tbuckley/cabot-search huggingface dataset:
Systemic sclerosis following human cytomegalovirus infection
Authors: C Ferri
Journal: Annals of the Rheumatic Diseases (2002)

Systemic sclerosis (SSc) is a connective tissue disease characterised by skin and visceral organ involvement.1,2 The cause of SSc is still unknown; it has been suggested that one or more factors may be responsible for the disease through a complex pathogenic mechanism.3,4 Immune system dysregulation, collagen hyperproduction by altered fibroblasts, and vascular alterations can variably contribute to SSc development. The presence of Raynaud's phenomenon and diffuse microangiopathy suggests that endothelial injury may represent the first step in the pathogenesis of the disease.4 Numerous genetic, environmental, and infectious agents have been proposed as possible triggering factors.3–6 Among these, human cytomegalovirus (HCMV) infection may play a part in the pathogenesis of the SSc owing to its ability to …
Polymeric‐Gold Nanohybrids for Combined Imaging and Cancer Therapy
Authors: Antonio Topete, Manuel Alatorre‐Meda, Eva M. Villar‐Alvarez, Susana Carregal‐Romero, Silvia Barbosa, Wolfgang J. Parak, Pablo Taboada, Víctor Mosquera
Journal: Advanced Healthcare Materials (2014)

Here, the use of folic acid (FA)‐functionalized, doxorubicin (DOXO)/superparamagnetic iron oxide nanoparticles (SPION)‐loaded poly(lactic‐ co ‐glycolic acid) (PLGA)‐Au porous shell nanoparticles (NPs) as potential nanoplatforms is reported for targeted multimodal chemo‐ and photothermal therapy combined with optical and magnetic resonance imaging in cancer. These polymeric‐gold nanohybrids (PGNH) are produced by a seeded‐growth method using chitosan as an electrostatic “glue” to attach Au seeds to DOXO/SPION‐PLGA NPs. In order to determine their potential as theranostic nanoplatforms, their physicochemical properties, cellular uptake, and photothermal and chemotherapeutic efficiencies are tested in vitro using a human cervical cancer (HeLa) cell line. The present NPs show a near‐infrared (NIR)‐light‐triggered release of cargo molecules under illumination and a great capacity to induce localized cell death in a well‐focused region. The functionalization of the PGNH NPs with the targeting ligand FA improves their internalization efficiency and specificity. Furthermore, the possibility to guide the PGNH NPs to cancer cells by an external magnetic field is also proven in vitro, which additionally increases the cellular uptake and therapeutic efficiency.
FAVORABLE EFFECT OF OMEGA-3 FATTY ACIDS ADMINISTRATION ON ARTERIAL FUNCTION IN HEALTHY SMOKERS
Authors: Marina Zaromitidou, Gerasimos Siasos, Dimitris Tousoulis, Aleksis Verveniotis, Evangelos Oikonomou, Elias Gialafos, Theodoros Ntoskas, Aris Plastiras, Konstantinos Maniatis, Thodoris Paraskevopoulos, Sevasti Manousakidi, Athanasios G. Papavassiliou
Journal: Journal of the American College of Cardiology (2011)
Clinical characteristics and outcomes of hematogenous vertebral osteomyelitis caused by gram-negative bacteria
Authors: Ki-Ho Park, Oh Hyun Cho, Myounghwa Jung, Kyung-Soo Suk, Jung Hee Lee, Ji Seon Park, Kyung Nam Ryu, Sung-Han Kim, Sang-Oh Lee, Sang-Ho Choi, In-Gyu Bae, Yang Soo Kim, Jun Hee Woo, Mi Suk Lee
Journal: Journal of Infection (2014)
Subcellular localization of Bcr, Abl, and Bcr-Abl proteins in normal and leukemic cells and correlation of expression with myeloid differentiation.
Authors: M Wetzler, M Talpaz, R A Van Etten, C Hirsh-Ginsberg, M Beran, R Kurzrock
Journal: Journal of Clinical Investigation (1993)

We used specific antisera and immunohistochemical methods to investigate the subcellular localization and expression of Bcr, Abl, and Bcr-Abl proteins in leukemic cell lines and in fresh human leukemic and normal samples at various stages of myeloid differentiation. Earlier studies of the subcellular localization of transfected murine type IV c-Abl protein in fibroblasts have shown that this molecule resides largely in the nucleus, whereas transforming deletion variants are localized exclusively in the cytoplasm. Here, we demonstrate that the murine type IV c-Abl protein is also found in the nucleus when overexpressed in a mouse hematopoietic cell line. However, in both normal and leukemic human hematopoietic cells, c-Abl is discerned predominantly in the cytoplasm, with nuclear staining present, albeit at a lower level. In contrast, normal endogenous Bcr protein, as well as the aberrant p210BCR-ABL and p190BCR-ABL proteins consistently localize to the cytoplasm in both cell lines and fresh cells. The results with p210BCR-ABL were confirmed in a unique Ph1-positive chronic myelogenous leukemia (CML) cell line, KBM5, which lacks the normal chromosome 9 and hence the normal c-Abl product. Because the p210BCR-ABL protein appears cytoplasmic in both chronic phase and blast crisis CML cells, as does the p190BCR-ABL in Ph1-positive acute leukemia, a change in subcellular location of Bcr-Abl proteins between cytoplasm and nucleus cannot explain the different spectrum of leukemias associated with p210 and p190, nor the transition from the chronic to the acute leukemia phenotype seen in CML. Further analysis of fresh CML and normal hematopoietic bone marrow cells reveals that p210BCR-ABL, as well as the normal Bcr and Abl proteins, are expressed primarily in the early stages of myeloid maturation, and that levels of expression are reduced significantly as the cells mature to polymorphonuclear leukocytes. Similarly, a decrease in Bcr and Abl levels occurs in HL-60 cells induced by DMSO to undergo granulocytic differentiation. The action of p210BCR-ABL and its normal counterparts may, therefore, take place during the earlier stages of myeloid development.
Effects of ischaemia and coronary reperfusion on regional myocardial blood flow and on the epicardial electrogram
Authors: G. A. BELLER, W. B. HOOD, T. W. SMITH
Journal: Cardiovascular Research (1977)

Effects of reperfusion on the epicardial electrogram and on regional myocardial blood flow were investigated in 3 groups of dogs undergoing acute anterior wall ischaemia for 1 (Group I), 2 (Group II), or 6 (Group III) hours. Regional blood flow was assessed utilising the microsphere technique. Rapid development of abnormal Q waves, associated with accelerated decrease or loss of R wave electromotive forces, was observed after reperfusion in the central ischaemic zone in 25% of dogs in Group I, 75% of dogs in Group II, and in 92% of animals in Group III. These rapidly evolving changes occurred concomitant with significant reductions in mean S-T segment elevation. In contrast to the epicardial electrogram changes in the central ischaemic zone, coronary reperfusion was not associated with development of abnormal Q waves or accelerated loss of R wave amplitude in the peripheral ischaemic zone or in the border zone in Group I animals. However, in Group II, Q waves appeared in the peripheral ischaemic zone in all but one of the dogs developing Q waves in the central ischaemic zone. Border zone Q waves appeared in only 17% of these animals. In Group III, Q waves appeared in the peripheral ischaemic zone in 92% and in the border zone in 75% of animals. Impaired reflow of blood to ischaemic zones was seen following coronary reperfusion. In Group I mean flow was 88±10% of nonischaemic flow in endocardial layers of the central ischaemic zone after reperfusion. In contrast, mean flow to this region in Group II and Group III animals was only restored to 59 ±17% and 53 ± 11% of nonischaemic flow, respectively. Pathological findings of subendocardial haemorrhage and transmural oedema were uniformly present in areas showing reduced reflow and abnormal 0 waves after reperfusion.
Low-dose oral etoposide-based induction regimen for children with acute lymphoblastic leukemia in first bone marrow relapse
Authors: N Hijiya, A Gajjar, Z Zhang, J T Sandlund, R C Ribeiro, J E Rubnitz, S Jeha, W Liu, C Cheng, S C Raimondi, F G Behm, G K Rivera, M V Relling, C-H Pui
Journal: Leukemia (2004)
The cutaneous T cell lymphoma, mycosis fungoides, is a human T cell lymphotropic virus-associated disease. A study of 50 patients.
Authors: B A Pancake, D Zucker-Franklin, E E Coutavas
Journal: Journal of Clinical Investigation (1995)

For nearly two decades it has been suspected that the cutaneous T cell lymphoma, mycosis fungoides (MF), and its leukemic variant, the Sézary syndrome, are caused by the human T lymphotropic virus (HTLV-I/II). Arguments against this concept included the finding that only a small number of MF patients have antibodies to HTLV-I/II and that attempts to detect proviral sequences by mere Southern hybridization of extracted DNA usually met with failure. However, we have reported repeatedly that HTLV-like particles emerge in blood mononuclear cell (PBMC) cultures of practically all patients with this disease. In several instances, the particles were identified as HTLV by immunoelectron microscopy as well as biomolecular analysis. With the assumptions that the virus in MF patients may have become detection by Southern hybridization alone, the extracts of freshly isolated PBMC of 50 consecutive patients were subjected to combined PCR/Southern analysis. Here we report the presence of HTLV pol and/or tax proviral sequences in 46 out of 50 (92%) of the patients tested. In addition, five of the patients, who lacked antibodies to HTLV-I/II structural proteins, were found to be seropositive for tax. It thus seems reasonable to conclude that MF/Sézary syndrome is an HTLV-associated disease and that lack of an immune response does not preclude infection with this type of virus.
Abstract 258: Growth factor signaling is critical in the maintenance of cancer stem cell population in head and neck squamous cell cancer.
Authors: Hui Sun Leong, Pui Hoon Sew, Fui Teen Chong, Daniel Shao-Weng Tan, Narayanan Gopalakrishna Iyer
Journal: Cancer Research (2013)

Abstract Tumor heterogeneity is an important concept in the carcinogenesis of solid tumors, and forms the background for the cancer-stem cell (CSCs) hypothesis. Emerging data suggests however that there is plasticity within various cancer sub-populations, and that CSCs exists in a contextually regulated equilibrium, which is multi-directional and less rigid than previously hypothesized. The aim of this study was to establish an in vitro system that recapitulates stem cell plasticity in head and neck squamous cell cancers (HNSCC), and identify factors that play a role in the maintenance and re-population of CSCs. Tumor spheres were established using patient-derived tumor cells via anchorage-independent cell culture techniques. RT-PCR showed higher expression of KLF4, SOX2 and Nanog in tumor spheres compared to monolayer culture cells. Cells grown as tumor spheres were more resistant to γ-radiation, 5-fluorouracil, cisplatin and etoposide treatment compared to cells grown in monolayer culture. Using the ALDEFLUOR assays to identify CSCs, we showed that more cells in tumor spheres had high aldehyde dehydrogenase (ALD+ cells) activity. Monolayer cultures were subject to single cell cloning to generate clones with high and low ALD+ fractions. As expected, ALDHigh clones showed higher expression of stem cell markers Oct4, Bmi1 and Nanog and EMT markers N-Cadherin, Slug, Snail, β-Catenin, Vimentin compared to ALDLow clones. When ALDHigh clones from HNSCC cells were cultured over time, ALD+ fractions were found to reduce gradually and equilibrate at a specified ALD+ fraction specific to each cell line grown in regular culture media. When growth factors EGF and/or insulin were added to the media, ALD+ fractions could be maintained at higher levels as compared to baseline. ALDHigh clones also showed increased EGFR and IGF-1R phosphorylation when grown in regular culture conditions, with increased activation of downstream factors involving the AKT and ERK pathways compared with ALDLow clones. Blocking these pathways using specific inhibitors against EGFR and IGFR reduced stem cell fractions drastically. Taken together, these results show that HNSCC CSCs exhibit plasticity, where the maintenance of the stem cell fraction was dependent on the EGF and IGF pathways, which are therefore vulnerable to therapeutic targeting. Citation Format: Hui Sun Leong, Pui Hoon Sew, Fui Teen Chong, Daniel Shao-Weng Tan, Narayanan Gopalakrishna Iyer. Growth factor signaling is critical in the maintenance of cancer stem cell population in head and neck squamous cell cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 258. doi:10.1158/1538-7445.AM2013-258
Is the human testis still an organ at risk?
Authors: S. Irvine
Journal: BMJ (1996)

withdraw completely from the feeding bottle market in India by November 1996 (Johnson and Johnson, personal communi- cation).Important questions must now be faced: who will fund research and conferences; who will provide health workers with information; and who will monitor the marketing practices of industry?Professional and voluntary bodies that believe in complete independence from the baby food industry, even if it means acute shortage of resources, must either raise money from their own members or through publications.Governments, international organisations, and non- governmental organisations (including independent charitable trusts and other appropriate sources that do not create conflict of interest) will need to step into the breach.In India, the Indian Council of Medical Research, the Department of Science and Technology, the Ministry of Health, and the Department ofWomen and Child Development, several chari- table trusts, and Unicef have been meeting such needs.Organisations such as the British Paediatric Association, which have apparently yet to realise that the interests ofmanu- facturers may conflict with those ofbreast feeding mothers and their children, should be guided by three thinkers who well understood human nature.In his book Raja-Yoga, SwamiVivekananda remarked that when one man receives a gift from another, he loses his independence."Milton Friedman said, "There's no such thing as a free lunch."And Aesop wrote, "Better starve free than be a fat slave."
Myths in medicine
Authors: C B. Perry, I. Bailey
Journal: BMJ (1995)

Data collection should be integrated with patient care EDITOR,-The editorial on making routine data adequate to support clinical audit mentions the high quality of data from the St Mary's maternity information system,' citing two recent papers on its validity.23The editorial's authors, however, have missed the point about why this particular system has proved so successful.The basis of the system is that midwives enter the data themselves and then in turn use the system for practical purposes directly associated with patients' care- for example, it generates summaries and discharge letters.The system is thus integrally associated with patients' care and is not a separate task.This experience strongly suggests that abandon- ing the normal practice of relegating the input of data to clerical staff results in better quality of data.This is both because the motivation of health care professionals is higher and, crucially, because of the reinforcing feedback loop involving the use of the information for patients' care.The Department of Health has introduced an information management and technology strategy for the NHS in England, which has many positive features.4Its potential Achilles' heel, however, is precisely this question of the quality of the data.Although it includes a data quality initiative, this is concerned mainly with administrative data (the postcode and codes for the provider, health authority, and general practitioner), the only clinical element being the code for the diagnosis.5We suggest that a great deal could be learnt from the strengths and weaknesses of existing systems, especially successful ones like St Mary's maternity information system, and could then be used in the development of the future information technology for health care.
CD28 Down-Regulation on CD4 T Cells Is a Marker for Graft Dysfunction in Lung Transplant Recipients
Authors: Sean M. Studer, M. Patricia George, Xuehai Zhu, Yifang Song, Vincent G. Valentine, Michael W. Stoner, Jigme Sethi, Chad Steele, Steven R. Duncan
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Repeated antigen-driven proliferations cause CD28 on T cells to down-regulate. We hypothesized that alloantigen-induced proliferations could cause CD28 down-regulation in lung transplant recipients.To ascertain if CD28 down-regulation on CD4 T cells associated with manifestations of allograft dysfunction in lung transplant recipients.Peripheral blood CD4 T cells from 65 recipients were analyzed by flow cytometry, cytokine multiplex and proliferative assays, and correlated with clinical events.Findings that CD28 was present on less than 90% of total CD4 T cells were predominantly seen among the recipients with bronchiolitis obliterans syndrome (specificity = 88%). Perforin and granzyme B were produced by >50% of the CD4(+)CD28(null) cells, but less than 6% of autologous CD4(+)CD28(+) cells (P < 0.006). CD4(+)CD28(null) cells also had increased productions of proinflammatory cytokines, but less frequently expressed regulatory T-cell marker FoxP3 (2.1 +/- 1.3%), compared with autologous CD4(+)CD28(+) (9.5 +/- 1.4; P = 0.01). Cyclosporine A (100 ng/ml) inhibited proliferation of CD4(+)CD28(null) cells by 33 +/- 11% versus 68 +/- 12% inhibition of CD4(+)CD28(+) (P = 0.025). FEV(1) fell 6 months later (0.35 +/- 0.04 L) in recipients with CD4(+)CD28(+)/CD4(total) less than 90% (CD28% Low) compared with 0.08 +/- 0.08 L among CD4(+)CD28(+)/CD4(total) (CD28% High) greater than 90% (CD28% High) recipients (P = 0.013). Two-year freedom from death or retransplantation in CD28% Low recipients was 32 +/- 10% versus 78 +/- 6% among the CD28% High subjects (P < 0.0001).CD28 down-regulation on CD4 cells is associated with bronchiolitis obliterans syndrome and poor outcomes in lung transplantation recipients. CD4(+)CD28(null) cells have unusual, potentially pathogenic characteristics, and could be important in the progression of allograft dysfunction. These findings may illuminate a novel paradigm of transplantation immunopathogenesis, and suggest that CD28 measurements could identify recipients at risk for clinical deteriorations.
Scientists develop vaccine strategy for peanut allergy
Authors: S. Gottlieb
Journal: BMJ (1999)

Researchers believe that they may be close to developing a new strategy to combat anaphylactic allergies-such as the increasingly common allergy to peanuts-in which doctors induce tolerance using an oral formulation containing a gene from the offending allergen.

Many established allergies have been traditionally treated by immunotherapy, in which subcutaneous injections of progressively increasing doses of purified allergen are given; a strategy that is effective only in some circumstances. Dr Kam Leong, professor of biomedical engineering at …
German randomized double-blind multicentre comparison of terbinafine and itraconazole for the treatment of toenail tinea infection
Authors: M. BRÁUTIGAM, S. NOLTTNG, R.E. SCHOPF
Journal: British Journal of Dermatology (1996)

One–hundred and ninety–five patients with toenail tinea unguium were recruited to a multicentre double–blind clinical trial. Patients were given 250mg terbinafine or 200 mg itraconazole daily for 12 weeks, with follow–up for a further 40 weeks. At the end of the study, mycological cure rates were 81% (70/86 assessed) for terbinafine and 63% (53/84 assessed) for itraconazole (two–tailed, P < 0·05). The length of unaffected nail was 9·44 mm in the terbinafine group and 7·85 mm in the itraconazole group (two–tailed, P < 0·05). Patient self–assessment also favoured terbinafine, with 65% evaluating it as good to very good, compared with 58% for itraconazole. Before treatment the terbinafine group had a mean of 6·7 and the itraconazole group 6·3 affected nails per patient. Total cure was achieved in 69% of terbinafine and 61% of itraconazole affected nails. We conclude that terbinafine is more effective than itraconazole In the treatment of toenail tinea infection.
Innate and Adaptive Immunity Interact to Quench Microbiome Flagellar Motility in the Gut
Authors: Tyler C. Cullender, Benoit Chassaing, Anders Janzon, Krithika Kumar, Catherine E. Muller, Jeffrey J. Werner, Largus T. Angenent, M. Elizabeth Bell, Anthony G. Hay, Daniel A. Peterson, Jens Walter, Matam Vijay-Kumar, Andrew T. Gewirtz, Ruth E. Ley
Journal: Cell Host & Microbe (2013)
Abstract 4377: Pulmonary inflammation and lung tumorigenesis in mice
Authors: Phouthone Keohavong, Beth Kahkonen, Edwina Kinchington, Jinling Yin, Jide Jin, Jill M. Siegfried, Peter Di
Journal: Cancer Research (2010)

Abstract Chronic inflammation has been suggested to be associated with an increased risk of human cancer, including lung cancer, the leading cause of cancer death in the United States. However, the mechanisms of lung tumorigenesis associated with chronic lung inflammation still remain poorly understood. The purpose of this study is to get insight into the molecular mechanisms by which bacterial endotoxin-elicited chronic lung inflammation increases carcinogen-induced lung tumorigenesis. Groups of FBV/N mice were treated weekly for a 15-week period with lipopolysaccharide (LPS), a major pro-inflammatory glycolipid component of the gram-negative bacterial cell wall, with or without a co-treatment of 4-(methyl-nitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), a major component of tobacco smoke and a potent lung carcinogen, during the first four weeks. Analysis of bronchoalveolar lavage fluid (BALF) at one day, one week, and fifteen weeks after LPS-treatment showed a significant increase in pro-inflammatory responses, including both in numbers of macrophages and inflammatory mediators in the mice treated with LPS alone and in those treated with LPS+NNK, compared with the mice treated with NNK alone or those treated with vehicles. These data were confirmed by pathological analysis and the presence of inflammatory cells and lung tissue injury from the groups of mice treated LPS or LPS+NNK, compared with those treated with NNK or vehicles. At week 15, the averaged number of lung tumors per mouse was 5.56 (100% tumor incidence; tumor numbers between 2-9) in mice treated with LPS+NNK and was significantly higher than 0.79 tumor per mouse (67% tumor incidence; tumor numbers between 0-2) in the mice treated with NNK alone (p&amp;lt;0.0001). No lung tumors were observed in the mice treated with LPS or those treated with vehicles alone. Furthermore, a higher proportion of lung tumors from mice treated with LPS+NNK harbored mutations, an GGT to GAT transition, in codon 12 of the K-ras oncogene, compared with the mice treated with NNK alone (76.7% versus 44.4%, p&amp;lt;0.05). Our data show that LPS-elicited chronic lung inflammation increases the risk of NNK-induced lung tumorigenesis in FBV/N mice, and suggest that such an increase occurs mostly through K-ras gene activation pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4377.
Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia
Authors: Irene Cortés-Puch, Dong Wang, Junfeng Sun, Steven B. Solomon, Kenneth E. Remy, Melinda Fernandez, Jing Feng, Tamir Kanias, Landon Bellavia, Derek Sinchar, Andreas Perlegas, Michael A. Solomon, Walter E. Kelley, Mark A. Popovsky, Mark T. Gladwin, Daniel B. Kim-Shapiro, Harvey G. Klein, Charles Natanson
Journal: Blood (2013)