The COVID-19 pandemic has caused unprecedented disruption, particularly in retail. Where essential demand cannot be fulfilled online, or where more stringent measures have been relaxed, customers must visit shop premises in person. This naturally gives rise to some risk of susceptible individuals (customers or staff) becoming infected.
View Article and Find Full Text PDFThe primary goal of bioprocess cell line development is to obtain high product yields from robustly growing and well-defined clonal cell lines in timelines measured in weeks rather than months. Likewise, high-throughput screening of B cells and hybridomas is required for most cell line engineering workflows. A substantial bottleneck in these processes is detecting and isolating rare clonal cells with the required characteristics.
View Article and Find Full Text PDFFor a therapeutic antibody to succeed, it must meet a range of potency, stability, and specificity criteria. Many of these characteristics are conferred by the amino acid sequence of the heavy and light chain variable regions and, for this reason, can be screened for during antibody selection. However, it is important to consider that antibodies satisfying all these criteria may be of low frequency in an immunized animal; for this reason, it is essential to have a mechanism that allows for efficient sampling of the immune repertoire.
View Article and Find Full Text PDFAntibody-targeted chemotherapy with immunoconjugates of calicheamicin is a clinically validated strategy in cancer therapy. This study describes the selection of a murine anti-CD22 mAb, m5/44, as a targeting agent, its conjugation to a derivative of calicheamicin (CalichDM) via either acid-labile or acid-stable linkers, the antitumor activity of CalichDM conjugated to m5/44, and its subsequent humanization by CDR grafting. Murine IgG1 mAb m5/44 was selected based on its subnanomolar affinity for CD22 and ability to be internalized into B cells.
View Article and Find Full Text PDFThere is very little published literature on pressure sores in children and most of the existing literature is qualitative. Using literature from paediatric and adult studies, a schedule was designed to collect quantitative data on aspects that may predispose children to pressure injury. The schedule was piloted in an incidence and a prevalence study at the Royal Liverpool Children's NHS Trust.
View Article and Find Full Text PDFBackground: We have evaluated the use of a mouse/human chimeric anti-platelet-derived growth factor-beta receptor antibody in combination with heparin to inhibit intimal hyperplasia in the saphenous artery of the baboon after balloon angioplasty.
Methods And Results: The study evaluated lesion development in sequential injuries made 28 days apart. Each animal received control treatment after the first injury and antibody/heparin therapy after the second injury to the contralateral artery.
In this study, we describe the activity of CT1746, an orally-active synthetic MMP inhibitor that has a greater specificity for gelatinase A, gelatinase B and stromelysin than for interstitial collagenase and matrilysin, in a nude mouse model that better mimics the clinical development of human colon cancer. The model is constructed by surgical orthotopic implantation (SOI) of histologically-intact tissue of the metastatic human colon tumor cell line Co-3. Animals were gavaged with CT1746 twice a day at 100 mg/kg for 5 days after the SOI of Co-3 for 43 days.
View Article and Find Full Text PDFActivated lamina propria T cells responding to luminal Ags are thought to be important in celiac disease and Crohn's disease, and T cells responding to foreign MHC products are also important in intestinal graft-vs-host disease and intestinal transplant rejection. However, the mechanism(s) by which T cells mediate damage in the gut is not known. We have previously shown that activation of lamina propria T cells by PWM in explant cultures of second trimester human small intestine produces severe tissue injury, with epithelial cell shedding and loss of villi.
View Article and Find Full Text PDFEnhanced matrix metalloproteinase-2 (MMP-2/72-kd type IV collagenase) action correlates with invasion in neoplasia. MMP-2 is inhibited in vivo by tissue inhibitors of metalloproteinases (TIMPs)-TIMP-1 and, especially, TIMP-2. A synthetic, biotinylated inhibitor specific for activated MMP-2 in solution phase, and immunohistochemistry were used to detect MMP-2 and TIMP-2 expression in cell lines and ovarian tumors and to analyze the surface-binding capacity of the inhibitors, which are potential therapeutic agents.
View Article and Find Full Text PDFBackground: Matrix metalloproteinases (MMPs), especially gelatinase A and gelatinase B (GLB), are believed to be important components of the metastatic process. Tissue Inhibitors of Metalloproteinases (TIMPs) form complexes with MMPs and inhibit cancer dissemination. After local secretion, MMPs and their complexes with TIMPs leach into the blood stream where their concentration can be measured, thereby serving as surrogate markers of disease.
View Article and Find Full Text PDFObjective: To determine whether plasma concentrations of stromelysin-1 and gelatinase A are increased in patients with various forms of arthritis.
Methods: A sensitive and specific sandwich enzyme linked immunosorbent assay (ELISA), which employs a murine monoclonal antibody and a rabbit polyclonal antibody to human stromelysin-1, was used to measure plasma stromelysin-1 in 53 healthy subjects, 113 patients with various forms of arthritis and connective tissue diseases, and 65 patients with cancer. Gelatinase A was also measured in these patients using specific polyclonal and monoclonal antibodies to gelatinase A in an ELISA:
Results: The plasma concentration of stromelysin-1 (X +/- SEM) was significantly increased (p < 0.
Br J Cancer
September 1994
Death from cancer results from the development of metastases or local progression of tumour. Metastasis and local progression may result from the inappropriate activity of metalloproteinases released by tumour cells or of their regulatory peptides. We have developed quantitative assays for interstitial collagenase, stromelysin 1 and tissue inhibitors of metalloproteinase (TIMP) 1 and 2, which have allowed the study of serum levels of these proteins.
View Article and Find Full Text PDFHuman gelatinase A, a member of the matrix metalloproteinase family, is secreted from cells as the M(r) 72,000 latent precursor, progelatinase A. The autolytic removal of an N-terminal propeptide generates the M(r) 66,000 active form. Mutants of recombinant progelatinase A, altered such that the proposed active site glutamic acid residue (E375) was replaced by either an aspartic acid (proE375-->D), an alanine (proE375-->A) or a glutamine (proE375-->Q), were purified from medium conditioned by transfected NS0 mouse myeloma cells.
View Article and Find Full Text PDFImmunoassays have been developed for human collagenase, stromelysin, tissue inhibitor of metalloproteinases (TIMP) and TIMP complexed with both of the active enzymes. Selection of antibodies of defined specificity enabled measurement of both the pro and active forms of the metalloproteinase. Free TIMP was quantified by the selection of a monoclonal antibody which did not recognise TIMP when complexed with metalloproteinases.
View Article and Find Full Text PDFThe aim of this study was to determine the proliferative activity within the epithelial cells of the normal human breast in 122 patients (6 reduction mammoplasties and 116 fibroadenoma excisions) in relation to age and the phase of the menstrual cycle. Thirty three of the patients were on oral contraceptives and 33 were parous. Thin tissue slices were incubated with tritiated thymidine and processed for autoradiography.
View Article and Find Full Text PDFFull PLM curves have been obtained for four sites in the mouse. The first peaks have been analysed by computer and the duration of the G2 + M and S phases determined together with their standard deviations. The full curves showed a general similarity for all four sites with no clear second peak.
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