tbuckley/cabot-search huggingface dataset:
The angiostatic activity of interferon-inducible protein-10/CXCL10 in human melanoma depends on binding to CXCR3 but not to glycosaminoglycan
Authors: Jinming Yang, Ann Richmond
Journal: Molecular Therapy (2004)

Human interferon-inducible protein 10 (IP-10; HGMW-approved gene symbol CXCL10) is an ELR− CXC chemokine that contains binding domains for both the chemokine receptor CXCR3 and glycosaminoglycans. IP-10 has been recently demonstrated to be a potent angiostatic protein in vivo. Whether IP-10 exerts its angiostatic function through binding to CXCR3, glycosaminoglycans, or both, is not clear. To clarify this issue, we created expression constructs for mutants of IP-10 that exhibit partial (IP-10C) or total (IP-10C22) loss of binding to CXCR3 or loss of binding to glycosaminoglycans (IP-10H and IP-10C22H). The A375 human melanoma cell line was transfected with these expression vectors, and stable clones were selected and inoculated subcutaneously into nude mice. As expected, tumor cells secreting wild-type IP-10 showed remarkable reduction in tumor growth compared to control vector-transfected tumor cells. Surprisingly, mutation of IP-10 resulting in partial loss of receptor binding (IP-10C), or loss of GAG binding (IP-10H), did not significantly alter the ability to inhibit tumor growth. This tumor growth inhibition was associated with a reduction in microvessel density, leading to the observed increase in both tumor cell apoptosis and necrosis. In contrast, expression of the IP-10C22 mutant failed to inhibit melanoma tumor growth. These data suggest that CXCR3 receptor binding, but not glycosaminoglycan binding, is essential for the tumor angiostatic activity of IP-10. We conclude that the arginine 22 amino acid residue of IP-10 is essential for both CXCR3 binding and angiostasis.
THE ACTION OF CERTAIN DIURETICS ON THE FUNCTION OF THE KIDNEY AS MEASURED BY THE UREA CLEARANCE TEST
Authors: Irvine H. Page
Journal: Journal of Clinical Investigation (1933)

A study of certain representative diuretics on renal function, as measured by the urea clearance test, has been undertaken to determine whether these substances have an accelerating or retarding action on the excretion of urea.Practically, it seemed important to know whether studies of kidney function may be carried out, without interference, during the often necessary administration of diuretics, or following the customary breakfast with coffee.Addis and Drury (1) found that the maximum clearance was increased by the ingestion of caffeine albeit to a small degree.We have selected caffeine and diuretin as representative of the xanthine diuretics and salyrgan as representative of the organic mercury diuretics for this study.METHOD
Adolescent Feline Heart Contains a Population of Small, Proliferative Ventricular Myocytes With Immature Physiological Properties
Authors: Xiongwen Chen, Rachel M. Wilson, Hajime Kubo, Remus M. Berretta, David M. Harris, Xiaoying Zhang, Naser Jaleel, Scott M. MacDonnell, Claudia Bearzi, Jochen Tillmanns, Irina Trofimova, Toru Hosoda, Federico Mosna, Leanne Cribbs, Annarosa Leri, Jan Kajstura, Piero Anversa, Steven R. Houser
Journal: Circulation Research (2007)

Recent studies suggest that rather than being terminally differentiated, the adult heart is a self-renewing organ with the capacity to generate new myocytes from cardiac stem/progenitor cells (CS/PCs). This study examined the hypotheses that new myocytes are generated during adolescent growth, to increase myocyte number, and these newly formed myocytes are initially small, mononucleated, proliferation competent, and have immature properties. Ventricular myocytes (VMs) and cKit(+) (stem cell receptor) CS/PCs were isolated from 11- and 22-week feline hearts. Bromodeoxyuridine incorporation (in vivo) and p16(INK4a) immunostaining were measured to assess myocyte cell cycle activity and senescence, respectively. Telomerase activity, contractions, Ca(2+) transients, and electrophysiology were compared in small mononucleated (SMMs) and large binucleated (LBMs) myocytes. Heart mass increased by 101% during adolescent growth, but left ventricular myocyte volume only increased by 77%. Most VMs were binucleated (87% versus 12% mononucleated) and larger than mononucleated myocytes. A greater percentage of SMMs was bromodeoxyuridine positive (SMMs versus LBMs: 3.1% versus 0.8%; P<0.05), and p16(INK4a) negative and small myocytes had greater telomerase activity than large myocytes. Contractions and Ca(2+) transients were prolonged in SMMs versus LBMs and Ca(2+) release was disorganized in SMMs with reduced transient outward current and T-tubule density. The T-type Ca(2+) current, usually seen in fetal/neonatal VMs, was found exclusively in SMMs and in myocytes derived from CS/PC. Myocyte number increases during adolescent cardiac growth. These new myocytes are initially small and functionally immature, with patterns of ion channel expression normally found in the fetal/neonatal period.
<i>In vitro</i> effects of H<sub>1</sub>‐antihistamines on histamine and PGD<sub>2</sub> release from mast cells of human lung, tonsil, and skin
Authors: Y. Okayama, R. C. Benyon, M. A. Lowman, M. K. Church
Journal: Allergy (1994)

Mast cells from different anatomic sites differ in cytochemistry and response to various secretory stimuli. We have investigated whether responsiveness to the second‐generation H 1 ‐receptor antagonists, which are important first‐line drugs for the relief of symptoms in patients with chronic urticaria and allergic rhinoconjunctivitis, also differs according to the site of origin of mast cells. The effects of terfenadine, ketotifen, and cetirizine were therefore examined in relation to the IgE‐dependent release of histamine and prostaglandin D 2 (PGD 2 ) from dispersed human lung, tonsil, and skin mast cells. Terfenadine had a biphasic effect on lung and skin mast cells: at low concentrations, a concentration‐dependent inhibition of histamine release from lung and skin mast cells was observed, whereas at higher concentrations the drug stimulated mediator release. Even at a high concentration, terfenadine inhibited mediator release from tonsil mast cells. Ketotifen had low potency as an inhibitor of mediator release from lung and tonsil mast cells. In skin mast cells, no inhibition of mediator release was observed below 1.0 μM, and above that concentration it induced mediator release. Cetirizine, a much less lipophilic drug than the others tested, did not induce mediator release from mast cells even at concentrations up to 100 μM. This drug showed concentration‐dependent inhibition of IgE‐dependent mediator release from lung and tonsil mast cells only. Our results show that human mast cells are heterogeneous with respect to modulation of mediator release by these H 1 ‐antihistamines. In particular, differences were observed between skin mast cells and those dispersed from lung and tonsils.
Rate dependence of ischaemic myocardial depolarisation: evidence for a novel membrane current
Authors: K. BLAKE, N. A SMITH, W. T CLUSIN
Journal: Cardiovascular Research (1986)

Depolarisation of ischaemic myocardial cells is at least partly due to loss of cellular potassium. Whereas most manifestations of ischaemia vary with heart rate potassium loss, however, reportedly does not. Cellular depolarisation was therefore correlated with extracellular potassium activity during serial coronary artery occlusions in Langendorff perfused canine hearts. Occlusions in sinus rhythm (92(11) beats·min−1) were alternated with rapidly paced occlusions (180 beats·min−1). For each occlusion cellular depolarisation was estimated from TQ depression and compared with the simultaneous increase in potassium electrode potential, ΔEK. Although potassium accumulation accounted for most of the estimated depolarisation at slow heart rates, a potassium independent mechanism predominated during rapid pacing. The potassium independent mechanism was especially important in the first minute of ischaemia when pacing increased depolarisation by 324%, with little increase in ΔEK. It appears that ischaemia induces a rate sensitive depolarising membrane current, which worsens conduction and promotes arrhythmias.
Appendage Tumors of the Skin
Authors: Robert Kim
Journal: JAMA (1969)

This monograph reviews the histogenesis and diagnostic features of dermal appendageal tumors, with particular emphasis on recent histochemical and electron microscopic findings. The authors describe the clinical, histological, histochemical, and electron-microscopic aspects of 31 tumors. The first half of the book covers sweat gland tumors, beginning with tables of the histochemical and ultrastructural characteristics of normal eccrine and apocrine glands. On the basis of related findings in sweat gland tumors, the authors reclassify syringocystadenoma papilliferum and clear cell hidradenoma aseccrine rather than apocrine tumors. They also discuss tumors with sebaceous, epidermal, and muscular differentiation; basal cell epithelioma; and malignant appendageal tumors, and in the discussion they stress histochemical and ultrastructural features. The fine structure of epidermal and dermal components comprising normal skin and newer related concepts are reviewed in the appendix. The text is well written, in the tradition of Lever's textbook. The illustrations, although excellent in quality, do not
THE STREPTOCOCCUS PYOGENES THE CAUSE OF DIPHTHERITIC CONJUNCTIVITIS IN A CASE OF MEASLES.
Authors: H. A. BRENNECKE
Journal: JAMA (1897)

<h3>INTERNE IN THE COOK COUNTY HOSPITAL, CHICAGO.</h3> The following case is thought to merit a somewhat complete report because it was diagnosed clinically as true diphtheria of the conjunctiva, by Dr. Cassius Wescott on the strength of the macroscopic appearance of the eye, whereas the microscopic examination demonstrated the absence of the diphtheria bacilli and the presence of the streptococcus pyogenes in short chains, not only in the eye but in the blood and various organs. The case occurred in a boy three years old. The patient had been living at "The Home of the Friendless" from which a number of patients with measles had been brought to the Cook Country Hospital into the service of Dr. W. L. Baum. The patient had been sick three days before admission, complaining of sore throat, headache, slight coryza and had vomited once. On examination the body was found well nourished, eyes with
Next-Generation Sequencing of Stage IV Squamous Cell Lung Cancers Reveals an Association of PI3K Aberrations and Evidence of Clonal Heterogeneity in Patients with Brain Metastases
Authors: Paul K. Paik, Ronglai Shen, Helen Won, Natasha Rekhtman, Lu Wang, Camelia S. Sima, Arshi Arora, Venkatraman Seshan, Marc Ladanyi, Michael F. Berger, Mark G. Kris
Journal: Cancer Discovery (2015)

Abstract Large-scale genomic characterization of squamous cell lung cancers (SQCLC) has revealed several putative oncogenic drivers. There are, however, little data to suggest that these alterations have clinical relevance. We performed comprehensive genomic profiling (including next-generation sequencing) of 79 stage IV SQCLCs and analyzed differences in the clinical characteristics of two major SQCLC subtypes: FGFR1 amplified and PI3K aberrant. Patients with PI3K-aberrant tumors had aggressive disease marked by worse survival (median overall survival, 8.6 vs. 19.1 months, P &amp;lt; 0.001), higher metastatic burden (&amp;gt;3 organs, 18% vs. 3%, P = 0.025), and greater incidence of brain metastases (27% vs. 0% in others, P &amp;lt; 0.001). We performed whole-exome and RNA sequencing on paired brain metastases and primary lung cancers to elucidate the metastatic process to brain. SQCLC primaries that gave rise to brain metastases exhibited truncal PTEN loss. SQCLC brain metastases exhibited a high degree of genetic heterogeneity and evidence of clonal differences between their primary sites. Significance: We performed next-generation sequencing of metastatic SQCLCs and primary lung–brain metastasis pairs, identifying PI3K-aberrant tumors as an aggressive subset associated with brain metastases. We identified genetic heterogeneity between lung primaries–brain metastases as well as clonal populations that may highlight alterations important in the metastatic process. Cancer Discov; 5(6); 610–21. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 565
Controlled study of the prevalence of radiological osteoarthritis in clinically unrecognised juxta-articular Paget's disease
Authors: P S Helliwell, G Porter
Journal: Annals of the Rheumatic Diseases (1999)

Paget's disease of bone is common and often undiagnosed in the population. The association of Paget's disease and osteoarthritis is well described but only in cases ascertained in secondary and tertiary care centres to which they have been referred largely because of pain. This study represents an attempt to confirm the association between Paget's disease and osteoarthritis in a population previously unknown to have Paget's disease.Radiographs of people over 55 years that included the entire pelvis, sacrum, femoral heads and lumbar spine (mostly plain abdominal radiographs) were obtained from hospital records for the period 1993-95. Films were screened by a trained observer and the positive films were reviewed by a consultant radiologist who also examined a 1 in 10 sample of the negative films. A sub-sample of 153 confirmed positive cases were matched for age and sex using cases without Paget's disease and these pairs were assessed by two observers working in tandem. The hip joints were scored 0-5 using a modification of the original descriptive classification of Kellgren and Lawrence and minimum joint space of the hip was also measured.Not all cases were available for assessment. A total of 248 films were included (137 without Paget's, 89 with unilateral and 22 with bilateral disease). The mean age of the cases and controls was 78.4 years and 77.4 years respectively with 66/45 male/female cases and 78/59 male/female controls. One hundred and twenty nine affected hips were available for comparison with 352 unaffected hips. Median joint space narrowing for the affected hip was 3 mm (range, 0-5 mm) and for the unaffected hip 4 mm (range, 0-6 mm, Mann-Whitney U test, p=0.00001). Median Kellgren and Lawrence grade for both groups was 0, with no statistical difference between the groups (Mann-Whitney U test, p=0.74). In terms of severity of osteoarthritis, there were 19 instances of grades 2+ in the unaffected hips, and only five in the affected hips.Pagetic coxopathy is characterised by loss of joint space, which may represent a secondary chondropathy. Although joint failure may result from this secondary chondropathy progression may be dependent on non-Pagetic factors. It is also possible that the usual radiological features of osteoarthritis may be modified or obscured by the Paget's disease.
Dupuytren's Contracture
Authors: J. A. Ross
Journal: BMJ (1952)

DURING THE PAST TWO YEARs 50 cases of Dupuytren's contracture (44 males, 6 females) have presented themselves for treatment at the Surgical Out-Patient Department, Edinburgh Royal Infinnary. Of these, 36 have submitted themselves to a questionnaire and review of their condition. Certain of their features are of interest, and appear worthy of consideration. They form the subject of the present study.
THE DIAGNOSIS OF BLINDNESS
Authors: EDWARD JACKSON
Journal: JAMA (1925)

A diagnosis is a decision, to be reached by careful consideration of all obtainable evidence. In a military commander or an executive, indecision may be more disastrous than a wrong decision. For a physician or surgeon, it may be quite as serious in its consequences. In cases of blindness, a decision on the extent or the cause of blindness may be the only professional service we can render. Every attempt to assist, to train, to compensate or to make economic provision for the blind renders the diagnosis of blindness more important. All human decisions are liable to error, but this does not make decision less important. Through ignorance of facts, distortion of them, prejudice, poor judgment, failure properly to appraise the relative value of evidence, wrong conclusions may be reached. This may be the case in military affairs or in executive business, with judges as to points of law, or
SWI/SNF Chromatin Remodeling and Human Malignancies
Authors: Julien Masliah-Planchon, Ivan Bièche, Jean-Marc Guinebretière, Franck Bourdeaut, Olivier Delattre
Journal: Annual Review of Pathology Mechanisms of Disease (2014)

The SWI/SNF complexes, initially identified in yeast 20 years ago, are a family of multi-subunit complexes that use the energy of adenosine triphosphate (ATP) hydrolysis to remodel nucleosomes. Chromatin remodeling processes mediated by the SWI/SNF complexes are critical to the modulation of gene expression across a variety of cellular processes, including stemness, differentiation, and proliferation. The first evidence of the involvement of these complexes in carcinogenesis was provided by the identification of biallelic, truncating mutations of the SMARCB1 gene in malignant rhabdoid tumors, a highly aggressive childhood cancer. Subsequently, genome-wide sequencing technologies have identified mutations in genes encoding different subunits of the SWI/SNF complexes in a large number of tumors. SWI/SNF mutations, and the subsequent abnormal function of SWI/SNF complexes, are among the most frequent gene alterations in cancer. The mechanisms by which perturbation of the SWI/SNF complexes promote oncogenesis are not fully elucidated; however, alterations of SWI/SNF genes obviously play a major part in cancer development, progression, and/or resistance to therapy.
Long-term continuous entecavir therapy in nucleos(t)ide-naïve chronic hepatitis B patients
Authors: Atsushi Ono, Fumitaka Suzuki, Yusuke Kawamura, Hitomi Sezaki, Tetsuya Hosaka, Norio Akuta, Masahiro Kobayashi, Yoshiyuki Suzuki, Satoshi Saitou, Yasuji Arase, Kenji Ikeda, Mariko Kobayashi, Sachiyo Watahiki, Rie Mineta, Hiromitsu Kumada
Journal: Journal of Hepatology (2012)
Screening by Mammography
Authors: Michael B. Shimkin
Journal: JAMA (2014)

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
Ouabain-insensitive K-adenosine triphosphatase in distal nephron segments of the rabbit.
Authors: L C Garg, N Narang
Journal: Journal of Clinical Investigation (1988)

An electrogenic H-ATpase sensitive to inhibition by N-ethyl-maleimide has been reported to be present in renal distal tubules. In contrast to another H-ATPase (gastric H-K-ATPase), the renal enzyme is not stimulated by K+ and is not inhibited by vanadate. However, our preliminary observations indicated that a K-stimulated ATPase (K-ATPase) sensitive to inhibition by vanadate is present in renal medullary collecting duct (MCD). To localize and further characterize this renal tubular K-ATPase, we measured K-ATPase activity in eight specific segments of the rabbit nephron. K-ATPase activity was the difference in ATPase activity in the presence and absence of KCl but in the presence of ouabain (to inhibit Na-K-ATPase). ATPase activity was determined by a fluorometric microassay in which ATP hydrolysis is coupled to the oxidation of NADH. There was a significant K-ATPase activity (expressed as pmol.min-1.mm-1) in the connecting tubule (CNT, 17.0 +/- 3.3), cortical collecting duct (CCD, 6.6 +/- 0.7), and MCD (8.8 +/- 1.7), but not in the proximal segments and the thick ascending limbs. The renal tubular K-ATPase was not only inhibited by vanadate but also by omeprazole and SCH 28080 (relatively specific inhibitors of gastric H-K-ATPase). It is concluded that K-ATPase present in the CNT, CCD, and MCD has some properties in common with gastric H-K-ATPase. However, the physiological role of K-ATPase in the distal nephron segments remains to be elucidated.
Simulators and Gastrointestinal Endoscopy Training
Authors: S Adamsen
Journal: Endoscopy (2000)

Over the last decades, training in gastrointestinal endoscopy has evolved from demonstrations via a lecture scope (passed around to as many as 25 colleagues [1]), over the use of live courses, to the present situation with emerging guidelines on competence thresholds, training programs, and training facilities from national and international committees and societies [2]. Recently, refinement of simulators has opened up the potential for training in scenarios very close to real life, as described in this issue of Endoscopy [3] [4] [5] [6] .
Chemokines — Chemotactic Cytokines That Mediate Inflammation
Authors: A D Luster
Journal: New England Journal of Medicine (1998)

The attraction of leukocytes to tissues is essential for inflammation and the host response to infection. The process is controlled by chemokines, which are chemotactic cytokines. This review introduces the burgeoning family of cytokines, with special emphasis on their role in the pathophysiology of disease and their potential as targets for therapy.Structure and Function of ChemokinesOver 40 chemokines have been identified to date, most of them in the past few years. The relations among chemokines were not initially appreciated, which led to an idiosyncratic nomenclature consisting of many acronyms. When initially identified, these proteins had no known biologic . . .
Clearance of proteoglycan from joint cavities.
Authors: D P Page-Thomas, D Bard, B King, J T Dingle
Journal: Annals of the Rheumatic Diseases (1987)

The rate of loss from the synovial cavity of proteoglycan subunit, a major constituent of cartilage, has been measured in rabbits with and without experimental arthritis. The effect of aggregation between proteoglycan and hyaluronic acid upon the rate of elimination has also been investigated. The results indicate that proteoglycan subunit has a clearance half life of around 12 hours in normal joints and that this rate is not significantly altered in the presence of an active synovitis. Neither injection of proteoglycan as an aggregate, nor in a form incapable of aggregation, had any significant effect on clearance rates. These data indicate that loss of proteoglycan from the joint is not retarded by its ability to aggregate with hyaluronic acid in the synovial fluid and, together with measurements of synovial fluid proteoglycan, may enable rates of cartilage breakdown in vivo to be calculated.