tbuckley/cabot-search huggingface dataset:
Activity and Expression of Na <sup>+</sup> -H <sup>+</sup> Exchanger Isoforms 1 and 3 in Kidney Proximal Tubules of Hypertensive Rats
Authors: M. P. Kelly, P. A. Quinn, J. E. Davies, L. L. Ng
Journal: Circulation Research (1997)

Increased activity of the cellular Na(+)-H+ exchangers (NHEs), especially isoform 1 (NHE-1), is a recognized intermediate phenotype of hypertension. NHE activity has been demonstrated to be increased in proximal tubules of the spontaneously hypertensive rat (SHR). However, with the recent cloning of other members of this family of transporters, it is unclear which isoforms may contribute to this increased activity. We have used specific antibodies raised against glutathione-S-transferase fusion proteins of rat NHE-1 and NHE-3 to determine the relative contributions of these isoforms to the NHE activity in freshly isolated and cultured proximal tubule cells from SHR and Wistar-Kyoto (WKY) normotensive control rats. In freshly isolated proximal tubule cells, NHE activity was elevated almost 3-fold in SHR cells (P < .001), and in both rat strains, the contribution from NHE-1 and NHE-3 was approximately equal. Western blots of membranes from these cells showed equal amounts of NHE-1 protein in SHR and WKY cells. However, NHE-3 protein expression was increased 50% in SHR cells (P < .001), and this may account for the elevated activity of this isoform in SHR. The effect of culturing these cells in vitro was then examined. Although total NHE activity in both cell types was decreased during culture, this was mainly due to loss of expression of NHE-3 protein. NHE-1 activity was persistently elevated in the SHR cells in culture. These findings suggest that elevated NHE activity in SHR proximal tubules could be mediated by two mechanisms: (1) increased NHE-1 activity without any increased NHE-1 protein content that persists despite culture and may resemble those changes described for extrarenal tissues and (2) increased NHE-3 activity due to increased expression of NHE-3 protein. Disappearance of NHE-3 during culture implies that our culture conditions did not replicate the in vivo environment and may have removed the factors contributing to the increased NHE-3 expression in SHR cells.
Knowledge about using auto-injectable adrenaline: review of patients' case notes and interviews with general practitioners
Authors: G. R Hayman
Journal: BMJ (2003)

In the United Kingdom, the rising incidence of anaphylaxis is of concern.Affected patients should avoid exposure to allergens; after inadvertent exposure, symptoms can be treated with emergency packs, which include adrenaline.In our clinic, we often prescribe preloaded devices for auto-injecting adult or paediatric doses of adrenaline.Because referred patients' (or their parents') knowledge about using these devices was poor at the first visit to the clinic, we assessed the knowledge of local general practitioners.
Automated Functional Imaging in Atrioventricular Delay Time Optimization in Patients with Dual Chamber Pacemakers
Authors: Osman Ziya Arık, Gülhan Yüksel Kalkan, Durmuş Yıldıray Şahin, Zafer Elbasan, Mustafa Gür, Osman Kuloğlu, Kamuran Tekin, Murat Gençaslan, Caner Türkoğlu, Haci Ali Uçak, Murat Çaylı
Journal: Journal of the American College of Cardiology (2013)
Understanding How Americans View Health Care Reform
Authors: Robert J. Blendon, John M. Benson
Journal: New England Journal of Medicine (2009)

Now that Congress has adjourned and most members are back in their own states or districts, they will be listening to what their constituents have to say about the debate over health care reform. We examined the results of 22 recent nationwide public opinion polls (see Recent Opinion Polls on Health Care Reform; polls are cited parenthetically hereafter), working with support from the Kaiser Family Foundation and the Robert Wood Johnson Foundation, to find out what our legislators might be hearing.On issues such as health care, we believe that public support for change is shaped by the interaction of . . .
Abstract 3947: AMG 161, a fully human monoclonal antibody to human RANKL, inhibits tumor-induced osteoclastogenesis and reduces skeletal tumor burden in mice that express chimeric (murine / human) RANKL.
Authors: Jude R. Canon, Rebecca Bryant, Martine Roudier, William C. Dougall
Journal: Cancer Research (2013)

Abstract Tumor cells can induce RANKL expression in the bone stroma, causing activation of osteoclasts which consequently mediate bone breakdown and subsequent tumor proliferation. RANKL is an essential mediator of osteoclast function and survival. RANKL inhibition by OPG-Fc can prevent tumor-induced osteolysis, decrease skeletal tumor burden, and increase survival in preclinical models. Denosumab is an anti-huRANKL antibody approved for the prevention of skeletal-related events due to bone metastases from solid tumors. Selective anti-huRANKL antibodies do not bind murine RANKL, therefore efficacy cannot be tested in typical mouse models. We developed a breast cancer bone metastasis model in mice in which exon 5 from murine RANKL was replaced with its human ortholog (“mu/huRANKL”). We tested the effect of AMG 161, an antibody which binds huRANKL and chimeric mu/huRANKL, on tumor burden and associated osteoclasts. After intra-cardiac injection of MCF-7Luc breast carcinoma cells, hind limb metastases formed and tumor burden was tracked by bioluminescence imaging (BLI). AMG 161 (0.3 or 3.0 mg/kg, 2x/week), OPG-Fc (3.0 mg/kg, 2x/week) or vehicle were administered beginning 10 days post tumor injection to treat established bone metastases until study termination at day 31. AMG 161 resulted in a dose-dependent decrease in skeletal tumor burden (3.0 mg/kg: 84% decrease vs. control p=0.0052) similar to that observed with OPG-Fc (85% decrease vs. control, p=0.0038). Histological analysis at the end of the study showed reductions in skeletal tumor burden consistent with the BLI. AMG 161 treatment resulted in a significant decrease in tumor-associated osteoclasts (TRAP staining) and inhibition of osteolytic lesions (X-ray). The inhibition of tumor burden by the anti-RANKL antibody was indirect via osteoclast inhibition since MCF-7Luc cells do not express RANK, and RANKL inhibition does not affect subcutaneous growth of MCF-7Luc cells. These data support the efficacy of anti-RANKL antibody treatment to inhibit tumor-induced osteoclastogenesis and to block the growth of bone metastases. Citation Format: Jude R. Canon, Rebecca Bryant, Martine Roudier, William C. Dougall. AMG 161, a fully human monoclonal antibody to human RANKL, inhibits tumor-induced osteoclastogenesis and reduces skeletal tumor burden in mice that express chimeric (murine / human) RANKL. [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 3947. doi:10.1158/1538-7445.AM2013-3947
Make health inequality history
Authors: Trish Groves
Journal: BMJ (2007)

James Tumwine, professor of paediatrics in Kampala, reckons most people would agree on the need for urgent action to reduce mortality in children in resource constrained countries. We have good evidence to underpin that action, he urges, and yet “expenditure on health has not improved substantially, and the hospital wards in many of these countries are best described as pathetic” (doi: 10.1136/bmj.39371.586076.80).

Three years ago 1 in 8 children with malaria in the national hospital in Guinea-Bissau were dying as inpatients. The introduction of special drug kits for children with severe and complicated malaria had not cut mortality, and it became …
Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VA CSDM): Results of the feasibility trial
Authors: Carlos Abraira, John A Colwell, Frank Q Nuttall, Clark T Sawin, Nancy Johnson Nagel, John P Comstock, Nicholas V Emanuele, Seymour R Levin, William Henderson, Hae Sook Lee
Journal: Diabetes Care (1995)

OBJECTIVE It is not clear whether intensive pharmacological therapy can be effectively sustained in non-insulin-dependent diabetes mellitus (NIDDM). The relative risks and benefits of intensive insulin therapy in NIDDM are not well defined. Accordingly, we designed a feasibility study that compared standard therapy and intensive therapy in a group of NIDDM men who required insulin due to sustained hyperglycemia. RESEARCH DESIGN AND METHODS A prospective trial was conducted in five medical centers in 153 men of 60 ± 6 years of age who had a known diagnosis of diabetes for 7.8 ± 4 years. They were randomly assigned to a standard insulin treatment group (one morning injection per day) or to an intensive therapy group designed to attain near-normal glycemia and a clinically significant separation of glycohemoglobin from the standard arm. A four-step plan was used in the intensive therapy group along with daily self-monitoring of glucose: 1) an evening insulin injection, 2) the same injection adding daytime glipizide, 3) two injections of insulin alone, and 4) multiple daily injections. Patient accrual and adherence, glycohemoglobin (HbA1c), side effects, and measurements of endpoints for a prospective long-term trial were assessed. RESULTS Accrual goals were met, mean follow-up time was 27 months (range 18–35 months), and patients kept 98.6% of scheduled visits. After 6 months, the mean HbA1c in the intensive therapy group was at or below 7.3% and remained 2% lower than the standard group for the duration of the trial. Most of the decrease in the mean HbA1c in the intensive group was obtained by a single injection of evening intermediate insulin, alone or with daytime glipizide. By the end of the trial, 64% of the patients had advanced to two or more injections of insulin a day, aiming for normal HbA1c. However, only a small additional fall in HbA1c was attained. Severe hypoglycemia was rare (two events per 100 patients per year) and not significantly different between the groups, nor were changes in weight, blood pressure, or plasma lipids. There were 61 new cardiovascular events in 40 patients and 10 deaths (6 due to cardiovascular causes). CONCLUSIONS Intense stepped insulin therapy in NIDDM patients who have failed glycemic control on pharmacological therapy is effective in maintaining near-normal glycemic control for &amp;gt; 2 years without excessive severe hypoglycemia, weight gain, hypertension, or dyslipidemia. Cardiovascular event rates are high at this stage of NIDDM. A long-term prospective trial is needed to assess the risk-benefit ratio of intensified treatment of hyperglycemia in NIDDM patients requiring insulin.
The Touchstone of Life: Molecular Information, Cell Communication, and the Foundations of Life
Authors: Harvey Rubin
Journal: Annals of Internal Medicine (1999)

Medical Writings: Book Notes6 July 1999The Touchstone of Life: Molecular Information, Cell Communication, and the Foundations of LifeHarvey Rubin, MD, PhDHarvey Rubin, MD, PhDUniversity of Pennsylvania Medical Center, Philadelphia, Pennsylvania. (Rubin)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-1-199907060-00034 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Lowenstein WR. 366 pages. New York: Oxford Univ Pr; 1999. $30.00. ISBN 0195118286. Order phone 800-451-7556.Field of medicine: Philosophy of science, cell biology, and biochemistry.Format: Hardcover book.Audience: Readers with a general background in science who are interested in the foundations of biology.Purpose: To propound a general theory of biology that explains the highly ordered nature of living organisms in terms of information science.Content: The scope of this book is broad. It starts with a discussion of information in the first chapter, moves through the origin of the universe and the evolution of the forces of ... Author, Article, and Disclosure InformationAffiliations: University of Pennsylvania Medical Center, Philadelphia, Pennsylvania. (Rubin) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMembraninių skaičiavimų technologija daiktų interneto įrenginių savitvarkai 6 July 1999Volume 131, Issue 1Page: 79KeywordsBiochemistryCell biologyCell communicationCell membranesComputer softwareConsciousnessGamesHormonesInformation technologyInformation theory Issue Published: 6 July 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Inactivation of Streptococcus pyogenes extracellular cysteine protease significantly decreases mouse lethality of serotype M3 and M49 strains.
Authors: S Lukomski, S Sreevatsan, C Amberg, W Reichardt, M Woischnik, A Podbielski, J M Musser
Journal: Journal of Clinical Investigation (1997)

Cysteine proteases have been implicated as important virulence factors in a wide range of prokaryotic and eukaryotic pathogens, but little direct evidence has been presented to support this notion. Virtually all strains of the human bacterial pathogen Streptococcus pyogenes express a highly conserved extracellular cysteine protease known as streptococcal pyrogenic exotoxin B (SpeB). Two sets of isogenic strains deficient in SpeB cysteine protease activity were constructed by integrational mutagenesis using nonreplicating recombinant plasmids containing a truncated segment of the speB gene. Immunoblot analyses and enzyme assays confirmed that the mutant derivatives were deficient in expression of enzymatically active SpeB cysteine protease. To test the hypothesis that the cysteine protease participates in host mortality, we assessed the ability of serotype M3 and M49 wild-type strains and isogenic protease-negative mutants to cause death in outbred mice after intraperitoneal inoculation. Compared to wild-type parental organisms, the serotype M3 speB mutant lost virtually all ability to cause mouse death (P < 0.00001), and similarly, the virulence of the M49 mutant was detrimentally altered (P < 0.005). The data unambiguously demonstrate that the streptococcal enzyme is a virulence factor, and thereby provide additional evidence that microbial cysteine proteases are critical in host-pathogen interactions.
Addiction or dependence?
Authors: H A Wendel
Journal: BMJ (1971)

describe four patients who developed acute myeloblastic leukaemia after treatment of a hypoplastic anaemia with oxymetholone.I should like to report a similar case.A 51-year-old man presented in April 1969.The blood count was: haemoglobin 9-4 g/100 ml, white cells 2,800/mm3 (neutrophils 44%0/, lymphocytes 500), plate- lets 58,000, and reticulocytes 0-8 %.The marrow aspirate was markedly hypoplastic, and there were no atypical cells.A trans- fusion was given but in July a similar blood count was found and treatment was there- after with oxymetholone 5 mg thrice daily and prednisone continuously, together with frequent blood transfusions.The total dosage of oxymetholone over the next 2 years was no more than 11 g.In July 1971 a rapid deterioration in the patient's health was observed and myelo- blasts appeared in the peripheral blood.
Provision of highly specialised services
Authors: P. Hindley
Journal: BMJ (1993)

pattern of pain is of no value in localising the site of the lesion.2We advocate consultation with a senior doctor and consideration of early computed tomography for patients with a good history of neck rotation at the time of impact.This increases the chance of bony injury,2 particularly between the occiput and C2, which is often poorly visualised in plain films.Computed tomography should also be considered in those with a fixed abnormal neck position, particularly if pain does not seem to be the restricting factor, and those with definite neurological signs and symptoms, even if their presenta- tion is delayed.
Methods for therapeutic trials in COPD: lessons from the TORCH trial
Authors: O. N. Keene, J. Vestbo, J. A. Anderson, P. M. A. Calverley, B. Celli, G. T. Ferguson, C. Jenkins, P. W. Jones
Journal: European Respiratory Journal (2009)

The TORCH (Towards a Revolution in COPD Health) trial has highlighted some important issues in the design and analysis of long term trials in chronic obstructive pulmonary disease. These include collection of off-treatment exacerbation data, analysis of exacerbation rates and the effect of inclusion of patients receiving inhaled corticosteroids (ICS) prior to randomisation. When effective medications are available to patients who withdraw, inclusion of off-treatment data can mask important treatment effects on exacerbation rates. Analysis of on-treatment data avoids this bias but it needs to be combined with careful analysis of withdrawal patterns across treatments. The negative binomial model is currently the best approach to statistical analysis of exacerbation rates, while analysis of time to exacerbation can supplement this approach. In the TORCH trial, exacerbation rates were higher among patients with previous use of ICS compared to those with no prior use on all study treatments. Retrospective subgroup analysis suggests ICS reduced exacerbation rates compared with placebo, regardless of prior use of ICS before entry to the study. Factorial analysis provides an alternative analysis for trials with combinations of treatments, but assumes no interaction between treatments, an assumption which cannot be verified by a significance test. No definitive conclusions can yet be drawn on whether ICS treatment has an effect on mortality.
IMMUNOLOGICAL MEMORY IN MICE
Authors: Johanna L'age-Stehr, Leonard A. Herzenberg
Journal: The Journal of Experimental Medicine (1970)

Plaque forming cells (PFC) of different immunoglobulin classes producing antibodies against sheep erythrocytes were separated according to their buoyant densities by means of equilibrium centrifugation in a stepwise BSA gradient. In the period of 7-10 days after immunization gammaM PFC are markedly enriched in fractions of low density and relatively depleted in fractions of high density. The distribution of total gammaG PFC shows less enrichment in the lower density fractions and less depletion in the higher density fractions. The density profile for gammaG(2a) PFC is even flatter, with a significant difference (depletion) relative to the unseparated spleen cells only in the highest density fraction. The density gradient distributions of cells able to transfer an adoptive immune response of the various immunoglobulin classes are markedly different from the PFC distribution. Cells obtained 7-10 days after immunization able to transfer an IgM response are present in the same proportions across the density gradient, whereas memory cells for gammaG(2a) obtained at this time are markedly enriched in fractions of low density and virtually depleted from high density fractions. With increasing time after primary immunization, the gammaG(2a) memory cells increase progressively in density and by 6 weeks the higher and lower density fractions have the same proportions of gammaG(2a) memory cells. The total gammaG (mainly gammaG(1)) memory cells by 7-10 days show slight enrichment in low density fractions and no depletion in high density fractions. The conclusions were reached that (a) memory for gammaG(1) develops earlier than memory for gammaG(2a) and (b) that memory for anti-SRBC antibodies of different classes is carried in separate cells. When gradient fractions enriched for PFC and memory cells for all classes were completely depleted of PFC using glass bead columns, the ability of this fraction to transfer memory for all classes was not diminished. This shows that memory cells are not identical with cells secreting antibodies.
Side-effects of psoralen photochemotherapy (PUVA)
Authors: K. WOLFF
Journal: British Journal of Dermatology (1990)

Although psoralen photochemotherapy (PUVA) is one of the most effective forms of therapy for psoriasis, the risk of potential long‐term side‐effects is, as yet, not clearly determined. Chronic degenerative and pigmentary skin changes similar to those of chronic solar exposure occur after long‐term PUVA treatment; PUVA also causes non‐melanoma skin cancers in man, although there is, as yet, no consensus as to what cumulative phototoxic PUVA dose is carcinogenic. Long‐term multicentre studies from the U.S.A. indicate a definite risk of squamous cell carcinoma for long‐term PUVA‐treated patients, whereas European studies reveal no overall increase in skin cancers in similar patients except for those exposed to other carcinogens. Assignment to PUVA should be based on the risk:benefit ratio for the individual patient. Careful patient selection is therefore mandatory and should be limited to those who can be monitored and controlled by informed, competent and conscientious physicians. Psoralen photochemotherapy (PUVA)'is one of the most effective forms of therapy for psoriasis2. It induces a complete clinical remission within a reasonably short period of time and, as maintenance therapy, can produce a remission for an extended period. In combination with retinoids,3 the clinical efficacy of PUVA is greatly improved and is likely to minimize the potential long‐term side‐effects. There is now considerable clinical experience regarding the short‐term safety of PUVA, but the risk of potential long‐term side‐effects is, as yet, not clearly determined.
Residents Benefit From Recent Budget Bill
Authors: John J. Whyte
Journal: JAMA (1997)

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Osteomyelitis-Mimicking Primary Bone Lymphoma at Hip Prosthetic Site
Authors: Te-Chun Hsieh, Chia-Hung Kao, Kuo-Yang Yen, Shung-Shung Sun
Journal: Clinical Nuclear Medicine (2007)

Primary bone lymphomas are rare manifestations not only in all malignant bone tumors but also in all extranodal lymphomas. Malignant bone lesions develop in peripheral bones at prosthetic sites are also rare and there is a tendency to have a higher incidence of prosthesis-associated bone malignancy than that in the general population. A 30-year-old woman had undergone right hip prosthetic replacement with recurrent pain in this area. Because of her history of pulmonary tuberculosis, periprosthetic infection was taken into consideration. The subsequent imaging studies (plain radiography, Tc-99m bone scan, and Ga-67 inflammation scan) were considered to be plausible for osteomyelitis in the periprosthetic bone, but was finally proven to be lymphoma. Similar findings have been found previously but they were not associated with radionuclide studies, such as Ga-67 scans.