tbuckley/cabot-search huggingface dataset:
SERUM AND VACCINE THERAPY IN CONNEXION WITH DISEASES OF THE EYE: The Middlemore Prize Essay, British Medical Association, 1911
Authors: C. W. G. Bryan
Journal: BMJ (1912)

THE sUlbjeCt of serumii aiid vaccinc, therapy in relationl to dliseases of the ey-e is onie -which hias received a large amIount of attenltionl.aind Oil wlhiicl a (great deal of work has been doiie during recent years.The treatmient of eye diseases by serumns anid vaccines differs fronti siiilar treatml-enit of disease in any-otlher palt of the bcdy oxwingf to the anatomiiical peculiarities of the blood and lyitiph suipply of thlis orgail.The coIrnlea and(i vitreous lhave in the healtlhy condition nio blood vessels, and are feebly nourislhed by lNnimpl; the lyniphi cirlctltion of tlle intrinsic parts of the ey-eball is, lhowvever, not free, and this is exeiiiplified by the rarity -with whliclh inaligmiant glrow-tlhs of the interior of tlle eve- ball give rise to secondary-deposits in glands until thle glrow th by direct spread lhas extended outside the scleriotic co:t.Again. in tllose parts of tile eve wlhere tlhere is a sulpply of 1)lood( v essels the distribuitioni of the blood in these vessels is constantly varying owing to the unceasing illm vellemnts of the eve as a wlhole.and of its various paitsthe iris, ciliary hody, etc.These miiovemtients are of iml)ortailce whlie the eye is infected, as tlhey cauise the settillg free of bacterial substances, toxiiis, etc.. in the blood streamii.Tllis subject of autoinoculation will be discutssed later in conniiexion witli vaccine therapy.Imimuniiiiity against disease dute to infectioni niiay be aciluired iactively -or passively.-V-accinietllerapy is con- crnued in the prodtuctioni of activeinllmulnity,seruim tlherapy dleals wvitlh tIme production of passive ilniiiunitv. Xwkccim THm xRAPY.Active immnunility cani be acquited in tw-o w-avs-eitlher by auto-iiiocillatioii by bacterial substances set free in time bloed streami fromii somie foctus of disease.or by the imetho'lcs of -lhetero-iiloculationi-that is, by tlle absorption of -accine, L.s;Lally injected inlto the sulbcutaneous tissues.In (lisease of tIe eye auito-inoculationi is an unsatisfactory mi-etlhod of producing iiimimuunit\ owing to tlle liiliited blood and(1 lymph flow in the eve.and to the fact that tIme size of the area of inifectioni, as conilpared w-ithl the bodyas a whole, is sim-all, and tllerefore great disturbance of this smiiall area would be necessary to plroduce alny iiarked auto-iiioculatioii.Ill using vaccines it is necessarv as far as pIossilble to preveilt aauto-inoctulation by keeping tlle diseased part at rest.anli this is a difficulty w-ith wlichl we lhave specially to contend iin dealing 'with eye diseases.If atuto-ineculatioll takes place at the timiie that treatiment by lieteroinoculation is beingf carried out.sulbstances of unkntown aiiioulnt niiav be set free in the blood stream at mlifavouir-Nov 1.3 14 1ii -m; 1718 1 I -)i ?1 2223 25 fi -3' § 1.
Failure of Translation of Human Adenovirus mRNA in Murine Cancer Cells Can be Partially Overcome by L4-100K Expression In Vitro and In Vivo
Authors: Anna-Mary Young, Kyra M Archibald, Laura A Tookman, Alexander Pool, Kate Dudek, Carolyn Jones, Sarah L Williams, Katrina J Pirlo, Anne E Willis, Michelle Lockley, Iain A McNeish
Journal: Molecular Therapy (2012)

Adaptive immune responses may be vital in the overall efficacy of oncolytic viruses in human malignancies. However, immune responses to oncolytic adenoviruses are poorly understood because these viruses lack activity in murine cells, which precludes evaluation in immunocompetent murine cancer models. We have evaluated human adenovirus activity in murine cells. We show that a panel of murine carcinoma cells, including CMT64, MOVCAR7, and MOSEC/ID8, can readily be infected with human adenovirus. These cells also support viral gene transcription, messenger RNA (mRNA) processing, and genome replication. However, there is a profound failure of adenovirus protein synthesis, especially late structural proteins, both in vitro and in vivo, with reduced loading of late mRNA onto ribosomes. Our data also show that in trans expression of the nonstructural late protein L4-100K increases both the amount of viral mRNA on ribosomes and the synthesis of late proteins, accompanied by reduced phosphorylation of eIF2α and improved anticancer efficacy. These results suggest that murine models that support human adenovirus replication could be generated, thus allowing evaluation of human adenoviruses in immunocompetent mice.
Lymphotoxin 252A&gt;G polymorphism is common and associates with myocardial infarction in patients with rheumatoid arthritis
Authors: V F Panoulas, S N Nikas, J P Smith, K M J Douglas, P Nightingale, H J Milionis, G J Treharne, T E Toms, M D Kita, G D Kitas
Journal: Annals of the Rheumatic Diseases (2008)

Cardiovascular disease (CVD) is more prevalent and more likely to lead to death in patients with rheumatoid arthritis (RA). Single nucleotide polymorphisms of the genes for lymphotoxin-A (LT-A) and its regulatory protein galectin-2 (LGALS2) have been implicated as genetic risk factors for acute cardiovascular events in the general population: we hypothesised that their risk alleles/genotypes (a) may be more frequent among patients with RA compared with non-RA controls (thus explaining some of the increased CVD in RA), and (b) may be more frequent among patients with RA with prevalent CVD compared with patients with RA without CVD.Genomic DNA samples were collected from 388 patients with RA and 399 local population controls without RA. LT-A gene intron 1 252A>G and LGALS2 intron 1 3279C>T single nucleotide polymorphisms were identified using real-time polymerase chain reaction and melting curve analysis.LT-A 252GG homozygotes were significantly more prevalent among patients with RA compared with controls (19.8% vs 11.8%, p = 0.002; OR(GG/GA,AA) = 1.85, 95% CI 1.25 to 2.75, p = 0.002). Patients with RA possessing LT-A 252 GG were significantly more likely to have had a myocardial infarction compared with those with LT-A 252 AA or GA (13% vs 5.5%, p = 0.02; adjusted OR(GG/GA,AA) = 3.03, 95% CI 1.2 to 7.68, p = 0.002). The frequency of LGALS2 polymorphisms was similar between RA and controls and was not associated with CVD among patients with RA.The LT-A 252GG genotype occurs more frequently among patients with RA than the general population. In RA, this genotype appears to associate with increased likelihood of suffering an myocardial infarction.
Spontaneous Feline Mammary Carcinoma Is a Model of HER2 Overexpressing Poor Prognosis Human Breast Cancer
Authors: Raffaella De Maria, Martina Olivero, Selina Iussich, Munekazu Nakaichi, Tomoaki Murata, Bartolomeo Biolatti, Maria Flavia Di Renzo
Journal: Cancer Research (2005)

Companion animal spontaneous tumors are suitable models for human cancer, primarily because both animal population and the tumors are genetically heterogeneous. Feline mammary carcinoma (FMC) is a highly aggressive, mainly hormone receptor-negative cancer, which has been proposed as a model for poor prognosis human breast cancer. We have identified and studied the feline orthologue of the HER2 gene, which is both an important prognostic marker and therapeutic target in human cancer. Feline HER2 (f-HER2) gene kinase domain is 92% similar to the human HER2 kinase. F-HER2-specific mRNA was found 3- to 18-fold increased in 3 of 3 FMC cell lines, in 1 of 4 mammary adenomas and 6 of 11 FMC samples using quantitative reverse transcription-PCR. Western blot showed that an anti-human HER2 antibody recognized a protein comigrating with the human p185HER2 in FMC cell lines. The same antibodies strongly stained 13 of 36 FMC archival samples. These data show that feline HER2 overexpression qualifies FMC as homologous to the subset of HER2 overexpressing, poor prognosis human breast carcinomas and as a suitable model to test innovative approaches to therapy of aggressive tumors.
Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer
Authors: R. Rosell, G. Robinet, A. Szczesna, R. Ramlau, M. Constenla, B.C. Mennecier, W. Pfeifer, K.J. O’Byrne, T. Welte, R. Kolb, R. Pirker, A. Chemaissani, M. Perol, M.R. Ranson, P.A. Ellis, K. Pilz, M. Reck
Journal: Annals of Oncology (2007)
AP1-Dependent Galectin-1 Expression Delineates Classical Hodgkin and Anaplastic Large Cell Lymphomas from Other Lymphoid Malignancies with Shared Molecular Features
Authors: Scott J. Rodig, Jing Ouyang, Przemyslaw Juszczynski, Treeve Currie, Kenneth Law, Donna S. Neuberg, Gabriel A. Rabinovich, Margaret A. Shipp, Jeffery L. Kutok
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Galectin-1 (Gal1) is an immunomodulatory glycan-binding protein regulated by an AP1-dependent enhancer in Hodgkin Reed-Sternberg cells. We recently found that Reed-Sternberg cell Gal1 promotes the immunosuppressive T-helper 2/T-regulatory cell–skewed microenvironment in classical Hodgkin lymphoma (cHL). We sought to investigate whether the coordinate expression of activated AP1 pathway components and Gal1 serves as a diagnostic signature of cHL. In addition, because there are common signaling and survival pathways in cHL and additional non–Hodgkin lymphomas, we also evaluated whether the AP1/Gal1 signature is shared by other molecularly or morphologically related lymphomas. Experimental Design: We evaluated 225 cases of primary cHL and non–Hodgkin lymphoma for evidence of a functional AP1/Gal1 signature by immunohistochemical techniques. Results: Gal1 is selectively expressed by malignant Reed-Sternberg cells in &amp;gt;90% of primary cHLs, and Gal1 expression is concordant with the activated AP1 component, c-Jun. In contrast, diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, and another Hodgkin-related entity, nodular lymphocyte–predominant Hodgkin lymphoma, do not express Gal1. However, anaplastic large cell lymphoma (ALCL), consistently expresses both Gal1 and its transcriptional regulator, c-Jun. The presence of activated c-Jun, indicative of functional AP1 activity, was confirmed by phospho-c-Jun immunostaining in cHL and ALCL. Conclusions: These findings establish a functional AP1 signature that includes Gal1 expression in cHL and ALCL and suggests a common mechanism for tumor immunotolerance in these diseases. In addition, the combination of Gal1 and c-Jun serve as diagnostic biomarkers that delineate cHL and ALCL from other lymphomas with shared morphologic and/or molecular features.
Human fat cells possess a plasma membrane-bound H2O2-generating system that is activated by insulin via a mechanism bypassing the receptor kinase.
Authors: H I Krieger-Brauer, H Kather
Journal: Journal of Clinical Investigation (1992)

Insulin caused a transient increase in H2O2 accumulation in human fat cell suspensions that was observed only in the presence of an inhibitor of catalase and heme-containing peroxidases, such as azide, and reached peak levels of 30 microM within 5 min. The cells contained a plasma membrane-bound NADPH oxidase, producing 1 mol H2O2/mol of NADPH oxidation, that was activated on exposure of intact cells to insulin at contrations that are physiologically relevant (0.1-10 nM). The hormone effect was rapid and was due to a selective increase in substrate affinity. The enzyme was magnesium dependent, required a flavine nucleotide for optimal activity, and was most active at pH 5.0-6.5. In contrast to all other hormone- or cytokine-sensitive NADPH oxidases that have been characterized in sufficient detail, the human fat cell oxidase retained its hormone responsiveness after cell disruption, and only Mn2+, but no ATP, was required for a ligand-induced activation in crude plasma membranes. The results demonstrate that insulin utilizes tyrosine kinase-independent pathways for receptor signaling and strongly support the view that H2O2 contributes to the intracellular propagation of the insulin signal.
Fibrous cap formation or destruction — the critical importance of vascular smooth muscle cell proliferation, migration and matrix formation
Authors: A Newby
Journal: Cardiovascular Research (1999)

Endothelial activation and infiltration of monocyte macrophages are essential prerequisites for fibrous cap formation, which comprises proliferation and migration of smooth muscle cells and net matrix deposition. Macrophage foam cells and endothelium act as a source of growth factors and chemoattractants for smooth muscle cells. However, growth factors alone do not stimulate smooth muscle cell proliferation or migration. This requires, in addition, the remodelling of the extracellular matrix, at least partly mediated by metalloproteinases. In particular, loss of basement membrane components and contact with the interstitial matrix appears to be required to release a brake on proliferation and migration exerted by the basement membrane. Unless there is a change in the phenotype of macrophages in advanced lesions, it is not clear why fibrous cap destruction rather than formation should take place in macrophage-rich shoulder regions of plaques. Impaired cap formation caused by smooth muscle senescence, mummification and propensity to apoptosis may be as important as increased cap destruction in promoting plaque rupture.
<i>CCR</i>20th Anniversary Commentary:<i>RAS</i>as a Biomarker for EGFR-Targeted Therapy for Colorectal Cancer—From Concept to Practice
Authors: E. Ramsay Camp, Lee M. Ellis
Journal: Clinical Cancer Research (2015)

Abstract Clinical data support the use of EGFR mAbs in patients with metastatic colorectal cancer (mCRC) with wild-type RAS status. This notion, hypothesized in the review article by Camp, Ellis, and colleagues in the January 1, 2005, issue of Clinical Cancer Research, serves as an example of the successful application of basic science principles to clinical practice. The exclusion of patients with mCRC with Ras-mutated tumors from therapy with EGFR mAbs has led to improved outcomes while sparing patients unnecessary and potentially harmful therapy. Clin Cancer Res; 21(16); 3578–80. ©2015 AACR. See related article by Camp et al., Clin Cancer Res 2005;11(1): January 1, 2005;397–405
Concentrations of Insulin and of Insulin Receptors in the Brain are Independent of Peripheral Insulin Levels
Authors: Jana Havrankova, Jesse Roth, Michael J. Brownstein
Journal: Journal of Clinical Investigation (1979)

In view of the potent influences of the central nervous system on glucose metabolism and on its hormonal regulators, and our recent finding of insulin and insulin receptors throughout the central nervous systsem, we have examined extreme conditions of hyperinsulinemia (obese mice) and hypoinsulinemia (streptozotocin-treated rats) with respect to changes in brain insulin and receptor content. Sprague-Dawley rats given streptozotocin (100 mg/kg body wt) developed severe diabetes and by 48 h showed no change in brain insulin. Rats given 65 mg/kg streptozotocin also had severe diabetes, but survived longer. Both at 7 d and at 30 d after streptozotocin treatment there was no significant change in brain insulin or in brain content of insulin receptors, despite the fact that peripheral hepatic receptors were elevated and pancreatic insulin was markedly depleted. The obese mice were studied at 8-10 wk when peripheral plasma insulin concentrations were 50-fold elevated and receptors on peripheral target cells were reduced to congruent with40-50% of normal; brain insulin concentrations and receptor content were indistinguishable from those of thin littermates. Thus, brain insulin, which is typically 10 times higher than plasma insulin concentrations, and brain receptor content, which is equivalent to receptor content on peripheral tissues, appears to be regulated entirely independently of hormone and receptor in the periphery. These findings are consistent with the hypothesis that insulin in the central nervous system is synthesized by the neural elements, and plays a role in the central nervous system which is unrelated to peripheral glucose metabolism.
Cisplatin, methotrexate, and vinblastine (CMV): an effective chemotherapy regimen for metastatic transitional cell carcinoma of the urinary tract. A Northern California Oncology Group study.
Authors: W G Harker, F J Meyers, F S Freiha, J M Palmer, L D Shortliffe, J F Hannigan, K M McWhirter, F M Torti
Journal: Journal of Clinical Oncology (1985)

Fifty-eight patients with metastatic transitional cell carcinoma of the urinary tract received cisplatin, methotrexate, and vinblastine (CMV) combination chemotherapy. Complete responses (CRs) were noted in 14 of the 50 (28%) evaluable patients and partial responses (PRs) in 14 patients for an overall response rate of 56% (95% confidence limits of 42% to 70%). The median duration of the 14 CRs was 9 months. Six of the 14 CRs (43%) remain in unmaintained remission from 6 + to 35 + months from onset of treatment. The median survival of evaluable patients receiving CMV was 8 months. Median survival for CRs was 11 months v 7 months for PRs (P less than .05) and 6 months for nonresponders. Renal and hematologic toxicities with this regimen were moderate. CMV is an effective regimen for patients with metastatic transitional cell carcinoma of the bladder. Prolonged disease-free survival may result from a CR to this regimen.
Isotonic mechanics of a pharyngeal dilator muscle and diaphragm in the rat before and after fatigue
Authors: P. Attal, C. Coirault, D Chemla, F-X. Blanc, P. Rocher, J-C. Pourny, S. Bobin, Y Lecarpentier
Journal: European Respiratory Journal (2000)

Pharyngeal and diaphragm muscles contract and relax in synergy, which is why it was decided to compare their mechanical performance throughout the overall load continuum. The effects of fatigue were also studied. The isotonic mechanics of rat sternohyoid (SH; n=10) and diaphragm (D; n=10) were investigated in vitro. Force and length were measured in muscles contracting from zero load up to isometry. Maximum isometric tension (Pmax), peak mechanical work (Wmax), maximum unloaded shortening velocity (vzL) and mechanical efficiency (eff(max)) were recorded. Data were obtained both at baseline and after fatigue. SH muscles had a lower Pmax (96.0+/-13.7 versus 119.5+/-22.7 mN x mm(-2); p<0.05), a lower Wmax (5.5+/-1.2 versus 8.0+/-2.1 mJ x g(-1); p<0.01), a lower eff(max) (56.0+/-6.9 versus 62.6+/-5.8%; p<0.05) and a higher vzL (4.8+/-0.4 versus 3.4+/-0.4 initial length (L0) x s(-1); p<0.001) than D muscles. Wmax occurred at a higher relative load in SH (40% Pmax) than in D (30% Pmax). Fatigue did not modify eff(max) in SH muscles, whereas it significantly improved eff(max) in D muscles. These findings suggest that under control conditions, economy of force generation was less efficient in sternohyoid than in diaphragm muscles. Fatigue in sternohyoid muscles induced unfavourable mechanical behaviour. This may partly explain pharyngeal dilator muscle failure in the presence of increased loads. Whether these findings are relevant to human sleep apnoea syndrome has yet to be determined.
Acyclovir and Other Chemotherapy for Herpes Group Viral Infections
Authors: H. H. Balfour
Journal: Annual Review of Medicine (1984)

The recent profusion of antiviral research has resulted in significant advances toward prevention and treatment of herpes group virus infections. The most promising new agent is acyclovir, which is available in topical, intravenous, and oral formulations. Results of clinical trials of acyclovir for prevention and treatment of herpes simplex, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus infections are discussed, and the potential problem of antiviral resistance considered. Vidarabine therapy is reviewed briefly, and future new drugs with activity against herpesviruses are mentioned.
Combined oral contraceptives in the treatment of polycystic ovary syndrome
Authors: J. Vrbíková, D. Cibula
Journal: Human Reproduction Update (2005)

Combined oral contraceptives (COC) are the most often used treatment modality for polycystic ovary syndrome (PCOS). Undisputedly, COC suppress androgen production, thus ameliorating skin androgenic symptoms and improving menstrual dysfunction. On the other hand, there are still many unresolved issues concerning their metabolic effects. COC could decrease insulin sensitivity and deteriorate glucose tolerance, although the negative influence on insulin sensitivity is dependent on other factors (especially obesity) and this need not be expressed in non-obese patients. It is probable that the impairment of glucose tolerance is reversible, as the incidence of diabetes is not increased in past COC users. The effects of COC on the lipid spectrum are dependent on the type of gestagen, but lipid levels usually remain within the reference limits. Combination therapy of COC with weight reduction or insulin sensitizers could further suppress androgen levels and improve metabolic parameters. The establishment of COC after laparoscopic ovarian drilling may further decrease androgen levels. The combination of COC and GnRH analogues is not superior to COC therapy alone. Prospective data about the influence of COC on the risk of diabetes mellitus, coronary artery disease and endometrial cancer in PCOS women are lacking.
Relation of Sleepiness to Respiratory Disturbance Index
Authors: DANIEL J. GOTTLIEB, CORALYN W. WHITNEY, WILLIAM H. BONEKAT, CONRAD IBER, GARY D. JAMES, MICHAEL LEBOWITZ, F. JAVIER NIETO, CARL E. ROSENBERG
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Obstructive sleep apnea syndrome is a well recognized cause of excessive sleepiness; however, the relation of sleepiness to mild sleep-disordered breathing (SDB), which affects as much as half the adult population, is uncertain. In order to explore this relation, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study, a longitudinal study of the cardiovascular consequences of SDB. The study sample comprises 886 men and 938 women, with a mean age of 65 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Sleep-disordered breathing was quantified by the respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, measured during in-home polysomnography. When RDI was categorized into four groups ( < 5, 5 to < 15, 15 to < 30, ⩾ 30), a significantly progressive increase in mean ESS score was seen across all four levels of SDB, from 7.2 (4.3) in subjects with RDI < 5 to 9.3 (4.9) in subjects with RDI ⩾ 30 (p < 0.001). There was no significant modification of this effect by age, sex, body mass index, or evidence of chronic restriction of sleep time or periodic limb movement disorder. The percentage of subjects with excessive sleepiness, defined as an ESS score ⩾ 11, increased from 21% in subjects with RDI < 5 to 35% in those with RDI ⩾ 30 (p < 0.001). We conclude that SDB is associated with excess sleepiness in community-dwelling, middle-aged and older adults, not limited to those with clinically apparent sleep apnea.