tbuckley/cabot-search huggingface dataset:
Retrospective comparison of 'Cheno' and 'Urso' in the medical treatment of gallstones.
Authors: T J Meredith, G V Williams, P N Maton, G M Murphy, H M Saxton, R H Dowling
Journal: Gut (1982)

In two groups of gallstone patients ideally suited for medical treatment, the effect of six to 18 months9 therapy was compared retrospectively in 52 given chenodeoxycholic acid (CDCA) and 46 given ursodeoxycholic acid (UDCA). The minimum dose (mg kg-1 day-1) required to desaturate bile consistently was 10.1 for UDCA and 14.3 for CDCA. In patients completing six months9 treatment, 23 of 35 (66%) taking a mean of 7.7 (+/- SEM 0.5) mg UDCA and 34 of 42 (81%) taking 14.7 +/- 0.2 mg CDCA showed partial or complete dissolution of gallstones. The mean dose in the UDCA-treated patients, however, was artefactually lowered by previous dose-response studies: in those who had not taken multiple doses, the mean UDCA intake in the 9responders9 at six months was 9.1 +/- 0.3 mg kg-1 day-1. At six months, more UDCA (five of 35 or 14.3%) than CDCA (four of 42 or 9.5%)-treated patients showed complete dissolution of gallstones, but, by one year, the situation was reversed, 20 of 41 (49%) CDCA-treated and eight of 30 (27%) UDCA-treated patients showing complete dissolution of gallstones. Cumulative efficacy at one year had risen to 76% for UDCA and 89% for CDCA. Both treatments reduced the frequency of dyspepsia and biliary colic; 37% of CDCA and 2.6% of UDCA-treated patients showed hypertransaminasaemia; diarrhoea developed in 60% of the CDCA group but in none of the UDCA group.
The Lasker Awards—Recognizing and Highlighting Oncology Research
Authors: Mary L. Disis
Journal: JAMA (2015)

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
Field defects in DNA repair: is loss of MGMT an initial event in colorectal carcinogenesis?
Authors: T. A. Graham, S. J. Leedham
Journal: Gut (2010)

The classical view of carcinogenesis begins with rate-limiting mutations in a tumour suppressor or oncogene resulting in immediate lesion growth. Tumour progression occurs as cells within the tumour acquire additional mutations; this is the Somatic Mutation Theory of carcinogenesis.1 However, it is increasingly clear that the road to cancer can begin long before any overt tumour growth; this is termed ‘pretumour progression’.

Pretumour mutations are the likely drivers of ‘field cancerisation’—the widespread replacement of the normal cell population with a histologically non-dysplastic but protumorigenic clone that harbours a genetic or epigenetic alteration.2–4 Identifying situations of field cancerisation has obvious clinical significance: (1) identifying protumorigenic fields may predict a patient's risk of neoplastic progression; and (2) limited tumour resections in situations where field cancerisation has occurred may leave significant residual disease.

Field cancerisation has been reported in many different tissues. In their seminal paper, Slaughter and colleagues recognised that field cancerisation could underlie the development of multifocal head and neck cancers.2 Subsequently, there has been unequivocal evidence of field cancerisation in many other tissues, most notably in the lung,5 in the development of Barrett's oesophagus-associated adenocarcinoma6 and in the inflammatory bowel disease ulcerative colitis.7 In each of these cases the identified mutant …
Oxygen Regulation of Tumor Perfusion by <i>S</i> -Nitrosohemoglobin Reveals a Pressor Activity of Nitric Oxide
Authors: Pierre Sonveaux, Andrew M. Kaz, Stacey A. Snyder, Rachel A. Richardson, L. Isabel Cárdenas-Navia, Rodney D. Braun, John R. Pawloski, Gillian M. Tozer, Joseph Bonaventura, Timothy J. McMahon, Jonathan S. Stamler, Mark W. Dewhirst
Journal: Circulation Research (2005)

In erythrocytes, S-nitrosohemoglobin (SNO-Hb) arises from S-nitrosylation of oxygenated hemoglobin (Hb). It has been shown that SNO-Hb behaves as a nitric oxide (NO) donor at low oxygen tensions. This property, in combination with oxygen transport capacity, suggests that SNO-Hb may have unique potential to reoxygenate hypoxic tissues. The present study was designed to test the idea that the allosteric properties of SNO-Hb could be manipulated to enhance oxygen delivery in a hypoxic tumor. Using Laser Doppler flowmetry, we showed that SNO-Hb infusion to animals breathing 21% O2 reduced tumor perfusion without affecting blood pressure and heart rate. Raising the pO2 (100% O2) slowed the release of NO bioactivity from SNO-Hb (ie, prolonged the plasma half-life of the SNO in Hb), preserved tumor perfusion, and raised the blood pressure. In contrast, native Hb reduced both tumor perfusion and heart rate independently of the oxygen concentration of the inhaled gas, and did not elicit hypertensive effects. Window chamber (to image tumor arteriolar reactivity in vivo) and hemodynamic measurements indicated that the preservation of tissue perfusion by micromolar concentrations of SNO-Hb is a composite effect created by reduced peripheral vascular resistance and direct inhibition of the baroreceptor reflex, leading to increased blood pressure. Overall, these results indicate that the properties of SNO-Hb are attributable to allosteric control of NO release by oxygen in central as well as peripheral issues.
Changes in citric acid cycle flux and anaplerosis antedate the functional decline in isolated rat hearts utilizing acetoacetate.
Authors: R R Russell, H Taegtmeyer
Journal: Journal of Clinical Investigation (1991)

To determine the temporal relationship between changes in contractile performance and flux through the citric acid cycle in hearts oxidizing acetoacetate, we perfused isolated working rat hearts with either glucose or acetoacetate (both 5 mM) and freeze-clamped the tissue at defined times. After 60 min of perfusion, hearts utilizing acetoacetate exhibited lower systolic and diastolic pressures and lower cardiac outputs. The oxidation of acetoacetate increased the tissue content of 2-oxoglutarate and glutamate and decreased the content of succinyl-CoA suggesting inhibition of citric acid cycle flux through 2-oxoglutarate dehydrogenase. Whereas hearts perfused with either acetoacetate or glucose were similar with respect to their function for the first 20 min, changes in tissue metabolites were already observed within 5 min of perfusion at near-physiological workloads. The addition of lactate or propionate, but not acetate, to hearts oxidizing acetoacetate improved contractile performance, although inhibition of 2-oxoglutarate dehydrogenase was probably not diminished. If lactate or propionate were added, malate and citrate accumulated indicating utilization of anaplerotic pathways for the citric acid cycle. We conclude that a decreased rate of flux through 2-oxoglutarate dehydrogenase in hearts oxidizing acetoacetate precedes, and may be responsible for, contractile failure and is not the result of decreased cardiac work. Further, anaplerosis play an important role in the maintenance of contractile function in hearts utilizing acetoacetate.
Mechanisms of Telomerase Induction During Vascular Smooth Muscle Cell Proliferation
Authors: T. Minamino, S. Kourembanas
Journal: Circulation Research (2001)

Telomeres are primarily controlled by a highly specialized DNA polymerase termed telomerase. Recent studies have demonstrated that introduction of the telomerase catalytic component (TERT) into telomerase-negative cells activates telomerase and extends cell life span, whereas mice lacking telomerase activity revealed impaired cell proliferation in some organs as well as reduced tumorigenesis. These reports suggest that telomerase plays an important role in long-term cell viability and cell proliferation. However, the mechanism or mechanisms by which telomerase is induced or regulated remains to be elucidated. We report here that primary vascular smooth muscle cells (VSMCs) express telomerase and that increased telomerase activity correlates with cell proliferation. Inhibition of telomerase diminished growth of VSMCs, which suggests a crucial role for telomerase activation in the regulation of VSMC proliferation. We propose a novel model whereby telomerase is first activated in the cytoplasm before cell proliferation, followed by accumulation of activity in the nucleus during the logarithmic phase of cell growth. Activation of telomerase in VSMCs was linked to phosphorylation of TERT. The protein kinase inhibitor H7 suppressed the activation of telomerase in the cytoplasm and also inhibited the accumulation of TERT as well as telomerase activity in the nucleus. These data suggest that posttranslational modification of TERT by phosphorylation is important for activation and accumulation of telomerase into the nucleus in the process of VSMC proliferation.
Clinical Management of Mid‐Root Fracture in Maxillary Central Incisors: Case Reports
Authors: Deepak J Parekh, Ramarao Sathyanarayanan, Mangala Tiptur Manjunath
Journal: International Journal of Oral Science (2010)

Management of mid‐root fractures presents a formidable challenge for clinicians because of the difficulty of achieving a stable reunion of fracture fragments. This article presents two varied treatment options for mid‐root fractures. A 15‐year‐old female reported an impact injury to the maxillary anterior teeth 2 days after its occurrence. Clinically, the maxillary left central incisor was palatally‐extruded with a negative vitality response and radiographic evidence of an oblique fracture at the middle third of the root. An endodontic implant was employed which utilized an open technique and has been on follow‐up for ten months. A 32‐year‐old male reported an injury, which resulted in a mobile maxillary right central incisor, three months after its occurrence. Through clinical and radiographic means, a discolored, extruded, and non‐vital maxillary right central incisor with an oblique root fracture at the alveolar‐crest level was observed. Exploratory surgery was performed; an apical barrier was created with a mineral trioxide aggregate and obturated with gutta percha. The fragments were stabilized with a fiber post and patient has been on follow‐up for five months. Short‐term follow‐up for both of the cases showed promising results both clinically and radiographically.
Role of glucose transporters in the cellular insulin resistance of type II non-insulin-dependent diabetes mellitus.
Authors: W T Garvey, T P Huecksteadt, S Matthaei, J M Olefsky
Journal: Journal of Clinical Investigation (1988)

To examine the role of glucose transport proteins in cellular insulin resistance, we studied subcutaneous adipocytes isolated from lean control, obese control (body mass index [BMI] 33.4 +/- 0.9), and untreated obese non-insulin-dependent diabetes mellitus (NIDDM) patients (BMI 35.2 +/- 2.1; fasting glucose 269 +/- 20 mg/dl). Glucose transporters were measured in plasma membrane (PM), low-density (LDM), and high-density (HDM) microsomal subfractions from basal and maximally insulin-stimulated cells using the cytochalasin B binding assay, and normalized per milligram of membrane protein. In all subgroups, insulin led to an increase in PM glucose transporters and a corresponding depletion of transporters in the LDM. Insulin recruited 20% fewer transporters to the PM in the obese subgroup when compared with lean controls, and this was associated with a decline in LDM transporters with enlarging cell size in the control subjects. In NIDDM, PM, and LDM, transporters were decreased 50% in both basal and stimulated cells when compared with obese controls having similar mean adipocyte size. Cellular depletion of glucose transporters was not the only cause of insulin resistance, because the decrease in rates of [14C]-D-glucose transport (basal and insulin-stimulated) was greater than could be explained by reduced numbers of PM transporters in both NIDDM and obesity. In HDM, the number of transporters was not influenced by insulin and was similar in all subgroups. We conclude that (a) in NIDDM and obesity, both reduced numbers and impaired activity of glucose transporters contribute to cellular insulin resistance, and (b) in NIDDM, more profound cellular insulin resistance is associated primarily with a further depletion of cellular transporters.
xIAP Induces Cell-Cycle Arrest and Activates Nuclear Factor-κB
Authors: Bodo Levkau, Kyle J. Garton, Nicola Ferri, Kerstin Kloke, Jerzy-Roch Nofer, Hideo A. Baba, Elaine W. Raines, Günter Breithardt
Journal: Circulation Research (2001)

Abstract —Survival of human vascular endothelial cells depends on their ability to activate the transcription factor nuclear factor-κB (NF-κB), a regulator of antiapoptotic genes, such as the X chromosome–linked inhibitor of apoptosis protein (xIAP). In the present study, we demonstrated expression of xIAP in the endothelial lining of normal human arteries and veins and elevated levels in highly malignant human endothelial tumors. Using retroviral infection of human endothelial cells, we identified two novel survival mechanisms mediated by xIAP in endothelial cells. First, xIAP can activate the transcription factor NF-κB, a known survival factor for human endothelial cells. This positive feedback loop induced by xIAP is mediated via phosphorylation and sustained degradation of inhibitor (I) κBα. Second, xIAP can inhibit cell proliferation via downregulation of cyclins A and D1 and induction of the cyclin-dependent kinase inhibitors p21 Cip1/Waf1 and p27 Kip1 . Cleavage of xIAP by caspases during endothelial cell apoptosis disables both of these biological functions of xIAP. Thus, caspase-mediated cleavage of xIAP interrupts a positive regulatory cytoprotective loop between NF-κB and xIAP and increases the vulnerability of the cell to apoptosis by releasing it from an xIAP-mediated quiescent state.
Synovial fluid copper and related variables in rheumatoid and degenerative arthritis.
Authors: P R Scudder, W McMurray, A G White, T L Dormandy
Journal: Annals of the Rheumatic Diseases (1978)

Copper, caeruloplasmin, transferrin, albumin, and total protein were measured in the serum and synovial fluid of 40 patients with rheumatoid arthritis and 40 patients with osteoarthrosis. A raised synovial fluid copper and caeruloplasmin have been found to be characteristic of rheumatoid effusions. The relation between copper and caeruloplasmin in synovial fluid differs from that in serum. Synovial fluid caeruloplasmin was increased disproportionately in relation to other plasma proteins present in rheumatoid effusions.
MULTIPLE SOMATIC COMPLAINTS AS A PRECURSOR OF SCHIZOPHRENIA
Authors: WILLIAM OFFENKRANTZ
Journal: American Journal of Psychiatry (1962)

Evidence has been presented to suggest that a significantly high proportion of a group of schizophrenic patients showed clinical evidence of a psychiatric disorder while in military service prior to the onset of the obvious schizophrenic illness. Furthermore, the evidence indicates that this earlier disorder was characterized in part by the presence of (multiple) somatic complaints, which may well represent the classical picture of true hypochondriasis.
Phase II Trial of Cisplatin/Etoposide and Concurrent Radiotherapy Followed by Paclitaxel/Carboplatin Consolidation for Limited Small-Cell Lung Cancer: Southwest Oncology Group 9713
Authors: Martin J. Edelman, Kari Chansky, Laurie E. Gaspar, Bryan Leigh, Geoffrey R. Weiss, Sarah A. Taylor, John Crowley, Robert Livingston, David R. Gandara
Journal: Journal of Clinical Oncology (2003)

Limited small-cell lung cancer (LSCLC) is characterized by a high initial response rate to chemoradiotherapy, but local or systemic relapse occurs in the majority of patients. Previous Southwest Oncology Group trials in LSCLC have utilized cisplatin and etoposide (PE) delivered concurrently with thoracic radiotherapy followed by two consolidation cycles. Newer chemotherapy regimens such as paclitaxel and carboplatin are active in small-cell lung cancer and hold the promise of improving both local and systemic control. S9713 evaluated the substitution of paclitaxel and carboplatin for PE consolidation in LSCLC.Between July 1998 and August 1999, 96 patients were accrued from 43 institutions. Eighty-nine patients were eligible; 87 were assessable for survival and response. Treatment consisted of cisplatin 50 mg/m(2) on days 1, 8, 29, and 36, and etoposide 50 mg/m(2) on days 1 to 5 and days 29 to 33, with concurrent radiotherapy of 61 Gy beginning on day 1. Consolidation therapy was carboplatin (area under the curve = 6) and paclitaxel 200 mg/m(2), both drugs administered on day 1 of a 21 day cycle for three cycles.The response rate was 86% (complete response, 33%; partial response, 53%). Median overall survival was 17 months (95% CI, 12.7 to 19.0). One- and 2-year overall survivals were 61% and 33%, respectively. Median progression-free survival (PFS) was 9 months, 1-year PFS was 40%, and 2-year PFS was 21%.Consolidation therapy with paclitaxel and carboplatin in LSCLC resulted in an outcome similar to that seen in prior Southwest Oncology Group trials. This study and others which have tested paclitaxel in small-cell lung cancer dampens enthusiasm for this agent in the primary management of LSCLC.
Smoking, rheumatoid factors, and rheumatoid arthritis
Authors: D. A HOUSSIEN, D. L SCOTT, T. JONSSON
Journal: Annals of the Rheumatic Diseases (1998)

Saag et al 1 reported that smokers were more often rheumatoid factor (RF) positive, had more often rheumatoid nodules and more radiographic erosions compared with non-smokers. Their report questions whether smoking stimulates RF production and thus affects the disease progression in RA. Their findings relate to previous reports that smoking increases the risk of RA,2-8 although not all studies agree.9 As raised RF, in particular IgA RF, is associated with poor prognosis in RA,10 we report a positive correlation between smoking and IgA RF.

We studied 59 RA patients participating in a prospective study on RA. They comprised 47 …
Overview of Molecular Relationships in the Voltage-Gated Ion Channel Superfamily
Authors: Frank H. Yu, Vladimir Yarov-Yarovoy, George A. Gutman, William A. Catterall
Journal: Pharmacological Reviews (2005)

Complex multicellular organisms require rapid and accurate transmission of information among cells and tissues and tight coordination of distant functions. In vertebrates, electrical signals and the resulting intracellular calcium transients control contraction of muscle, secretion of hormones,
Contribution of alpha-adrenoceptor activation to the pathogenesis of norepinephrine cardiomyopathy.
Authors: S E Downing, J C Lee
Journal: Circulation Research (1983)

Graded doses of norepinephrine and methoxamine were given to rabbits over a standard 90-minute infusion period to assess their potential for inducing myocardial injury. Lesions of myofiber necrosis and leukocytic infiltration were graded semiquantitatively in animals killed 2 days later. A close correlation was found between the dose of norepinephrine and the histological score (r = 0.912, P less than 0.001). Mean arterial pressure rose from 100 mm Hg to a maximum of 129 mm Hg, and averaged 115 mm Hg during infusion of 2 micrograms/min per kg. However, heart rate fell from 287 beats/min to average 208 beats/min. The pressure-rate product, an index of metabolic demand, showed no significant change and did not differ from saline-infused controls. Beta-adrenergic blockade with practolol (4 mg/kg) or propranolol (1 mg/kg) failed to significantly reduce cardiac injury with norepinephrine. However, alpha-adrenoceptor blockade with phentolamine (10 mg), alone or in combination with either of the beta-antagonists, markedly reduced lesion formation as reflected by the histological score (P less than 0.02). Administration of the alpha-agonist methoxamine produced dose-related increases in the intensity of myocardial injury (r = 0.938, P less than 0.01), morphologically identical with those resulting from norepinephrine. Hemodynamic changes also were comparable. Phentolamine markedly reduced methoxamine injury. It may be concluded from these studies that norepinephrine cardiomyopathy results in large part from activation of the alpha-adrenergic system in the rabbit model. Ischemia or a supply-demand mismatch are unlikely mechanisms. We speculate that alterations in myofiber Ca++ translocation, uptake, and binding induced by alpha 1-receptor activation may contribute to membrane damage.
Urinary eicosanoids and the assessment of glomerular inflammation.
Authors: J B Lefkowith, J Pippin, T Nagamatsu, V Lee
Journal: Journal of the American Society of Nephrology (1992)

Nephrotoxic nephritis, a model system for glomerulonephritis, is characterized by glomerular inflammation, proteinuria, and a marked increase in ex vivo glomerular eicosanoid production. This study addressed whether urinary eicosanoids might serve as noninvasive markers for glomerular inflammation and damage with nephrotoxic nephritis and its accelerated variant. Accelerated nephritis, relative to simple nephritis, was characterized by more substantial glomerular inflammation, particularly that due to neutrophils. Correspondingly, accelerated nephritis was accompanied by greater proteinuria and more marked elevations in glomerular eicosanoids generated ex vivo. With respect to urinary eicosanoids, thromboxane, but not leukotriene B4, was detected in the urine of normal animals. After the induction of nephrotoxic nephritis, urinary thromboxane was moderately elevated (twofold) and urinary leukotriene B4 was variably present (three of seven animals). In accelerated nephritis, urinary thromboxane was more markedly elevated (sixfold) and leukotriene B4 was consistently present. The presence of urinary leukotriene B4 was confirmed by gas chromatography/mass spectrometry. Urinary eicosanoids together correlated with glomerular leukocyte numbers and proteinuria by linear regression. Urinary leukotriene B4 individually correlated with glomerular neutrophil numbers. Renal metabolism of leukotriene B4 to omega oxidation products by the rat kidney was not apparent. These data validate that the enhanced glomerular eicosanoid metabolism seen in nephrotoxic nephritis takes place in vivo and additionally suggest that both urinary thromboxane and leukotriene B4 may serve as noninvasive markers for glomerular inflammation and damage. In light of these and prior studies, urinary thromboxane may be a general marker of glomerular inflammation and leukotriene B4 may be a more specific index of acute inflammation.