tbuckley/cabot-search huggingface dataset:
P component in the synovium in rheumatoid and osteoarthritis.
Authors: M G Butler, A J D'Ardenne, D L Scott
Journal: Annals of the Rheumatic Diseases (1988)

P component is present in amyloid deposits, normal serum, and normal tissues in relation to elastic fibres. Its pathological role in inflammatory synovitis was investigated. Its distribution was determined immunohistologically in 33 synovia: 15 rheumatoid; seven osteoarthritic; seven traumatic controls; and four infected biopsy specimens. P component was present in two circumscribed distributions: extracellular fibrils in dense fibroelastic tissue of the more fibrotic synovia; and in the arterial wall, where it was confined to a single elastic lamina in some cases and in others showed reduplication and fragmentation. These were not related to amyloid material. It shows no disease specificity, but P component categorises the nature of the pathological reaction and is typically in biopsy specimens showing the development of chronic fibrosis. There was close codistribution of P component with elastic tissue, though this was not absolute. P component had a different distribution from C reactive protein (in synovial lining cell layer), and fibronectin, which was absent from fibrotic areas. Understanding the pathological interactions of P component may help elucidate why some synovial reactions remain inflammatory and other progress to chronic fibrosis.
EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer
Authors: J.V. Heymach, S.J. Lockwood, R.S. Herbst, B.E. Johnson, A.J. Ryan
Journal: Annals of Oncology (2014)

ZODIAC was a randomized phase III study of second-line treatment in patients with advanced non-small cell lung cancer (NSCLC) that evaluated the addition of vandetanib to docetaxel. The study showed a statistically significant improvement in progression-free survival and objective response rate, but not in overall survival for unselected patients. This study evaluated epidermal growth factor receptor (EGFR) gene mutation, copy number gain, and protein expression, and KRAS gene mutation, in pretreatment tumor samples as potential biomarkers predicting benefit from vandetanib as second-line treatment of NSCLC.After progression following first-line chemotherapy, 1391 patients with locally advanced or metastatic (stage IIIB/IV) NSCLC were randomized 1 : 1 to receive vandetanib (100 mg/day) plus docetaxel (75 mg/m(2) every 21 days) or placebo plus docetaxel in the ZODIAC study. Archival tumor samples (n = 570) were collected from consenting patients (n = 958) for predefined, prospective biomarker analyses.Of evaluable samples, 14% were EGFR mutation positive, 35% were EGFR FISH positive, 88% were EGFR protein expression positive, and 13% were KRAS mutation positive. Compared with the overall study population, in which progression-free survival (PFS) [hazard ratio (HR) = 0.79] but not OS (HR = 0.91) were significantly improved with vandetanib, there was greater relative clinical benefit for patients with EGFR mutation-positive tumors [PFS HR 0.51, confidence interval (CI) 0.25-1.06 and OS HR 0.46, CI 0.14-1.57] and EGFR FISH-positive tumors (PFS HR 0.61, CI 0.39-0.94 and OS HR 0.48, CI 0.28-0.84). Similarly, patients with EGFR mutation or FISH-positive tumor samples who received vandetanib had an increased chance of objective tumor response (odds ratios 3.34, CI 0.8-13.89, and 3.90, CI 1.02-14.82, respectively). There did not appear to be benefit for vandetanib in patients with KRAS mutation-positive tumors.High EGFR gene copy number or activating EGFR mutations may identify patient subgroups who receive increased clinical benefit from vandetanib in combination with docetaxel in second-line NSCLC.NCT00312377.
Breast cancer risk following radiotherapy for Hodgkin lymphoma: modification by other risk factors
Authors: Deirdre A. Hill, Ethel Gilbert, Graça M. Dores, Mary Gospodarowicz, Flora E. van Leeuwen, Eric Holowaty, Bengt Glimelius, Michael Andersson, Tom Wiklund, Charles F. Lynch, Mars van't Veer, Hans Storm, Eero Pukkala, Marilyn Stovall, Rochelle E. Curtis, James M. Allan, John D. Boice, Lois B. Travis
Journal: Blood (2005)
Transplantation of melanocytes in vitiligo
Authors: M.J. OLSSON, L. JUHLIN
Journal: British Journal of Dermatology (2006)

We report the results of a study on 100 patients (aged 12-68) with vitiligo, who were treated by transplantation of cultured autologous melanocytes to the depigmented areas, after removal of the epidermis at the recipient site by dermabrasion. The melanocytes were cultured from a 2 x 3 cm2 superficial shave biopsy taken from pigmented buttock skin. After 2-3 weeks in culture, 700-1000 cells per mm2 were applied on 60-500 cm2 dermabraded areas, and occluded for 1 week. The repigmented portion of the total treated area amounted to 95-100% in 40 patients, 65-94% in 32, 20-64% in 22, and 0-19% in six. It was more difficult to achieve complete pigmentation on the fingers, elbows and knees. In the first few months following the procedure, the treated areas were often hypo- or hyperpigmented, but after 6-8 months they had acquired the same colour as the surrounding skin. No scarring or other side-effects occurred. The donor site had repigmented after 3-6 months in all but two patients, who also showed poor pigmentation in the transplanted areas. At follow-up after 1 and 2 years in 50 and 10 patients, respectively, the repigmented areas remained unchanged. The method is time-consuming, but the results obtained indicate that the procedure can be valuable in motivated patients, when the extent of vitiligo does not exceed 30% of the total body area, and when the areas to be treated are not actively extending.
Predictive Value of Hormone Measurements in Maternal and Fetal Complications of Pregnancy
Authors: Fernando M. Reis, Donato D’Antona, Felice Petraglia
Journal: Endocrine Reviews (2002)

Intrauterine tissues (placenta, amnion, chorion, decidua) express hormones and cytokines that play a decisive role in maternal-fetal physiological interactions. The excessive or deficient release of some placental hormones in association with gestational diseases may reflect an abnormal differentiation of the placenta, an impaired fetal metabolism, or an adaptive response of the feto-placental unit to adverse conditions. This review is focused on the applicability of hormone measurements in the risk assessment, early diagnosis, and management of pregnancies complicated by Down's syndrome, fetal growth restriction, preeclampsia, preterm delivery, and diabetes mellitus. Combined hormonal tests or the combination of hormones and ultrasound may achieve reasonable sensitivity, but research continues to simplify the screening programs without sacrificing their accuracy. Only in a few instances is there sufficient evidence to firmly recommend the routine use of hormone tests to predict maternal and fetal complications, but the judicious use of selected tests may enhance the sensitivity of the risk assessment based solely on clinical and ultrasound examination.
The soluble form of the tumor suppressor Lrig1 potently inhibits in vivo glioma growth irrespective of EGF receptor status
Authors: Mikael Johansson, Anaïs Oudin, Katja Tiemann, Amandine Bernard, Anna Golebiewska, Olivier Keunen, Fred Fack, Daniel Stieber, Baofeng Wang, Håkan Hedman, Simone P. Niclou
Journal: Neuro-Oncology (2013)

Deregulated growth factor signaling is a major driving force in the initiation and progression of glioblastoma. The tumor suppressor and stem cell marker Lrig1 is a negative regulator of the epidermal growth factor receptor (EGFR) family. Here, we addressed the therapeutic potential of the soluble form of Lrig1 (sLrig1) in glioblastoma treatment and the mechanism of sLrig1-induced growth inhibition. With use of encapsulated cells, recombinant sLrig1 was locally delivered in orthotopic glioblastoma xenografts generated from freshly isolated patient tumors. Tumor growth and mouse survival were evaluated. The efficacy of sLrig1 and the affected downstream signaling was studied in vitro and in vivo in glioma cells displaying variable expression of wild-type and/or a constitutively active EGFR mutant (EGFRvIII). Continuous interstitial delivery of sLrig1 in genetically diverse patient-derived glioma xenografts led to strong tumor growth inhibition. Glioma cell proliferation in vitro and tumor growth in vivo were potently inhibited by sLrig1, irrespective of EGFR expression levels. Of importance, tumor growth was also suppressed in EGFRvIII-driven glioma. sLrig1 induced cell cycle arrest without changing total receptor level or phosphorylation. Affected downstream effectors included MAP kinase but not AKT signaling. Of importance, local delivery of sLrig1 into established tumors led to a 32% survival advantage in treated mice. To our knowledge, this is the first report demonstrating that sLrig1 is a potent inhibitor of glioblastoma growth in clinically relevant experimental glioma models and that this effect is largely independent of EGFR status. The potent anti-tumor effect of sLrig1, in combination with cell encapsulation technology for in situ delivery, holds promise for future treatment of glioblastoma.
* Age should not be a barrier to performing capsule endoscopy in the elderly with anaemia
Authors: R. Sidhu, I. Muhammad, M. E. McAlindon
Journal: Gut (2011)

<h3>Introduction</h3> Capsule endoscopy (CE) has developed an important role in the investigation of patients with obscure gastrointestinal bleeding (OGB). There is paucity in the published literature on the use of CE in OGB in the elderly. We conducted a study to investigate the utility of CE in the elderly with recurrent anaemia ± overt bleeding and impact on subsequent management compared to the younger cohort. <h3>Methods</h3> A retrospective review of consecutive patients that underwent CE over a seven year period (2002–2009) for OGB was conducted. Data was collected on demographics, CE findings and subsequent change in management for patients in group 1(≤70 years) and group 2 (&lt;70 years). <h3>Results</h3> 779 patients underwent CE for OGB in the time period. Thirty five percent of patients (n=272) were ≤70 years (group 1) with a median age of 76 years (range 70–92 years). The majority of patients in group 1 underwent CE for the indication of recurrent anaemia (n=200) while overt bleeding consisted of 27% (n=72). The diagnostic yield of CE in group 1 was 53%. There was no significant difference in the yield between those with anaemia or overt bleeding (52% versus 58%, p=0.3). The commonest diagnosis in the elderly was angioectasia in 34% of patients. The other findings included small bowel carcinoid tumours (n=2), Crohn9s disease (n=2), fresh bleeding in the small bowel (n=8) small bowel diverticulae (n=2), small bowel ulcers (n=18) and miscellaneous (n=8). In 8% of patients, pathology was found outside the small bowel. In 5 patients, pathology were found in the caecum which included caecal angiodysplasia (n=3), ulcers (n=1) and a colonic tumour (n=1) while pathology in the upper gastrointestinal tract consisted of 6%. Of these gastric antral vascular ectasia was seen in eight patients that had been misdiagnosed as gastritis. On logistic regression, factors which predicted a higher yield with CE included age (p=0.03), anticoagulation (p=0.045) and previous blood transfusions (p=0.04). Management was altered in 33% in the form of enteroscopy ± APC or polypectomy, repeating colonoscopy, surgery for resection of tumour or sewing of angiomata and treatment of peptic ulcer disease. In comparison to patients &lt; 70 years, the diagnostic yield was significantly higher in the elderly for both the indication of anaemia (51% vs 37%, p=0.003, OR 1.8, 95% CI 1.3 to 2.5) and OB (60% versus 40%, p=0.007, OR 2, CI 1.2 to 3.9). Management was also altered in a significant greater proportion of the elderly (p=0.002, OR 1.8, CI 1.3 to 2.5). <h3>Conclusion</h3> CE has a high diagnostic yield and positive impact on management in patients &gt; 70 years. Age should not be a barrier to performing CE in the elderly.
MARGINAL ZONE B CELLS
Authors: Shiv Pillai, Annaiah Cariappa, Stewart T. Moran
Journal: Annual Review of Immunology (2004)

Our views regarding the origins and functions of splenic marginal zone B cells have changed considerably over the past few years. Perspectives regarding the development and function of these cells vary considerably between investigators studying human and rodent immunology. Marginal zone B cells are now recognized to constitute a distinct naive B lymphoid lineage. Considerable progress has been made regarding the mechanisms involved in marginal zone B cell development in the mouse. Many of the molecular events that participate in the retention of this lineage of B cells in the marginal zone have been identified. Here, we discuss the functions of these cells in both innate and adaptive immunity. We also attempt to reconcile differing viewpoints regarding the generation and function of marginal zone B cells in rodents and primates.
Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell responses in rheumatoid arthritis and osteoarthritis
Authors: H de Jong, S E Berlo, P Hombrink, H G Otten, W van Eden, F P Lafeber, A H M Heurkens, J W J Bijlsma, T T Glant, B J Prakken
Journal: Annals of the Rheumatic Diseases (2009)

Objectives: To explore potential T-cell epitopes of the core protein of human cartilage proteoglycan aggrecan (PG) in patients with rheumatoid arthritis (RA) or osteoarthritis. Methods: Peptide-specific T-cell proliferation and cytokine/chemokine production in response to PG-specific peptides were measured in RA and osteoarthritis patients and in healthy controls. Results: Peptides representing amino acid regions 16–39 and 263–282 of PG were most frequently recognised by T cells in a subset of patients with RA or osteoarthritis. Peripheral blood mononuclear cells from these PG-reactive RA and osteoarthritis patients showed increased production of proinflammatory cytokines/chemokines in response to PG peptide stimulation. As PG p263–282 was found to show high sequence homology with Yersinia Yop protein, the corresponding bacterial (Yersinia) peptide was also tested. Remarkably, RA and osteoarthritis patients responding to the Yersinia peptide also responded to p263–282 of PG suggesting a possibility of molecular mimicry in these patients. Conclusions: These results indicate that PG-specific peptides, located in the G1 domain of PG, can induce (auto)antigenic T-cell responses in RA and osteoarthritis patients. These peptides might thus be involved in the immune pathogenesis and/or cartilage degradation in RA and osteoarthritis.
Diaphragm strength and cross-bridge properties during chronic growth hormone hypersecretion
Authors: Y. Lecarpentier, C. Coirault, B Riou, D Chemla, J.j Mercadier
Journal: European Respiratory Journal (1999)

The aim of the study was to determine diaphragm performance and cross-bridge properties in rats bearing a growth hormone (GH)-secreting tumour. The tumour was induced by subcutaneous injection of GH-hypersecreting cells (GC cells) into the flank. Eighteen weeks after GC cell injection, rats developed a GH-secreting tumour (45.4+/-5.1 g) and the GH plasma level reached 5,408+/-648 microg x L(-1) in GH rats versus 7.2+/-2.2 microg x L(-1) in control rats (p<0.001). Diaphragm mechanics and cross-bridge properties were studied by applying the equations of A. Huxley in isolated diaphragm strips (control rats: n=12; GH rats n=20). In comparison to control rats, the total tension and total number of cross-bridges x mm(-2) in GH rats were lower in both twitch and tetanus (p<0.001). A linear relationship was observed between total tension and total cross-bridge number (r=0.94; p<0.001). Conversely, the cross-bridge single force and peak mechanical efficiency did not differ between control and GH rats, in either twitch or tetanus modes. In conclusion, the diaphragm strength was significantly lower in rats bearing growth hormone secreting tumours, and this was essentially determined by the lower cross-bridge number x mm(-2) without change in cross-bridge single force.
A Small Interfering CD147-Targeting RNA Inhibited the Proliferation, Invasiveness, and Metastatic Activity of Malignant Melanoma
Authors: Xiang Chen, Jing Lin, Takuro Kanekura, Juan Su, Wei Lin, Hongfu Xie, Yixi Wu, Juan Li, Mingliang Chen, Jing Chang
Journal: Cancer Research (2006)

Abstract CD147 plays a critical role in the invasive and metastatic activity of malignant melanoma cells by stimulating the surrounding fibroblasts to express matrix metalloproteinases and vascular endothelial growth factor. We developed a system that blocks CD147 in the human malignant melanoma cell line, A375, using RNA interference. By transfecting melanoma cells with the small interfering RNA (siRNA) that targets human CD147, we were able to establish two stable clones in which CD147 expression was significantly down-regulated. This resulted in the decreased proliferation and invasion of A375 cells in vitro. CD147 siRNA also down-regulated the expression of vascular endothelial growth factor in these cells and reduced the migration of vascular endothelial cells. The reduction in the CD147 level suppressed the size of s.c. tumors and the microvessel density in an A375 s.c. nude mouse xenograft model. In addition, the in vivo metastatic potential of A375 cells transfected with CD147 siRNA was suppressed in a nude mouse model of pulmonary metastasis. (Cancer Res 2006; 66(23): 11323-30)
Defective Neutrophil Recruitment in Leukocyte Adhesion Deficiency Type I Disease Causes Local IL-17–Driven Inflammatory Bone Loss
Authors: Niki M. Moutsopoulos, Joanne Konkel, Mojgan Sarmadi, Mehmet A. Eskan, Teresa Wild, Nicolas Dutzan, Loreto Abusleme, Camille Zenobia, Kavita B. Hosur, Toshiharu Abe, Gulbu Uzel, WanJun Chen, Triantafyllos Chavakis, Steven M. Holland, George Hajishengallis
Journal: Science Translational Medicine (2014)

Inflammatory bone loss from periodontal infections in leukocyte adhesion deficiency disease can be reversed by treatment with antibodies to IL-17 or IL-23.
Complex Oncogenic Translocations with Gene Amplification Are Initiated by Specific DNA Breaks in Lymphocytes
Authors: Sarah M. Wright, Yong H. Woo, Travis L. Alley, Bobbi-Jo Shirley, Ellen C. Akeson, Kathy J. Snow, Sarah A. Maas, Rachel L. Elwell, Oded Foreman, Kevin D. Mills
Journal: Cancer Research (2009)

Chromosomal instability is a hallmark of many tumor types. Complex chromosomal rearrangements with associated gene amplification, known as complicons, characterize many hematologic and solid cancers. Whereas chromosomal aberrations, including complicons, are useful diagnostic and prognostic cancer markers, their molecular origins are not known. Although accumulating evidence has implicated DNA double-strand break repair in suppression of oncogenic genome instability, the genomic elements required for chromosome rearrangements, especially complex lesions, have not been elucidated. Using a mouse model of B-lineage lymphoma, characterized by complicon formation involving the immunoglobulin heavy chain (Igh) locus and the c-myc oncogene, we have now investigated the requirement for specific genomic segments as donors for complex rearrangements. We now show that specific DNA double-strand breaks, occurring within a narrow segment of Igh, are necessary to initiate complicon formation. By contrast, neither specific DNA breaks nor the powerful intronic enhancer Emu are required for complicon-independent oncogenesis. This study is the first to delineate mechanisms of complex versus simple instability and the first to identify specific chromosomal elements required for complex chromosomal aberrations. These findings will illuminate genomic cancer susceptibility and risk factors.
IFN-γ Production during Initial Infection Determines the Outcome of Reinfection with Respiratory Syncytial Virus
Authors: Young-Mok Lee, Nobuaki Miyahara, Katsuyuki Takeda, John Prpich, Anita Oh, Annette Balhorn, Anthony Joetham, Erwin W. Gelfand, Azzeddine Dakhama
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Severe respiratory syncytial virus (RSV) bronchiolitis has been associated with deficient IFN-γ production in humans, but the role of this cytokine in determining the outcome of reinfection is unknown.Objectives: To define the role of IFN-γ in the development of RSV-mediated airway hyperresponsiveness (AHR) and lung histopathology in mice.Methods: Wild-type (WT) and IFN-γ knockout mice were infected with RSV in the newborn or weaning stages and reinfected 5 weeks later. Airway responses were assessed on Day 6 after the primary or secondary infection.Measurements and Main Results: Both WT and IFN-γ knockout mice developed similar levels of AHR and airway inflammation after primary infection. After reinfection, IFN-γ knockout mice, but not WT mice, developed AHR, airway eosinophilia, and mucus hyperproduction. Intranasal administration of IFN-γ during primary infection but not during reinfection prevented the development of these altered airway responses on reinfection in IFN-γ knockout mice. Adoptive transfer of WT T cells into IFN-γ knockout mice before primary infection restored IFN-γ production in the lungs and prevented the development of altered airway responses on reinfection. Treatment of mice with IFN-γ during primary neonatal infection prevented the enhancement of AHR and the development of airway eosinophilia and mucus hyperproduction on reinfection.Conclusions: IFN-γ production during primary RSV infection is critical to the development of protection against AHR and lung histopathology on reinfection. Provision of IFN-γ during primary infection in infancy may be a potential therapeutic approach to alter the course of RSV-mediated long-term sequelae.
STATE SICKNESS AND INVALIDITY INSURANCE
Authors: H. Hick
Journal: BMJ (1911)

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Siglec-9 transduces apoptotic and nonapoptotic death signals into neutrophils depending on the proinflammatory cytokine environment
Authors: Stephan von Gunten, Shida Yousefi, Michael Seitz, Stephan M. Jakob, Thomas Schaffner, Reinhard Seger, Jukka Takala, Peter M. Villiger, Hans-Uwe Simon
Journal: Blood (2005)