tbuckley/cabot-search huggingface dataset:
Effects of ion substitution on bile acid-dependent and -independent bile formation by rat liver.
Authors: R W Van Dyke, J E Stephens, B F Scharschmidt
Journal: Journal of Clinical Investigation (1982)

To characterize the transport mechanisms responsible for formation of canalicular bile, we have examined the effects of ion substitution on bile acid-dependent and bile acid-independent bile formation by the isolated perfused rat liver. Complete replacement of perfusate sodium with choline and lithium abolished taurocholate-induced choleresis and reduced biliary taurocholate output by greater than 70%. Partial replacement of perfusate sodium (25 of 128 mM) by choline reduced bile acid-independent bile formation by 30% and replacement of the remaining sodium (103 mM) by choline reduced bile acid-independent bile formation by an additional 64%. In contrast, replacement of the remaining sodium (103 mM) by lithium reduced bile acid-independent bile formation by only an additional 20%, while complete replacement of sodium (128 mM) by lithium reduced bile formation by only 17%, and lithium replaced sodium as the predominant biliary cation. Replacement of perfusate bicarbonate by Tricine, a zwitterionic amino acid buffer, decreased bile acid-independent bile formation by greater than or equal to 50% and decreased biliary bicarbonate output by approximately 60%, regardless of the accompanying cation. In separate experiments, replacement of sodium by lithium essentially abolished Na,K-ATPase activity measured either as ouabain-suppressible ATP hydrolysis in rat liver or kidney homogenates, or as ouabain-suppressible 86Rb uptake by cultured rat hepatocytes. These studies indicate that bile acid(taurocholate)-dependent bile formation by rat liver exhibits a specific requirement for sodium, a finding probably attributable to the role(s) of sodium in hepatic sodium-coupled taurocholate uptake and/or in maintenance of Na,K-ATPase activity. The surprising finding that bile acid-independent bile formation was substantially unaltered by complete replacement of sodium with the permeant cation lithium does not appear to be explained by Na,K-ATPase-mediated lithium transport. Although alternative interpretations exist, this observation is consistent with the hypothesis that much of basal bile acid-independent bile formation is attributable to an ion pump other than Na,K-ATPase, which directly or indirectly mediates bicarbonate transport.
Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas
Authors: Xiang Jun Shen, John F. Rawls, Thomas A. Randall, Lauren Burcall, Caroline Mpande, Natascha Jenkins, Biljana Jovov, Zaid Abdo, Robert S. Sandler, Temitope O. Keku
Journal: Gut Microbes (2010)

The human large bowel is colonized by complex and diverse bacterial communities. However, the relationship between commensal bowel bacteria and adenomas (colorectal cancer precursors) is unclear. This study aimed to characterize adherent bacteria in normal colon and evaluate differences in community composition associated with colorectal adenomas. We evaluated adherent bacteria in normal colonic mucosa of 21 adenoma and 23 non-adenoma subjects enrolled in a cross sectional study. Terminal restriction fragment length polymorphism, clone sequencing and fluorescent in-situ hybridization analysis of the 16S rRNA genes were used to characterize adherent bacteria. A total of 335 clones were sequenced and processed for phylogenetic and taxonomic analysis. Differences in bacterial composition between cases and controls were evaluated by UniFrac and analysis of similarity matrix. Overall, Firmicutes (62%), Bacteroidetes (26%) and Proteobacteria (11%) were the most dominant phyla. The bacterial composition differed significantly between cases and controls (UniFrac P&lt;0.001). We observed significantly higher abundance of Proteobacteria (p&lt;0.05) and lower abundance of Bacteroidetes (p&lt;0.05) in cases compared to controls. At the genus level, case subjects showed increased abundance of Dorea spp. (p&lt;0.005), Faecalibacterium spp. (p&lt;0.05), and lower proportions of Bacteroides spp. (p&lt;0.03) and Coprococcus spp. (p&lt; 0.05) than controls. Cases had higher bacterial diversity and richness than controls. These findings reveal that alterations in bacterial community composition associated with adenomas may contribute to the etiology of colorectal cancer. Extension of these findings could lead to strategies to manipulate the microbiota to prevent colorectal adenomas and cancer as well as to identify individuals at high risk.
Learning for consultants
Authors: Kieran Walsh
Journal: BMJ (2006)

observation of failed diagnosis in about 1% of cases may be an overestimate because about half of these cases either miscarried or had major abnormalities detected by the routine second trimester scan.In summary, a policy of initially doing rapid aneuploidy exclusion for chromosomes 13, 18, 21, X, and Y in the first trimester, with full karyotyping only if the fetal NT thickness is increased, would reduce the economic costs of a first trimester screening programme for trisomy 21, allowing for rapid delivery of results and minimising parental anxiety and the risk of unnecessary termination of pregnancy.
Nearly half of US births were covered by Medicaid in 2010
Authors: J. H. Tanne
Journal: BMJ (2013)

Medicaid paid for 48% of the 3.8 million births in the United States in 2010, an increase of 19% in only two years, a study has calculated.

Next year, when the Affordable Care Act goes into effect, Medicaid will cover many previously uninsured low income women of childbearing age, not just pregnant women.

“Low income women of childbearing age will be able to obtain more continuous coverage before and between …
Asthma morbidity among inner-city adolescents receiving guidelines-based therapy: Role of predictors in the setting of high adherence
Authors: Rebecca S. Gruchalla, Hugh A. Sampson, Elizabeth Matsui, Gloria David, Peter J. Gergen, Agustin Calatroni, Mark Brown, Andrew H. Liu, Gordon R. Bloomberg, James F. Chmiel, Rajesh Kumar, Carin Lamm, Ernestine Smartt, Christine A. Sorkness, Suzanne F. Steinbach, Kelly D. Stone, Stanley J. Szefler, William W. Busse
Journal: Journal of Allergy and Clinical Immunology (2009)
Insulin receptor of human cerebral gliomas. Structure and function.
Authors: G Grunberger, W L Lowe, A McElduff, R P Glick
Journal: Journal of Clinical Investigation (1986)

The insulin receptor from human brain tumors of glial origin was examined for the first time using intact cells (from an established cultured human glioblastoma cell line) and partially purified solubilized membranes (from cultured cells and freshly isolated human brain tumors). The structure of the glial insulin receptor subunits was assessed by affinity cross-linking of 125I-insulin with the alpha-subunit of the receptor, neuraminidase treatment of the cross-linked receptor, behavior of the receptor on lectin columns, and electrophoretic mobility of the phosphorylated beta-subunit. The functions of the insulin receptor were examined by measuring specific 125I-insulin binding (receptor concentration, affinity, specificity, pH-, time-, and temperature dependence), insulin-induced down-regulation of the receptor, insulin-stimulated autophosphorylation of the beta-subunit, and phosphorylation of exogenous substrates as well as insulin-stimulated glucose uptake in glioblastoma cells. All of these properties were typical for the insulin receptor from target tissues for insulin action. The insulin receptor of the normal human brain showed the altered electrophoretic mobility and lack of neuraminidase sensitivity of its alpha-subunit previously reported for the rat brain receptor. There was no difference, however, in the functions of the receptor subunits (binding, phosphorylation) from the normal brain tissue and the eight human gliomal tumors. Since the glial elements compose a majority of the brain cells, the "normal" structure and function of their insulin receptor might provide a key to understanding the role of insulin in the carbohydrate metabolism of the human central nervous system.
DR5 Activation of Caspase-8 Induces DC Maturation and Immune Enhancement In Vivo
Authors: Michael A Chattergoon, Karuppiah Muthumani, Yutaka Tamura, Mathura Ramanathan, Jason P Shames, Vera Saulino, Tara M Robinson, Luis J Montaner, David B Weiner
Journal: Molecular Therapy (2007)

Non-homeostatic tissue apoptosis in vivo has been shown to induce inflammatory responses and facilitate the cross-presentation of proteins within apoptotic bodies. We hypothesize that in the presence of foreign antigens, the apoptotic-inflammatory process improves immune priming; further, molecules that trigger apoptosis may be adapted for use as immune adjuvants. One very attractive molecule in this context is the tumor necrosis factor receptor (TNFR) family molecule DR5/TRAIL-receptor 2. We show a significant improvement in CD8+ T-cell mediated vaccine immunity with the use of death receptor-5 (DR5) as an immune adjuvant, a property that is correlated with the activation of caspases-8 (casp8) and dependent on its ability to induce apoptosis in vivo. Non-homeostatic tissue apoptosis in vivo has been shown to induce inflammatory responses and facilitate the cross-presentation of proteins within apoptotic bodies. We hypothesize that in the presence of foreign antigens, the apoptotic-inflammatory process improves immune priming; further, molecules that trigger apoptosis may be adapted for use as immune adjuvants. One very attractive molecule in this context is the tumor necrosis factor receptor (TNFR) family molecule DR5/TRAIL-receptor 2. We show a significant improvement in CD8+ T-cell mediated vaccine immunity with the use of death receptor-5 (DR5) as an immune adjuvant, a property that is correlated with the activation of caspases-8 (casp8) and dependent on its ability to induce apoptosis in vivo.
Specific binding of alloantigens to T cells activated in the mixed lymphocyte reaction.
Authors: Z Nagy, B E Elliott, M Nabholz, P H Krammer, B Pernis
Journal: The Journal of Experimental Medicine (1976)

Immunoglobulin (Ig) is present on a large fraction of T cells from unfractionated lymphocytes activated by in vitro stimulation with H-2-incompatible cells (mixed lymphocyte reaction [MLR]). Removal of bursa equivalent-derived (B) cells from the responder cell population before mixed culture, by filtration through nylon wool columns, reduces the percentage of Ig-bearing responder T blasts to background levels. Thus, Ig on the T blast is probably of B cell origin. A large fraction of T blasts activated against the stimulator cells. This staining occurs with "early" and hyperimmune alloantisera, including the 7S fraction of the latter. B-depleted responder cells were activated against a mixture of two different stimulator cells and the resulting T blasts stained with different concentrations of sera directed either against one or both stimulator cells. We obtained results which strongly suggest that most or all responder T blasts stain with only one antistimulator serum. When antisera directed against different segments of the H-2 complex of the stimulator cells were used, it seemed that most responder T cells only bound antibody directed against a single segment. We propose that T cells activated in MLR carry stimulator alloantigens on their surface, and that this is due to specific antigen binding, not requiring the presence of B-cell-derived antibody. These histocompatibility antigen-binding T blasts can be detected by appropriate antistimulator alloantibodies.
In vivo gene therapy for hyperlipidemia: phenotypic correction in Watanabe rabbits by hepatic delivery of the rabbit LDL receptor gene.
Authors: J Li, B Fang, R C Eisensmith, X H Li, I Nasonkin, Y C Lin-Lee, M P Mims, A Hughes, C D Montgomery, J D Roberts
Journal: Journal of Clinical Investigation (1995)

Elevations of plasma total or LDL cholesterol are major risk factors for cardiovascular disease. Efforts directed at preventing and treating cardiovascular disease have often focused on reducing the levels of these substances in the blood. The Watanabe Heritable Hyperlipidemic Rabbit, which has exceedingly high plasma cholesterol levels resulting from an LDL receptor deficiency, provides an excellent animal model for testing new treatments. A recombinant adenoviral vector containing the rabbit LDL receptor cDNA was administered to Watanabe rabbits. Plasma total cholesterol levels in the treated animals were reduced from 825.5 +/- 69.8 (mean +/- SD) to 247.3 +/- 61.5 mg/dl 6 d after infusion. These animals also demonstrated a 300-400% increase in plasma levels of HDL cholesterol and apo AI 10 d after treatment. As a result, the LDL:HDL ratio exhibited a dramatic decrease. Because only the rabbit LDL receptor gene was used for treatment, the results strongly suggest that the elevations of plasma HDL cholesterol and apo AI were secondary to a reduction in plasma total cholesterol in the treated animals. These results suggest an inverse relationship between plasma LDL and HDL cholesterol levels and imply that reduction of LDL cholesterol levels may have a beneficial effect on plasma HDL cholesterol.
Pitfalls in Nonrandomized Outcomes Studies
Authors: Shi Wu Wen
Journal: JAMA (1995)

To assess the short-term outcomes of incidental appendectomy through analysis of hospital administrative data and determine the consistency and plausibility of the observed results.Population-based historical cohort study.All general hospitals in Ontario between 1981 and 1990.Patients undergoing open primary cholecystectomy with (7846 exposed) and without (191,599 unexposed) incidental appendectomy.In-hospital fatality rates, complication rates, and lengths of hospital stay.Crude comparisons showed a striking and paradoxical reduction in mortality after cholecystectomy when incidental appendectomy was performed (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.23 to 0.57; P < .001); mean length of stay was also lower by -0.46 day (P < .001). After adjustment for confounding differences, such as comorbidity and nonelective surgery, mortality and lengths of stay were similar for exposed and unexposed patients; but exposed patients showed a significant increase in nonfatal complications (OR, 1.53; 95% CI, 1.39 to 1.68; P < .001). Adverse effects from incidental appendectomy emerged consistently for all three outcomes only after restricting the analysis to subgroups of patients at low surgical risk. The increased mortality for exposed patients was largest among low-risk groups; for example, among those younger than 70 years undergoing elective surgery, the OR was 2.65 (95% CI, 1.25 to 5.64; P < .001).These findings suggest that incidental appendectomy is associated with a small but definite increase in adverse postoperative outcomes. However, plausible and consistent findings were only obtained after restricting the analysis to low-risk subgroups in which unmeasured differences in patients' baseline characteristics were less likely to confound adjusted outcome comparisons. This exercise highlights the potential pitfalls in nonrandomized outcomes comparisons using data sources with limited clinical detail, such as hospital discharge abstracts.
Case 6-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, David P. Faxon, James F. Southern
Journal: New England Journal of Medicine (1987)

Presentation of CaseA 65-year-old man was admitted to the hospital because of recurrent chest pain.He was well except for asthmatic bronchitis until nine years earlier, when exertional angina pectoris developed. One year later he was admitted to this hospital because of crescendo angina. An electrocardio-gram demonstrated prominent inversion of T waves that reflected the anterolateral surface. An intraaortic balloon pump was inserted through the left femoral artery, and a coronary angiographic examination showed 50 percent stenosis of the left main coronary artery and greater than 90 percent stenosis of the proximal left anterior descending artery; left ventricular function . . .
The human spleen as revealed by scanning electron microscopy
Authors: Marion I. Barnhart, Jeanne M. Lusher
Journal: American Journal of Hematology (1976)

Abstract The three‐dimensional world of the spleen was explored by scanning electron microscopy on both arterially perfused and nonperfused specimens, as well as on plastic corrosion casts of splenic vasculatures. Of 25 spleens studied, 18 were examples of hypersplenism. These were contrasted to 7 essentially normal spleens taken from children being staged for treatment of Hodgkin's disease whose spleens proved to be uninvolved in the pathologic process. Splenic sinuses in all 25 spleens were typified by a degree of porosity. RBC were caught in the act of entering sinuses from splenic cords. These sinus windows thus represent one end of an “open” circulatiion pathway. In casts of microvasculature, direct arteriovenous connections were demonstrated, thus establishing an anatomical basis for an often disputed “closed” circulation pathway. Spleens from 7 patients with hereditary spherocytosis had a super abundance of red pulp. Splenic cords were thickened and crowded with spherocytes, many of which presented slightly wrinkled membranes, as were also noted on the peripheral blood RBC. It is possible that these membrane features are unique for HS and reflect the intrinsic membrane abnormality in protein composition. The 7 spleens from chronic idiopathic thrombocytopenic purpura had white pulp as the predominant region. Germinal centers were frequent. Lymphocytes and plasma cells with well‐developed microvilli were suggestive that relese of antiplatelet antibody might be occurring in white pulp. Platelets were especially notable in peripheral white pulp and marginal zones. Platelet clumps were observed, generally adjacent to splenic macrophages.
Arsenite as the probable active species in the human carcinogenicity of arsenic: mouse micronucleus assays on Na and K arsenite, orpiment, and Fowler's solution.
Authors: H Tinwell, S C Stephens, J Ashby
Journal: Environmental Health Perspectives (1991)

Sodium arsenite, potassium arsenite, and Fowler's solution (arsenic trioxide dissolved in potassium bicarbonate) are equally active in the mouse bone marrow micronucleus assay (approximately 10 mg/kg by IP injection). The natural ore orpiment (principally As2S3) was inactive despite blood levels of arsenic of 300 to 900 ng/mL in treated mice at 24 hr. Sodium arsenite was active in three strains of mice. It is suggested that the human lung cancer observed among arsenic ore smelters and the skin cancer among people exposed therapeutically to Fowler's solution, have, as their common origin, the genotoxic arsenite ion AsO2-. The difficulty experienced when attempting to demonstrate rodent carcinogenicity for derivatives of arsenic suggests that the bone marrow micronucleus assay may act as a useful assay for potentially carcinogenic arsenic derivatives.
High-Density Lipoproteins and the Risk of Atherosclerosis
Authors: Robert S. Lees, Ann M. Lees
Journal: New England Journal of Medicine (1982)

Atherosclerosis, the most common lethal disease in our population, has no obvious single cause. Although hypertension, cigarette smoking, and hyperlipidemia are all prominent risk factors for atherosclerotic disease of the coronary, cerebral, and peripheral arteries, the disease develops in a small percentage of subjects without any of these factors. This observation has led to a search for additional risk factors. Many studies, both old1 and more recent2 , 3 have correlated decreased plasma concentrations of high-density (alpha) lipoproteins (HDLs) with the development of atherosclerosis. The measurement that was specifically correlated with the disease was the cholesterol content of HDL, but this is . . .
Incidental Diagnosis of Endometrial Carcinoma in a Patient With Breast Cancer by FDG PET/CT
Authors: Chin-Chuan Chang, Yu-Wen Chen, Ming-Feng Hou
Journal: Clinical Nuclear Medicine (2007)

FDG PET has been widely used to delineate the metabolic status of neoplasms for diagnosis, staging, and restaging. However, incidental diagnosis of endometrial carcinoma for multiple primary neoplasms by FDG PET/CT is rare. A 57-year-old woman with left breast cancer underwent whole-body FDG PET/CT examination as a result of elevation of serum titers of tumor markers but free of other clinical symptoms. The image revealed a high-grade uptake of FDG-avid lesion within the endometrium of the uterus, but no abnormal FDG accumulation in the rest of the body. The final pathology disclosed endometrial adenocarcinoma.
Nongastric marginal zone B‐cell lymphoma: Analysis of 247 cases
Authors: Sung Yong Oh, Baek‐Yeol Ryoo, Won Seog Kim, Yeon Hee Park, Kihyun Kim, Hyun Jung Kim, Jung Mi Kwon, Jeeyun Lee, Young Hye Ko, Yong Chan Ahn, Suk Joong Oh, Soon Il Lee, Hyo‐Jin Kim, Hyuk‐Chan Kwon, Soo Mee Bang, Jung Han Kim, Jinny Park, Seung‐Sook Lee, Ho Young Kim, Keunchil Park
Journal: American Journal of Hematology (2007)

Nongastric marginal zone B-cell lymphoma (NG-MZL) is a relatively uncommon indolent lymphoma. From 1990 to 2005, a total of 247 patients with histologically confirmed NG-MZL were analyzed. Ann Arbor stage I/II disease was present in 78% (167 out of 215). One hundred eighty-six patients out of two hundred eight were categorized into the low/low-intermediate risk group (89%) according to International Prognostic Index (IPI). Eighty percent (172/215) were in low risk group according to Follicular Lymphoma International Prognostic Index (FLIPI). Complete and partial remissions (CR and PR) were achieved in 140 (92.7%) and 8 (5.3%) of the 151 stage I/II patients. Especially, radiation containing treatment achieved 96% CR rate (108 out of 113). In 38 patients with stage III/IV, CR and PR were achieved in 17 (44.7%) and 11 (26.3%), respectively. The estimated five-year overall survival (OS) and progression-free survival (PFS) were 93.8% and 70.1%, respectively. Although anthracycline-containing regimen could achieve higher CR rate, it did not improve PFS. Stage III/IV, low hemoglobin, poor performance status, high/high-intermediate IPI, poor risk FLIPI, and nodal MZL were poor prognostic factors for PFS. NG-MZL is an indolent disease. FLIPI has strong power to predict the prognosis of NG-MZL.
Postoperative deaths from bowel cancer fall for fourth year in row, audit shows
Authors: G. Iacobucci
Journal: BMJ (2012)

The proportion of postoperative deaths from bowel cancer has fallen for the fourth year in succession, show the latest findings from the National Bowel Cancer Audit, although the high number of emergency admissions of people with the condition remains a “major concern.”

The audit, which examined data from more than 29 000 patients whose bowel cancer was diagnosed in 2010-11, found that 5.1% of these patients had died 90 days after their operation, down from 6.4% of those whose disease was diagnosed in 2007-8.

The report, produced by the NHS Health and Social Care …