrocardiographic monitoring units. Thus, the role of such units is the identification, early recognition, treatment, and prevention of dangerous arrhythmias. The most common arrhythmias that are potentially life-threat­ ening are related to increased irritability of the ventricular myocardium. The purpose of this review is to examine the rationale for the therapy of ventricular arrhythmias in acute myocardial infarction-both the fundamen­ tal and practical considerations.
Insulin’s Role in Diabetes Management: After 90 Years, Still Considered the Essential “Black Dress”
Authors: William T. Cefalu, Julio Rosenstock, Derek LeRoith, Matthew C. Riddle
Journal: Diabetes Care (2015)

It has been 93 years since Banting and Best extracted insulin in Scottish physiologist J.J.R. Macleod’s laboratory and, with the help of their fellow Canadian chemist James B. Collip, used it to successfully treat a cachectic boy, Leonard Thompson, who suffered from life-threatening diabetes. Since that time, insulin therapy has become the mainstay of treatment for patients with type 1 diabetes and a cornerstone therapy for many individuals with type 2 diabetes.

Over the years, many changes in insulin therapy have occurred, including new formulations, new delivery systems, and additional therapeutic tactics. We are on the brink of a new and exciting era with increasingly reliable and easy-to-use continuous glucose monitoring as part of a closed-loop delivery system. This new “artificial pancreas” system, with its carefully modulated insulin (which remains the key component), may soon be ready for clinical use. In addition, an impressive array of new oral and injectable agents for type 2 diabetes has been developed over the past 20 years. Many thought that these could replace injected insulin in a therapeutic regimen, or at least delay its use. Yet, the reality is that insulin will always be needed for type 1 diabetes until a cure is found and progressive insulin deficiency is a fundamental defect of type 2 diabetes.

Furthermore, supplementation of endogenous insulin continues to be necessary for large numbers of individuals with type 2 diabetes. Meanwhile, the other classes of therapeutic agents are vying for a strategic position alongside insulin in clinical regimens for type 2 diabetes, and there is an unmet need for adjuvant therapies to mitigate the treatment challenges in type 1 diabetes as well.

To dramatize the continuing role of insulin in the management of diabetes, we propose an analogy from the world of clothing and fashion: Insulin is and will remain …
Salvage therapy with ProMACE-MOPP followed by intensive chemoradiotherapy and autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma who failed to respond to first-line CHOP.
Authors: L F Verdonck, A W Dekker, G C de Gast, M L van Kempen, H M Lokhorst, H K Nieuwenhuis
Journal: Journal of Clinical Oncology (1992)

We used alternative chemotherapy immediately followed in early-response patients by high-dose chemoradiotherapy and autologous bone marrow transplantation (ABMT) to treat patients with non-Hodgkin's lymphoma (NHL) who had failed to respond to first-line chemotherapy.Thirty-one patients with NHL of intermediate- or high-grade malignancy who had failed to respond to first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy were treated. Seventeen patients had primary refractory disease and 14 had relapsed from first complete response (CR). The treatment consisted of prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, and procarbazine (ProMACE-MOPP) salvage chemotherapy, followed, in case of responsive disease (at least partial response [PR]), by high-dose cyclophosphamide and total-body irradiation (TBI) with ABMT.Twenty-eight of 31 (90%) patients achieved PR (23 patients) or CR (five patients) with ProMACE-MOPP, and three failed to respond. Seventeen of 28 (61%) patients who responded underwent the ABMT procedure, which resulted in CR in 14 patients (82%); three failed to respond. Eleven responsive patients were not transplanted because of residual bone marrow infiltration (five patients), patient refusal (four patients), and ProMACE-MOPP-related mortality (two patients). To date, nine patients are alive and in CR, seven with a median follow-up of 41 months (range, 17 to 84 months). Referring to the original CHOP treatment, five of 17 (29%) patients with primary refractory disease remain free of disease at a median of 36 months after ABMT, and four of 14 (29%) patients in first relapse remain free of disease at a median of 33 months after ABMT. One patient died of AMBT-related toxicity.ProMACE-MOPP salvage chemotherapy produces a high early-response rate in patients who fail to respond to first-line CHOP, and more than half of the responding patients can be scheduled to receive ABMT, resulting in disease-free survival (DFS) at 3 years in 50% of the transplanted patients and in 25% of the original number of patients intended to receive this treatment.
Hydatid Disease in Toronto
Authors: D M Finlayson, A Fergus
Journal: JAMA (1963)

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
Whole-body MRI of patients with polymyalgia rheumatica identifies a distinct subset with complete patient-reported response to glucocorticoids
Authors: Sarah Louise Mackie, Colin Thomas Pease, Eiji Fukuba, Emma Harris, Paul Emery, Richard Hodgson, Jane Freeston, Dennis McGonagle
Journal: Annals of the Rheumatic Diseases (2015)

Objectives To determine whether whole-body MRI defines clinically relevant subgroups within polymyalgia rheumatica (PMR) including glucocorticoid responsiveness. Methods 22 patients with PMR and 16 with rheumatoid arthritis (RA), untreated and diagnosed by consultant rheumatologists, underwent whole-body, multiple-joint MRI, scored by two experts. Patients with PMR reported whether they felt ‘back to normal’ on glucocorticoid therapy and were followed for a median of 2 years. Results All patients with PMR were deemed to respond to glucocorticoids clinically. A characteristic pattern of symmetrical, extracapsular inflammation, adjacent to greater trochanter, acetabulum, ischial tuberosity and/or symphysis pubis, was observed in 14/22 of the PMR cases. In PMR, this pattern was associated with complete glucocorticoid response (p=0.01), higher pretreatment C-reactive protein (CRP) and serum interleukin-6 (IL-6), and better post-treatment fatigue and function. Only 1/14 in the extracapsular group could stop glucocorticoids within 1 year, compared with 4/7 of the others. A score derived from the five sites discriminating best between PMR and RA correlated with IL-6 (p&lt;0.002). IL-6 levels ≥16.8 pg/mL had 86% sensitivity and 86% specificity for the extracapsular MRI pattern. Conclusions A subset of patients with rheumatologist-diagnosed PMR had a characteristic, extracapsular pattern of MRI inflammation, associated with elevated IL-6/CRP and with complete patient-reported glucocorticoid responsiveness.
Autologous bone-marrow transplantation: host effects of high-dose BCNU.
Authors: T Takvorian, L M Parker, F H Hochberg, G P Canellos
Journal: Journal of Clinical Oncology (1983)

Thirty-five patients with solid tumors received 44 courses of bis-chlorethylnitrosourea (BCNU) at doses ranging between 600 and 1,400 mg/m2 with cryopreserved or fresh autologous bone-marrow support. Eight patients treated at 600 mg/m2 received no bone-marrow support for their first course of BCNU. Maximum follow-up was 25 months (median, four months). Myelosuppression was severe and dose related but was less prolonged in the marrow-supported groups (p = 0.01) and was not dose limiting. Myelosuppression-related toxicity of infection and hemorrhage occurred in 21 (47%) of 44 courses of treatment. Pulmonary toxicity occurred in seven of 35 patients; abnormal liver function occurred in 18 of 30 patients greater than one month from treatment; and central nervous system symptoms that may have been drug related occurred in six of 35 patients. There was no renal or cardiac toxicity. Except for myelosuppression, toxicity was not dose related. Treatment-related deaths included four with pulmonary toxicity, two with liver toxicity, sepsis in four, and gastrointestinal tract toxicity in one patient. We conclude that the limiting side effect of high-dose BCNU (greater than or equal to 600 mg/m2) is visceral toxicity; the extent of myelosuppression is shortened by the infusion of bone marrow, whether cryopreserved or fresh; and marked tumor regression can be achieved with high-dose BCNU.
Abstract 1211: Metabolite assays to illuminate cellular energy networks
Authors: Mary Sobol, Jolanta Vidugiriene, Donna Leippe, Gediminas Vidugiris, Wenhui Zhou, James Cali
Journal: Cancer Research (2015)

Abstract Every organism requires cellular energy metabolism to meet developmental needs. When cells change from a resting to a proliferative state, the metabolic pathways are reprogrammed to meet the demands of proliferation. Diseases such as cancer can occur when changes in the metabolic pathways support unwanted functions such as uncontrolled proliferation. Assays for analyzing metabolites and metabolic enzymes are needed to understand cellular metabolic requirements and energy network regulation under normal and disease conditions. We exploited the robustness, sensitivity and broad dynamic range of bioluminescence detection to develop assays for the key metabolites lactate, glucose, glutamate and glucose-6-phosphate. The technology involves using specific dehydrogenases to couple metabolite levels to NAD(P)H production. In the presence of NAD(P)H, a novel proluciferin is converted to a substrate for luciferase resulting in light signals proportional to the starting metabolite concentration. Samples (e.g. mammalian cells, culture media, tissues, 3D microtissues) are added to the metabolite detection reagent in a 1:1 ratio. An inactivation solution added to complex biological samples lowers the background and increases sensitivity by lysing the cells, inactivating cellular enzymes, and destroying endogenous NAD(P)H. The sensitivity (1-5 pmol/sample) and broad assay window (maximum signal-to-background &amp;gt; 100 fold) of the assays allows simultaneous detection of multiple metabolites from the same set of samples. The wide assay window allows detection of very small changes in metabolite concentration, an advantage over conventional fluorescent and colorimetric detection methods. The assays adapt to various formats (96, 384-well plates) and require no instrumentation other than a luminometer. The assays can be used to measure the levels of critical metabolites and to monitor the effects of inhibitors and activators of glycolysis. The shift from oxidative phosphorylation to glycolysis can be monitored by measuring lactate production and secretion as well as glucose consumption from the same set of samples. The assays easily multiplex with cell viability assays enabling analysis of drug effects on cell proliferation, cell metabolism and mitochondria function. Citation Format: Mary Sobol, Jolanta Vidugiriene, Donna Leippe, Gediminas Vidugiris, Wenhui Zhou, James Cali. Metabolite assays to illuminate cellular energy networks. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1211. doi:10.1158/1538-7445.AM2015-1211
BRAIN METABOLISM, VIII
Authors: S. BERNARD WORTIS, DONALD SHASKAN, DAVID IMPASTATO, RENATO ALMANSI
Journal: American Journal of Psychiatry (1941)

1. Adrenalin, caffeine and cocaine, in high concentrations in the dextrose substrate, inhibit oxygen uptake, whereas nicotine has no such effect. 2. Picrotoxin, prostigmine and tyramine when injected subcutaneously into the rat, tend to increase brain oxygen uptake in plain Ringer's phosphate. 3. Dextrose has a protective action against the depressive effect of drugs. 4. Electrical convulsions inhibit oxygen uptake; this effect is greater after repeated shocks and is more marked in the dextrose substrate. 5. Electrical convulsions and to a greater extent, insulin, interfere with oxygen uptake, in contrast to metrazol and camphor which are metabolic stimulants. The availability or utilizability of dextrose by the brain may account for this difference.
An Introduction to the Fine Structure of Cells and Tissues.
Journal: JAMA (1963)

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
Pop in, pop out: a novel gene-targeting strategy for use with CRISPR-Cas9
Authors: Ralf Kühn, Van Trung Chu
Journal: Genome biology (2015)

The CRISPR-Cas9 system is frequently used to create small deletions in the genomes of mammalian cells, but the isolation of precisely targeted mutants is still challenging. A new, two-step 'pop in & out' targeting approach facilitates this task.
IL‐17A increases TNF‐α‐induced COX‐2 protein stability and augments PGE<sub>2</sub> secretion from airway smooth muscle cells: impact on β<sub>2</sub>‐adrenergic receptor desensitization
Authors: N. N. Rumzhum, B. S. Patel, P. Prabhala, I. C. Gelissen, B. G. Oliver, A. J. Ammit
Journal: Allergy (2015)

IL-17A plays an important role in respiratory disease and is a known regulator of pulmonary inflammation and immunity. Recent studies have linked IL-17A with exacerbation in asthma and COPD. We have shown that the enzyme cyclooxygenase-2 (COX-2) and its prostanoid products, prostaglandin E2 (PGE2 ) in particular, are key contributors in in vitro models of infectious exacerbation; however, the impact of IL-17A was not known.We address this herein and show that IL-17A induces a robust and sustained upregulation of COX-2 protein and PGE2 secretion from airway smooth muscle (ASM) cells. COX-2 can be regulated at transcriptional, post-transcriptional and/or post-translational levels. We have elucidated the underlying molecular mechanisms responsible for the sustained upregulation of TNF-α-induced COX-2 by IL-17A in ASM cells and show that is not via increased COX-2 gene expression. Instead, TNF-α-induced COX-2 upregulation is subject to regulation by the proteasome, and IL-17A acts to increase TNF-α-induced COX-2 protein stability as confirmed by cycloheximide chase experiments. In this way, IL-17A acts to amplify the COX-2-mediated effects of TNF-α and greatly enhances PGE2 secretion from ASM cells.As PGE2 is a multifunctional prostanoid with diverse roles in respiratory disease, our studies demonstrate a novel function for IL-17A in airway inflammation by showing for the first time that IL-17A impacts on the COX-2/PGE2 pathway, molecules known to contribute to disease exacerbation.
Diseases of the Respiratory System Interpretations of Tests of Function
Authors: R V Christie, D V Bates
Journal: Annual Review of Medicine (1955)

The lungs are perfectly designed to fulfill their function of ensuring full oxygenation of the blood and they achieve this by possession of the follow­ ing properties: (a) The distensibility and elasticity of the lungs enables a large volume of gas to be moved in and out of the alveoli at a rapid rate and with minimal effort. (b) Gas drawn into the lungs is distributed almost evenly to all alveoli and the blood perfusing the lungs goes equally to all parts. (c) The alveolar membrane is so fine that gas diffusion through it is very rapid. (d) The very large alveolar surface (ca. 55 sq. m.) and the relatively small volume of blood contained within the alveolar capillaries (ca. 60 cc.) ensures the saturation with oxygen of blood passing through the lungs. (e) The pulmonary vascular bed can accommodate a considerable increase of blood flow withou t a corresponding increase in pulmonary arterial pressure. It might be thou ght that such detailed knowledge of the attributes of the normal lung would have led to the development of tests precise enough to measure quantitively all the various disturbances of function that occur in disease. This is not the case. One of the reasons for this state of affairs is the difficulty in assessing the normality of one function in the presence of impairment of others. Another is that the methods of investigation are often technically difficult to perform and until the introduction of rapid physical methods of gas analysis, the tests of most value were often extremely time consuming. Pulmonary function tests are concerned with the first three of the attri­ butes of normal lung function detailed above, and may be conveniently considered under the following headings:(a) the mechanical efficiency of breathing and the subdivisions of lung volume, (b) measurements of the uni­ formity of gas distribution within the lungs, (c) measurements of the effi­ ciency of haemo-respiratory exchange. In this review, an attempt is made to assess the clinical value of some of these tests, although in our opinion their main valu e is in research. In general,