tbuckley/cabot-search huggingface dataset:
P658Adaptation to continuous normobaric hypoxia affects mitochondrial enzymes in spontaneously hypertensive rat hearts
Authors: M Kalous, R Weissova, Z Drahota, I Brabcova, J Zurmanova, O Novakova, M Pravenec, F Kolar, J Neckar
Journal: Cardiovascular Research (2014)

Purpose: Adaptation to continuous normobaric hypoxia (CNH) increases cardiac ischemic tolerance. The protective role of cardiac mitochondria has been suggested in CNH. The present study investigated the effects of CNH on the expression and activity of selected mitochondrial proteins in spontaneously hypertensive rats (SHR), and in a novel conplastic strain SHR-mtBN. This strain is characterized with a selective replacement of the mitochondrial genome of SHR with more ischemic tolerant Brown Norway (BN) strain. Methods: Rats were kept 21 days at CNH (inspired O2 fraction 0.1). Left ventricular homogenate was used to assess the enzyme activity of malate dehydrogenase (MDH), citrate synthase (CS), NADH-cytochrome c oxidoreductase, succinate-cytochrome c oxidoreductase and cytochrome oxidase (COX). Protein and mRNA expression of the subunits of oxidative phosphorylation complexes (CI - Ndufa9, CII - Sdha, CIII- Uqcrc2, CIV - COX-4 and MTCO1, CV - Atp5a1) were evaluated using immunoblotting and RT-PCR. Results: Normoxic SHR-mtBN has by 14% lower amount of complex IV subunit MTCO1 (encoded by BN mitochondrial genome) compared to SHR. Adaptation to CNH resulted in raised content of complex IV subunits by 17% in both strains compared to normoxic controls. In addition, MDH activity decreased by 23% only in hypoxic SHR. These changes resulted in significant differences between SHR and SHR-mtBN after adaptation to CNH. As compared both hypoxic strains, SHR-mtBN demonstrated higher MDH activity and protein amount of Ndufa9 subunit of complex I, whereas the protein content of COX-4 and MTCO1 subunits of complex IV were lower compared to SHR. The expression on the mRNA level was decreased for CS (by 45%) as well as for cytochrome oxidase isoforms subunits COX 4.1 and COX 4.2 (by 22% and 23%, respectively) in the conplastic strain adapted to CNH compared to normoxic control. However, in the CNH adapted SHR strain, the decrease in mRNA level was found for COX 4.1 only (by 28%). Conclusions: Adaptation to CNH affected myocardial expression and activity of mitochondrial proteins in hypertensive strains, and replacement of the mitochondrial genome of SHR with BN modified the response to CNH. This work was supported by the Czech Science Foundation grant no. 13-10267S
Soluble neuregulin-1 modulates disease pathogenesis in rodent models of Charcot-Marie-Tooth disease 1A
Authors: Robert Fledrich, Ruth M Stassart, Axel Klink, Lennart M Rasch, Thomas Prukop, Lauren Haag, Dirk Czesnik, Theresa Kungl, Tamer A M Abdelaal, Naureen Keric, Christine Stadelmann, Wolfgang Brück, Klaus-Armin Nave, Michael W Sereda
Journal: Nature Medicine (2014)
Clinical, Morphologic and Immunologic Studies on the Natural History of Acute Post-Streptococcal Glomerulonephritis.
Authors: Kurt Lange
Journal: Annals of Internal Medicine (1966)

s1 May 1966Clinical, Morphologic and Immunologic Studies on the Natural History of Acute Post-Streptococcal Glomerulonephritis.Kurt Lange, M.D., F.A.C.P., Gerhard Treser, M.D., Edward Wasserman, M.D., Theodore Ehrenreich, M.D., Richard Ores, M.D., Antonia Ty, M.D.Kurt Lange, M.D., F.A.C.P.Search for more papers by this author, Gerhard Treser, M.D.Search for more papers by this author, Edward Wasserman, M.D.Search for more papers by this author, Theodore Ehrenreich, M.D.Search for more papers by this author, Richard Ores, M.D.Search for more papers by this author, Antonia Ty, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1180_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTwenty-one patients (20 children and 1 adult) with acute poststreptococcal glomerulonephritis were biopsied within a month of onset of their disease and again 10 to 84 months later. The biopsies were studied by light- and electron microscopy and by immunohistology for gamma globulin and complement. At the time of repeat biopsy all patients were clinically well, and 15 had no abnormal laboratory findings. Of six remaining patients (28%), one had a 1+ proteinuria, five a trace proteinuria, two of them with more than 1.5 million RBC/mm3 in the Addis counts.Among the patients rebiopsied 20 months or more after the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1180-1181KeywordsBiopsyChildrenClinical immunologyElectron microscopyGlobulinsGlomerulonephritisProteinuriaResearch laboratories Issue Published: 1 May 1966 PDF DownloadLoading ...
Care of the Dying
Authors: E. Wilkes
Journal: BMJ (1973)

<h3>Abstract</h3> CRISPR-Cas systems provide adaptive immunity for prokaryotic cells by recognizing and eliminating the recurrent genetic invaders whose sequences had been captured in a prior infection and stored in the CRISPR arrays as spacers. However, the biological factors determining the efficiency of this adaptive immune system have not been fully characterized. Recent studies in cultured bacteria showed that slowing the growth rate of bacterial cells could promote their acquisition of novel spacers. This paper reports a positive correlation between the minimal doubling time and the spacer abundance across the bacteria domain. The correlation is still significant after controlling for the effect of growth temperature. This observation provides evidence for the existence of the trade-off between bacterial growth and defense proposed in the “Killing the Winner” hypothesis.
Lunatic and Manic Fringe Cooperatively Enhance Marginal Zone B Cell Precursor Competition for Delta-like 1 in Splenic Endothelial Niches
Authors: Joanne B. Tan, Keli Xu, Kira Cretegny, Ioana Visan, Julie S. Yuan, Sean E. Egan, Cynthia J. Guidos
Journal: Immunity (2009)
P3 INVALIDATION OF OSTEOPONTIN AGGRAVATES HEPATIC INJURY INDUCED BY ISCHEMIA–REPERFUSION IN MICE
Authors: S. Patouraux, D. Rousseau, A. Rubio, J. Lauron, S. Bonnafous, V.J. Lavallard, M.-C. Saint-Paul, B. Bailly-Maitre, A. Tran, D. Crenesse, P. Gual
Journal: Journal of Hepatology (2014)
Legionnaires' Disease Legacies
Authors: Gary L. Lattimer
Journal: JAMA (1980)

<h3>To the Editor.—</h3> The editorial comments by Samuel Vaisrub, MD, on historical aspects of Legionnaires' disease (243:1747, 1980) might well have included one additional legacy: its impact on the ill-fated swine influenza vaccination program.<sup>1</sup> It may be recalled that, in the spring of 1976 the American public had been warned of the strong probability of an impending epidemic of swine influenza. Indeed, the federal government had pushed for a massive inoculation program designed to vaccinate every person in the United States. However, by June 1976, the program stalled because vaccine manufacturers refused to accept liability that might result from injury or death caused by the vaccine. Private insurers also would not take the risk; therefore, legislation was proposed that would make the federal government liable for adverse effects caused by the vaccine. Members of the congressional committee reviewing the proposal questioned the wisdom of the government accepting this liability,
Chronic Varicose Ulcers Treated by Lumbar Sympathectomy
Authors: J. Borrie, E. V. Barling
Journal: BMJ (1948)

500 units, but in such patients he should aspirate the gastric contents, as extreme gastric dilatation is sure to be present and the patient may improve enough to vomit in the ambulance and inspire his vomit.Any physician who has ever treated diabetic coma in the patient's own home must agree that, though of course one may succeed, the difficulties are so great and the unpleasant surprises so numerous that home treatment should rarely if ever be undertaken. SummaryThe line of treatment of diabetic coma given by Root and his colleagues in Boston is advocated.The essential point is large insulin dosage at an early stage.Physicians less experienced than Root and working in less well- equipped clinics should deliberately err on the side of giving larger doses than the experts, for there is no danger in giving too much and every danger in giving too little.Gastric aspiration must be carried out as routine in every case and nothing be given by the mouth during the critical first few hours.Intravenous saline is needed by many cases and by all the severe cases, sometimes in very large quantities.The syndrome of potassium depletion must be rare, but the possibility should be kept in mind.Glucose must not be given by any route until clinical recovery has been achieved, but after this it may safely be given to prevent hypoglycaemic attacks.
Public health funding should be ringfenced when transferred to local councils, doctors say
Authors: A. Gulland
Journal: BMJ (2010)

Public health doctors in England have urged the government to protect the public health budget in the wake of demands from local councils that the money go into general funds.

The calls were made in the light of a news report that councils were demanding that they spend the money as they see fit when public health is transferred to council control with the abolition of primary care trusts. The details of the budget are due to be made clearer with the publication this week of the public health white paper.

With the abolition of primary care trusts, councils are to regain control of public health for the first time since 1974.

Lindsey …
Renal Hilar Lymph
Authors: CHARLES C. O'MORCHOE, PATRICIA J. O'MORCHOE, NIALL M. HENEY
Journal: Circulation Research (1970)

Renal lymph was collected from single hilar lymphatics in 58 anesthetized dogs (1) to study the mechanism by which lymph production is affected during diuresis and (2) to determine whether a medullary contribution to renal lymph could be defined by changes in the electrolyte concentration of hilar lymph with concomitant alterations in the concentration gradient of the renal medulla. When diuresis was induced by a solute load (mannitol), lymph flow increased by 25 to 300%. On the other hand, when diuresis was induced without such a solute load, lymph flow was either unaffected (mersalyl) or slightly reduced (furosemide). It was concluded that the effect of mannitol on renal lymph flow was mediated primarily through its general effect on extracellular fluid rather than through any specific intrarenal consequence of the diuresis itself. Control hilar lymph-to-plasma concentration ratios for Na + (1.057 ± 0.040), Cl - (1.129 ± 0.040) and Ca 2+ (0.770 ± 0.046) but not K + (0.0986 ± 0.086) were found to be significantly different from 1.0. Failure of mannitol diuresis to alter significantly the lymph-plasma ratios of Na + and Cl - provided evidence that the high electrolyte concentrations of the inner medulla were not reflected in hilar lymph. The finding that furosemide abolished the lymph-plasma concentration difference for Na + and significantly reduced that for Cl - was taken as evidence that the outer medulla was a significant source of renal hilar lymph.
Poliomyelitis in Children
Authors: P. A. M. Auld, S.V. Kevy, R. C. Eley
Journal: New England Journal of Medicine (1960)

IN view of the optimistic opinion expressed by many that paralytic poliomyelitis will be reduced to a bare minimum once the practice of immunization with the currently employed vaccine has become nationwide, it appears pertinent to report and to have a permanent record of the 1035 patients assumed to have acute poliomyelitis who were admitted to the Children's Hospital in Boston during the New England epidemic of 1955.During the summer of 1955 Massachusetts suffered its most severe epidemic of poliomyelitis; 3950 cases were reported, of which 2771 were paralytic,1 and in all probability, a number of milder cases were . . .
Toward a generative transformational approach to visual perception
Authors: Douglas Vickers
Journal: Behavioral and Brain Sciences (2001)

Shepard's notion of “internalisation” is better interpreted as a simile than a metaphor. A fractal encoding model of visual perception is sketched, in which image elements are transformed in such a way as to maximise symmetry with the current input. This view, in which the transforming system embodies what has been internalised, resolves some problems raised by the metaphoric interpretation. [Hecht; Shepard]
De novo mutations in HCN1 cause early infantile epileptic encephalopathy
Authors: Caroline Nava, Carine Dalle, Agnès Rastetter, Pasquale Striano, Carolien G F de Kovel, Rima Nabbout, Claude Cancès, Dorothée Ville, Eva H Brilstra, Giuseppe Gobbi, Emmanuel Raffo, Delphine Bouteiller, Yannick Marie, Oriane Trouillard, Angela Robbiano, Boris Keren, Dahbia Agher, Emmanuel Roze, Suzanne Lesage, Aude Nicolas, Alexis Brice, Michel Baulac, Cornelia Vogt, Nady El Hajj, Eberhard Schneider, Arvid Suls, Sarah Weckhuysen, Padhraig Gormley, Anna-Elina Lehesjoki, Peter De Jonghe, Ingo Helbig, Stéphanie Baulac, Federico Zara, Bobby P C Koeleman, Thomas Haaf, Eric LeGuern, Christel Depienne
Journal: Nature Genetics (2014)
Pregnancy Outcomes in Familial Hypercholesterolemia
Authors: Ieva Toleikyte, Kjetil Retterstøl, Trond Paul Leren, Per Ole Iversen
Journal: Circulation (2011)

Women with familial hypercholesterolemia (FH) are prone to early cardiovascular disease and death. It is unknown whether FH adversely affects pregnant women and birth outcomes. We determined whether heterozygous FH women are at higher risk of premature birth (<37 gestational weeks), delivering children with low birth weight (<2500 g) and/or with congenital malformations compared to women in general.We linked information from the Medical Genetics Laboratory with that of the Medical Birth Registry of Norway. We included 1869 FH women (≥ 14 years) from the Medical Genetics Laboratory and about 2 million (general population) from the Medical Birth Registry of Norway during the period 1967 to 2006. The registry match resulted in analysis of 2319 births of 1093 women with heterozygous FH. The mean (SD) prepregnancy total cholesterol concentration was 9.59 (2.06) mmol/L (370 [80 mg/dL]), whereas the concentration of total cholesterol was not available during pregnancy. The frequencies of prematurity, low birth weight, and congenital malformations for the 40-year period in the FH population were 6.8, 5.0, and 3.3, respectively. The corresponding values for the general population were 6.2, 5.2, and 3.2. The corresponding odds ratios were 1.11 (95 confidence interval 0.94-1.31; P=0.23), 0.96 (0.79-1.15; P=0.64), and 1.09 (0.87-1.37; P=0.45).Women with FH do not appear to have a higher risk of preterm delivery or of having infants with low birth weight or congenital malformations than women in general, but, although this is unlikely, some undetected bias may obscure the real differences.
Cancer-Associated Retinopathy (CAR Syndrome) with Antibodies Reacting with Retinal, Optic-Nerve, and Cancer Cells
Authors: Charles E. Thirkill, Paul FitzGerald, Robert C. Sergott, Alan M. Roth, Nancy K. Tyler, John L. Keltner
Journal: New England Journal of Medicine (1989)

A VARIETY of neurologic disorders are associated with different forms of cancer.1 2 3 4 5 6 7 Secondary neurologic effects that become manifest in the absence of metastasis are collectively called paraneoplastic phenomena, and they include the rapid loss of sight.8 9 10 11 There have been several published reports of central nervous system autoantibodies in patients with cancer, primarily small-cell carcinoma of the lung with associated neuropathies.12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 We previously described30 high titers of serum antibodies reactive with retinal components in patients with cancer who experienced a sudden, unexplained reduction in vision before the cancer was diagnosed. This study involved a patient with symptoms of cancer-associated retinopathy (the . . .
Ian Cameron Geddes
Authors: J. E. Riding, R. S. Jones
Journal: BMJ (2010)

Ian Cameron Geddes was born at Edinburgh in 1922 and graduated from St Andrews in 1945, having been awarded a Full Blue for athletics. After service in the Royal Air Force he enrolled on the postgraduate course in anaesthesia at Liverpool University in 1949. After experience in Liverpool hospitals and as a research fellow in the Department of Anaesthesia, University of Liverpool, he spent two years at Montreal General Hospital and Research Institute. There he studied the properties and metabolism of local analgesic drugs. This work formed the basis for a thesis for which he was awarded an MD …
Fees waived for university researchers publishing through BioMed Central
Authors: T. Delamothe
Journal: BMJ (2003)

Biomedical researchers at 180 UK universities will soon be able to share their findings at no cost to readers as the result of a deal struck between the open access publisher BioMed Central and the Joint Information Systems Committee (a joint committee of UK further and higher education funding bodies).

From 1 July, charges for processing articles will be waived for all …
International Medical Graduates and Others Invited to Join the AMA-IMG Section
Authors: J Jacobson
Journal: JAMA (1998)

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
PWE-013 Selective cytotoxicity of aberrantly glycosylated MUC1 binding-PS1 photoimmunoconjugates for oesophageal adenocarcinoma targeted photodynamic therapy in primary and metastatic disease
Authors: M A Butt, I Stamati, H Pye, G Yahioglu, R J Haidry, D Oukrif, M R Novelli, M P Deonarain, L B Lovat
Journal: Gut (2012)

<h3>Introduction</h3> Targeted photodynamic therapy (PDT) has the potential to overcome current limitations of PDT agents by offering specific tumour kill with reduced side effects. We have previously shown expression of AG-MUC1, an epithelial cancer target bound by the antibody HuHMFG1, in patients with Barrett9s with dysplasia, oesophageal adenocarcinoma (OA) and on OE19, an OA cell line. We have recently developed and characterised photoimmunoconjugates (PIC) of Hu-HMFG1 with the photosensitiser PS1 to specifically target PDT to OA. This is the first study to test the cytotoxic efficacy of HuHMFG1:PS1 PIC9s against cancer cells in vitro. <h3>Methods</h3> Hu-HMFG1 was conjugated with PS1 (PhotoBiotics) using recently optimised methods. Binding of the HuHMFG1:PS1 PIC to the cancer cell lines SKOV-3 (ovarian), MCF-7 (breast), OE-19 (oesophageal) and HT-29 (colon) was examined with flow cytometetry and analysed with FlowJo software. The efficacy of HMFG1:PS1 PICs on these lines were compared with equivalent free PS1 in the presence or absence of laser activation. Power was set to a clinically relevant light dose. Cell viability was measured with standard MTS assay and the plates read on an ELISA plate reader at 490 nm. <h3>Results</h3> Flow cytometry confirmed binding of HMFG1:PS1 PIC to SKOV-3, OE19 and MCF-7 but not HT-29 cells. Cell viability counts in all plates were initially corrected for untreated plate controls and then plotted on a log scale to produce dose response curves. This confirmed significantly superior cytotoxic efficacy of HuHMFG1:PS1 over PS1 in SKOV-3 (F=104.93, p=0.00051) and OE-19 (F=11.13, p=0.0125), and a trend towards effect for MCF-7 (F=3.13, p=0.116) cells using linear regression analysis and an F test to compare treatments. HuHMFG1:PS1 did not kill HT-29 effectively over control (p=0.84) or differ significantly from PS1 in its efficacy (F=0.155, p=0.71) confirming cytotoxicity to be limited to HuHMFG1 expressing cells. <h3>Conclusion</h3> This pilot study is the first to successfully demonstrate binding and potential cytotoxicity of targeting HuHMFG1:PS1 PICs against OA cells in vitro. Absence of photosensitiser effect in the negative control (HT29 cells) confirmed selective cytotoxicity of HuHMFG1:PS1 to AG-MUC1 expressing cells. We further demonstrated that HuHMFG1:PS1 can effectively kill other AG-MUC1 expressing tumours which have historically been treated with HuHMFG1 related therapies. <h3>Competing interests</h3> None declared.
PD05-07: Prospective Validation and Characterization of HER2 Positive Circulating Tumor Cells in Patients with HER2 Negative Metastatic Breast Cancer.
Authors: EM Olson, LM Flores, JS Najita, C Curley, J Jeong, K Murray, JJ Savoie, EP Winer, IE Krop
Journal: Cancer Research (2011)

Abstract Background: Circulating tumor cells (CTCs) with evidence of HER2 amplification can occur in patients (pts) with clinically HER2 negative metastatic breast cancer. While these findings potentially have profound implications for CTCs as a biomarker for treatment, prospective validation and characterization of this subgroup is necessary. Methods: We created a prospective cohort of pts with metastatic breast cancer that were HER2 negative by IHC and/or FISH on all available primary and metastatic biopsies. Blood samples were collected at study entry and then again at ≥ 3 weeks if available. CTCs were enumerated by a modification of the Veridex CellSearch Profile kit. FISH was performed on each CTC sample and reported as positive if the HER2/CEP17 ratio was ≥ 2.0. Analyses are descriptive. Results: 66 pts were consented for study and this report includes the 65 pts with detectable CTCs. Median number of CTCs was 226 (range 112 to &amp;gt; 3000). At initial testing, 23 pts (35%) had HER2 positive CTCs, median HER2:CEP17 ratio of 3.4. 50% (11 of 22) of the pts with lobular or ductal/lobular histology had HER2 amplified CTCs, compared to only 27% (10 of 36) of patients with ductal histology. Women with ER positive disease had HER2 positive CTCs in 40% of cases (20 of 49) compared to 19% of ER negative pts (3 of 16). To assess concordance of HER2 amplification of CTCs over time, 34 pts consented to be retested at a median 5.9 weeks after initial screening (range 3.3 - 17 weeks) and all but 1 had detectable CTCs. Baseline characteristics of these 34 pts were similar to the original population, with HER2 amplified CTCs detected in 35% (12 of 34) pts at initial screening. HER2 positive CTCs were concordant at time of retesting in 83% (10 of 12) pts; the 2 women with discordant CTCs were receiving HER2 directed therapy. Of the pts with HER2 negative CTCs at initial screening, 81% (17 of 21) continued to have HER2 negative CTCs at time of retesting. Conclusion: We observed a higher prevalence of HER2 positive CTCs among pts with ER positive disease and evidence of lobular histology. The presence of HER2 positive CTCs is concordant over time in the majority of pts. The functional significance of HER2 positive CTCs in patients with clinically HER2 negative breast cancer will be tested in a prospective study with HER2−directed therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-07.