tbuckley/cabot-search huggingface dataset:
Inhibition by recombinant human interleukin-6 of the glucagon-dependent induction of phosphoenolpyruvate carboxykinase and of the insulin-dependent induction of glucokinase gene expression in cultured rat hepatocytes: Regulation of gene transcription and messenger RNA degradation
Authors: Bruno Christ Phd., Annegret Nath, Peter C. Heinrich, Kurt Jungermann
Journal: Hepatology (1994)

The influence of recombinant human interleukin-6, the major mediator of the inflammatory response in liver, on the glucagon- and insulin-dependent induction of the phosphoenolpyruvate carboxykinase and glucokinase gene, respectively, was monitored on the level of gene transcription, mRNA abundance and enzyme activity in cultured rat hepatocytes. As control markers of the interleukin-6–induced acute-phase response the mRNA levels of the acute phase proteins α2-macroglobulin and β-fibrinogen were determined. In cultured rat hepatocytes, recombinant human interleukin-6, added simultaneously with glucagon and insulin, lowered the maximal increase in glucagon-induced phosphoenolpyruvate carboxykinase mRNA levels after 2 hr and the maximal increase in glucokinase mRAN levels after 3 hr to about 30%, respectively. It inhibited the glucagon-induced increase in phosphoenolpyruvate carboxykinase gene transcription and phosphoenolpyruvate carboxykinase enzyme activity, as well as the insulin-induced increases in glucokinase gene transcription and glucokinase enzyme activity. Recombinant human interleukin-6 increased the mRNA levels of the acute-phase proteins α2-macroglobulin and β-fibrinogen gradually over 4 to 6 hr. Recombinant human interleukin-6, added 2 hr after glucagon or 3 hr after insulin at the maximum of the hormone-induced enzyme mRNA levels, almost doubled the decay rate of phosphoenolpyruvate carboxykinase mKNA and glucokinase mRNA. The results show that interleukin-6 induced the expression of inflammatory proteins and simultaneously inhibited the hormone-induced expression of enzymes of intermediary metabolism. This inhibition occurred by way of both a decrease in the synthesis of specific mRNA and an acceleration of the degradation of mRNA, whereas the induction of the inflammatory proteins is known to occur at the transcriptional level. (Hepatology 1994;20:1577–1583).
MPs call for shake-up in how NICE reviews cost effectiveness of drugs
Authors: Andrew Cole
Journal: BMJ (2008)

The House of Commons health select committee has called for a major shake-up in the way the National Institute for Health and Clinical Excellence (NICE) assesses new treatments.

In a hard hitting report the committee says that NICE has a vital role in rationing health care at a time when more drugs are being marketed and when funding of the NHS is due to tail off. But it says that the current system is often perceived as unfair and too time consuming.

It recommends that the institute make a “rough and ready” assessment of all treatments when they are first launched …
Preferential replication of HIV-1 in the CD45RO memory cell subset of primary CD4 lymphocytes in vitro.
Authors: C A Spina, H E Prince, D D Richman
Journal: Journal of Clinical Investigation (1997)

The ability of HIV-1 to establish an infection and replicate to high copy number in CD4 lymphocytes is dependent on both the activation state of the cell and virus-encoded regulatory proteins that modulate viral gene expression. To study these required virus-cell interactions, we have used an in vitro cell model of acute HIV infection of quiescent, primary CD4 lymphocytes and subsequent induction of T cell activation and virus replication by lectin or CD3 receptor cross-linking. Experiments were done to determine if the capacity of HIV to establish infection and complete replication was impacted by the maturational state of the CD4 cell target or the specific signal induction pathway engaged during activation. Primary CD4 cells were FACS-sorted into the major phenotypic subsets representative of memory (CD45RO) and naive (CD45RA) cells. Levels of virus replication were compared between infection with wild-type NL4-3 virus and an isogenic mutant containing a deletion in nef regulatory gene. PHA mitogen stimulation was compared with anti-CD3, with and without anti-CD28 costimulation, for induction of cell proliferation and virus replication. In both infected and uninfected cells, the RA cell subset exhibited significantly greater response to CD3/CD28 stimulation than did the RO cell subset. In contrast, the majority of virus replication occurred consistently in the RO cell subset. Deletion of HIV nef function caused a severe reduction in viral replication, especially in the RA naive cell subset after CD3 induction. PCR analysis of viral DNA formation, during infection of quiescent cells, demonstrated that the observed differences in HIV replication capacity between RO and RA cell subsets were not due to inherent differences in cell susceptibility to infection. Our results indicate that HIV replication is enhanced selectively in CD45RO memory phenotype cells through the probable contribution of specialized cellular factors which are produced during CD3-initiated signal transduction.
Radiographic Appearance of Primary Tuberculosis
Authors: Julio A. Leey, W. Paul McKinney
Journal: Annals of Internal Medicine (2007)

Letters6 March 2007Radiographic Appearance of Primary TuberculosisJulio A. Leey, MD and W. Paul McKinney, MDJulio A. Leey, MDFrom University of Louisville School of Medicine, Louisville, Kentucky.Search for more papers by this author and W. Paul McKinney, MDFrom University of Louisville School of Medicine, Louisville, Kentucky.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-146-5-200703060-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: During a recent morning report at the University of Louisville Hospital, a case of primary tuberculosis was presented that was accompanied by a discussion of the recent Update in Infectious Diseases by Lorber (1). The Update highlighted an earlier article (2) that described predictors of the radiographic appearance of tuberculosis.The original article was a retrospective cohort study based on all adult patients with culture-proven pulmonary tuberculosis at Columbia University Medical Center between 1990 and 1999. Clustered cases (≥2 cases with same strain by restriction fragment length polymorphism analysis) were assumed to be due to recent transmission, ...References1. Lorber B. Update in infectious diseases. Ann Intern Med. 2006;145:354-60. [PMID: 16954360] LinkGoogle Scholar2. Geng E, Kreiswirth B, Burzynski J, Schluger NW. Clinical and radiographic correlates of primary and reactivation tuberculosis: a molecular epidemiology study. JAMA. 2005;293:2740-5. [PMID: 15941803] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Julio A. Leey, MD; W. Paul McKinney, MDAffiliations: From University of Louisville School of Medicine, Louisville, Kentucky.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoUpdate in Infectious Diseases Bennett Lorber Metrics 6 March 2007Volume 146, Issue 5Page: 395KeywordsCohort studiesConflicts of interestDiagnostic radiologyHIVImmunodeficienciesInfectious diseasesLesionsRestriction fragment length polymorphism analysisThoraxTuberculosis ePublished: 6 March 2007 Issue Published: 6 March 2007 Copyright & PermissionsCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Nonsteroidal Anti-inflammatory Drugs and High Blood Pressure
Authors: Anthony G. Johnson
Journal: Annals of Internal Medicine (1995)

Letters1 March 1995Nonsteroidal Anti-inflammatory Drugs and High Blood PressureAnthony G. Johnson, Tuan V. Nguyen, and Richard O. DayAnthony G. JohnsonSearch for more papers by this author, Tuan V. NguyenSearch for more papers by this author, and Richard O. DaySearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-122-5-199503010-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Dr. Radack for his interest in our meta-analysis and for his comments on it. Several issues, however, require correction. Dr. Radack noted that his study [1] included 41 patients. In fact, 45 patients were enrolled, but 41 completed the trial. Importantly, 30 patients who completed this parallel study had been randomly assigned to receive ibuprofen or placebo, and the remainder received acetaminophen. Chalmers and colleagues [2] reported that acetaminophen (called paracetamol in Australia) produced an elevation in blood pressure. Consequently, only the data obtained for the 30 patients receiving ibuprofen or placebo could be included in ...References1. Radack KL, Deck CC, Bloomfield SS. Ibuprofen interferes with the efficacy of antihypertensive drugs. A randomized, double-blind, placebo-controlled trial of ibuprofen compared with acetaminophen. Ann Intern Med. 1987; 107:628-35. Google Scholar2. Chalmers JP, West MJ, Wing LM, Bune AJ, Graham JR. Effects of indomethacin, sulindac, naproxen, aspirin and paracetamol in treated hypertensive patients. Clin Exp Hypertens. 1984; 6:1077-93. Google Scholar3. Johnson AG, Nguyen TV, Day RO. Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann Intern Med. 1994; 121:289-300. Google Scholar4. Radack K, Deck C. Do nonsteroidal anti-inflammatory drugs interfere with blood pressure control in hypertensive patients? J Gen Intern Med. 1987; 2:108-12. Google Scholar5. Sacks HS, Berrier J, Reitman D, Ancona-Berk VA, Chalmers TC. Meta-analysis of randomized controlled trials. N Engl J Med. 1987; 316:450-5. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1995Volume 122, Issue 5Page: 397KeywordsBlood pressureClinical trialsDrugsIbuprofenMorbidityNSAIDsPrimary hypertensionSystolic pressure Issue Published: 1 March 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Characteristics of Hypertension in the Black Population
Authors: MARGARET M. KILCOYNE, GERALD E. THOMSON, GEORGE BRANCHE, MICHAEL WILLIAMS, CHARLES GARNIER, BENNY CHILES, TOVE SOLAND
Journal: Circulation (1974)

The renin-angiotensin system was examined in 146 black patients with essential hypertension. Classification into three categories was made according to plasma renin activity as measured by the radioimmunoassay of Angiotensin I and the accompanying sodium excretion. Differences among patients in the three renin groups (low, normal, and high) were not observed with respect to the incidence of cerebrovascular and cardiovascular events. No other discriminating variables could be identified by multivariate discriminant analysis. Low renin patients were distinguished in having a reduced sodium excretion compared to normal and high renin patients. Although total exchangeable sodium was not measured in this group of patients, other investigators have reported a higher exchangeable sodium in low renin patients than in those with normal or high values. This possibility, together with recent evidence in experimental models of low renin hypertension, that the affinity of angiotensin for its vascular receptors may be sodium dependent suggests that the incidence of vascular events may relate more specifically to angiotensin-vascular receptor interaction than to measurements of circulating renin.
Evaluation of Islet-Cell Function in Man
Authors: Ronald A. Arky, Robert H. Knopp
Journal: New England Journal of Medicine (1971)

THE functional capacity of an endocrine organ such as the islets of Langerhans can be evaluated by measurement of the amounts of circulating hormones produced by its cells and by observation of the clinical and biochemical indexes affected by its hormones. Approximately 75 per cent of the cellular elements that comprise 1,000,000 or more islets of the human pancreas are beta cells, about 20 per cent are alpha cells, and the remainder are delta cells. Glucagon and insulin, the products of alpha and beta cells, respectively, are usually secreted in a fashion such that their actions on carbohydrate, lipid and . . .
Fraction of LOH on chromosome 17 and 18 (LOH-ratio) predicts colorectal cancer outcome
Authors: T. Kanazawa, T. Watanabe, H. Nagawa
Journal: Journal of Clinical Oncology (2006)

20114 Background: Identification of patients at high risk for recurrence remains a central issue in the treatment of colorectal cancer. Our goal was to identify predictive factors for recurrence in colorectal cancer patients. Methods: DNA from 84 colorectal cancers were analyzed for wide-ranging allelotyping. Using 27 microsatellite markers spanning every 10cM on chromosome 17 and 18, we defined the LOH-ratio as the proportion of markers which show LOH out of 27 markers. Tumors were grouped into two groups by the median value of LOH-ratio (0.19). Recurrence free survival was compared with Kaplan-Meier analysis and log rank statistic. The Cox proportional hazards regression model was used for both univariate and multivariate analysis of recurrence free survival. Results: Log rank statistic revealed that LOH-ratio, stage, lymph node metastasis significantly related to recurrence free survival. On univariate analysis, significant predictors of Recurrence free survival were LOH-ratio, lymph node metastasis, Dukes’ classification, and pathological type. On multivariate analysis, LOH-ratio (HR 3.1, p = 0.02) and lymph node metastasis (HR 5.2, p = 0.002) independently predicted for recurrence free survival. Conclusions: LOH-ratio and lymph node metastasis were the only independent predictors of recurrence free survival. Altogether with lymph node metastasis, LOH-ratio could help to improve postoperative surveillance and adjuvant therapy. No significant financial relationships to disclose.
Nanoparticles Based on Star Polymers as Theranostic Vectors: Endosomal‐Triggered Drug Release Combined with MRI Sensitivity
Authors: Yang Li, Hien T. T. Duong, Sophie Laurent, Alexandre MacMillan, Renee Megan Whan, Luce Vander Elst, Robert N. Muller, Jinming Hu, Andrew Lowe, Cyrille Boyer, Thomas P. Davis
Journal: Advanced Healthcare Materials (2014)

Dual‐functional star polymers (diameters 15 nm) are synthesized producing nanoparticles with excellent colloidal stability in both water and serum. The nanoparticles are built with aldehyde groups in the core and activated esters in the arms. The different reactivity of the two functional groups to sequentially react with different amino compounds is exploited; doxorubicin (DOX) and 1‐(5‐amino‐3‐aza‐2‐oxypentyl)‐4,7,10‐tris( tert ‐butoxycarbonylmethyl)‐1,4,7,10‐tetraazacyclododecane (DO3A‐ t Bu‐NH 2 )—a chelating agent effective for the complexation of Gadolinium ions (Gd). The activated ester group is employed to attach the DO3A chelating agent, while the aldehyde groups are exploited for DOX conjugation, providing a controlled release mechanism for DOX in acidic environments. DOX/Gd‐loaded nanoparticles are rapidly taken up by MCF‐7 breast cancer cells, subsequently releasing DOX as demonstrated using in vitro fluorescence lifetime imaging microscopy (FLIM). Endosomal, DOX release is observed, using a phasor plot representation of the fluorescence lifetime data, showing an increase of native DOX with time. The MRI properties of the stars are assessed and the relaxivity of Gd loaded in stars is three times higher than conventional organic Gd/DO3A complexes. The DOX/Gd‐conjugated nanoparticles yield a similar IC 50 to native DOX for breast cancer cell lines, confirming that DOX integrity is conserved during nanoparticle attachment and release.
Systemic lupus erythematosus: new molecular targets
Authors: J. C Crispin, V. Kyttaris, Y.-T. Juang, G. C Tsokos
Journal: Annals of the Rheumatic Diseases (2007)

T cells from patients with systemic lupus erythematosus exhibit a notable array of defects that probably contribute to the origin and development of the disease. Such abnormalities include an abnormal response to stimulation, aberrant expression of molecules that play key roles in intracellular signalling pathways, altered transcription factor activation and binding, and skewed gene expression. The combination of these alterations leads the cell to the expression of a particular phenotype that intense research has gradually uncovered over the last years. The aim of this article is to review the findings that have allowed us to better understand the behaviour of the lupus T cell and highlight the molecules that represent potential therapeutic targets.
Spontaneous rupture of the spleen in AL amyloidosis
Authors: B. Oran, D.G. Wright, D.C. Seldin, D. McAneny, M. Skinner, V. Sanchorawala
Journal: American Journal of Hematology (2003)

Abstract The frequency of splenic involvement in AL amyloidosis is not precisely known. However, splenomegaly has been reported in 4–13% of patients. We report four cases of spontaneous splenic rupture in patients with AL amyloidosis. Splenic rupture was the initial manifestation of the disease in one of these patients. The other three experienced splenic rupture during or after high‐dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT): one during stem cell mobilization with G‐CSF prior to HDM/SCT and two after hematopoietic recovery following treatment. Two of the four patients had Factor X deficiency, the most common coagulation abnormality associated with AL amyloidosis. All four patients underwent splenectomy without significant postoperative complications. Splenic rupture in AL amyloidosis as a complication of aggressive treatment with HDM/SCT has not been reported previously. Am. J. Hematol. 74:131–135, 2003. © 2003 Wiley‐Liss Inc.
Diagnosis of Simultaneous Multiple Gastric Cancers by the Endoscopic Congo Red - Methylene Blue Test
Authors: H. Iishi, M. Tatsuta, S. Okuda
Journal: Endoscopy (1988)

The clinicopathological features of simultaneous multiple gastric cancers, and the accuracy of their diagnosis by routine endoscopic examination were analyzed. In addition, the accuracies of diagnosis of coexisting early gastric cancers by routine endoscopic examination and by the endoscopic Congo red - methylene blue test developed in our hospital were compared. The results showed that multiple cancers occurred frequently in elderly male patients, in patients with early gastric cancer of the flat and elevated types and the depressed type without converging folds, and in patients with advanced cancer of Borrmann type I. These patients frequently have early cancers of the flat or depressed types without converging folds, and advanced cancers of Borrmann type I. The coexisting lesions are very difficult to diagnose by routine endoscopic examination: a correct diagnosis of coexisting early cancers was made in only 28.3 % of the cases by routine endoscopic examination. But with the Congo red - methylene blue test, the diagnostic rate was raised significantly to 88.9 %. In this test, Congo red and methylene blue are sprayed on the surface of the stomach and are bleached within 2 to 5 minutes on the surface of a tumor, but not on the surface of unaffected mucosa.
Monitoring Quality of Care
Authors: Philip W. Taylor
Journal: JAMA (1988)

To the Editor.  —In their recent article, Drs Brook and Lohr 1 provide two suggestions for monitoring the quality of care given to Medicare patients. The authors state that nearly all quality studies over the past two decades have found important clinical deficiencies. This statement is not referenced by the authors. The charge that there is a problem with quality of care within the Medicare system should be substantiated before planning any attempts to alter patterns of medical care. Drs Brook and Lohr should begin with a well-referenced critical appraisal of evidence that indicates that poor medical care is being rendered to the Medicare population.
Some NHS care is unacceptable
Authors: C. Hamon
Journal: BMJ (1998)

Editorial by McKenna

Are we prepared to accept inhumane hospitals? Are we prepared to condone staffing levels which we know will inevitably push staff beyond the limits of their stamina and compassion, and will cause patients to suffer?

During the Christmas period of 1997, Simon, the husband of a good friend of mine, died in hospital, 12 days after his admission and nine days after major surgery. During his hospital stay two other patients died in his bay of the ward. One was in the bed next to Simon. In the few hours before his death he was incontinent of faeces six times. The man found this distressing and repeatedly apologised. Although a nurse cleaned him up each time, his body was left on the ward for two hours after his death, during which time Simon was aware of the strong smell of his faeces. It would have been preferable …
GP confronts health minister over pressures of the job
Authors: G. Iacobucci
Journal: BMJ (2013)

The health minister Earl Howe has insisted that the government is “doing its best” to alleviate the workload strain on general practitioners, as GPs voiced their anger at the pressures being placed on practices in England.

In a speech to delegates at the Best Practice 2013 conference in Birmingham, Howe said that the government was conscious of the pressures being felt by the profession, which stemmed from increasing demand and current contractual targets. He said that upcoming negotiations over changes to GPs’ contracts would reflect a need to reduce bureaucracy.

Best Practice is the new name for the conference of the National Association of Primary Care which brings together GPs, commissioners, practice managers, and others involved in delivering services in the community.

But after the speech, Jo Loughton, a GP from …
BLASTOMYCOSIS OF THE EYELID.
Authors: WILLIAM H. WILDER
Journal: JAMA (1904)

The condition known as cutaneous blastomycosis which was first described in 1896 by Gilchrist<sup>1</sup>under the name blastomycetic dermatitis, is one that should be of interest to the ophthalmologist, inasmuch as among its favorite sites are the face and the eyelids. The deformities produced by its action on the skin of these parts may prove to be very serious, and difficult to treat, as illustrated by the case that I shall record. As stated by Drs. J. Nevins Hyde and Frank H. Montgomery,<sup>2</sup>who have made most valuable contributions to the subject, "the disorder is probably more common than is generally supposed, and possibly has been confounded in the past with verrucous tuberculosis, unusual forms of carcinoma and with atypical manifestations of syphilis." The following is a report of a case of this interesting disease which for the last six months has been under my care:
The Thyroid Gland
Authors: Solomon A. Berson
Journal: JAMA (1964)

This two-volume work is a collection of 28 separate monographs covering most aspects of thyroidal morphology, physiology, and chemistry in health and disease. Volume 1 deals largely with the more basic aspects of thyroid function and the action of the thyroid hormones; volume 2 is concerned principally with subjects of clinical interest. However, the clinician will make frequent reference also to the last two chapters of the first volume, which discuss the antithyroid drugs and clinical applications of radioactive iodine. Each chapter stands by itself and can be read independently as a definitive review. The treatment of individual topics meets high standards throughout; most chapters are written by workers who have themselves made distinguished contributions to the field. As a whole, the work not only includes an impressive mountain of experimental and clinical information documented by reference to almost 4,000 publications but also bears the stamp of authoritative opinion on