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91.

Background

Adenovirus (ADV) reactivation can cause significant morbidity and mortality in children after allogeneic stem cell transplantation. Antiviral drugs can control viremia, but viral clearance requires recovery of cell-mediated immunity.

Method

This study was an open-label phase 1/2 study to investigate the feasibility of generating donor-derived ADV-specific T cells (Cytovir ADV, Cell Medica) and to assess the safety of pre-emptive administration of ADV-specific T cells in high-risk pediatric patients after allogeneic hematopoietic stem cell transplantation (HSCT) to treat adenoviremia. Primary safety endpoints included graft-versus-host disease (GvHD), and secondary endpoints determined antiviral responses and use of antiviral drugs.

Results

Between January 2013 and May 2016, 92 donors were enrolled for the production of ADV T cells at three centers in the United Kingdom (UK), and 83 products were generated from 72 mobilized peripheral blood harvests and 20 steady-state whole blood donations. Eight children received Cytovir ADV T cells after standard therapy and all resolved ADV viremia between 15 and 127 days later. ADV-specific T cells were detectable using enzyme-linked immunospot assay (ELISpot) in the peripheral blood of all patients analyzed. Serious adverse events included Grade II GvHD, Astrovirus encephalitis and pancreatitis.

Conclusion

The study demonstrates the safety and feasibility of pre-emptively manufacturing peptide pulsed ADV-specific cells for high-risk pediatric patients after transplantation and provides early evidence of clinical efficacy.  相似文献   
92.
Monocultures have been the preferred production route in the bio-industry, where contamination has been a major bottleneck. In nature, microorganisms usually exist as part of organized communities and consortia, gaining benefits from co-habitation, keeping invaders at bay. There is increasing interest in the use of co-cultures to tackle contamination issues, and simultaneously increase productivity and product diversity. The feasibility of extending the natural phenomenon of co-habitation to the biomanufacturing industry in the form of co-cultures requires careful and systematic consideration of several aspects. This article will critically examine and review current work on microbial co-cultures, with the intent of examining the concept and proposing a design pipeline that can be developed in a biomanufacturing context.  相似文献   
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Lacalli, T. C. and Gilmour, T. H. J. 2001. Locomotory and feeding effectors of the tornaria larva of Balanoglossus biminiensis . — Acta Zoologica (Stockholm) 82 : 117–126
The tornaria ciliary bands and oesophagus were examined ultrastructurally to identify the neural components that control larval behaviour. The circumoral ciliary band is known to be innervated in part by fibres from the apical plate and adoral nerve centres. Within the band itself, however, the only neurones we could find were multipolar cells, an unusual cell type with apical processes that traverse the surface of the band. Similar cells occur in the circumoral bands of echinoderm larvae. The tornaria telotroch has a much larger nerve, but no neurones were found either in the band or nearby, so the source of the fibres in the telotroch nerve remains unknown. In addition to having different innervation, the two bands also respond differently to cholinergic agonists, which elicit telotroch arrests but have no visible effect on the circumoral band. The oesophagus has a well-developed musculature and an extensive nerve plexus. During feeding, the oesophagus repeatedly contracts, forcing excess water out along two lateral channels prior to swallowing. These channels are also sites of gill slit formation, so there is evidently a continuity between the water bypass mechanism of the larva and that of the postmetamorphic juvenile.  相似文献   
95.
Apoptosis at the site of rupture has been proposed to play a role in premature rupture of the fetal membranes, a condition associated with increased risk of neonatal sepsis and preterm birth. We investigated the ability of peroxisome proliferator-activated receptor (PPAR)-gamma ligands 15-deoxy-delta12,14PGJ2 (15d-PGJ2), delta12PGJ2, ciglitizone and rosiglitazone to induce apoptosis in the amnion-like WISH cell line. 15d-PGJ2 (10 microM) induced morphological characteristics of apoptosis within 2 h, with biochemical indices (caspase activation and substrate cleavage) following shortly after; maximum cell death (approximately 60%) was observed by 16 h, with an EC50) of approximately 7 microM 15d-PGJ2. Delta12-PGJ2 also induced apoptosis but was less potent and acted at a much slower rate. While ciglitizone also induced apoptosis, rosiglitazone had no effect on cell viability. The mechanism of induction of apoptosis by 15d-PGJ2 and delta12PGJ2, which may be independent of PPAR-gamma activation, requires further elucidation.  相似文献   
96.
The extracellular speciation of mercury may control bacterial uptake and methylation. Mercury-polysulfide complexes have recently been shown to be prevalent in sulfidic waters containing zero-valent sulfur. Despite substantial increases in total dissolved mercury concentration, methylation rates in cultures of Desulfovibrio desulfuricans ND132 equilibrated with cinnabar did not increase in the presence of polysulfides, as expected due to the large size and charged nature of most of the complexes. In natural waters not at saturation with cinnabar, mercury-polysulfide complexes would be expected to shift the speciation of mercury from HgS0(aq) toward charged complexes, thereby decreasing methylation rates.  相似文献   
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ObjectiveTo compare the use and effect of a computer based information system for cancer patients that is personalised using each patient''s medical record with a system providing only general information and with information provided in booklets.DesignRandomised trial with three groups. Data collected at start of radiotherapy, one week later (when information provided), three weeks later, and three months later.Participants525 patients started radical radiotherapy; 438 completed follow up.InterventionsTwo groups were offered information via computer (personalised or general information, or both) with open access to computer thereafter; the third group was offered a selection of information booklets.OutcomesPatients'' views and preferences, use of computer and information, and psychological status; doctors'' perceptions; cost of interventions.ResultsMore patients offered the personalised information said that they had learnt something new, thought the information was relevant, used the computer again, and showed their computer printouts to others. There were no major differences in doctors'' perceptions of patients. More of the general computer group were anxious at three months. With an electronic patient record system, in the long run the personalised information system would cost no more than the general system. Full access to booklets cost twice as much as the general system.ConclusionsPatients preferred computer systems that provided information from their medical records to systems that just provided general information. This has implications for the design and implementation of electronic patient record systems and reliance on general sources of patient information.  相似文献   
100.
By crossing TG.AC v-Ha-ras and K6/ODC transgenic mice, we found previously that an activated ras and follicular ornithine decarboxylase (ODC) overexpression cooperate to generate spontaneous tumors in the skin. Cellular proliferation was dramatically increased in the K6/ODC transgenic skin, as evidenced by elevated proliferating cell nuclear antigen and Ki67 expression compared with nontransgenic littermates. Keratinocytes isolated from transgenic skin also displayed increased clonal growth. Paradoxically, expression of the growth inhibition-associated proteins p53, p21Waf1, p27Klp1, and Bax was increased with ODC overexpression in the skin. ODC overexpression did not affect cyclin D/cyclin-dependent kinase 4 (Cdk4)-dependent phosphorylation of retinoblastoma protein but stimulated cyclin E/Cdk2 and cyclin A/Cdk2-associated kinase activity, with minimal effect on the levels of these proteins. Thus, ODC/polyamine-induced activation of cyclin E/Cdk2 and cyclin A/Cdk2-associated kinase activity may cooperate with the ras induction of cyclin D/Cdk4/6-associated retinoblastoma protein phosphorylation to not only stimulate proliferation but ultimately contribute to tumor development.  相似文献   
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