tbuckley/cabot-search huggingface dataset:
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Reverses Mesenchymal to Epithelial Phenotype and Inhibits Metastasis in Inflammatory Breast Cancer
Authors: Dongwei Zhang, Tiffany A. LaFortune, Savitri Krishnamurthy, Francisco J. Esteva, Massimo Cristofanilli, Ping Liu, Anthony Lucci, Balraj Singh, Mien-Chie Hung, Gabriel N. Hortobagyi, Naoto T. Ueno
Journal: Clinical Cancer Research (2009)

Inflammatory breast cancer (IBC) is a rare but aggressive type of advanced breast cancer. Epidermal growth factor receptor (EGFR) expression is an independent poor prognostic factor in IBC. The purpose of this study was to determine the effect on IBC tumorigenicity and metastasis of blocking the EGFR pathway.IBC cell lines, which express high level of EGFR, were treated with EGFR small interfering RNA and with the EGFR tyrosine kinase inhibitor erlotinib. The role of EGFR in IBC cell proliferation, motility, invasiveness, and change of the expression levels of epithelial-mesenchymal transition markers was examined. The role of extracellular signal-regulated kinase (ERK)-1/2 in erlotinib activity was also studied. The activity of erlotinib in tumor growth and metastasis was examined in an orthotopic xenograft model of IBC.Erlotinib inhibited proliferation and anchorage-independent growth of IBC cells, and this inhibition was ERK dependent. Erlotinib inhibited cell motility and invasiveness and reversed the mesenchymal phenotype of IBC cells to epithelial phenotype in three-dimensional culture. Erlotinib dramatically inhibited IBC tumor growth in a xenograft model. Interestingly, erlotinib inhibited spontaneous lung metastasis, even at a low dose that had no significant effect on primary tumor growth. These erlotinib-treated tumors were converted to epithelial phenotype from mesenchymal phenotype.The EGFR pathway is involved in tumor growth and metastasis of IBC. Targeting EGFR through the ERK pathway may represent an effective therapeutic approach to suppress tumorigenicity and prevent metastasis in EGFR-expressing IBC.
Inflammatory microcrystals differentially regulate the secretion of macrophage inflammatory protein 1 and interleukin 8 by human neutrophils: a possible mechanism of neutrophil recruitment to sites of inflammation in synovitis.
Authors: M Hachicha, P H Naccache, S R McColl
Journal: The Journal of Experimental Medicine (1995)

Human neutrophils at inflammatory sites may be an important source of the chemotactic cytokines macrophage inflammatory protein 1 alpha (M1P-1 alpha; a C-C chemokine) and interleukin 8 (IL-8; a C-X-C chemokine). In this study, we show that the inflammatory microcrystals monosodium urate monohydrate (MSU) and calcium pyrophosphate dihydrate (CPPD), the major mediators of gout and pseudogout, differentially regulate the production of these two chemokines by human neutrophils. Both MSU and CPPD increased the secretion of IL-8 by neutrophils in a dose- and time-dependent manner, but had no effect on that of MIP-1 alpha. Since inflammatory cytokines are likely to be present in the synovium during crystal-induced inflammation, we examined the interaction between TNF-alpha and GM-CSF and the crystals. Both TNF-alpha and GM-CSF stimulated IL-8 production; however, only TNF-alpha exerted a significant effect on MIP-1 alpha secretion in neutrophils. IL-8 production induced by TNF-alpha and GM-CSF was synergistically enhanced in the presence of MSU or CPPD, whereas MIP-1 alpha secretion induced by TNF was completely inhibited in the presence of either MSU or CPPD. Interestingly, no interaction between the crystals and the inflammatory cytokines was observed with respect to synthesis of the C-X-C chemokine MGSA in neutrophils. These results suggest that the combination of TNF-alpha and GM-CSF with MSU or CPPD will lead to the production of IL-8 by neutrophils and abolish the release of MIP-1 alpha, an event that will theoretically lead to recruitment of neutrophils but not mononuclear cells. These results are in accordance with the pathological state of gout and pseudogout, where the predominant inflammatory cell is the neutrophil.
Notes on Long Sea-Voyages for Chest-Disease
Authors: R. S. Smith
Journal: BMJ (1876)

TilE influence of climate in the treatment of chest-disease is a question of such world-wide interest, and on which such a diversity of opinion exists, that data from various sources are desirable, in order that general principles may be cstablished.Dr. Theodore Villiams, in his Lettso- mian Lectures, published in the early numbers of the BRITISH MEDICAL JOURNXAL for this year, has summed up the whole question, and has given statistics showing the results of treatment by climate in various parts of the world, and of treatment by long sea-voyages.Personal experience of this latter method induces me to contribute a few notes on some points which have occurred to me whilst perusing the above- mentioned lectures.
Regional Primary Care Team to Deliver Best-Practice Diabetes Care
Authors: Leonie Segal, Matthew J. Leach, Esther May, Catherine Turnbull
Journal: Diabetes Care (2013)

Best-practice diabetes care can reduce the burden of diabetes and associated health care costs. But this requires access to a multidisciplinary team with the right skill mix. We applied a needs-driven evidence-based health workforce model to describe the primary care team required to support best-practice diabetes care, paying particular attention to diverse clinic populations.
Pulmonary fibrosis: patterns and perpetrators
Authors: Paul W. Noble, Christina E. Barkauskas, Dianhua Jiang
Journal: Journal of Clinical Investigation (2012)

Pulmonary fibrosis occurs in a variety of clinical settings, constitutes a major cause of morbidity and mortality, and represents an enormous unmet medical need. However, the disease is heterogeneous, and the failure to accurately discern between forms of fibrosing lung diseases leads to inaccurate treatments. Pulmonary fibrosis occurring in the context of connective tissue diseases is often characterized by a distinct pattern of tissue pathology and may be amenable to immunosuppressive therapies. In contrast, idiopathic pulmonary fibrosis (IPF) is a progressive and lethal form of fibrosing lung disease that is recalcitrant to therapies that target the immune system. Although animal models of fibrosis imperfectly recapitulate IPF, they have yielded numerous targets for therapeutic intervention. Understanding the heterogeneity of these diseases and elucidating the final common pathways of fibrogenesis are critical for the development of efficacious therapies for severe fibrosing lung diseases.
Aldosterone Stimulates Proliferation of Mesangial Cells by Activating Mitogen-Activated Protein Kinase 1/2, Cyclin D1, and Cyclin A
Authors: Yoshio Terada, Takahiko Kobayashi, Hitoshi Kuwana, Hiroyuki Tanaka, Seiji Inoshita, Michio Kuwahara, Sei Sasaki
Journal: Journal of the American Society of Nephrology (2005)

Recently, attention has been focused on the role of aldosterone in the pathophysiology of hypertension and cardiovascular disease. Several clinical and experimental data support the hypothesis that aldosterone contributes to the progression of renal injury. However, the molecular mechanisms of the effects of aldosterone in signal transduction and the cell-cycle progression of mesangial cells are not well known. For determining the signaling pathway of aldosterone in cultured mesangial cells, the effects of aldosterone on the mitogen-activated protein kinase 1/2 (MAPK1/2) pathway and the promoter activities of cyclin D1, cyclin A, and cyclin E were investigated. First, it was shown that the mineralocorticoid receptor (MR) was expressed in rat mesangial cells and glomeruli and that aldosterone stimulated the proliferation of mesangial cells via the MR and MAPK1/2 pathway. Next, it was demonstrated that aldosterone stimulated Ki-RasA, c-Raf kinase, MEK1/2, and MAPK1/2 in rat mesangial cells. Aldosterone induced cyclin D1 and cyclin A promoter activities and protein expressions, as well as the increments of CDK2 and CDK4 kinase activities. The presence of CYP11B2 and 11beta-HSD2 mRNA in rat mesangial cells also was shown. In conclusion, aldosterone seems to exert mainly MR-induced effects that stimulate c-Raf, MEK1/2, MAPK1/2, the activities of CDK2 and CDK4, and the cell-cycle progression in mesangial cells. MR antagonists may serve as a potential therapeutic approach to mesangial proliferative disease.
All change for home oxygen services in England and Wales
Authors: J A Wedzicha
Journal: Thorax (2005)

Changes to the home oxygen service effective from February 2006

Although it was clearly rational to increase the arterial oxygen tension of patients with chronic hypoxaemia, it was not until the publication of two key randomised controlled trials on the effects of long term oxygen therapy (LTOT) in the early 1980s1,2 that home oxygen services were developed in many countries where they now form an integral part of the management of chronic respiratory disability. Although these trials addressed the role of oxygen in prolonging life for patients with COPD, three main forms of home oxygen services have developed with rather different goals:



1.  LTOT is prescribed for patients with chronic hypoxaemia (Pao2 ⩽7.3 kPa (55 mm Hg)) for continuous use at home and is one of the few interventions to date that has been shown to reduce mortality in patients with COPD.

2.  Ambulatory oxygen therapy refers to the provision of oxygen therapy with a portable device during exercise and daily activities.

3.  Short burst oxygen therapy refers to the intermittent use of oxygen at home, usually provided by stationary cylinders for periods of 10–20 minutes at a time to relieve the symptom of breathlessness. Although short burst oxygen is widely prescribed in the UK for relief of breathlessness, there is little evidence currently available for its benefit3,4 and delivery of cylinders to the home is costly.



In the UK, provision of LTOT through the prescription of home oxygen concentrators became available in November 1985 and since then concentrators have been installed and maintained by contractors.5 Although in Scotland LTOT can be prescribed in secondary care, in England and Wales oxygen concentrators can only be prescribed by primary care physicians. However, this prescription usually takes place on the recommendation of secondary care physicians and concentrators are …
Failure to monitor independent centres prevents comparison, says watchdog
Authors: Michael Day
Journal: BMJ (2007)

A “cock-up” by the UK government has impeded the ability of the Healthcare Commission to assess independent sector treatment centres (ISTCs), says the watchdog's chief executive, Anna Walker.

She says that a government oversight has impeded the commission's ability to assess the safety and quality of the centres.

The commission declared this week that the Department of Health had failed to ensure that the data collected on the controversial clinics were compatible with the data used to monitor the rest of the NHS.

The commission had aimed to review the first 23 centres, which were set up to carry out high volumes of straightforward elective surgery to cut NHS waiting lists. The commission interviewed 2000 …
Combination of pegylated interferon and lamivudine is superior to lamivudine monotherapy in the treatment of chronic hepatitis B — a randomized trial
Authors: J.J.Y. Sung, H.L.Y. Chan, A.Y. Hui, F.K.L. Chan, A.M.L. Chim, M.L. Wong, N.W.Y. Leung
Journal: Journal of Hepatology (2003)
BORDERLANDS OF PETIT MAL
Authors: MAURICE H. CHARLTON
Journal: American Journal of Psychiatry (1965)

Petit mal is an apparently autonomous clinical entity which in fact has subtle and complex relations to other forms of epilepsy, in particular grand mal and psychomotor attacks. The EEG is of value in elucidating these relationships in rare but interesting presentations of petit mal. There are several psychiatric aspects to the full understanding of petit mal: prolonged 3/second spike and wave discharges may lead to a confusional state known as "petit mal status epilepticus." There are relationships, as yet not fully elucidated, between discharges of petit mal and depression of intellectual function. Petit mal may be self-induced in retarded or disturbed patients. Aberrant EEG aspects of the disease are discussed and avenues now open for future research.
Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model
Authors: Marion A. Hofmann, Evanthia Lalla, Yan Lu, Michelle Ryu Gleason, Bonnie M. Wolf, Nozomu Tanji, Luis J. Ferran, Brigitte Kohl, Vijay Rao, Walter Kisiel, David M. Stern, Ann Marie Schmidt
Journal: Journal of Clinical Investigation (2001)

Although hyperhomocysteinemia (HHcy) is a well-known risk factor for the development of cardiovascular disease, the underlying molecular mechanisms are not fully elucidated. Here we show that induction of HHcy in apoE-null mice by a diet enriched in methionine but depleted in folate and vitamins B6 and B12 increased atherosclerotic lesion area and complexity, and enhanced expression of receptor for advanced glycation end products (RAGE), VCAM-1, tissue factor, and MMP-9 in the vasculature. These homocysteine-mediated (HC-mediated) effects were significantly suppressed, in parallel with decreased levels of plasma HC, upon dietary supplementation with folate and vitamins B6/B12. These findings implicate HHcy in atherosclerotic plaque progression and stability, and they suggest that dietary enrichment in vitamins essential for the metabolism of HC may impart protective effects in the vasculature.
Steroid-Sparing Effect of Corticorelin Acetate in Peritumoral Cerebral Edema Is Associated With Improvement in Steroid-Induced Myopathy
Authors: Lawrence Recht, Laszlo L. Mechtler, Eric T. Wong, Patrick C. O'Connor, Bruce E. Rodda
Journal: Journal of Clinical Oncology (2013)

To compare the safety and efficacy of corticorelin acetate (CrA) and placebo in patients with malignant brain tumors requiring chronic administration of dexamethasone (DEX) to control the signs and symptoms of peritumoral brain edema (PBE).Prospective, randomized, double-blind study of 200 patients with PBE on a stable dose of DEX. Initially, DEX dose was decreased by 50% over a 2-week period and then held at this level for 3 weeks. The primary end point was the proportion of patients who responded to treatment-patients who achieved a ≥ 50% DEX reduction from baseline and achieved stable or improved neurologic examination score and Karnofsky performance score at week 2, and then continued to respond at week 5.One hundred patients received subcutaneous injections of 1 mg twice per day of CrA and 100 patients received placebo for the duration of the study period. Although results did not attain statistical significance (at the P < .05 level), a clinically important difference in the proportion of responders between the CrA group (57.0%) and the placebo group (46.0%; P = .12) was observed. In addition, the maximum percent reduction in DEX dose achieved during the double-blind 12-week study was significantly greater in the CrA group (62.7%) than in placebo group (51.4%; P < .001). Patients receiving CrA demonstrated an improvement in myopathy and were less likely to develop signs of Cushing syndrome.CrA enables a reduction in steroid requirement for patients with PBE and is associated with a reduction in the incidence and severity of common steroid adverse effects, including myopathy.
Treatment of LADA With Etanercept
Authors: Vince N. Montes, Irl B. Hirsch
Journal: Diabetes Care (2012)

Latent autoimmune diabetes of adults (LADA) is a subset of type 1 diabetes. The disease accounts for ∼2–12% of all cases of diabetes (1). The pathogenesis of the disease involves autoimmune destruction of the β-cells of the pancreatic islet that produce insulin. There is a cell-mediated effect, via islet-reactive T cells (2), and a humoral immune response via autoantibodies (3). Studies have indicated that the GAD and islet cell antibodies are the most common in patients with LADA (4). Despite the priority of hyperglycemia, treating the underlying pathogenesis should be considered. Some of these efforts may include interfering with the cytokines that are implicated in the inflammatory process, which include tumor necrosis factor-α and interleukin-1β, among others. A tumor necrosis factor-α blocker, …
Osteoprotegerin Levels in Women With Prior Gestational Diabetes Mellitus
Authors: Eszter Madarász, Gyula Tamás, Ádám Gy. Tabák, Gábor Speer, Péter Lakatos, Zsuzsa Kerényi
Journal: Diabetes Care (2008)

Osteoprotegerin (OPG), an inhibitor of bone resorption, seems to be elevated in patients with diabetes as well as in nondiabetic subjects with cardiovascular disease (1).

Following a pregnancy complicated by gestational diabetes mellitus (GDM), women present with an increased prevalence of glucose intolerance and an unfavorable cardiovascular risk profile, although definite cardiovascular diseases or late diabetes complications have only rarely been confirmed (2).

Hence, our aim was to study OPG levels and their association with other cardiovascular risk factors in a sample of 30 former GDM (by World Health Organization criteria) and 14 age-matched women with normal glucose tolerance during pregnancy in an average 4 years after delivery. During the study investigation an assisted questionnaire was completed, followed by a detailed physical examination, …
Sports injuries and illnesses during the second Asian Beach Games
Authors: Sultan Al-Shaqsi, Ammar Al-Kashmiri, Ahmed Al-Risi, Suleiman Al-Mawali
Journal: British Journal of Sports Medicine (2012)

Background Prevention of sport injuries and illnesses is a focus for epidemiological surveillance. Objectives To record and analyse all sports injuries and illnesses registered during the second Asian Beach Games. Design A descriptive epidemiological study using the International Olympic Committee Surveillance system to register injuries and illnesses during the second Asian Beach Games. Methods The second Asian Beach Games hosted 1132 athletes from 43 countries competing in 14 beach sports. All National Olympic Committees' physicians of the participating teams were invited to report all injuries and illnesses. In addition, medical officers at the different Olympic venues and the main Olympic village reported injuries and illnesses treated at the clinics on a daily basis. Results A total of 177 injuries were reported equating to an incidence rate of 156.4 per 1000 registered athletes. Tent pegging recorded the highest incidence of injuries with 357 per 1000 registered athletes. The most prevalent injuries were in the foot/toe with 14.1% of all reported injuries. The majority of injuries were incurred during competition (75.4%). In addition, the most common mechanism of injury was contact with another athlete (n=42, 23.7%) and combined sudden and gradual overuse contributed to 30% of the total injury burden. Furthermore, 118 illnesses were reported resulting in an incidence rate of 104.2 illnesses per 1000 registered athletes. The most affected system was the respiratory tract (39.1%) with infection being the most common cause (n=33, 38.0%). The incidence of injury and illness differed significantly among the 14 sports. Conclusion The data indicate that the risk of injury from beach games is sport dependant. This means that any preventive measures have to be tailored for each discipline. Furthermore, the study showed that respiratory infections are the commonest illness in beach sports and therefore, event organisers should focus improving public health measures and hygiene awareness.
Mycobacterium Avium Complex (MAC) Infection In 2 Siblings with Autosomal Recessive Interferon Gamma (INFγ) Receptor Deficiency (I87T)
Authors: C. Cotronei-Cascardo, E. Secord, S. Ebbinghaus, S. Patel, S. Holland
Journal: Journal of Allergy and Clinical Immunology (2006)
Interstitial Flow and Its Effects in Soft Tissues
Authors: Melody A. Swartz, Mark E. Fleury
Journal: Annual Review of Biomedical Engineering (2007)

Interstitial flow plays important roles in the morphogenesis, function, and pathogenesis of tissues. To investigate these roles and exploit them for tissue engineering or to overcome barriers to drug delivery, a comprehensive consideration of the interstitial space and how it controls and affects such processes is critical. Here we attempt to review the many physical and mathematical correlations that describe fluid and mass transport in the tissue interstitium; the factors that control and affect them; and the importance of interstitial transport on cell biology, tissue morphogenesis, and tissue engineering. Finally, we end with some discussion of interstitial transport issues in drug delivery, cell mechanobiology, and cell homing toward draining lymphatics.
RASSF1A promoter methylation and expression analysis in normal and neoplastic kidney indicates a role in early tumorigenesis
Authors: Inga Peters, Kristina Rehmet, Nadine Wilke, Markus A Kuczyk, Jörg Hennenlotter, Tyark Eilers, Stefan Machtens, Udo Jonas, Jürgen Serth
Journal: Molecular Cancer (2007)

Epigenetic silencing of the RAS association domain family 1A (RASSF1A) tumor suppressor gene promoter has been demonstrated in renal cell carcinoma (RCC) as a result of promoter hypermethylation. Contradictory results have been reported for RASSF1A methylation in normal kidney, thus it is not clear whether a significant difference between RASSF1A methylation in normal and tumor cells of the kidney exists. Moreover, RASSF1A expression has not been characterized in tumors or normal tissue as yet.Using combined bisulfite restriction analysis (COBRA) we compared RASSF1A methylation in 90 paired tissue samples obtained from primary kidney tumors and corresponding normal tissue. Bisulfite sequence analysis was carried out using both pooled amplicons from the tumor and normal tissue groups and subclones obtained from a single tissue pair. Expression of RASSF1A was analyzed by the use of tissue arrays and immunohistochemistry. We found significantly increased methylation in tumor samples (mean methylation, 20%) compared to corresponding normal tissues (mean methylation, 11%; P < 0.001). Densely methylated sequences were found both in pooled and individual sequences of normal tissue. Immunohistochemical analysis revealed a significant reduced expression of RASSF1A in most of the tumor samples. Heterogeneous expression patterns of RASSF1A were detected in a subgroup of histologically normal tubular epithelia.Our methylation and expression data support the hypothesis that RASSF1A is involved in early tumorigenesis of renal cell carcinoma.