tbuckley/cabot-search huggingface dataset:
Recurrence of pulmonary embolism during anticoagulant treatment: a prospective study.
Authors: P Girard, M Mathieu, G Simonneau, P Petitpretz, J Cerrina, P Herve, J Rosso, D Musset, J Mensch, P Duroux
Journal: Thorax (1987)

The risk of early recurrence of pulmonary embolism in patients with venous thromboembolic disease treated by anticoagulants is not well established. To determine the risk linked to contemporary proximal deep venous thrombosis, a prospective study was organised to give clinical and scintigraphic surveillance to 50 patients with angiographically proved pulmonary embolism plus phlebographically proved proximal deep vein thrombosis during the first 15 days of anticoagulant treatment. Perfusion lung scans were performed initially and on days 3, 7, and 15. Only two patients had a recurrence of pulmonary embolism during this period; both episodes were revealed by new symptoms, and one recurrence was fatal. The systematic performance of angiography in four patients found to have new scintigraphic defects led to the diagnosis of "spurious scintigraphic recurrence" in three of them. It is concluded that (a) adjusted anticoagulant treatment showed an effectiveness of 96% for preventing early recurrence of pulmonary embolism in this group of supposed high risk patients, and (b) in patients with recent pulmonary embolism new defects on systematic perfusion lung scans are not specific indicators of recurrent pulmonary embolism.
CD40L Proinflammatory and Profibrotic Effects on Proximal Tubular Epithelial Cells
Authors: Paola Pontrelli, Michele Ursi, Elena Ranieri, Carmen Capobianco, Francesco P. Schena, Loreto Gesualdo, Giuseppe Grandaliano
Journal: Journal of the American Society of Nephrology (2006)

Chronic allograft nephropathy (CAN) is the main cause of renal graft loss, but its pathogenic mechanisms are still unclear. Immune system activation has been suggested as a key event in the development of CAN. CD40 is a co-stimulatory protein whose expression is upregulated in proximal tubular epithelial cells (PTEC) in acute rejection. This receptor interacts with CD40L, expressed by activated T cells. CD40L induces the production by PTEC of different proinflammatory cytokines, but very little is known of its profibrotic effects. The aim of this study was to investigate the effect of CD40/CD40L interaction on PTEC expression of plasminogen activator inhibitor-1 (PAI-1), a powerful profibrotic mediator, and monocyte chemoattractant protein-1 (MCP-1), a proinflammatory cytokine, and to investigate the signaling pathways that lead to these effects. Soluble CD40L induced a time-dependent increase in both PAI-1 and MCP-1 gene expression and protein production in PTEC. CD40 cross-linking on PTEC caused TNF-R-associated factors 2 and 6 membrane translocation. This event led to NF-kappaB activation, through the NF-kappaB-inducing kinase, and to a significant increase in the phosphorylation of lyn, a src-related tyrosine kinase. Lyn, upon phosphorylation, became strictly associated with caveolin-1, a scaffolding protein enriched in caveolae. Lyn inhibition did not have any effect on CD40L-induced NF-kappaB activation and MCP-1 expression but abolished PAI-1 induction. On the contrary, NF-kappaB inhibition significantly reduced only MCP-1 expression. In conclusion, CD40L could play a key role in the pathogenesis of CAN through PAI-1 induction. CD40L profibrotic and proinflammatory effects are mediated by different signaling pathways, suggesting that drugs that inhibit inflammation may not be equally effective in reducing fibrosis.
A novel method for bone area measurement provides new insights into osteoarthritis and its progression
Authors: Michael A Bowes, Graham R Vincent, Christopher B Wolstenholme, Philip G Conaghan
Journal: Annals of the Rheumatic Diseases (2013)

Modern image analysis enables the accurate quantification of knee osteoarthritis (OA) bone using MRI. We hypothesised that three-dimensional changes in bone would be characteristic of OA and provide a responsive measure of progression.1312 participants with radiographic knee OA, and 885 non-OA controls with MRIs at baseline, 1, 2 and 4 years were selected from the NIH Osteoarthritis Initiative. Automated segmentation of all knee bones and calculation of bone area was performed using active appearance models. In a subset of 352 participants, responsiveness of bone area change was compared with change in radiographic joint space width (JSW) and MRI cartilage thickness over a 2-year period.All OA knee compartments showed increased bone area over time compared with non-OA participants: for example, the 4-year percentage change from baseline in medial femur area for OA (95% CI) was 1.87(0.13), non-OA 0.43 (0.07); p<0.0001. Bone area change was more responsive than cartilage thickness or JSW; 2-year SRM for bone area in the medial femur was 0.83, for the most responsive cartilage thickness measure central medial femorotibial composite (cMFTC): 0.38, JSW: 0.35. Almost half of all knees had change greater than smallest detectable difference at 2 years. Body mass index, gender and alignment had only a small effect on the rate of change of bone area.Changes in bone area discriminated people with OA from controls and was more responsive than the current and impending standards for assessing OA progression. The shape change in OA bone provides a new window on OA pathogenesis and a focus for clinical trials.
The Role of Macrophages in T Cell–mediated Autoimmune Diabetes in Nonobese Diabetic Mice
Authors: Hee-Sook Jun, Chang-Soon Yoon, Lori Zbytnuik, Nico van Rooijen, Ji-Won Yoon
Journal: The Journal of Experimental Medicine (1999)

We have shown previously that the inactivation of macrophages in nonobese diabetic (NOD) mice results in the prevention of diabetes; however, the mechanisms involved remain unknown. In this study, we found that T cells in a macrophage-depleted environment lost their ability to differentiate into β cell–cytotoxic T cells, resulting in the prevention of autoimmune diabetes, but these T cells regained their β cell–cytotoxic potential when returned to a macrophage-containing environment. To learn why T cells in a macrophage-depleted environment lose their ability to kill β cells, we examined the islet antigen–specific immune response and T cell activation in macrophage-depleted NOD mice. There was a shift in the immune balance, a decrease in the T helper cell type 1 (Th1) immune response, and an increase in the Th2 immune response, due to the reduced expression of the macrophage-derived cytokine IL-12. As well, there was a deficit in T cell activation, evidenced by significant decreases in the expression of Fas ligand and perforin. The administration of IL-12 substantially reversed the prevention of diabetes in NOD mice conferred by macrophage depletion. We conclude that macrophages play an essential role in the development and activation of β cell–cytotoxic T cells that cause β cell destruction, resulting in autoimmune diabetes in NOD mice.
THE FREQUENCY OF SYPHILITIC PRIMARY OPTIC ATROPHY IN DEMENTIA PARALYTICA
Authors: WALTER L. BRUETSCH
Journal: American Journal of Psychiatry (1948)

Complete syphilitic optic atrophy in dementia paralytica, including taboparalysis, has been observed in 2%. Incipient and intermediate stages of optic atrophy are much more frequent and have been found in 62.5%, on histologic examination, of the optic pathways of 32 general paralytic patients. There is no convincing evidence that syphilitic primary optic atrophy occurs with so much greater frequency in taboparalysis than in general paralysis, as has been reported in the literature.
Computer simulation of arrhythmias in a network of coupled excitable elements.
Authors: F J van Capelle, D Durrer
Journal: Circulation Research (1980)

Arrhythmias were simulated in sheets or cables, consisting of coupled excitable elements, which were characterized by a simple regenerative mechanism. The geometry of the network, the amount of coupling among individual elements, and the properties of the elements relating to excitability, automaticity, and duration of the refractory period could be adjusted arbitrarily in an interactive computer program. When a critical amount of coupling was present between automatic and non-automatic cells, sustained repetitive activity could be initiated and stopped by stimulation of the elements. Using this mechanism, it also was possible to evoke reciprocal activity in a one-dimensional cable. In uniform sheets of coupled elements, circus movement of the activation front could be evoked. The presence of an obstacle or dispersion of the refractory periods of the elements was not a prerequisite for the initiation of circus movements. The vortex of circus movements in the homogeneous sheets consisted of elements which were inactivated by depolarizing currents from the circulating wavefront. In sheets of sufficient size, multiple vortices could be present.
Retrospective Analysis of Selective Lymphadenectomy in Apparent Early-Stage Endometrial Cancer
Authors: Janiel M. Cragun, Laura J. Havrilesky, Brian Calingaert, Ingrid Synan, Angeles Alvarez Secord, John T. Soper, Daniel L. Clarke-Pearson, Andrew Berchuck
Journal: Journal of Clinical Oncology (2005)

Selective lymphadenectomy is widely accepted in the management of endometrial cancer. Purported benefits are individualization of adjuvant therapy based on extent of disease and resection of occult metastases. Our goal was to assess effects of the extent of selective lymphadenectomy on outcomes in women with apparent stage I endometrial cancer at laparotomy.Patients with endometrial cancer who received primary surgical treatment between 1973 and 2002 were identified through an institutional tumor registry. Inclusion criteria were clinical stage I/IIA disease and procedure including hysterectomy and selective lymphadenectomy (pelvic or pelvic + aortic). Exclusion criteria included presurgical radiation, grossly positive lymph nodes, or extrauterine metastases at laparotomy. Recurrence and survival were analyzed using Kaplan-Meier analysis and Cox proportional hazards model.Among 509 patients, the median number of lymph nodes removed was 15 (median pelvic, 11; median aortic, three). Pelvic and aortic node metastases were found in 24 (5%) of 509 patients and 11 (3%) of 373 patients, respectively. Patients with poorly differentiated cancers having more than 11 pelvic nodes removed had improved overall survival (hazard ratio [HR], 0.25; P < .0001) and progression-free survival (HR, 0.26; P < .0001) compared with patients having poorly differentiated cancers with 11 or fewer nodes removed. Number of nodes removed was not predictive of survival among patients with cancers of grade 1 to 2. Performance of aortic selective lymphadenectomy was not associated with survival. Three (27%) of 11 patients with microscopic aortic nodal metastasis are alive without recurrence.These data add to the literature documenting the possible therapeutic benefit of selective lymphadenectomy in management of patients with apparent early-stage endometrial cancer.
Self-sampling for analysis of respiratory viruses in a large-scale epidemiological study in Sweden
Authors: A Plymoth, M Rotzén-Östlund, B Zweygberg-Wirgart, C G Sundin, A Ploner, O Nyrén, A Linde
Journal: Eurosurveillance (2015)

Viral diagnosis of respiratory tract infections has so far required sampling by health professionals, hampering large-scale epidemiological studies of virus-specific disease outcomes. As part of a population-based, prospective study of work-related risk factors for transmission of viral infections (SWEDE-I), we developed a scheme for self-sampling with nasal swabs. Random selection from the gainfully employed population of a medium-sized town in central Sweden resulted in a study cohort of 2,237 men and women aged 25 to 63 years. From September 2011 through May 2012, the cohort reported all instances of respiratory tract infection or gastroenteritis and participants concomitantly sent self-sampled nasal swabs for analysis using regular mail. Diagnosis of 14 viruses was performed. A total of 1,843 samples were received. The week-wise average delay between disease onset and arrival of the specimens at the laboratory varied between four and six days, and the corresponding median delay was between 3.5 and six days. In line with previous community-based studies, picorna- and coronaviruses dominated in specimens obtained from the self-sampling scheme. The results of self-sampling were contrasted to those from contemporaneous routine clinical sampling, on the same age group, in the adjacent Stockholm county. Although higher proportions of positive samples for respiratory syncytial virus and influenza were observed in the clinical sampling scheme, estimations of seasonality for influenza A and picornaviruses derived from both schemes were similar. Our findings show that nasal self-sampling is feasible in large-scale surveillance of respiratory infections and opens new prospects for population-based, virologically verified research on virus spread, burden of disease, and effects of environmental factors or interventions.
Learning From the Paradoxes of Domestic Violence
Authors: Anne Flitcraft
Journal: JAMA (1997)

"The assailant called the police after his wife had placed a call for help to show her that 'nobody was going to come.' When the police arrived, the victim initially denied that she had been assaulted and reported that her husband, who was standing behind the drapes with a pistol in hand, had left."<sup>1</sup> In this brief scenario, Brookoff et al<sup>1</sup>capture the contradictions that frequently surround domestic violence. The assailant and victim use police services in paradoxical ways: The assailant, confident of the general ineffectiveness of law enforcement interventions, actually calls the police as part of a pattern of threatening behavior. The victim appears to protect her assailant when police arrive, but in the final analysis her behavior is a strategic attempt to prevent further violence, protecting herself and police officers on the scene. The victim bears little evidence of assault, yet her risk of serious injury
Investigation of the Prognostic and Predictive Value of Thymidylate Synthase, p53, and Ki-67 in Patients With Locally Advanced Colon Cancer
Authors: Carmen J. Allegra, Allyson L. Parr, Lester E. Wold, Michelle R. Mahoney, Daniel J. Sargent, Patrick Johnston, Pam Klein, Katie Behan, Michael J. O’Connell, Ralph Levitt, John W. Kugler, Maria Tria Tirona, Richard M. Goldberg
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To evaluate the value of thymidylate synthase (TS), Ki-67, and p53 as prognostic markers in patients with Dukes’ B2 and C colon carcinoma. METHODS: We conducted a retrospective analysis to evaluate the prognostic value of TS, Ki-67, and p53 in 465 patients with Dukes’ B2 (220 patients) or Dukes’ C (245 patients) colon carcinoma. Patients represent a nonrandom subset obtained from five randomized phase III trials and were treated with either surgery alone (151 patients) or surgery plus fluorouracil-based chemotherapy (314 patients). All three markers were assayed using immunohistochemical techniques. RESULTS: With a minimum follow-up of 5 years, our retrospective analysis failed to demonstrate a consistent and significant association between TS, Ki-67, or p53 and either disease-free survival or overall survival. Exploratory analyses did not reveal a convincing explanation for these results that are in conflict with the published literature. Notable interactions were observed. In particular, high Ki-67 levels were associated with increased (decreased) survival in patients with low (high) TS intensity. Patients whose tumors stained positively for p53 seemed to benefit substantially from the use of adjuvant chemotherapy compared with those who were not treated (P = .05). CONCLUSION: This retrospective investigation failed to demonstrate a significant association between TS, Ki-67, or p53 staining and clinical outcome.
Widespread Interspecific Divergence in Cis-Regulation of Transposable Elements in the Arabidopsis Genus
Authors: F. He, X. Zhang, J.-Y. Hu, F. Turck, X. Dong, U. Goebel, J. O. Borevitz, J. de Meaux
Journal: Molecular Biology and Evolution (2011)

Transposable elements (TEs) are so abundant and variable that they count among the most important mutational sources in genomes. Nonetheless, little is known about the genetics of their variation in activity or silencing across closely related species. Here, we demonstrate that regulation of TE genes can differ dramatically between the two closely related Arabidopsis species A. thaliana and A. lyrata. In leaf and floral tissues of F1 interspecific hybrids, about 47% of TEs show allele-specific expression, with the A. lyrata copy being generally expressed at higher level. We confirm that TEs are generally expressed in A. lyrata but not in A. thaliana. Allele-specific differences in TE expression are associated with divergence in epigenetic modifications like DNA and histone methylation between species as well as with sequence divergence. Our data demonstrate that A. thaliana silences TEs much better than A. lyrata. For long terminal repeat retrotransposons, these differences are more pronounced for younger insertions. Interspecific differences in TE silencing may have a great impact on genome size changes.
Trans-acting element(s) operating across species barriers positively regulate expression of major histocompatibility complex class II genes.
Authors: R S Accolla, L Scarpellino, G Carra, J Guardiola
Journal: The Journal of Experimental Medicine (1985)

Raji, a human B lymphoma line, expresses high levels of major histocompatibility complex (MHC) class II antigens. Conversely, none of the detectable human Ia antigens is present in RJ 2.2.5, an immunoselected Raji variant. Clonal analysis, biochemical characterization, and nucleic acid hybridization studies of hybrids between mouse spleen cells and RJ 2.2.5 show that MHC class II gene expression is regulated in trans by a factor which, as judged by dominance studies, has the characteristics of an activator. Such a positive trans acting factor is expressed in mouse spleen cells, and is able to implement MHC class II gene expression across species boundaries. Expression of this factor in spleen cells strongly suggests that it plays a role in in vivo regulation of Ia expression. Additional data suggest that different subsets of class II genes such as DR and DQ may, in part, be regulated by different mechanisms. It has also been possible to show that the amount of In chain-specific mRNA, present at reduced levels in RJ 2.2.5 cells compared to the parental Raji cells, drastically increased in human X mouse cells hybrids reexpressing human Ia antigens, suggesting that the In chain gene and the class II genes, although located on different chromosomes, are regulated in a concerted fashion, either directly through the same implementing factor, or indirectly through a cascade mechanism.
Bone Marrow Cells Differentiate in Cardiac Cell Lineages After Infarction Independently of Cell Fusion
Authors: Jan Kajstura, Marcello Rota, Brian Whang, Stefano Cascapera, Toru Hosoda, Claudia Bearzi, Daria Nurzynska, Hideko Kasahara, Elias Zias, Massimiliano Bonafé, Bernardo Nadal-Ginard, Daniele Torella, Angelo Nascimbene, Federico Quaini, Konrad Urbanek, Annarosa Leri, Piero Anversa
Journal: Circulation Research (2004)

Recent studies in mice have challenged the ability of bone marrow cells (BMCs) to differentiate into myocytes and coronary vessels. The claim has also been made that BMCs acquire a cell phenotype different from the blood lineages only by fusing with resident cells. Technical problems exist in the induction of myocardial infarction and the successful injection of BMCs in the mouse heart. Similarly, the accurate analysis of the cell populations implicated in the regeneration of the dead tissue is complex and these factors together may account for the negative findings. In this study, we have implemented a simple protocol that can easily be reproduced and have reevaluated whether injection of BMCs restores the infarcted myocardium in mice and whether cell fusion is involved in tissue reconstitution. For this purpose, c-kit–positive BMCs were obtained from male transgenic mice expressing enhanced green fluorescence protein (EGFP). EGFP and the Y-chromosome were used as markers of the progeny of the transplanted cells in the recipient heart. By this approach, we have demonstrated that BMCs, when properly administrated in the infarcted heart, efficiently differentiate into myocytes and coronary vessels with no detectable differentiation into hemopoietic lineages. However, BMCs have no apparent paracrine effect on the growth behavior of the surviving myocardium. Within the infarct, in 10 days, nearly 4.5 million biochemically and morphologically differentiated myocytes together with coronary arterioles and capillary structures were generated independently of cell fusion. In conclusion, BMCs adopt the cardiac cell lineages and have an important therapeutic impact on ischemic heart failure.
ANDREW BALFOUR MEMORIAL
Authors: J. Crichton-Browne, J. Currie, M. H. G. Fell, W. H. N. Goschen, D. L. Grant, W. W. Jameson, P. S. Lelean, None Lloyd, M. C. Norman, W. G. A. Ormsby-Gore, A. T. Stanton, H. S. Wellcome, C. M. Wenyon, R. Wingate
Journal: BMJ (1932)
Pegylated interferon α-2b plus ribavirin for the treatment of chronic hepatitis C in HIV-coinfected patients
Authors: Esther Voigt, Christian Schulz, Gerd Klausen, Joerg Goelz, Stefan Mauss, Guenther Schmutz, Heiko Jessen, Lutwin Weitner, Antonius Mutz, Dietmar Schranz, Juergen K. Rockstroh, None for the KAAD study group
Journal: Journal of Infection (2005)
Kupffer cell-derived IL-10 plays a key role in maintaining humoral immune tolerance in hepatitis B virus-persistent mice
Authors: Long Xu, Wenwei Yin, Rui Sun, Haiming Wei, Zhigang Tian
Journal: Hepatology (2013)

The liver is considered as a unique lymphoid organ favoring the induction of immune tolerance, rather than immunity. Biologists and clinicians alike have a long-standing interest in how the liver induces systemic immune tolerance, but the mechanism has not yet been well elucidated. Here, we employed hepatitis B virus (HBV)-carrier mice generated by hydrodynamically injecting phosphor-adeno-associated virus/HBV1.2 plasmid as a model for adult chronic HBV infection, which we found were unable to respond to hepatitis B surface antigen vaccination. Humoral tolerance induced in HBV-carrier mice could be transferred into Rag1(-/-) mice, because anti-HBV immunity in immunologically reconstituted Rag1(-/-) mice was inhibited by adoptive transfer of splenocytes from HBV-carrier mice. Humoral tolerance needed at least 7 days for induction and persisted to 3 months after a single HBV plasmid injection. Kupffer cell (KC) depletion or interleukin (IL-10) deficiency broke this humoral tolerance, and exogenous injection of IL-10 could effectively induce this tolerance. KCs in HBV-carrier mice expressed more IL-10 and mediated the systemic tolerance induction in an IL-10-dependent manner. This previously undescribed humoral tolerance regarding HBV infection will help to explore new approaches to reverse liver-sustained systemic immune tolerance in liver disease.