tbuckley/cabot-search huggingface dataset:
Functionalization of a Collagen–Hydroxyapatite Scaffold with Osteostatin to Facilitate Enhanced Bone Regeneration
Authors: Elaine Quinlan, Emmet M. Thompson, Amos Matsiko, Fergal J. O'Brien, Adolfo López‐Noriega
Journal: Advanced Healthcare Materials (2015)

Defects within bones caused by trauma and other pathological complications may often require the use of a range of therapeutics to facilitate tissue regeneration. A number of approaches have been widely utilized for the delivery of such therapeutics via physical encapsulation or chemical immobilization suggesting significant promise in the healing of bone defects. The study focuses on the chemical immobilization of osteostatin, a pentapeptide of the parathyroid hormone (PTHrP107‐111), within a collagen–hydroxyapatite scaffold. The chemical attachment method via crosslinking supports as little as 4% release of the peptide from the scaffolds after 21 d whereas non‐crosslinking leads to 100% of the peptide being released by as early as 4 d. In vitro characterization demonstrates that this cross‐linking method of immobilization supports a pro‐osteogenic effect on osteoblasts. Most importantly, when implanted in a critical‐sized calvarial defect within a rat, these scaffolds promote significantly greater new bone volume and area compared to nonfunctionalized scaffolds (** p &lt; 0.01) and an empty defect control (*** p &lt; 0.001). Collectively, this study suggests that such an approach of chemical immobilization offers greater spatiotemporal control over growth factors and can significantly modulate tissue regeneration. Such a system may be adopted for a range of different proteins and thus offers the potential for the treatment of various complex pathologies that require localized mediation of drug delivery.
Isolated pulmonary amyloidosis: Case report and review of the literature
Authors: Marshall W. Pitz, Ian W. Gibson, James B. Johnston
Journal: American Journal of Hematology (2006)

The respiratory tract is rarely the site of localized tracheobronchial or nodular amyloid deposits. We present an unusual case of isolated nodular amyloidosis of the lung and review the current literature related to this disorder. Am. J. Hematol. 81:212–213, 2006. © 2006 Wiley-Liss, Inc.
Epstein-Barr Virus Infection of Human Natural Killer Cell Lines and Peripheral Blood Natural Killer Cells
Authors: Yasushi Isobe, Koichi Sugimoto, Lixin Yang, Kenji Tamayose, Motoki Egashira, Takako Kaneko, Kenzo Takada, Kazuo Oshimi
Journal: Cancer Research (2004)

Abstract Although considerable part of natural killer (NK) cell neoplasms possess EBV genome, there has been no direct evidence that EBV infects human NK cells in vitro. In this study, we demonstrated EBV entry into NK cells using a recombinant EBV, which contains enhanced green fluorescent protein (EGFP) gene in its genome (EGFP-EBV). After 48 h of exposure to EGFP-EBV, we detected EGFP signals in ∼30% of NK-92 and NKL cells and &amp;gt;40% of peripheral blood NK cells from three healthy volunteers. Reverse transcription-PCR analysis of various EBV-associated genes confirmed EBV infection. In situ hybridization for EBERs and BHLFs showed that latent and lytic infections coexisted at the early phase of EBV infection in two NK cell lines. Although BHLF-positive cells in the early lytic phase were round-shaped, EBER-positive cells in latent EBV infection tended to show a bizarre shape. Flow cytometric analysis of EGFP-EBV-exposed NK cell lines showed that most of EBV-infected cells entered early apoptosis after 72 h of EBV exposure, which explains the difficulties to establish EBV-carrying NK clones. Flow cytometry and reverse transcription-PCR analysis indicated that two NK cell lines may fuse with EBV using HLA class II after binding to the virus through a distinct molecule from CD21. We established two EBV-carrying NKL clones showing latency types I and II, both of which are recognized in EBV-associated NK cell neoplasms. Because EBV-infected NKL cells showed only type I latency during the early phase of infection, the temporal profile of latent gene expression is similar to that of T cells. We first report in vitro EBV infection of human NK cells and establishment of EBV-carrying NK clones, which should contribute to elucidate the role of EBV in the development of NK cell neoplasms.
Cardiovascular determinants of survival in cirrhosis
Authors: S. S Lee, H. Liu
Journal: Gut (2007)

Diastolic response as the strongest determinant of mortality after TIPS

    My heart,    Where either I must live or bear no life,    The fountain from which my current runs    Or dries up    William Shakespeare, Othello 

Cirrhosis is a fatal condition. Although mild cirrhosis can be associated with prolonged survival, most diseases that induce cirrhosis progress, at variable rates, to end-stage liver failure. Deaths from hepatic failure, variceal bleeding and infection are common in advanced cirrhosis, and even the rate of sudden unexplained death is increased compared with that in a normal population.1 Moreover, patients with cirrhosis are well known to be fragile, and do poorly after invasive or stressful procedures. It is logical and intuitive to assume that the sickest patients—that is, those with the most advanced degree of liver failure—will have the poorest outcome after challenges. Indeed, this is what virtually all studies on risk factors for morbidity and mortality in cirrhosis show.2 Mortality following a variceal bleed is strongly correlated with the degree of liver dysfunction as estimated by the Child–Pugh score, with death rates of 10–15% in class A, 20–30% in class B and 40–50% in class C patients. Similar correlations have been shown using the Model End-stage Liver Disease (MELD) score to estimate liver function. Cardiovascular surgery carries greater risks in those with advanced liver dysfunction than in those with mild liver dysfunction.3

In all these studies, the assumption was made that deaths were wholly or predominantly due to liver failure. Indeed, a recent exhaustive systematic review of the entire world literature to 2006, analysing 118 studies that examined risk factors predictive of death in patients with cirrhosis, found that liver function, as assessed by the Child–Pugh score or the MELD score, consistently emerged as the best predictor of mortality in the majority of …
Transcutaneous immunotherapy via laser‐generated micropores efficiently alleviates allergic asthma in <scp>P</scp>hl p 5–sensitized mice
Authors: D. Bach, R. Weiss, M. Hessenberger, S. Kitzmueller, E. E. Weinberger, W. D. Krautgartner, C. Hauser‐Kronberger, C. Boehler, J. Thalhamer, S. Scheiblhofer
Journal: Allergy (2012)

Abstract Background Specific immunotherapy via the subcutaneous or oral route is associated with local and, in some cases, systemic side effects and suffers from low patient compliance. Due to its unique immunological features, the skin represents a promising target tissue for effective and painless treatment of type I allergy. The current study was performed to compare the efficacy of transcutaneous immunotherapy via laser‐generated micropores to subcutaneous injection. Methods BALB /c mice were sensitized by intraperitoneal injection of recombinant grass pollen allergen P hl p 5 together with alum. Subsequently, lung inflammation was induced by repeated intranasal challenge. During the treatment phase, adjuvant‐free P hl p 5 was applied in solution to microporated skin or was subcutaneously injected. Lung function and cellular infiltration; P hl p 5–specific serum levels of I g G 1, I g G 2a, and I g E ; and cytokine levels in bronchoalveolar lavage fluids as well as in supernatants of splenocyte cultures were assessed. Results Both therapeutic approaches reduced airway hyperresponsiveness and leukocyte infiltration into the lungs. Whereas subcutaneous immunotherapy induced a systemic increase in T h2‐associated cytokine secretion, transcutaneous application revealed a general downregulation of T h1/ T h2/ T h17 responses. Successful therapy was associated with induction of I g G 2a and an increase in FOXP 3+ CD 4+ T cells. Conclusions Transcutaneous immunotherapy via laser microporation is equally efficient compared with conventional subcutaneous treatment but avoids therapy‐associated boosting of systemic T h2 immunity. Immunotherapy via laser‐microporated skin combines a painless application route with the high efficacy known from subcutaneous injections and therefore represents a promising alternative to established forms of immunotherapy.
Disruption of <i>Nrf2</i> enhances susceptibility to severe airway inflammation and asthma in mice
Authors: Tirumalai Rangasamy, Jia Guo, Wayne A. Mitzner, Jessica Roman, Anju Singh, Allison D. Fryer, Masayuki Yamamoto, Thomas W. Kensler, Rubin M. Tuder, Steve N. Georas, Shyam Biswal
Journal: The Journal of Experimental Medicine (2005)

Oxidative stress has been postulated to play an important role in the pathogenesis of asthma; although a defect in antioxidant responses has been speculated to exacerbate asthma severity, this has been difficult to demonstrate with certainty. Nuclear erythroid 2 p45-related factor 2 (Nrf2) is a redox-sensitive basic leucine zipper transcription factor that is involved in the transcriptional regulation of many antioxidant genes. We show that disruption of the Nrf2 gene leads to severe allergen-driven airway inflammation and hyperresponsiveness in mice. Enhanced asthmatic response as a result of ovalbumin sensitization and challenge in Nrf2-disrupted mice was associated with more pronounced mucus cell hyperplasia and infiltration of eosinophils into the lungs than seen in wild-type littermates. Nrf2 disruption resulted in an increased expression of the T helper type 2 cytokines interleukin (IL)-4 and IL-13 in bronchoalveolar lavage fluid and in splenocytes after allergen challenge. The enhanced severity of the asthmatic response from disruption of the Nrf2 pathway was a result of a lowered antioxidant status of the lungs caused by lower basal expression, as well as marked attenuation, of the transcriptional induction of multiple antioxidant genes. Our studies suggest that the responsiveness of Nrf2-directed antioxidant pathways may act as a major determinant of susceptibility to allergen-mediated asthma.
Establishment of Perineural Invasion Models and Analysis of Gene Expression Revealed an Invariant Chain (CD74) as a Possible Molecule Involved in Perineural Invasion in Pancreatic Cancer
Authors: Norimasa Koide, Taketo Yamada, Rie Shibata, Taisuke Mori, Mariko Fukuma, Ken Yamazaki, Koichi Aiura, Motohide Shimazu, Setsuo Hirohashi, Yuji Nimura, Michiie Sakamoto
Journal: Clinical Cancer Research (2006)

Perineural invasion causes frequent local recurrence even after resection and a poor prognosis for pancreatic cancer. We established perineural invasion models and analyzed the molecular mechanism of perineural invasion in pancreatic cancer.Seven pancreatic cancer cell lines with or without human peripheral nerves were s.c. implanted in nonobese diabetes/severe combined immunodeficient mice. We compared expression profiles among high and low perineural invasion cell lines by using an oligonucleotide microarray. We examined up-regulation of the invariant chain (CD74) in high perineural invasion cell lines in mRNA and protein levels and surgical cases immunohistochemically.Four of seven pancreatic cancer cell lines (CaPan1, CaPan2, CFPAC, and MPanc96) showed perineural invasion to s.c. transplanted human peripheral nerves. Moreover, CaPan1 and CaPan2 (high perineural invasion group) also resulted in a high frequency of perineural invasion to mouse s.c. peripheral nerves, whereas three pancreatic cancer cell lines HPAFII, AsPC1, and Panc1 (low perineural invasion group) did not show perineural invasion to either human or mouse nerves. We identified 37 up-regulated genes and 12 down-regulated genes in the high perineural invasion group compared with the low perineural invasion group. Among them, CD74 was up-regulated in the high perineural invasion group in mRNA and protein levels. Furthermore, immunohistochemical expression of CD74 in clinical cases revealed its significant overexpression in pancreatic cancer with perineural invasion (P < 0.008).This is the first report of perineural invasion models using human pancreatic cancer cell lines. In combination with gene expression profiling, it was indicated that CD74 could be a candidate molecule involved in perineural invasion. These models provide new approaches for study of perineural invasion in pancreatic cancer.
HALOPERIDOL IN THE PSYCHIATRIC DISORDERS OF OLD AGE
Authors: A. ARTHUR SUGERMAN, BENJAMIN H. WILLIAMS, ARTHUR M. ADLERSTEIN
Journal: American Journal of Psychiatry (1964)

The effects of haloperidol in the management of elderly patients with chronic brain syndrome with cerebral arteriosclerosis or senile brain disease were investigated in an initial open phase (6 patients) and a subsequent randomized double-blind placebo-controlled phase (18 patients). Haloperidol appears to be an effective compound in patients who are agitated, overactive and hostile. Side effects include sedation and extrapyramidal symptoms. The dose level should be considerably lower than that generally used in schizophrenic patients and should probably not exceed 4 mg. daily. Maintenance doses of about 1 mg. daily appear adequate in most cases. Hypotension was not a complication and no untoward effects on liver function or bone marrow were noted.
Design of Health Care Technologies for the Developing World
Authors: Robert A. Malkin
Journal: Annual Review of Biomedical Engineering (2007)

Approximately 20 years ago, the international community embarked on a project to bring health care to everyone by the year 2000 featuring, among other things, technologies that were known to be effective and economical. It was largely a failure. In fact, health care deteriorated in many of the target nations. Problems such as public mistrust, lack of spare parts, lack of required consumables, lack of reliable power and water, lack of public infrastructure such as roads, lack of technical expertise, and other problems plague health care technology in the developing world. Biomedical engineers are just beginning to quantify and address the barriers to technology unique to the developing world. This article reviews the barriers, both real and perceived, to the introduction of health care technology with a main focus on health care technology in hospitals.
Restoration of Tumor Immunosurveillance via Targeting of Interleukin-13 Receptor-α2
Authors: Stefan Fichtner-Feigl, Masaki Terabe, Atsushi Kitani, Cheryl A. Young, Ivan Fuss, Edward K. Geissler, Hans-Jürgen Schlitt, Jay A. Berzofsky, Warren Strober
Journal: Cancer Research (2008)

In previous studies, we described a "counter-immunosurveillance" mechanism initiated by tumor-activated, interleukin-13 (IL-13)-producing natural killer T cells that signal Gr-1(+) cells to produce transforming growth factor-beta(1) (TGF-beta(1)), a cytokine that suppresses the activity of tumor-inhibiting cytolytic CD8(+) T cells. Here, we show that in two tumor models (the CT-26 metastatic colon cancer and the 15-12RM fibrosarcoma regressor models), this counter-surveillance mechanism requires the expression of a novel IL-13 receptor, IL-13R alpha(2), on Gr-1(intermediate) cells, because down-regulation of IL-13R alpha(2) expression or the activator protein-1 signal generated by the receptor via in vivo administration of specific small interfering RNA or decoy oligonucleotides leads to loss of TGF-beta(1) production. Furthermore, acting on prior studies showing that IL-13R alpha(2) expression is induced (in part) by tumor necrosis factor-alpha (TNF-alpha), we show that receptor expression and TGF-beta(1) production is inhibited by administration of a TNF-alpha-neutralizing substance, TNF-alpha R-Fc (etanercept). Taking advantage of this latter fact, we then show in the CT-26 model that counter-immunosurveillance can be inhibited, anti-CT-26-specific CD8(+) cytolytic activity can be restored, and CT-26 metastatic tumor nodules can be greatly decreased by administration of TNF-alpha R-Fc. Corroborative data were obtained using the 15-12RM fibrosarcoma model. These studies point to the prevention of metastatic cancer with an available agent with already known clinically acceptable adverse effects and toxicity.
The strength of female sex as a prognostic factor in small-cell lung cancer: a pooled analysis of chemotherapy trials from the Manchester Lung Group and Medical Research Council Clinical Trials Unit
Authors: P. Wheatley-Price, C. Ma, L.F. Ashcroft, M. Nankivell, R.J. Stephens, S.C. White, P. Lorigan, N. Thatcher, F.H. Blackhall, F.A. Shepherd
Journal: Annals of Oncology (2009)
Depression, Disability Days, and Days Lost From Work in a Prospective Epidemiologic Survey
Authors: W. Eugene Broadhead
Journal: JAMA (1990)

We describe the relationship of depression and depressive symptoms to disability days and days lost from work in 2980 participants in the Epidemiologic Catchment Area Study in North Carolina after 1 year of follow-up. Compared with asymptomatic individuals, persons with major depression had a 4.78 times greater risk of disability (95% confidence interval, 1.64 to 13.88), and persons with minor depression with mood disturbance, but not major depression, had a 1.55 times greater risk (95% confidence interval, 1.00 to 2.40). Because of its prevalence, individuals with minor depression were associated with 51% more disability days in the community than persons with major depression. This group was also at increased risk of having a concomitant anxiety disorder or developing major depression within 1 year. We conclude that the threshold for identifying clinically significant depression may need to be reevaluated to include persons with fewer symptoms but measurable morbidity. Only by changing our nosology can the societal impact of depression be adequately addressed.
Anastomotic intimal hyperplasia in prosthetic arteriovenous fistulas for hemodialysis is associated with initial high flow velocity and not with mismatch in elastic properties.
Authors: L Hofstra, D C Bergmans, K M Leunissen, A P Hoeks, P J Kitslaar, M J Daemen, J H Tordoir
Journal: Journal of the American Society of Nephrology (1995)

Stenotic intimal thickening at the venous end of prosthetic arteriovenous (AV) fistulas for hemodialysis has been associated with perianastomotic mismatch in elastic properties, and low shear rates. In a prospective way, the role of these factors on the occurrence of intimal hyperplasia in prosthetic AV fistulas in hemodialysis patients was investigated. In 24 hemodialysis patients, the elastic properties were assessed in the distal graft segment and the outflow vein postoperatively with the use of Vessel Wall Doppler Tracking (VWDT), a noninvasive ultrasound technique. In addition, normalized peak systolic velocity (nPSV) was calculated from diameter (VWDT) and peak systolic velocity. The initial mismatch around the venous anastomoses and local nPSV were correlated with the occurrence of stenoses during follow-up (2 yr). The detection of a stenosis was performed with both Duplex ultrasound and angiography. In four cases, a stenosis developed in the venous anastomosis; in eight cases, a stenosis developed in the venous outflow segment; and in four cases, stenoses developed at both sites. A better initial match in elastic properties around the venous anastomosis was observed in the fistulas developing a stenosis at this site as compared with the nonstenotic fistulas (P < 0.05). The initial local nPSV values at the site of the later stenosis were higher in the fistulas developing a stenosis as compared with the nonstenotic fistulas (P < 0.05). It was concluded that the occurrence of stenoses in prosthetic AV fistulas for hemodialysis in or adjacent to the venous anastomoses is associated with a high initial flow velocity but not with a mismatch in elastic properties.
Unfractionated and Low-Molecular-Weight Heparin as Adjuncts to Thrombolysis in Aspirin-Treated Patients With ST-Elevation Acute Myocardial Infarction
Authors: John W. Eikelboom, Daniel J. Quinlan, Shamir R. Mehta, Alexander G. Turpie, Ian B. Menown, Salim Yusuf
Journal: Circulation (2005)

Background— There is uncertainty about the role of intravenous unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in patients with ST-elevation myocardial infarction (STEMI) treated with aspirin and thrombolysis. Methods and Results— We performed a meta-analysis of the randomized trials to assess the effect of UFH and LMWH on reinfarction, death, stroke, and bleeding. Fourteen trials involving a total of 25 280 patients were included (1239 comparing intravenous UFH versus placebo or no heparin; 16 943 comparing LMWH versus placebo; and 7098 comparing LMWH versus intravenous UFH). Intravenous UFH during hospitalization did not reduce reinfarction (3.5% versus 3.3%; odds ratio [OR], 1.08; 95% CI, 0.58 to 1.99) or death (4.8% versus 4.6%; OR, 1.04; 95% CI, 0.62 to 1.78) and did not increase major bleeding (4.2% versus 3.4%; OR, 1.21; 95% CI, 0.67 to 2.18) but increased minor bleeding (19.6% versus 12.5%; OR, 1.72; 95% CI, 1.22 to 2.43). During hospitalization/at 7 days, LMWH compared with placebo reduced the risk of reinfarction by approximately one quarter (1.6% versus 2.2%; OR, 0.72; 95% CI, 0.58 to 0.90; number needed to treat [NNT]=167) and death by &amp;10% (7.8% versus 8.7%; OR, 0.90; 95% CI, 0.80 to 0.99; NNT=111) but increased major bleeding (1.1% versus 0.4%; OR, 2.70; 95% CI, 1.83 to 3.99; number needed to harm [NNH]=143) and intracranial bleeding (0.3% versus 0.1%; OR, 2.18; 95% CI, 1.07 to 4.52; NNH=500). The reduction in death with LMWH remained evident at 30 days. LMWH compared with UFH during hospitalization/at 7 days reduced reinfarction by &amp;45% (3.0% versus 5.2%; OR, 0.57; 95% CI, 0.45 to 0.73; NNT=45), did not reduce death (4.8% versus 5.3%; OR, 0.92; 95% CI, 0.74 to 1.13) or increase major bleeding (3.3% versus 2.5%; OR, 1.30; 95% CI, 0.98 to 1.72), but increased minor bleeding (22.8% vs 19.4%; OR, 1.26; 95% CI, 1.12 to 1.43). The reduction in reinfarction remained evident at 30 days. Conclusions— In aspirin-treated patients with STEMI who are treated with thrombolysis, intravenous UFH has not been shown to prevent reinfarction or death. LMWH given for 4 to 8 days compared with placebo reduces reinfarction by approximately one quarter and death by &amp;10% and when directly compared with UFH reduces reinfarction by almost one half. These data suggest that LMWH should be the preferred antithrombin in this setting.
Myotoxicity occurring with ciclosporin in a patient with atopic dermatitis
Authors: S. Wahie, S.J. Meggitt
Journal: British Journal of Dermatology (2005)

Journal Article Myotoxicity occurring with ciclosporin in a patient with atopic dermatitis Get access S. Wahie, S. Wahie Department of Dermatology, Royal Victoria Infirmary, Newcastle‐upon‐Tyne, U.K. E‐mail: shyamalwahie@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar S.J. Meggitt S.J. Meggitt Department of Dermatology, Royal Victoria Infirmary, Newcastle‐upon‐Tyne, U.K. E‐mail: shyamalwahie@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 6, 1 December 2005, Page 1238, https://doi.org/10.1111/j.1365-2133.2005.06980.x Published: 01 December 2005