tbuckley/cabot-search huggingface dataset:
Role of Pectinate Muscle Bundles in the Generation and Maintenance of Intra-atrial Reentry
Authors: Tsu-Juey Wu, Masaaki Yashima, Fagen Xie, Charles A. Athill, Young-Hoon Kim, Michael C. Fishbein, Zhilin Qu, Alan Garfinkel, James N. Weiss, Hrayr S. Karagueuzian, Peng-Sheng Chen
Journal: Circulation Research (1998)

Abstract —To determine the role of pectinate muscle (PM) bundles in the formation of intra-atrial reentry, 10 isolated canine right atrial tissues were perfused with Tyrode’s solution containing 1 to 2.5 μmol/L acetylcholine (ACh). The endocardium was mapped using 477 bipolar electrodes with 1.6-mm resolution. Reentry was induced by a premature stimulus (S 2 ). Computer simulation studies were used to investigate the importance of regional myocardial thickness in reentry formation. A total of 40 episodes of reentry were induced; 28 episodes were stationary, and the remaining 12 were nonstationary. The stationary reentry was induced either immediately after the S 2 stimuli (n=9) or after an initial period of irregular activations that lasted 1460±1077 ms (n=19). Of 28 episodes, 20 were initiated by conduction block along large PM ridges, leading to wave break and the initiation of reentry. The reentrant wave fronts remained stationary and rotated around these ridges as anchoring sites. During the transition from the initial irregular activations to stationary reentry, the electrogram morphology converted from “fibrillation-like” to “flutter-like” activity. In 8 episodes, initially stationary reentry converted to irregular activations because of interference with outside wave fronts (n=5) or spontaneous separation of waves from the ridges (n=3). Compared with stationary reentry, nonstationary reentry always occurred over an area without large PMs, and the mean life span was much shorter (102±151 versus 3.8±1.1 rotations, P &lt;0.001). Computer simulation studies showed that a critical ridge thickness is needed for reentry to anchor, thereby converting fibrillation to flutter. We conclude that PM ridge forms an area where wave break occurs, allowing the initiation of reentry. It also provides a natural anchor to the reentrant wave front, lengthening the life span of reentry. The attachment and detachment of the reentrant wave front to and from the ridge determine “flutter-like” or “fibrillation-like” activity.
Vesicular Stomatitis Virus-Infected L1210 Murine Leukemia Cells: Increased Immunogenicity and Altered Surface Antigens2
Authors: Kim S. Wise
Journal: JNCI Journal of the National Cancer Institute (1977)

Homogenates of L1210 cells infected in vitro with vesicular stomatitis virus (VSV) were immunogenic agains a tumor graft of 100 times the LD50 dose of L1210 cells" whereas those of uninfected cells were not. The immunogenicity of intact X-irradiated L1210 cells was distinguishable from that of VSV-infected cell homogenates on the basis of the susceptibility of immunogenicity to experimental procedures used in preparation of the immunogenic homogenates: Homogenization of intact X-irradiated cells or their infection with VSV prior to irradiation led to loss of immunogenicity. In addition, uninfected cell homogenates were not made immunogenic nor was the immunogenicity of VSV-infected cell homogenates eliminated by X-irradiation. At the time of tumor challenge, sera from mice that were effectively immunized with VSV-infected cell homogenate showed a high VSV-neutralizing titer but no complement-dependent cytotoxicity for L1210 cells. Quantitative absorption studies demonstrated that VSV infection led to a marked reduction in L1210 surface antigens recognized by cytotoxic alloantibody; spatial association between these antigens and VSV antigens was not demonstrable on VSV-infected cells. Antigens recognized by heterologous antiserum to L1210 cells were also reduced following VSV infection.
Stratified Patient-Centered Care in Type 2 Diabetes
Authors: Annabelle S. Slingerland, William H. Herman, William K. Redekop, Rob F. Dijkstra, J. Wouter Jukema, Louis W. Niessen
Journal: Diabetes Care (2013)

OBJECTIVE Diabetes treatment should be effective and cost-effective. HbA1c-associated complications are costly. Would patient-centered care be more (cost-) effective if it was targeted to patients within specific HbA1c ranges? RESEARCH DESIGN AND METHODS This prospective, cluster-randomized, controlled trial involved 13 hospitals (clusters) in the Netherlands and 506 patients with type 2 diabetes randomized to patient-centered (n = 237) or usual care (controls) (n = 269). Primary outcomes were change in HbA1c and quality-adjusted life years (QALYs); costs and incremental costs (USD) after 1 year were secondary outcomes. We applied nonparametric bootstrapping and probabilistic modeling over a lifetime using a validated Dutch model. The baseline HbA1c strata were &amp;lt;7.0% (53 mmol/mol), 7.0–8.5%, and &amp;gt;8.5% (69 mmol/mol). RESULTS Patient-centered care was most effective and cost-effective in those with baseline HbA1c &amp;gt;8.5% (69 mmol/mol). After 1 year, the HbA1c reduction was 0.83% (95% CI 0.81–0.84%) (6.7 mmol/mol [6.5–6.8]), and the incremental cost-effectiveness ratio (ICER) was 261 USD (235–288) per QALY. Over a lifetime, 0.54 QALYs (0.30–0.78) were gained at a cost of 3,482 USD (2,706–4,258); ICER 6,443 USD/QALY (3,199–9,686). For baseline HbA1c 7.0–8.5% (53–69 mmol/mol), 0.24 QALY (0.07–0.41) was gained at a cost of 4,731 USD (4,259–5,205); ICER 20,086 USD (5,979–34,193). Care was not cost-effective for patients at a baseline HbA1c &amp;lt;7.0% (53 mmol/mol). CONCLUSIONS Patient-centered care is more valuable when targeted to patients with HbA1c &amp;gt;8.5% (69 mmol/mol), confirming clinical intuition. The findings support treatment in those with baseline HbA1c 7–8.5% (53–69 mmol/mol) and demonstrate little to no benefit among those with HbA1c &amp;lt;7% (53 mmol/mol). Further studies should assess different HbA1c strata and additional risk profiles to account for heterogeneity among patients.
Intramyocardial Peptide Nanofiber Injection Improves Postinfarction Ventricular Remodeling and Efficacy of Bone Marrow Cell Therapy in Pigs
Authors: Yi-Dong Lin, Ming-Long Yeh, Yu-Jen Yang, Da-Ching Tsai, Ting-Yu Chu, Ya-Yun Shih, Min-Yao Chang, Yen-Wen Liu, Alan C.L. Tang, Tsai-Yun Chen, Chwan-Yau Luo, Kung-Chao Chang, Jyh-Hong Chen, Hua-Lin Wu, Tin-Kan Hung, Patrick C.H. Hsieh
Journal: Circulation (2010)

Background— Growing evidence suggests that intramyocardial biomaterial injection improves cardiac functions after myocardial infarction (MI) in rodents. Cell therapy is another promising approach to treat MI, although poor retention of transplanted cells is a major challenge. In this study, we hypothesized that intramyocardial injection of self-assembling peptide nanofibers (NFs) thickens the infarcted myocardium and increases transplanted autologous bone marrow mononuclear cell (MNC) retention to attenuate cardiac remodeling and dysfunction in a pig MI model. Methods and Results— A total of 40 mature minipigs were divided into 5 groups: sham, MI+normal saline, MI+NFs, MI+MNCs, and MI+MNCs/NFs. MI was induced by coronary occlusion followed by intramyocardial injection of 2 mL normal saline or 1% NFs with or without 1×10 8 isolated autologous MNCs. NF injection significantly improved diastolic function and reduced ventricular remodeling 28 days after treatment. Injection of MNCs alone ameliorated systolic function only, whereas injection of MNCs with NFs significantly improved both systolic and diastolic functions as indicated by +dP/dt and −dP/dt (1214.5±91.9 and −1109.7±91.2 mm Hg/s in MI+NS, 1693.7±84.7 and −1809.6±264.3 mm Hg/s in MI+MNCs/NFs, respectively), increased transplanted cell retention (29.3±4.5 cells/mm 2 in MI+MNCs and 229.4±41.4 cells/mm 2 in MI+MNCs/NFs) and promoted capillary density in the peri-infarct area. Conclusions— We demonstrated that NF injection alone prevents ventricular remodeling, whereas cell implantation with NFs improves cell retention and cardiac functions after MI in pigs. This unprecedented combined treatment in a large animal model has therapeutic effects, which can be translated to clinical applications in the foreseeable future.
A Pitfall of Propidium Iodide Staining in Fluorescence-Activated Cell Sorting Cell Cycle Analysis?
Authors: Franz Buchegger, Yves Marc Dupertuis, Florence Perillo-Adamer
Journal: Cancer Research (2007)

To the Editor: 

We read with great interest the recent article by Fischer et al. ( [1][1]) on uracil-DNA glycosylase and its expression modulated by fluorodeoxyuridine (FdUrd). As a particular observation, the authors provide evidence that FdUrd-induced uracil-DNA glycosylase degradation occurred
A CASE OF RAT-BITE FEVER
Authors: J. O. Symes
Journal: BMJ (1923)

RAT-BITE FEVER.L 1017diameter, its walls thickened and rigid.Realizing the existence of an intussusception, I followed the small gut upwards and came upon the commencement of the lesion some twelve inches.from the ileo-caecal valve.Attempts to " milk " back the intussuscepted bowel were ineffectual, and I therefore removed the appendix, enlarged the opening so left in the caecum, and with two fingers inside the caecum reduced the protruding gut through the ileo- caecal valve.It was only by patient and careful manipulation that this could be done, so tightly was the small bowel gripped by the valve.The whole of the intussusception was then, with com- parative ease, reduced, and as the last portion emerged a Meckel's diverticulum turned itself inside out, resuming its normal position and appearance.The wound in the caecum was then closed.The diverticulum was on the antimesenteric border, was short and its lumen wide.On each side of it the bowel was ecchymosed and of very doubtful vitality.Within the lumen of the gut, at the level of the diverticulum, there could be felt a soft swelling.I removed six inches of ileum, including the diverticulum, performed a lateral anastomosis, and after fixing the mobile caecum in its normal position by catgut sutures, closed the abdomen without drainage.Recovery was uneventful, and the patient left hospital three weeks later free from symptoms, the pregnancy continuing normally.The pathologist reported: " The intussusceptum con- sisted of a portion of bowel in a state of acute congestion and commencing gangrene from strangulation of the blood supply.It coIntained in its cavity a mass of breaking-down blood clot."A CASE OF RAT-BITE FEVER.
How the doctor's nose has shortened over time; a historical overview ofthe truth-telling debate in the doctor-patient relationship
Authors: D. K. Sokol
Journal: Journal of the Royal Society of Medicine (2006)

In medicine, the legitimacy of deception has been the subject of debate for centuries. Fletcher called the issue of truth-telling an ‘old and perennial problem, giving cause in every age to complaints against doctors as masters of equivocation.’1 Despite the categorical rejection of deception in several codes of ethics, the moral acceptability of deception is still a contentious issue in contemporary medicine.2-4 In many parts of the world, it is common for doctors to withhold a diagnosis of cancer from their patients.5-8 In this article, I shall not debate the ethics of truth-telling and deception, but will rather present some historical antecedents to the debate and provide reasons behind the transition, in the Western context, from a deception-friendly professional disposition to an overtly deception-phobic one. However, many of the ethical arguments for and against benignly intended deception are as germane today as they were at the time.
A survey of thoracic ultrasound and pleural procedures in the West Midlands
Authors: Jumaa Bwika, Clare Lynch, Edward Nash
Journal: European Respiratory Journal (2013)

Introduction 

Pleural procedures are common in the practice of respiratory medicine and they have been associated with serious complications [National Patient Safety Agency 2008]. In the UK, the British Thoracic Society (BTS) strongly recommends bedside image guidance for drainage of all pleural collections. Criteria for competence in thoracic ultrasonography (TUS) is published [Royal college of radiologists 2008] and level 1 competence is the minimum for independence. Skills laboratory competence in chest drain insertion with TUS is included in the General Internal Medicine (GIM) Specialist Trainee (ST) curriculum.

Methods 

We designed a 10-point questionnaire using a web based survey tool. A link was emailed to all GIM trainees and all Respiratory consultants in the West Midlands. We used the chi-square test.

Results 

We received 80 responses and 43/80 (54%) were Respiratory physicians. More consultants had TUS competence 9/22 (41%) than trainees 12/58 (21%) p=0.07

Most had formal TUS training 40/80 course, 14/80 (18%) ‘hands on’, and 26/80(32%) had none. Majority use TUS for pleural procedures 34/80 (43%) independently at the bedside, 14/80 (18%) at the bedside with TUS by someone else and 11/80 (14%) TUS done remotely. 18/80 do not do pleural procedures and 3/80 perform procedures without TUS.

Radiologists 39/78 perform half the procedures (32/80 respiratory trainees and 7/78 respiratory consultants).

Discussion 

Majority of physicians in the region are not competent at TUS although many have formal training and employ it independently for pleural procedures. Use of TUS and level of competence of operators should be captured in future BTS pleural audits.
Local expression of B7-H1 promotes organ-specific autoimmunity and transplant rejection
Authors: Sumit K. Subudhi, Ping Zhou, Lisa M. Yerian, Robert K. Chin, James C. Lo, Robert A. Anders, Yonglian Sun, Lieping Chen, Yang Wang, Maria-Luisa Alegre, Yang-Xin Fu
Journal: Journal of Clinical Investigation (2004)

A number of studies have suggested B7-H1, a B7 family member, inhibits T cell responses. Therefore, its expression on nonlymphoid tissues has been proposed to prevent T cell-mediated tissue destruction. To test this hypothesis, we generated transgenic mice that expressed B7-H1 on pancreatic islet beta cells. Surprisingly, we observed accelerated rejection of transplanted allogeneic B7-H1-expressing islet beta cells. Furthermore, transgenic B7-H1 expression broke immune tolerance, as some of the mice spontaneously developed T cell-dependent autoimmune diabetes. In addition, B7-H1 expression increased CD8+ T cell proliferation and promoted autoimmunity induction in a T cell adoptive transfer model of diabetes. Consistent with these findings, B7-H1.Ig fusion protein augmented naive T cell priming both in vitro and in vivo. Our results demonstrate that B7-H1 can provide positive costimulation for naive T cells to promote allograft rejection and autoimmune disease pathogenesis.
Hepatic expression of ABC transporters G5 and G8 does not correlate with biliary cholesterol secretion in liver transplant patients
Authors: Erwin Geuken, Dorien S. Visser, Henri G.D. Leuvenink, Koert P. de Jong, Paul M.J.G. Peeters, Maarten J.H. Slooff, Folkert Kuipers, Robert J. Porte
Journal: Hepatology (2005)

Abstract The adenosine triphosphate (ATP)-binding cassette (ABC)-transporters ABCG5 and ABCG8 have been shown to mediate hepatic and intestinal excretion of cholesterol. In various (genetically modified) murine models, a strong relationship was found between hepatic expression of ABCG5/ABCG8 and biliary cholesterol content. Our study aimed to relate levels of hepatic expression of ABCG5 and ABCG8 to biliary excretion of cholesterol in man. From 24 patients who had received a liver transplant, bile samples were collected daily after transplantation over a 2-week period to determine biliary composition. Expression of ABCG5, ABCG8, MDR3, and BSEP was assessed by real-time polymerase chain reaction (PCR) in liver biopsy specimens collected before and after transplantation. Levels of hepatic ABCG5, ABCG8, and MDR3 messenger RNA (mRNA) were strongly correlated. After transplantation, the biliary secretion rate of cholesterol continuously increased, coinciding with gradual increases in bile salt and phospholipid secretion. In contrast, hepatic levels of ABCG5 and ABCG8 mRNA remained unchanged. Surprisingly, no correlation was found between the hepatic expression of ABCG5 and ABCG8 and rates of biliary cholesterol secretion, normalized for biliary phospholipid secretion. As expected, the concentration of biliary phospholipids correlated well with MDR3 expression. In conclusion , the strong relationship between ABCG5 and ABCG8 gene expression is consistent with the coordinate regulation of both genes, and in line with heterodimerization of both proteins into a functional transporter. Hepatic ABCG5/ABCG8 expression, at least during the early phase after transplantation, is not directly related to biliary cholesterol secretion in humans. This finding suggests the existence of alternative pathways for the hepatobiliary transport of cholesterol that are not controlled by ABCG5/ABCG8. (Hepatology 2005;42:1166–1174.)
Migration matters: regulatory T-cell compartmentalization determines suppressive activity in vivo
Authors: Kerstin Siegmund, Markus Feuerer, Christiane Siewert, Saeed Ghani, Uta Haubold, Anja Dankof, Veit Krenn, Michael P. Schön, Alexander Scheffold, John B. Lowe, Alf Hamann, Uta Syrbe, Jochen Huehn
Journal: Blood (2005)
Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition.
Authors: K Miyake, C B Underhill, J Lesley, P W Kincade
Journal: The Journal of Experimental Medicine (1990)

A cell adhesion model was previously used to select a series of monoclonal antibodies (mAbs), which were subsequently found to recognize CD44/Pgp-1. Interest in these reagents increased with the finding that they totally inhibited production of lymphoid or myeloid cells in long-term bone marrow cultures. Further investigation has now revealed that hyaluronate is a potential ligand for CD44 and that hyaluronate recognition accounts for the adhesion between B lineage hybridoma and stromal cells. The hybridoma cells adhered to hyaluronate-coated plastic wells as well as to monolayers of stromal cells. The adhesion in both cases was inhibited by treatment with hyaluronidases, and did not require divalent cations. Addition of exogenous hyaluronate also diminished binding of lymphoid cells to stromal cells. One of several mAbs to Pgp-1/CD44 was particularly effective at blocking these interactions. Since hyaluronate and Pgp-1/CD44 were present on both cell types, experiments were done to determine the cellular location of interacting molecules required for the adhesion process. Treatment of lymphoid cells with an anti-Pgp-1/CD44 antibody was more inhibitory than antibody treatment of the stromal cells. Conversely, hyaluronidase treatment of stromal cells reduced subsequent binding more than treatment of the lymphoid cells. Adhesive interactions that involve hyaluronate and CD44 could contribute to a number of cell recognition processes, including ones required for normal lympho-hemopoiesis.
Simvastatin Prevents Vascular Hyporeactivity During Inflammation
Authors: Johannes Pleiner, Georg Schaller, Friedrich Mittermayer, Stefan Zorn, Claudia Marsik, Stefan Polterauer, Stylianos Kapiotis, Michael Wolzt
Journal: Circulation (2004)

There is growing evidence that statins exert anti-inflammatory and antioxidative vascular actions that are independent of lipid lowering. We tested whether hyporeactivity to the endothelium-dependent vasodilator acetylcholine (ACh) and the vasoconstrictor norepinephrine (NE) during acute experimental inflammation could be prevented by simvastatin.In a randomized, placebo-controlled, parallel group study, forearm blood flow (FBF) responses to NE, ACh, and the endothelium-independent vasodilator nitroglycerin (NTG) were assessed at baseline, after 4 days of simvastatin 80 mg PO or placebo treatment, and during Escherichia coli endotoxin (lipopolysaccharide [LPS])-induced inflammation in 20 healthy volunteers. Additionally, markers of inflammation and neutrophil oxidative burst were assessed. Simvastatin and placebo had no effect on FBF or oxidative/inflammatory markers. LPS administration decreased the responses of FBF to NE by 43% (P<0.05) and decreased responses to ACh by 48% (P<0.05) but did not decrease FBF responses to NTG. Simvastatin completely preserved responses to NE and to ACh. The LPS-induced increases in neutrophil oxidative burst and plasma tumor necrosis factor-alpha concentrations were mitigated by simvastatin (P<0.05 versus placebo).This study demonstrates potent vasoprotective properties of high-dose simvastatin during endotoxemia that may be useful for patients with acute systemic inflammation and associated vascular hyporeactivity.
P<scp>hosphoinositide</scp>3-K<scp>inase</scp>: Diverse Roles in Immune Cell Activation
Authors: Jonathan A. Deane, David A. Fruman
Journal: Annual Review of Immunology (2004)

Cells of the immune system carry out diverse functions that are controlled by surface receptors for antigen, costimulatory molecules, cytokines, chemokines, and other ligands. A shared feature of signal transduction downstream of most receptors on immune cells, as in nonhematopoietic cell types, is the activation of phosphoinositide 3-kinase (PI3K). The mechanism by which this common signaling event is elicited by distinct receptors and contributes to unique functional outcomes is an intriguing puzzle. Understanding how specificity is achieved in PI3K signaling is of particular significance because altered regulation of this pathway is observed in many disease states, including leukemia and lymphoma. Here we review recent advances in the understanding of PI3K signaling mechanisms in different immune cells and receptor systems. We emphasize the concept that PI3K and its products are components of complex networks of interacting proteins and second messengers, rather than simple links in linear signaling cascades.
Driving ability in sleep apnoea patients before and after CPAP treatment: evaluation on a road safety platform
Authors: S. Mazza, J-L. Pépin, B. Naëgelé, E. Rauch, C. Deschaux, P. Ficheux, P. Lévy
Journal: European Respiratory Journal (2006)

Sleepiness is considered to be the major cause of increased traffic accidents in patients with obstructive sleep apnoea syndrome (OSAS). Until now, OSAS patients′ driving ability has been assessed using driving simulators, but no assessment in a more natural driving environment has been carried out to date. The aim of the present study was to evaluate driving parameters in OSAS and in controls on a road safety platform, and to compare them with attentional in-laboratory measures before and after continuous positive airway pressure treatment. The parameters measured were: reaction time; distance to stop and number of collisions on the platform; maintenance of wakefulness; and sustained, selective and divided attention in laboratory. Patients exhibited much longer reaction times than controls, leading to a lengthening of the vehicle′s stopping distance of 8.8 m at 40 km·h -1 and to twice the number of collisions. Patients did not demonstrate objective sleepiness or selective and sustained attention deficits. Divided attention deficits were found. However, they did not allow the prediction of real driving impairment. After CPAP treatment, there was no longer any difference between patients and controls regarding driving and attention performances. Driving abilities are significantly impaired in obstructive sleep apnoea syndrome. After continuous positive airway pressure treatment, deficits were normalised. This stresses the importance of evaluating attentional parameters in apnoeic patients and of offering continuous positive airway pressure treatment even to non-sleepy subjects.