Abstract
The emergence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) reawakened the need to rapidly understand the molecular etiologies, pandemic potential, and prospective ...treatments of infectious agents. The lack of existing data on SARS-CoV-2 hampered early attempts to treat severe forms of coronavirus disease-2019 (COVID-19) during the pandemic. This study coupled existing transcriptomic data from severe acute respiratory syndrome-related coronavirus 1 (SARS-CoV-1) lung infection animal studies with crowdsourcing statistical approaches to derive temporal meta-signatures of host responses during early viral accumulation and subsequent clearance stages. Unsupervised and supervised machine learning approaches identified top dysregulated genes and potential biomarkers (e.g. CXCL10, BEX2, and ADM). Temporal meta-signatures revealed distinct gene expression programs with biological implications to a series of host responses underlying sustained Cxcl10 expression and Stat signaling. Cell cycle switched from G1/G0 phase genes, early in infection, to a G2/M gene signature during late infection that correlated with the enrichment of DNA damage response and repair genes. The SARS-CoV-1 meta-signatures were shown to closely emulate human SARS-CoV-2 host responses from emerging RNAseq, single cell, and proteomics data with early monocyte-macrophage activation followed by lymphocyte proliferation. The circulatory hormone adrenomedullin was observed as maximally elevated in elderly patients who died from COVID-19. Stage-specific correlations to compounds with potential to treat COVID-19 and future coronavirus infections were in part validated by a subset of twenty-four that are in clinical trials to treat COVID-19. This study represents a roadmap to leverage existing data in the public domain to derive novel molecular and biological insights and potential treatments to emerging human pathogens.
To determine whether transfused colorectal surgery patients were at increased risk for postoperative infections in a tertiary care teaching hospital and whether transfusion alone was the only ...significant risk factor. A retrospective study. A single tertiary care teaching hospital. All patients admitted to St. Boniface General Hospital, Winnipeg, for colorectal surgery during the period Apr. 1, 1995, through Mar. 31, 1996, were studied (N = 154). The overall infection rate was 17%: nontransfused patients, 13%, and transfused patients, 28% (p < 0.038). Patients who received albumin perioperatively had a significantly higher infection rate (38%) than those who did not (13%) (p < 0.001). Stepwise logistic regression analysis identified transfusion and albumin administration as the only independent risk factors for postoperative infection. Perioperative transfusion or albumin administration significantly increases the risk of postoperative infection in colorectal surgery patients.
Head and neck cancer represent about 7% of all malignancies in North America, the majority of these tumors being squamous cell carcinomas (SCC) which metastasize to local and regional lymph nodes. In ...Manitoba, they cause over 70 deaths each year. The goal of the present study was to investigate and develop novel minimally invasive techniques that could allow enhanced evaluation and treatment of patients with head and neck SCC. Human and animal experiments in this study included measurements of tumor microvascularization using dynamic contrast enhanced (DCE) and tumor oxygenation using blood oxygen level dependent (BOLD) and compared them to tumor histology. The detection and identification of sentinel lymph nodes was also investigated. VX-2 tumors in rabbits demonstrated applicability of the DCE and BOLD techniques to a model of SCC. VX-2 tumors showed reduced contrast uptake and decreased oxygenation during development of central necrosis. In patients with SCC, size distribution of microvasculature was shown to be related to tumor recurrence and survival. DCE functions were related to microvessel size distribution, tumor size, and nodal status while BOLD oxygenation studies correlated with tumor microvasculature. Positive nodal status was correlated with a widened oxygenation distribution in the tumors. An MRI based interstitial lymphangiography (MRII,) method using a USPIO contrast agent was developed and proved comparable to the isosulfan blue method. MRIL provides significantly improved anatomic information compared to current sentinel node techniques. Overall, these minimally invasive techniques showed significant promise for enhancing the treatment of patients with head and neck squamous cell carcinoma.* *This dissertation includes a CD that is multimedia (contains text and other applications that are not available in a printed format). The CD requires the following applications: Windows 95/98, Microsoft Office, Internet Access, Corel Draw, Photoshop, Microsoft Photo Editor, Paint.
The focus of our study was to determine whether allogeneic thyroid graft tolerance could be achieved in outbred rabbits. In the experimental group (n = 5), recipient rabbits (NZW) received an ...intrathymic injection of donor (California) lymphocytes $(5\times 10\sp7)$ and a single treatment of 165 g of antilymphocyte serum (ALS). Controls (n = 5) received intrathymic cell culture medium and ALS treatment. Donor-recipient allogenicity was monitored with mixed lymphocyte culture (MLC) before and at one, seven, and eighteen weeks following intrathymic injection. Donor thyroid tissue was placed into recipient gluteal muscle fibres one week following the last MLC measurement. A third group of rabbits (n = 4) received thyroid autografts without any other treatment. Biopsies of the thyroid grafts were taken one and six weeks following graft placement. One experimental group donor-recipient pair was lost due to late death of the recipient (respiratory complication). There were no differences in MLC stimulation indices between the control and experimental group. MLC did not change within groups over the eighteen week monitoring period. All thyroid autografts survived over a two week monitoring period and demonstrated normal thyroid follicles on histologic examination. All thyroid allografts resulted in severe acute rejection reactions noted on the one week biopsy, with rare intact follicles visible. No intact follicles were seen in any allograft recipient at six weeks following grafting. The reason for the failure to induce tolerance in the outbred rabbit model is unknown. (Abstract shortened by UMI.)
Lymph node. Evaluation Peters, Bill; Torchia, Mark G
Journal of biocommunication,
2002, Volume:
29, Issue:
1
Journal Article
The photographs represent a novel clinical approach to the identification of sentinel lymph nodes (SLN). They are unique in the photographer's Canadian institution as they represent the first example ...of digital photography where time was limited by the nature of the medical procedure. The photographs were shot using an Olympus C2500 at 1712 x 1368 pixels using the super macro feature of the camera, manually white balanced to the operating room lights.
