tbuckley/cabot-search huggingface dataset:
Survival of Blood Platelets Labeled with Chromium5112
Authors: Knut A. Aas, Frank H. Gardner
Journal: Journal of Clinical Investigation (1958)

Various criteria exist for the evaluation of the integrity, viability and physiological activity of human blood platelets.Alterations in platelet morphology, clot promoting and clot retracting activities, oxygen consumption, clinical effect on bleeding disorders, and the life span of platelets in thrombocytopenic recipients have been used as measurements of platelet function.The transfu- sion studies in thrombocytopenic recipients indi- cate that platelets have a life span of three to seven days and have been helpful in the classification of certain pathological disorders (2).These ob- servations have been dependent upon obtaining donors with high platelet counts and accepting the errors associated with platelet counting.The diffi- culty in procuring adequate donors and the de- sirability of measurements other than platelet enu- meration have initiated numerous studies of the in vivo survival of platelets labeled with radio- active isotopes.The earlier studies concerning measurement of the life span of blood platelets with isotopes prior to 1955 have been reviewed by Odell, Tausche and Furth (3).In Table I the various isotope tech- niques previously reported are tabulated for com- parison.The recent report by Leeksma and Cohen (13) has demonstrated a life span of labeled platelets of eight to nine days.These investiga- tors followed the activity of radioactive phosphorus in platelets after the recipient had received diisopropylfluorophosphonate (DFP32) parenterally.
Immunogenetic basis of environmental lung disease: lessons from the berylliosis model
Authors: C Saltini, M Amicosante, A Franchi, G Lombardi, L Richeldi
Journal: European Respiratory Journal (1998)

The role of genetic factors has been hypothesized in the pathogenesis of a number of chronic inflammatory lung diseases. The genes of the major histocompatibility complex (MHC) locus on human chromosome 6 have been identified as important determinants in diseases caused both by inorganic and organic compounds such as beryllium, gold, acid anhydrides, isocyanates and grass pollens. Since many environmental factors are the determinants of the immunopathogenesis of asthma, pulmonary granulomatous disorders, hypersensitivity pneumonitis and fibrotic lung disorders, an understanding of the interaction between environmental factors is crucial to epidemiology, prevention and treatment of these disorders. Berylliosis is an environmental chronic inflammatory disorder of the lung caused by inhalation of beryllium dusts. A human leukocyte antigen class II marker (HLA-DP Glu69) has been found to be strongly associated with the disease. In in vitro studies, the gene has been shown to play a direct role in the immunopathogenesis of the disease. In human studies, the gene has been shown to confer increased susceptibility to beryllium in exposed workers, thus suggesting that HLA gene markers may be used as epidemiological probes to identify population groups at higher risk of environmental lung diseases, to identify environmental levels of lung immunotoxicants that would be safe for the entire population and to prevent disease risk associated with occupation, manufactured products and the environment. Studies on the associations between human leukocyte antigens and chronic inflammatory lung disorders are reviewed in the context of the berylliosis model.
Fungus Infections of the Skin
Authors: F. R. Bettley
Journal: BMJ (1951)

Most fungus infections of the skin involve only the epidermis and its appendages, the hair and the nails, with comparatively little reaction of the underlying tissues.For this reason they are not a very potent .cause of serious disability except when complications arise.Their increasing prevalence, however, gives this group of infections importance.I propose to deal with them in roughly their order of frequency in this country at the present time.Tinea Pedis This occurs in two very different clinical forms, which are, however, often associated together either simultaneously or at different times in the same patient.The vesicular form nearly always starts in the centre of the sole, under the arch of the foot,'as a group of perhaps half a dozen watery vesicles of large pin-head size which after a few days become superficial pustules.At this stage irritation may be considerable, but the thickness of the corneous layer is usually sufficient to keep the vesicles intact in spite of scratching.The pustules gradually dry up and, as they do so, take on a brownish colour so that they are eventually shed in the form of thick brown scales a quarter of an inch or so across.It is a week or ten days before these scales are formed, and by this time fresh vesicles are often forming near by.This process may continue for some weeks, eventually appearing on the sides of the feet and toes and even on the dorsum of the foot.Even without treatment, however, the process eventu- ally seems to burn itself out and the attack subsides for a time.The interdigital form develops more insidiously and may consist of no more than a maceration of the skin
BLT1-mediated T cell trafficking is critical for rejection and obliterative bronchiolitis after lung transplantation
Authors: Benjamin D. Medoff, Edward Seung, John C. Wain, Terry K. Means, Gabriele S.V. Campanella, Sabina A. Islam, Seddon Y. Thomas, Leo C. Ginns, Nir Grabie, Andrew H. Lichtman, Andrew M. Tager, Andrew D. Luster
Journal: The Journal of Experimental Medicine (2005)

Leukotriene B4 is a lipid mediator that recently has been shown to have potent chemotactic activity for effector T lymphocytes mediated through its receptor, BLT1. Here, we developed a novel murine model of acute lung rejection to demonstrate that BLT1 controls effector CD8+ T cell trafficking into the lung and that disruption of BLT1 signaling in CD8+ T cells reduces lung inflammation and mortality in the model. In addition, we used BLT1-deficient mice and a BLT1 antagonist in two tracheal transplant models of lung transplantation to demonstrate the importance of BLT1 for the recruitment of T cells into tracheal allografts. We also show that BLT1-mediated CD8+ T cell recruitment plays an important role in the development of airway fibroproliferation and obliteration. Finally, in human studies of lung transplant recipients, we found that BLT1 is up-regulated on T lymphocytes isolated from the airways of patients with obliterative bronchiolitis. These data demonstrate that BLT1 contributes to the development of lung rejection and obliterative bronchiolitis by mediating effector T lymphocyte trafficking into the lung. This is the first report that describes a pathologic role for BLT1-mediated T lymphocyte recruitment in disease and identifies BLT1 as a potential therapeutic target after lung transplantation.
Intratumoral Delivery of β-Lapachone via Polymer Implants for Prostate Cancer Therapy
Authors: Ying Dong, Shook-Fong Chin, Elvin Blanco, Erik A. Bey, Wareef Kabbani, Xian-Jin Xie, William G. Bornmann, David A. Boothman, Jinming Gao
Journal: Clinical Cancer Research (2008)

Abstract Purpose: β-Lapachone (ARQ 501, a formulation of β-lapachone complexed with hydroxypropyl-β-cyclodextrin) is a novel anticancer agent with selectivity against prostate cancer cells overexpressing the NAD(P)H:quinone oxidoreductase-1 enzyme. Lack of solubility and an efficient drug delivery strategy limits this compound in clinical applications. In this study, we aimed to develop β-lapachone–containing polymer implants (millirods) for direct implantation into prostate tumors to test the hypothesis that the combination of a tumor-specific anticancer agent with site-specific release of the agent will lead to significant antitumor efficacy. Experimental Design: Survival assays in vitro were used to test the killing effect of β-lapachone in different prostate cancer cells. β-Lapachone release kinetics from millirods was determined in vitro and in vivo. PC-3 prostate tumor xenografts in athymic nude mice were used for antitumor efficacy studies in vivo. Results: β-Lapachone killed three different prostate cancer cell lines in an NAD(P)H:quinone oxidoreductase-1–dependent manner. Upon incorporation of solid-state inclusion complexes of β-lapachone with hydroxypropyl-β-cyclodextrin into poly(d,l-lactide-co-glycolide) millirods, β-lapachone release kinetics in vivo showed a burst release of ∼0.5 mg within 12 hours and a subsequently sustained release of the drug (∼0.4 mg/kg/d) comparable with that observed in vitro. Antitumor efficacy studies showed significant tumor growth inhibition by β-lapachone millirods compared with controls (P &amp;lt; 0.0001; n = 10 per group). Kaplan-Meier survival curves showed that tumor-bearing mice treated with β-lapachone millirods survived nearly 2-fold longer than controls, without observable systemic toxicity. Conclusions: Intratumoral delivery of β-lapachone using polymer millirods showed the promising therapeutic potential for human prostate tumors.
Psoriasiform lesions induced by tumour necrosis factor antagonists: a skin-deep medical conundrum
Authors: J D Carter, H C Gerard, A P Hudson
Journal: Annals of the Rheumatic Diseases (2008)

Rarely, tumour necrosis factor (TNF)α antagonist therapy has been associated with de novo psoriasiform eruptions. This is unusual in that these same drugs are used to treat psoriasis. Most of these cases involve the palms and soles, yet palmoplantar pustular psoriasis represents only 1.7% of all cases of psoriasis. Keratoderma blenorrhagicum is a psoriasiform rash that occurs primarily on the palms and soles of some patients with reactive arthritis. It is grossly and histologically indistinguishable from pustular psoriasis. <i>Chlamydia trachomatis</i> is a common aetiological agent for reactive arthritis, and in vitro studies have shown that chlamydial replication is inversely proportional to TNFα levels. Three patients taking TNFα antagonists are presented who developed such lesions and who were found to be positive for <i>C trachomatis</i> DNA in the affected skin. It is proposed that these psoriasiform lesions may not be psoriasis, but rather keratoderma blenorrhagicum.
Rapid Inhibition of Cancer Cell Growth Induced by Lentiviral Delivery and Expression of Mutant-Template Telomerase RNA and Anti-telomerase Short-Interfering RNA
Authors: Shang Li, Jonathan E. Rosenberg, Annemarie A. Donjacour, Inna L. Botchkina, Yun Kit Hom, Gerald R. Cunha, Elizabeth H. Blackburn
Journal: Cancer Research (2004)

Abstract In human cancers, telomeres are commonly maintained by elevated levels of the ribonucleoprotein enzyme telomerase, which contains an intrinsic templating RNA moiety (human telomerase RNA; hTER) and the core protein (human telomerase reverse transcriptase). We developed a lentiviral system for efficient overexpression of mutant-template human telomerase RNA (MT-hTer) to add mutant DNA to telomeres in cancer cells. We show that such MT-hTer overexpression rapidly inhibits cell growth and induces apoptosis in telomerase-positive precancerous or cancer cells but not in telomerase-negative cells. These rapid effects occurred independent of wild-type p53 and telomere length. Tumor growth and progression were significantly decreased in xenografts of human tumor cells overexpressing MT-hTers. Expression of a hairpin short-interfering RNA that specifically targeted the endogenous wild-type hTER template region, but spared the MT-hTers, also caused p53-independent cell growth inhibition and apoptosis, and when coexpressed with MT-hTer, synergistically killed cancer cells. Hence, anti-wild-type-hTER short-interfering RNA and MT-hTers may act through distinct pathways and, particularly in combination, represent a promising approach to anticancer therapies.
Dermatology Life Quality Index: influence of an illustrated version
Authors: W.J. Loo, V. Diba, M. Chawla, A.Y. Finlay
Journal: British Journal of Dermatology (2003)

An illustrated version of the Dermatology Life Quality Index (DLQI) was developed in order to improve the ease with which this standard questionnaire is answered.To compare the illustrated version with the text-only version of the DLQI.The two versions were administered to 206 patients attending Dermatology outpatient clinics. The time taken to complete either the illustrated or the text-only version was noted in 52 additional patients.One hundred and ninety-one of 206 patients completed both questionnaires satisfactorily. Their mean DLQI scores were 6.4 (median 4.0, lower quartile 1.0, upper quartile 11.0) for the illustrated version and 6.3 (median 4.0, lower quartile 1.0, upper quartile 10.0) for the text-only version. For the 98 patients who answered the illustrated version first, the mean DLQI scores were 6.9 (median 4.0, lower quartile 1.9, upper quartile 11.9) for the illustrated version and 6.4 (median 4.0, lower quartile 1.8, upper quartile 11.0) for the text-only version. For the 93 patients who answered the text-only version first, the mean DLQI scores were 5.9 (median 4.0, lower quartile 1.7, upper quartile 10.2) for the illustrated version and 6.2 (median 5.0, lower quartile 0.5, upper quartile 9.5) for the text-only version. The median time taken to complete the text-only version was 124 s (mean +/- SD 126 +/- 65, n = 27) and 88 s (mean +/- SD 101 +/- 52, n = 25) for the illustrated version (P = 0.08). There was a very close correlation (r = 0.98) between the scores of the text-only and the illustrated versions; 82.2% of patients either scored the same or had a DLQI score difference of only 1. One hundred and seven (59.8%) patients preferred using the illustrated version and 66 (36.9%) preferred the text-only version. One hundred and four (57.5%) found the illustrated version easier to use.The illustrated version was superior to the text-only version in terms of patient preference and ease of use, but it was not possible to demonstrate exact equivalence between the two versions.
Proteomic analysis of plasma identifies the Toll-like receptor agonists S100A8/A9 as a novel possible marker for systemic sclerosis phenotype
Authors: L van Bon, M Cossu, A Loof, F Gohar, H Wittkowski, M Vonk, J Roth, W van den Berg, W van Heerde, J C A Broen, T R D J Radstake
Journal: Annals of the Rheumatic Diseases (2014)

Systemic sclerosis (SSc) is an autoimmune disease characterised by fibrosis of the skin and the internal organs. Except for anticentromere, antitopoisomerase I and antipolymerase III antibodies, there are no reliable circulating markers predicting susceptibility and internal organ complications. This study has exploited a proteome-wide profiling method with the aim to identify new markers to identify SSc phenotype.40 SSc patients were included for proteomic identification. Patients were stratified as having diffuse cutaneous SSc (dcSSc) (n=19) or limited cutaneous SSc (lcSSc) (n=21) according to the extent of skin involvement. As controls 19 healthy donors were included. Blood was drawn and plasma was stored before analysing with the SELDI-TOF-MS. For replication in serum, the cohort was extended with 60 SSc patients.Proteomic analysis revealed a list of 25 masspeaks that were differentially expressed between SSc patients and healthy controls. One of the peaks was suggestive for S100A8, a masspeak we previously found in supernatant of plasmacytoid dendritic cells from SSc patients. Increased expression of S100A8/A9 in SSc patients was confirmed in replication cohort compared with controls. Intriguingly, S100A8/A9 was highest in patients with limited cutaneous SSc having lung fibrosis.S100A8/A9 was robustly found to be elevated in the circulation of SSc patients, suggesting its use as a biomarker for SSc lung disease and the need to further explore the role of TLR in SSc.
Ciclesonide is well tolerated and has minimal oropharyngeal side effects at once-daily doses of 80 $mu;g, 160 $mu;g, and 320 $mu;g in the treatment of patients with mild-to-moderate asthma*1
Authors: WE Berger, L Mansfield, C Pinter, J Fish, S Kundu, J Williams, D Banerji, P Hamedani
Journal: Journal of Allergy and Clinical Immunology (2004)
Cross-Sectional Dating of Novel Haplotypes of HERV-K 113 and HERV-K 115 Indicate These Proviruses Originated in Africa before Homo sapiens
Authors: Aashish R. Jha, Satish K. Pillai, Vanessa A. York, Elizabeth R. Sharp, Emily C. Storm, Douglas J. Wachter, Jeffrey N. Martin, Steven G. Deeks, Michael G. Rosenberg, Douglas F. Nixon, Keith E. Garrison
Journal: Molecular Biology and Evolution (2009)

The human genome, human endogenous retroviruses (HERV), of which HERV-K113 and HERV-K115 are the only known full-length proviruses that are insertionally polymorphic. Although a handful of previously published papers have documented their prevalence in the global population; to date, there has been no report on their prevalence in the United States population. Here, we studied the geographic distribution of K113 and K115 among 156 HIV-1+ subjects from the United States, including African Americans, Hispanics, and Caucasians. In the individuals studied, we found higher insertion frequencies of K113 (21%) and K115 (35%) in African Americans compared with Caucasians (K113 9% and K115 6%) within the United States. We also report the presence of three single nucleotide polymorphism sites in the K113 5′ long terminal repeats (LTRs) and four in the K115 5′ LTR that together constituted four haplotypes for K113 and five haplotypes for K115. HERV insertion times can be estimated from the sequence differences between the 5′ and 3′ LTR of each insertion, but this dating method cannot be used with HERV-K115. We developed a method to estimate insertion times by applying coalescent inference to 5′ LTR sequences within our study population and validated this approach using an independent estimate derived from the genetic distance between K113 5′ and 3′ LTR sequences. Using our method, we estimated the insertion dates of K113 and K115 to be a minimum of 800,000 and 1.1 million years ago, respectively. Both these insertion dates predate the emergence of anatomically modern Homo sapiens.
Ambroxol suppresses influenza-virus proliferation in the mouse airway by increasing antiviral factor levels
Authors: B. Yang, D.F. Yao, M. Ohuchi, M. Ide, M. Yano, Y. Okumura, H. Kido
Journal: European Respiratory Journal (2002)

The protective effect of ambroxol, a mucolytic agent which has antioxidant properties and stimulates the release of pulmonary surfactant, against influenza-virus proliferation in the airway was investigated in mice. Ambroxol or the vehicle was administered intraperitoneally twice a day for 5-7 days to mice shortly after intranasal infection with a lethal dose of influenza A/Aichi/68 (H3N2) virus, and the survival rate, virus titre and levels of factors regulating virus proliferation in the airway fluid were analysed. Ambroxol significantly suppressed virus multiplication and improved the survival rate of mice. The effect of ambroxol reached a peak at 10 mg x kg(-1) x day(-1), higher doses being less effective. Ambroxol stimulated the release of suppressors of influenza-virus multiplication, such as pulmonary surfactant, mucus protease inhibitor, immunoglobulin (Ig)-A and IgG, although it stimulated the release of a trypsin-type protease that potentiates virus proliferation. In addition, ambroxol transiently suppressed release of the cytokines, tumour necrosis factor-alpha, interferon-gamma and interleukin-12, into airway fluid. Although ambroxol had several negative effects on the host defence system, overall it strikingly increased the concentrations of suppressors of influenza-virus multiplication in the airway.
Sentinel Node Dissection Is Safe in the Treatment of Early-Stage Vulvar Cancer
Authors: Ate G.J. Van der Zee, Maaike H. Oonk, Joanne A. De Hullu, Anca C. Ansink, Ignace Vergote, René H. Verheijen, Angelo Maggioni, Katja N. Gaarenstroom, Peter J. Baldwin, Eleonore B. Van Dorst, Jacobus Van der Velden, Ralph H. Hermans, Hans van der Putten, Pierre Drouin, Achim Schneider, Wim J. Sluiter
Journal: Journal of Clinical Oncology (2008)

To investigate the safety and clinical utility of the sentinel node procedure in early-stage vulvar cancer patients.A multicenter observational study on sentinel node detection using radioactive tracer and blue dye was performed in patients with T1/2 (< 4 cm) squamous cell cancer of the vulva. When the sentinel node was found to be negative at pathologic ultrastaging, inguinofemoral lymphadenectomy was omitted, and the patient was observed with follow-up for 2 years at intervals of every 2 months. Stopping rules were defined for the occurrence of groin recurrences.From March 2000 until June 2006, a sentinel node procedure was performed in 623 groins of 403 assessable patients. In 259 patients with unifocal vulvar disease and a negative sentinel node (median follow-up time, 35 months), six groin recurrences were diagnosed (2.3%; 95% CI, 0.6% to 5%), and 3-year survival rate was 97% (95% CI, 91% to 99%). Short-term morbidity was decreased in patients after sentinel node dissection only when compared with patients with a positive sentinel node who underwent inguinofemoral lymphadenectomy (wound breakdown in groin: 11.7% v 34.0%, respectively; P < .0001; and cellulitis: 4.5% v 21.3%, respectively; P < .0001). Long-term morbidity also was less frequently observed after removal of only the sentinel node compared with sentinel node removal and inguinofemoral lymphadenectomy (recurrent erysipelas: 0.4% v 16.2%, respectively; P < .0001; and lymphedema of the legs: 1.9% v 25.2%, respectively; P < .0001).In early-stage vulvar cancer patients with a negative sentinel node, the groin recurrence rate is low, survival is excellent, and treatment-related morbidity is minimal. We suggest that sentinel node dissection, performed by a quality-controlled multidisciplinary team, should be part of the standard treatment in selected patients with early-stage vulvar cancer.