tbuckley/cabot-search huggingface dataset:
Molecular epidemiology unmasks the tubercle bacillus: new techniques reveal new aspects of virulence
Authors: P D O Davies
Journal: Thorax (2004)

Molecular methods show that TB is being transmitted with surprising efficiency

Two papers in this month’s edition of Thorax show how the use of strain typing of Mycobacterium tuberculosis can reveal new aspects of tuberculosis (TB) transmission.1,2 The study by Ruddy et al ,1 based around an outbreak of isoniazid resistant TB in north London, shows that a single outbreak can extend over many years and affect a broad range of individuals including medical staff. The second study by Hernandez-Garduno et al 2 suggests that sputum smear negative disease can have an appreciable transmission rate. Although molecular epidemiology can unmask the problem, solutions may be more difficult to develop.

Using IS6110 restriction fragment length polymorphism (RFLP) analysis, at the time of writing Ruddy et al had identified over 70 cases, ominously adding that, on epidemiological modelling, the peak had not yet been reached. Initial estimates by the end of December 2003 suggest that the outbreak may already have reached 132 (Dr Helen Maguire, personal communication).

This is the biggest outbreak ever identified in the UK, although not from a single point source, as was the more spectacular Leicester outbreak.3 The outbreak of isoniazid resistant TB in north London reported by Ruddy and colleagues seems to have been largely among groups of young adults of mixed ethnic backgrounds, particularly black Caribbean and white, although some were of business or professional backgrounds. Drug misuse and/or prison detention were common to many cases. Although the association between prison and TB has been well established in countries such as Russia and the USA,4,5 this is the first prison outbreak to be documented in the UK. We have previously been quite proud of our record of …
Animal Models of Calcium Cholelithiasis
Authors: Alan F. Hofmann
Journal: Hepatology (1984)

Bile contains four calcium anions which are readily precipitated by calcium: bilirubinate, "palmitate", carbonate and phosphate. Precipitation of insoluble calcium salts is common in calculous biliary disease. All animal models of calcium cholelithiasis probably share a common pathogenesis--an increased concentration of a calcium-sensitive anion. In calcium bilirubinate cholelithiasis, an increased concentration of bilirubinate occurs. In mice, this occurs in animals having a genetic hemolytic anemia; in rats, it may be induced by an essential fatty acid in combination with diet modification; in dogs, by a low-taurine, low-protein diet; and in prairie dogs, by ileal resection which probably increases the bilirubinate/bile acid ratio in bile. In the two models of calcium-bile acid cholelithiasis, an increased biliary concentration of a calcium-sensitive glycine conjugated bile acid is induced by administration of a suitable precursor. In the rabbit, gallstones composed mostly of calcium allodeoxycholyl glycine are induced by the feeding of 5 beta-cholestan-3 beta-ol. In the taurine-deficient rat, the feeding of lithocholate leads to formation of gallstones which contain a mixture of calcium lithocholyl glycine and 3 alpha, 6 beta-dihydroxy cholanoyl glycine. These animal models may be of value in testing agents designed to lower calcium activity in bile.
Cardioprotection and Myocardial Reperfusion
Authors: Richard S. Vander Heide, Charles Steenbergen
Journal: Circulation Research (2013)

With the advent of thrombolytic therapy and angioplasty, it has become possible to reduce myocardial infarct size through early reperfusion. Enormous effort has been expended to find therapies that can further reduce infarct size after early intervention. Animal studies have identified many cardioprotective pathways that have the potential to reduce infarct size if activated before the onset of ischemia. More recently, interventions effective at the onset of reperfusion have been described. Although basic research has identified many targets, most has been conducted in rodent models which may not be directly applicable to human disease and even promising agents have been disappointing in large-scale clinical trials. There are many potential explanations for this failure which is the subject of this review. Potential factors include (1) the variability inherent in the patient population, whereas animal studies usually use single sex homogeneous groups maintained on standard diets in carefully controlled environments; (2) the duration of ischemia is generally shorter in animal studies, resulting in potentially more salvageable myocardium than is often the case in patients; (3) that the animals are usually young without comorbidities, whereas the patient population is generally older and has significant comorbidities; (4) animals are not treated with medications a priori, whereas the patient population is often taking medications that may affect ischemic injury; and (5) animal studies may not involve thorough assessment of effects on organs other than the heart, whereas patients can experience adverse effects of treatment in other organs that can preclude clinical use.
Effect of Injection of Foreign Bone Marrow on the Lymphatic Tissues of Normal Mice
Authors: C. C. Congdon
Journal: JNCI Journal of the National Cancer Institute (1962)

Mice that received rat bone marrow intravenously as a primary or secondary injection showed marked cellular alterations in white pulp of the spleen and, to a lesser extent, in the other lymphatic tissues. The secondary response to rat marrow resembled an accelerated version of the primary response in the white pulp of the spleen. Throughout the white pulp, dissociated growth of Ab-forming cells, probably derived from germinal-center cells, was the characteristic cellular change. Hyperplasia of germinal centers in the spleen was present during the restitution phase. After an intravenous injection of homologous bone marrow, dissociated growth of Ab-forming cells was present in the white pulp. It lasted several days longer than the dissociated growth after injection of heterologous marrow. Hyperplastic germinal centers persisted for 6 weeks, and growth of the hyperplastic germinal centers characterized the secondary response to homologous marrow. Injection of isologous bone marrow did not cause changes in the white pulp of the spleen.
Uteroplacental Blood Flow, Cardiac Function, and Pregnancy Outcome in Women With Congenital Heart Disease
Authors: Petronella G. Pieper, Ali Balci, Jan G. Aarnoudse, Marlies A.M. Kampman, Krystyna M. Sollie, Henk Groen, Barbara J.M. Mulder, Martijn A. Oudijk, Jolien W. Roos-Hesselink, Jerome Cornette, Arie P.J. van Dijk, Marc E. Spaanderman, Willem Drenthen, Dirk J. van Veldhuisen
Journal: Circulation (2013)

Pregnant women with congenital heart disease (CHD) are susceptible to cardiovascular, obstetric, and offspring complications. In women with CHD, cardiac dysfunction may compromise uteroplacental flow and contribute to the increased incidence of obstetric and offspring events.We performed a prospective multicenter cohort study of pregnant women with CHD and healthy pregnant women. We compared clinical, laboratory, echocardiographic, and uteroplacental Doppler flow (UDF) parameters at 20 and 32 weeks gestation, and pregnancy outcome. We related cardiovascular parameters to UDF parameters and pregnancy outcome in women with CHD. We included 209 women with CHD and 70 healthy women. Cardiovascular parameters (N-terminal pro-B-type natriuretic peptide, left and right ventricular function) differed between both groups. UDF parameters were impaired in CHD women (umbilical artery pulsatility and resistance index at 32 weeks in CHD versus healthy women, P=0.0085 and P=0.017). The following cardiovascular parameters prepregnancy and at 20 weeks gestation were associated with UDF (umbilical artery resistance index) at 32 weeks at multivariable analysis: (1) right ventricular function (tricuspid annular plane systolic excursion) (P=0.002), (2) high N-terminal pro-B-type natriuretic peptide (P=0.085), (3) systemic (P=0.001), and (4) pulmonary (P=0.045) atrioventricular valve regurgitation. Women with CHD had more obstetric (58.9% versus 32.9%, P<0.0001) and offspring events (35.4% versus 18.6%, P=0.008) than healthy women. Impaired UDF was associated with adverse obstetric and offspring outcome.UDF parameters are abnormal in pregnant women with CHD. Cardiovascular function is associated with an abnormal pattern of UDF. Compromised UDF may be a key factor in the high incidence of offspring and obstetric complications in this population.
The hepatic, biliary, and pancreatic network of stem/progenitor cell niches in humans: A new reference frame for disease and regeneration
Authors: Giacomo Lanzoni, Vincenzo Cardinale, Guido Carpino
Journal: Hepatology (2015)

Stem/progenitors for liver, biliary tree, and pancreas exist at early stages of development in the definitive ventral endoderm forming the foregut. In humans, they persist postnatally as part of a network, with evidence supporting their contributions to hepatic and pancreatic organogenesis throughout life. Multiple stem cell niches persist in specific anatomical locations within the human biliary tree and pancreatic ducts. In liver and pancreas, replication of mature parenchymal cells ensures the physiological turnover and the restoration of parenchyma after minor injuries. Although actively debated, multiple observations indicate that stem/progenitor cells contribute to repair pervasive, chronic injuries. The most primitive of the stem/progenitor cells, biliary tree stem cells, are found in peribiliary glands within extrahepatic and large intrahepatic bile ducts. Biliary tree stem cells are comprised of multiple subpopulations with traits suggestive of maturational lineage stages and yet capable of self‐replication and multipotent differentiation, being able to differentiate to mature liver cells (hepatocytes, cholangiocytes) and mature pancreatic cells (including functional islet endocrine cells). Hepatic stem cells are located within canals of Hering and bile ductules and are capable of differentiating to hepatocyte and cholangiocyte lineages. The existence, phenotype, and anatomical location of stem/progenitors in the adult pancreas are actively debated. Ongoing studies suggest that pancreatic stem cells reside within the biliary tree, primarily the hepatopancreatic common duct, and are rare in the pancreas proper. Pancreatic ducts and pancreatic duct glands harbor committed pancreatic progenitors. Conclusion: The hepatic, biliary, and pancreatic network of stem/progenitor cell niches should be considered as a framework for understanding liver and pancreatic regeneration after extensive or chronic injuries and for the study of human chronic diseases affecting these organs. (H epatology 2016;64:277‐286)
Differential expression of MHC class I antigens on the placenta of the rat. A mechanism for the survival of the fetal allograft.
Authors: A Kanbour, H N Ho, D N Misra, T A MacPherson, H W Kunz, T J Gill
Journal: The Journal of Experimental Medicine (1987)

In some mating combinations in rats, there is a maternal antibody response to the maternal antigenic components of the placenta without any previous immunization of the mother. The highest response occurs in the WF (u) female mated to the DA (a) male, and it is against a unique MHC-encoded class I antigen, the Pa antigen, and not against the major allele-specific transplantation antigen of the DA strain, RT1.Aa. The development of mAbs to the Pa and Aa antigens allowed us to localize these antigens on the placenta and to explore the reason for the differential antibody response to them using immunohistochemical and biochemical techniques. Both antibodies reacted with the WF X DA placenta and stained the endovascular and interstitial trophoblast of the decidua, the basal trophoblast, Reichert's membrane, and the yolk sac epithelium, but they did not stain the labyrinthine trophoblast. Blocking studies showed that each antibody reacted with a separate molecule in the placenta. Anti-class II mAbs reactive with the a or u haplotype did not stain the WF X DA, DA X DA, or WF X WF placenta; hence, there are no class II antigens in the placenta. Electron microscopic studies of the semiallogeneic WF X DA placenta using the immunogold technique with both single- and double-labeling showed that only the Pa antigen was expressed on the surface of the basal trophoblast, but that both the Pa and Aa antigens were in the cytoplasm of these cells; neither antigen was found in the labyrinthine trophoblast. By contrast, the placenta from the syngeneic DA X DA mating expressed both the Pa and Aa antigens on the surface of the basal trophoblast as well as in the cytoplasm; neither antigen was found in the labyrinthine trophoblast. These observations were quantified morphometrically using electron photomicrographs of single-labeled tissues. Both the Pa and Aa antigens isolated from the plasma membrane of lymphocytes have heavy chains of 46 kD, but those antigens isolated from the plasma membrane of basal trophoblast cells have heavy chains of 43 kD. Based on densitometric measurements of autoradiographs, the Pa/Aa ratio in the basal trophoblast membrane is 23.5, whereas it is 0.46 in lymphocyte membranes. These studies show that there is differential regulation of the expression of class I antigens on basal trophoblast cells in semiallogeneic pregnancies, but not in syngeneic pregnancies, such that the major allele-specific transplantation antigen is scarcely expressed on the surface of the basal trophoblast.(ABSTRACT TRUNCATED AT 400 WORDS)
Infectious disease associations in advanced stage, indolent lymphoma (follicular and nonfollicular): developing a lymphoma prevention strategy
Authors: C.S. Portlock, P. Hamlin, A. Noy, W. Chey, C.A. Gaydos, L. Palomba, I. Schwartz, S. Corcoran, L. Rosenzweig, D. Walker, G. Papanicolaou, A. Markowitz
Journal: Annals of Oncology (2007)
Paradoxical simultaneous regression and progression of lesions in a phase II study of everolimus in classic Kaposi sarcoma
Authors: S. Mourah, R. Porcher, M. Battistella, D. Kerob, B. Guillot, T. Jouary, F. Agbalika, F. Morinet, V. Furlan, H.M. Teisserenc, N. Dupin, C. Lebbé
Journal: British Journal of Dermatology (2015)

Funding sources: INSERM (French Health and Medical Research Institute) sponsored this study. Conflicts of interest: none declared. Dear Editor, The phosphatidylinositide 3‐kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is activated in Kaposi sarcoma (KS) lesions in humans.1 2 Sirolimus, an mTOR complex 1 (mTORC1) inhibitor, was effective in preclinical models of KS,1 and is considered to be the standard of care post‐transplantation in patients with KS.2 3 4 We aimed to investigate, in a phase II study, if everolimus, another mTORC1 inhibitor already approved in transplantation and oncology, would be a possible alternative treatment in classic or endemic KS. We hypothesized that 6 months of treatment with everolimus 10 mg daily would result in a clinical response, associated with a pharmacodynamic response in sequential tumour biopsies, in at least 50% of patients. Study design, evaluation criteria of response, pharmacodynamic studies and statistical methods are available online (see Supporting Information). Between June and October 2008, 11 patients [median age 74 years (range 56–81)] were included in the study. The inclusion criteria are summarized in Table S1 (see Supporting Information). The median time since the diagnosis of KS was 3·7 years (range 0·9–20·0). Eastern Cooperative Oncology Group performance score was 0 in eight patients (82%) and 1 in two patients (18%). All patients had classic KS. Seven patients had received at least one line of systemic KS therapy (taxanes, liposomal anthracyclin, vinblastine, etoposide, bleomycin and/or interferon). The median time since the last KS therapy was 5 months. At baseline, seven patients had > 50 lesions, and eight patients had lymphoedema.
Improving management of obesity in primary care: cluster randomised trial
Authors: H. Moore
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To evaluate a training programme intended to improve the management of obesity, delivered to general practice teams. <b>Design</b> Cluster randomised trial. <b>Setting</b> Northern and Yorkshire region of England <b>Participants</b> 44 general practices invited consecutively attending obese adults to participate; 843 patients attended for collection of baseline data and were subsequently randomised. <b>Intervention</b> 4.5 hour training programme promoting an obesity management model. <b>Main outcome measures</b> Difference in weight between patients in intervention and control groups at 12 months (main outcome measure) and at 3 months and 18 months; change in practitioners9 knowledge and behaviour in obesity management consultations. <b>Results</b> Twelve months after training the patients in the intervention group were 1 (95% confidence interval - 1.9 to 3.9) kg heavier than controls (P = 0.5). Some evidence indicated that practitioners9 knowledge had improved. Some aspects of the management model, including recording weight, target weight, and dietary targets, occurred more frequently in intervention practices after the training, but in absolute terms levels of implementation were low. <b>Conclusion</b> A training package promoting a brief, prescriptive approach to the treatment of obesity through lifestyle modification, intended to be incorporated into routine clinical practice, did not ultimately affect the weight of this motivated and at risk cohort of patients.
Goals are not selfish
Authors: William von Hippel, Frank A. von Hippel
Journal: Behavioral and Brain Sciences (2014)

Abstract The metaphor of selfish goals is misguided. Organisms can be considered vessels that further the interests of their genes, but not vessels that further the interests of their goals. Although goals can act at cross-purposes to each other and to longevity, such trade-offs are predicted by evolutionary theory. The metaphor of selfish goals provides no purchase on this problem.
Value of Noncontact Mapping for Identifying Left Ventricular Scar in an Ovine Model
Authors: Aravinda Thiagalingam, Elisabeth M. Wallace, Craig R. Campbell, Anita C. Boyd, Vicki E. Eipper, Karen Byth, David L. Ross, Pramesh Kovoor
Journal: Circulation (2004)

We assessed the hypothesis that "virtual electrograms" from a noncontact mapping system (EnSite 3000) could be used to localize myocardial scar.Myocardial infarctions were induced in sheep by inflating an angioplasty balloon in the left anterior descending coronary artery for 3 hours. Scar mapping was performed on 8 sheep without inducible ventricular tachycardia by use of the noncontact mapping system and a 256-channel contact mapping system. Transmural mapping needles were inserted into myocardial regions that were (1) scarred, (2) peripheral to the scar, and (3) distant from the scar. Unipolar electrograms were exported from both systems and analyzed on a personal computer workstation. The percentage of myocardial scarring at each needle site was assessed histologically. Pearson's correlation was used to assess the degree of association between various electrogram characteristics and the presence of myocardial scarring. The only noncontact electrogram characteristic that showed any association with the presence of myocardial scarring was the negative slope duration (contact, r=0.62, P<0.001; noncontact, r=0.23, P=0.004). The other electrogram characteristics studied were electrogram maximal deflection (contact, r=0.38, P<0.001; noncontact, r=0.03, P=0.75) and minimal slope (contact, r=0.42, P<0.001; noncontact, r=0.05, P=0.54).Noncontact electrograms do not reliably identify ventricular scar. Alternative strategies such as importing computed tomography images into the geometry should be used when scar localization is important.
Zidovudine plus interferon alfa-2b treatment in patients with HIV and chronic active viral hepatitis.
Authors: G Visco, L Alba, S Grisetti, P Guarascio, P Narciso, P Sette, C Struglia, G Tossini, V Tozzi
Journal: Gut (1993)

Results are reported for a small study of 11 patients positive for HIV and with chronic active viral hepatitis. Low dose zidovudine/interferon alfa-2b combined treatment produced a general reduction in alanine aminotransferase activities and increased the CD4 lymphocyte count, hepatitis B e seroconversion, and the loss of HIV p24 antigen. The treatment was well tolerated and progression of HIV disease was not seen.
Effect of Atorvastatin and Irbesartan, Alone and in Combination, on Postprandial Endothelial Dysfunction, Oxidative Stress, and Inflammation in Type 2 Diabetic Patients
Authors: Antonio Ceriello, Roberta Assaloni, Roberto Da Ros, Amabile Maier, Ludovica Piconi, Lisa Quagliaro, Katherine Esposito, Dario Giugliano
Journal: Circulation (2005)

Background— Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction and inflammation through oxidative stress. Statins and angiotensin type 1 receptor blockers have been shown to reduce oxidative stress and inflammation, improving endothelial function. Methods and Results— Twenty type 2 diabetic patients ate 3 different test meals: a high-fat meal, 75 g glucose alone, and a high-fat meal plus glucose. Glycemia, triglyceridemia, endothelial function, nitrotyrosine, C-reactive protein, intercellular adhesion molecule-1, and interleukin-6 were assayed during the tests. Subsequently, diabetics took atorvastatin 40 mg/d, irbesartan 300 mg/d, both, or placebo for 1 week. The 3 tests were performed again between 5 and 7 days after the start of each treatment. High-fat load and glucose alone produced a decrease in endothelial function and increases in nitrotyrosine, C-reactive protein, intercellular adhesion molecule-1, and interleukin-6. These effects were more pronounced when high-fat load and glucose were combined. Short-term atorvastatin and irbesartan treatments significantly counterbalanced these phenomena, and their combination was more effective than either therapy alone. Conclusions— This study confirms an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function and inflammation, suggesting oxidative stress as a common mediator of such an effect. Short-term treatment with atorvastatin and irbesartan may counterbalance this phenomenon; the combination of the 2 compounds is most effective.