tbuckley/cabot-search huggingface dataset:
THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS
Authors: Richard T. Johnson
Journal: The Journal of Experimental Medicine (1964)

The pathogenesis of herpes simplex virus encephalitis and myelitis was studied in suckling mice using routine titration procedures and fluorescent antibody staining for the identification of infected cells. After intracerebral inoculation virus was shown to disperse rapidly in the cerebrospinal fluid (CSF), multiply in meninges and ependyma, and then invade the underlying parenchyma infecting both neurons and glia. Following extraneural inoculation virus gained access to the central nervous system (CNS) by both hematogenous and neural pathways. After intraperitoneal and intranasal inoculation virus was found to multiply in viscera and produce viremia; foci of CNS infection then developed around small cerebral vessels. After subcutaneous and intranasal inoculation neural spread of virus was demonstrated along corresponding peripheral and cranial nerves. This spread resulted from the centripetal infection of endoneural cells (Schwann cells and fibroblasts). Antigen was not found in axons even after infection of the corresponding ganglion cell perikaryon. Subsequent spread within the CNS was unrelated to neural tracts, and there was no evidence of axonal spread of virus in the host-virus system studied. These findings are discussed in relation to previous and current theories of the viral "blood-brain barrier" and neural pathways of infection.
Formation strategies, mechanism of intracellular delivery and potential clinical applications of pH-sensitive liposomes
Authors: Xin Liu, Guihua Huang
Journal: Asian Journal of Pharmaceutical Sciences (2013)

pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum. So pH-sensitive liposomes can effectively deliver drug or gene fragments into the cytoplasm via the endocytotic pathway. Furthermore, pH-sensitive liposomes can be successfully used in clinical if they enable the encapsulated drugs to be targeted to pathological tissues (such as primary tumors, metastases, local ischemia, inflammation and infection) of the body in which pH is less than the normal physiological value. That's the reason why a growing amount of literatures described the development and applications of pH-sensitive liposomes to improve the therapeutic index of the encapsulated active ingredients. In this review, the commonly used pH-sensitive molecules for pH-sensitive liposome and the mechanisms of intracellular delivery of pH-sensitive liposomes were addressed. Besides, the potential clinical applications were fully discussed in detail with an expectation to contribute to the clinical research of pH-sensitive liposomes.
Drug-related adverse events may predict efficacy in sorafenib therapy for hepatocellular carcinoma
Authors: Yan Zhao, Man Yang, Xingshun Qi, Guohong Han, Daiming Fan
Journal: Hepatology (2012)

We read with great interest the recent study by Iavarone et al.,1 in which the authors report that the patients receiving a half-dose of sorafenib for >70% of the treatment period had a longer median survival than those maintained on a full dose (21.6 versus 9.6 months). However, the authors failed to further analyze this surprising difference in survival. It is noteworthy that the main reason which caused dose reduction was drug-related adverse events (AEs). Here, we propose that the patients in this study who experienced AEs responded better to sorafenib than those who did not, which indicates that the drug-related AEs may presumably predict the efficacy of sorafenib therapy (Fig. 1). Different outcomes are attributed to different responses to sorafenib. Dashed arrow shows the possible predictive role of AEs (adverse events). As we know, most AEs related to sorafenib are downstream effects of suppressed vascular endothelial growth factor (VEGF) signaling in endothelial cells in normal organs.2 It is also suggested that the lack of AEs indicates the absence of an antitumor effect.3 For example, the inhibition of VEGF signaling can not only achieve an antiangiogenic effect, but also decrease the production of the vasodilators nitric oxide (NO) and prostacyclin and consequently result in hypertension.4 The study by Maitland et al.5 also shows that elevated blood pressure is a biomarker for the efficacy of VEGF inhibition. Furthermore, in recent years some researchers have focused on the correlation between AEs related to small molecular compounds or monoclonal antibodies and response or efficacy (Table 1). More solid evidence on this matter is provided by the recent study of Vincenzi et al.6 The authors found a correlation between the development of a rash during sorafenib therapy and both longer time to progression and better disease control. As a result, we consider that the study by Iavarone et al. provides additional evidence for the correlation between AEs related to sorafenib and efficacy. The predictive value of AEs merits better-designed studies. Yan Zhao XX*, Man Yang XX*, Xingshun Qi XX*, Guohong Han XX*, Daiming Fan XX* , * Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China, State Key laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial
Authors: Christina Davies, Hongchao Pan, Jon Godwin, Richard Gray, Rodrigo Arriagada, Vinod Raina, Mirta Abraham, Victor Hugo Medeiros Alencar, Atef Badran, Xavier Bonfill, Joan Bradbury, Michael Clarke, Rory Collins, Susan R Davis, Antonella Delmestri, John F Forbes, Peiman Haddad, Ming-Feng Hou, Moshe Inbar, Hussein Khaled, Joanna Kielanowska, Wing-Hong Kwan, Beela S Mathew, Indraneel Mittra, Bettina Müller, Antonio Nicolucci, Octavio Peralta, Fany Pernas, Lubos Petruzelka, Tadeusz Pienkowski, Ramachandran Radhika, Balakrishnan Rajan, Maryna T Rubach, Sera Tort, Gerard Urrútia, Miriam Valentini, Yaochen Wang, Richard Peto
Journal: The Lancet (2012)
A CUTANEOUS REACTION IN SYPHILIS
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1911)

1. I have proposed the name luetin for an emulsion or extract of pure cultures of Treponema pallidum which is designed to be employed for obtaining, in suitable cases, a specific cutaneous reaction that may become a valuable diagnostic sign in certain stages or forms of syphilitic infection. 2. The repeated inoculation of either living or killed pallida into the testicles of rabbits leads to a condition in which an intradermic injection of luetin is followed by a well marked inflammatory reaction. A corresponding reaction has been obtained neither in rabbits suffering from active syphilitic orchitis, nor in those in which the condition had been cured by the administration of salvarsan four months previously. Normal rabbits, likewise, do not react to the luetin. 3. The luetin produces a similar cutaneous reaction in syphilitic and parasyphilitic patients that is most constant and severe in the tertiary and hereditary affections. In my series of cases, it was present constantly (100 per cent.) in the manifest tertiary affection, in 94 per cent. of latent tertiary affection, and in 96 per cent. of the hereditary affection. 4. During the primary and secondary stages, the reaction is infrequent, and when present it is of mild degree. An exception has been found in cases in which energetic treatment has been or is being carried out and in which clinical signs of syphilis are absent. Such cases may show a severe reaction. Apparently this is true especially of the cases treated with salvarsan. 5. In certain cases of old infection in which no treatment has been taken and in which no symptoms have appeared for many years, and in the course of which miscarriages have not occurred, the cutaneous reaction has failed to appear. But, despite the absence of symptoms, mothers who have young syphilitic children have usually given the reaction. 6. It remains to be determined in how far the cutaneous reaction with luetin can be used to supplement the Wassermann reaction in determining the complete and permanent suppression of a syphilitic affection. 7. It appears probable that the Wassermann reaction is more constant in the primary and secondary, and the cutaneous reaction in the tertiary and latent forms of syphilis. Moreover, it appears that the Wassermann reaction is more directly and immediately affected by antisyphilitic treatment than is the cutaneous reaction. 8. A more active preparation of luetin can certainly be produced by improved methods. This phase of the subject is being considered at the present time and will be reported upon in a later paper.
T cell receptor engagement by peptide–MHC ligands induces a conformational change in the CD3 complex of thymocytes
Authors: Diana Gil, Adam G. Schrum, Balbino Alarcón, Ed Palmer
Journal: The Journal of Experimental Medicine (2005)

The T cell receptor (TCR) can recognize a variety of cognate peptide/major histocompatibility complex (pMHC) ligands and translate their affinity into distinct cellular responses. To achieve this, the nonsignaling αβ heterodimer communicates ligand recognition to the CD3 signaling subunits by an unknown mechanism. In thymocytes, we found that both positive- and negative-selecting pMHC ligands expose a cryptic epitope in the CD3 complex upon TCR engagement. This conformational change is induced in vivo and requires the expression of cognate MHC. We conclude that TCR engagement with a cognate pMHC ligand induces a conformational change in the CD3 complex of thymocytes and propose that this marks an initial event during thymic selection that signals the recognition of self-antigen.
Polymorphisms in the PTPN22 region are associated with psoriasis of early onset
Authors: Rh.Ll. Smith, R.B. Warren, S. Eyre, X. Ke, H.S. Young, M. Allen, D. Strachan, W. McArdle, M.P. Gittins, J.N.W.N. Barker, C.E.M. Griffiths, J. Worthington
Journal: British Journal of Dermatology (2008)

Psoriasis, a chronic inflammatory skin disease, affects approximately 2% of the population worldwide. Although the aetiology of psoriasis is poorly understood, patients with disease of early onset (Type I, age of onset<or=40 years) usually have a strong genetic component to the disease.The purpose of this study was to investigate the role of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene region in susceptibility to Type I psoriasis.Thirteen single nucleotide polymorphisms (SNPs) mapping to the PTPN22 region were genotyped in 647 patients with Type I psoriasis and 566 normal controls.The rs2476601 (R620W) SNP, widely associated with other inflammatory autoimmune diseases, showed no evidence of association with susceptibility to Type I psoriasis. Two SNPs (rs1217414 and rs3789604) demonstrated significant association with Type I psoriasis and were subsequently genotyped in a further 253 unrelated patients and 2024 normal controls. rs1217414 and rs3789604 were also significantly associated with Type I psoriasis in the combined datasets (P=0.003 and P=0.0002, respectively); furthermore carriage of both risk alleles was also significantly associated (P=0.002).This study demonstrates evidence of association of two SNPs (rs1217414 and rs3789604) in the PTPN22 region with Type I psoriasis, providing evidence for a role of this gene in Type I psoriasis that is not conferred by the R620W variant previously associated with a number of inflammatory diseases.
Microarray-Based Screening for Molecular Markers in Medulloblastoma Revealed <b> <i>STK15</i> </b> as Independent Predictor for Survival
Authors: Kai Neben, Andrey Korshunov, Axel Benner, Gunnar Wrobel, Meinhard Hahn, Felix Kokocinski, Andrey Golanov, Stefan Joos, Peter Lichter
Journal: Cancer Research (2004)

Abstract Medulloblastoma, a primitive neuroectodermal tumor of the cerebellum, is one of the most common central nervous system malignancies of childhood. Despite aggressive multimodal therapy, including surgery, irradiation, and chemotherapy, 5-year survival rates have only approached 50–60%. To identify potential candidate genes that predict for overall survival (OS), we performed a gene expression profiling analysis in 35 newly diagnosed medulloblastoma neoplasms. Subsequently, the nine most promising candidate genes were analyzed by immunohistochemistry and fluorescence in situ hybridization on tumor tissue microarrays representing a series of 180 tumors. We found 54 genes in which expression levels predicted for unfavorable survival in medulloblastoma. In line with the gene expression profiling analysis, a positive staining for STK15 (P = 0.0006), stathmin 1 (P = 0.001), and cyclin D1 (P = 0.03) was associated with an unfavorable OS, whereas cyclin B1, DAXX, Ki-67, MYC, NRAS, and p53 showed no statistical significant effect. In comparison to clinically defined parameters such as gender, age, metastatic stage, extent of tumor resection, application of chemotherapy, and tumor grade, positive staining for STK15 was identified as an independent prognostic factor for OS (P = 0.026). Moreover, additional gene copy numbers of MYC (P = 0.003) and STK15 (P = 0.05) predicted for poor survival. The combination of gene expression profiling with tissue microarray experiments allowed the identification of a series of candidate genes that predicts for survival in medulloblastoma. Of the results highlighted by the various data analysis procedures, genes associated with cell proliferation (cyclin D1), transcription (MYC), and especially mitosis (stathmin 1, STK15) appear particularly intriguing with respect to medulloblastoma pathomechanism.