排序方式: 共有39条查询结果,搜索用时 31 毫秒
21.
R.R. TIDWELL S. G. KILGORE K.A. OKEMENG J.D. GERATZ JAMES EDWIN HALL 《The Journal of eukaryotic microbiology》1989,36(1):74S-76S
Seven analogs of pentamidine were tested for their activity against an immunosuppressed rat model of Pneumocystis carinii pneumonia. Structural alterations of the pentamidine molecule included variations of the alkyl chain linking the two p-amidino phenoxy moieties and relocation of the amidine groups from the para to the meu position on the phenoxy rings. All analogs of pentamidine were active against P. carinii pneumonia when compared to a saline-treated control group. One derivative, 1, 4-di(4'-amidinophenoxy)butanc, proved to be statistically more active than the parent drug. 相似文献
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Maria Benitez‐Guijarro Cesar Lopez‐Ruiz Žygimantė Tarnauskaitė Olga Murina Mahwish Mian Mohammad Thomas C Williams Adeline Fluteau Laura Sanchez Raquel Vilar‐Astasio Marta Garcia‐Canadas David Cano Marie‐Jeanne HC Kempen Antonio Sanchez‐Pozo Sara R Heras Andrew P Jackson Martin AM Reijns Jose L Garcia‐Perez 《The EMBO journal》2018,37(15)
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Michael J Gramer Ewald TJ van den Bremer Muriel D van Kampen Amitava Kundu Peter Kopfmann Eric Etter David Stinehelfer Justin Long Tom Lannom Esther H Noordergraaf Jolanda Gerritsen Aran F Labrijn Janine Schuurman Patrick HC van Berkel Paul WHI Parren 《MABS-AUSTIN》2013,5(6):962-973
The manufacturing of bispecific antibodies can be challenging for a variety of reasons. For example, protein expression problems, stability issues, or the use of non-standard approaches for manufacturing can result in poor yield or poor facility fit. In this paper, we demonstrate the use of standard antibody platforms for large-scale manufacturing of bispecific IgG1 by controlled Fab-arm exchange. Two parental antibodies that each contain a single matched point mutation in the CH3 region were separately expressed in Chinese hamster ovary cells and manufactured at 1000 L scale using a platform fed-batch and purification process that was designed for standard antibody production. The bispecific antibody was generated by mixing the two parental molecules under controlled reducing conditions, resulting in efficient Fab-arm exchange of >95% at kg scale. The reductant was removed via diafiltration, resulting in spontaneous reoxidation of interchain disulfide bonds. Aside from the bispecific nature of the molecule, extensive characterization demonstrated that the IgG1 structural integrity was maintained, including function and stability. These results demonstrate the suitability of this bispecific IgG1 format for commercial-scale manufacturing using standard antibody manufacturing techniques. 相似文献
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Abhilash K Venugopal S Sameer Kumar Ghantasala Lakshmi Dhevi N Selvan Anita Mahadevan Santosh Renuse Praveen Kumar Harsh Pawar Nandini A Sahasrabhuddhe Mooriyath S Suja Yarappa L Ramachandra Thottethodi S Keshava Prasad Shampur N Madhusudhana Harsha HC Raghothama Chaerkady Parthasarathy Satishchandra Akhilesh Pandey Susarla K Shankar 《Clinical proteomics》2013,10(1):3
Introduction
Rabies is a fatal acute viral disease of the central nervous system, which is a serious public health problem in Asian and African countries. Based on the clinical presentation, rabies can be classified into encephalitic (furious) or paralytic (numb) rabies. Early diagnosis of this disease is particularly important as rabies is invariably fatal if adequate post exposure prophylaxis is not administered immediately following the bite.Methods
In this study, we carried out a quantitative proteomic analysis of the human brain tissue from cases of encephalitic and paralytic rabies along with normal human brain tissues using an 8-plex isobaric tags for relative and absolute quantification (iTRAQ) strategy.Results and conclusion
We identified 402 proteins, of which a number of proteins were differentially expressed between encephalitic and paralytic rabies, including several novel proteins. The differentially expressed molecules included karyopherin alpha 4 (KPNA4), which was overexpressed only in paralytic rabies, calcium calmodulin dependent kinase 2 alpha (CAMK2A), which was upregulated in paralytic rabies group and glutamate ammonia ligase (GLUL), which was overexpressed in paralytic as well as encephalitic rabies. We validated two of the upregulated molecules, GLUL and CAMK2A, by dot blot assays and further validated CAMK2A by immunohistochemistry. These molecules need to be further investigated in body fluids such as cerebrospinal fluid in a larger cohort of rabies cases to determine their potential use as antemortem diagnostic biomarkers in rabies. This is the first study to systematically profile clinical subtypes of human rabies using an iTRAQ quantitative proteomics approach. 相似文献27.
Thottethodi Subrahmanya Keshava Prasad Renu Verma Satish Kumar Raja Sekhar Nirujogi Gajanan J Sathe Anil K Madugundu Jyoti Sharma Vinuth N Puttamallesh Anjali Ganjiwale Vithal P Myneedu Aditi Chatterjee Akhilesh Pandey HC Harsha Jayasuryan Narayana 《Clinical proteomics》2013,10(1):8
Background
Purified protein derivative (PPD) has been used for more than half a century as an antigen for the diagnosis of tuberculosis infection based on delayed type hypersensitivity. Although designated as “purified,” in reality, the composition of PPD is highly complex and remains ill-defined. In this report, high resolution mass spectrometry was applied to understand the complexity of its constituent components. A comparative proteomic analysis of various PPD preparations and their functional characterization is likely to help in short-listing the relevant antigens required to prepare a less complex and more potent reagent for diagnostic purposes.Results
Proteomic analysis of Connaught Tuberculin 68 (PPD-CT68), a tuberculin preparation generated from M. tuberculosis, was carried out in this study. PPD-CT68 is the protein component of a commercially available tuberculin preparation, Tubersol, which is used for tuberculin skin testing. Using a high resolution LTQ-Orbitrap Velos mass spectrometer, we identified 265 different proteins. The identified proteins were compared with those identified from PPD M. bovis, PPD M. avium and PPD-S2 from previous mass spectrometry-based studies. In all, 142 proteins were found to be shared between PPD-CT68 and PPD-S2 preparations. Out of the 354 proteins from M. tuberculosis–derived PPDs (i.e. proteins in either PPD-CT68 or PPD-S2), 37 proteins were found to be shared with M. avium PPD and 80 were shared with M. bovis PPD. Alignment of PPD-CT68 proteins with proteins encoded by 24 lung infecting bacteria revealed a number of similar proteins (206 bacterial proteins shared epitopes with 47 PPD-CT68 proteins), which could potentially be involved in causing cross-reactivity. The data have been deposited to the ProteomeXchange with identifier PXD000377.Conclusions
Proteomic and bioinformatics analysis of different PPD preparations revealed commonly and differentially represented proteins. This information could help in delineating the relevant antigens represented in various PPDs, which could further lead to development of a lesser complex and better defined skin test antigen with a higher specificity and sensitivity. 相似文献28.
KAP1 regulates endogenous retroviruses in adult human cells and contributes to innate immune control
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Christopher HC Tie Liane Fernandes Lucia Conde Luisa Robbez‐Masson Rebecca P Sumner Tom Peacock Maria Teresa Rodriguez‐Plata Greta Mickute Robert Gifford Greg J Towers Javier Herrero Helen M Rowe 《EMBO reports》2018,19(10)
Endogenous retroviruses (ERVs) have accumulated in vertebrate genomes and contribute to the complexity of gene regulation. KAP1 represses ERVs during development by its recruitment to their repetitive sequences through KRAB zinc‐finger proteins (KZNFs), but little is known about the regulation of ERVs in adult tissues. We observed that KAP1 repression of HERVK14C was conserved in differentiated human cells and performed KAP1 knockout to obtain an overview of KAP1 function. Our results show that KAP1 represses ERVs (including HERV‐T and HERV‐S) and ZNF genes, both of which overlap with KAP1 binding sites and H3K9me3 in multiple cell types. Furthermore, this pathway is functionally conserved in adult human peripheral blood mononuclear cells. Cytosine methylation that acts on KAP1 regulated loci is necessary to prevent an interferon response, and KAP1‐depletion leads to activation of some interferon‐stimulated genes. Finally, loss of KAP1 leads to a decrease in H3K9me3 enrichment at ERVs and ZNF genes and an RNA‐sensing response mediated through MAVS signaling. These data indicate that the KAP1‐KZNF pathway contributes to genome stability and innate immune control in adult human cells. 相似文献
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Quantitation of junctional and extrajunctional acetylcholine receptors by electron microscope autoradiography after (125)I-α-bungarotoxin binding at mouse neuromuscular junctions
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The distribution and quantitation of 125I-alpha-bungarotoxin (alpha-BTX) binding sites and thus acetylcholine receptor (AChR) were determined in mouse sternomastoid muscle by electron microscope autoradiography. We found that a valid criterion for receptor saturation at the neuromuscular junction was the complete elimination of neurally evoked tetanic muscle contractions, since, when such a criterion was used for the endpoint of toxin incubation, alpha-BTX was bound to approximately 90% of total available endplate sites. When, without implying localization, the presynaptic axonal membrane was used as a convenient reference structure, the concentration of alpha-BTX relative to this membrane was determined to be 46,000 +/- 27% sites/mum2. 相似文献
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YONG LIU RICHARD R. TIDWELL MICHAEL J. LEIBOWITZ 《The Journal of eukaryotic microbiology》1994,41(1):31-38
Unlike its mammalian hosts, the opportunistic fungal pathogen Pneumocystis carinii harbors group I self-splicing introns in its chromosomal genes encoding rRNA. This difference between pathogen and host suggests that intron splicing is a promising target for chemotherapy. We have found that intron splicing in vitro is inhibited by the anti- Pneumocystis agent pentamidine and by a series of pentamidine analogues, as well as by some aminoglycosides, tetracycline, L-arginine and ethidium bromide. Further studies will be needed to determine if this is the mechanism of action of pentamidine against P. carinii . 相似文献