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Biomedical subjects

T Partridge

Publications and source records attributed to T Partridge.

At least 19 recordsLinked to original sources
PubMed2000

The current status of myoblast transfer.

As a means of correcting the defect in the muscles of Duchenne muscular dystrophy (DMD) patients, myoblast transplantation has the advantage of utilizing normal biological mechanisms of repair of this tissue. Thus, it has the potential not only for correcting or complementing the genetic defect, but also for restoring the structure and function of pathologically damaged muscle tissue. However, it is also subject to many of the problems of other genetic therapies for muscle tissue, especially the problem of dispersing the therapeutic agent throughout the muscle mass and that of immune rejection of the genetically corrected tissue. In this article, these problems are discussed. In addition the history of cell transplantation therapy for DMD is presented as an example of the practical difficulties that arise from over eager application to human trials of preliminary data from animal experiments. Recent demonstrations that stem or early precursor cells from a muscle and from the bone marrow are able to disperse to sites of muscle damage via the blood vascular system and to participate in muscle repair raise the hope that this mode of therapy may be applicable to muscular dystrophies.

Animals↗
PubMed2000

T-cell-dependent fibrosis in the mdx dystrophic mouse.

In Duchenne muscular dystrophy patients, the pathological hallmark of the disease, namely, the chronic accumulation of sclerotic scar tissue in the interstitial space of skeletal muscle is attributed to manifestation of secondary pathological processes. Such anomalous generation of matrix protein is thought to be driven by the continuous degeneration and regeneration of muscle both in Duchenne Muscular Dystrophy and in the mdx mouse homolog. We examined mdx and the control strain C57bl/10 mice over a range of ages with respect to the amounts of collagen present in muscles and other organs, finding that the mdx have significantly higher collagen content at later time points in their kidney and lung as well as their muscles. Surprisingly, when we bred the mdx mice on the nu/nu background, the time course of fibrogenesis was modified depending on the tissue and the collagen content was significantly different in age-matched mice. Transplantation of normal thymic tissue into the mdx-nu/nu mice replenished their T-cells and concomitantly altered the collagen content in their tissues to levels comparable with those in immunocompetent mdx mice. This suggests that T-cells play a role in the onset of the fibrotic events that undermines the ability of dystrophic muscle to regenerate.

Aging↗
PubMed2000

Response rate comparisons of e-mail- and mail-distributed student evaluations.

BACKGROUND: The proliferation of electronic information delivery systems has led to increasing use of e-mail as a rapid method of gathering information. Little research has been conducted on the use of e-mail for collecting curriculum evaluations. PURPOSE: To compare e-mailed and mailed educational evaluations for 4th-year medical students. METHODS: Curriculum evaluations were sent to 4th-year medical students who were randomly assigned to receive the survey either by mail or e-mail. RESULTS: Mailed evaluations yielded a higher return rate, fewer number of students omitting items, and shorter responses to an open-ended question than evaluations completed via e-mail. CONCLUSIONS: Although the findings have limited generalizability because of low response rates and small sample sizes, the results suggest caution when using e-mail to collect curriculum evaluations from 4th-year medical students.

Clinical Clerkship↗
PubMed1999

Differential expression and secretion of alpha 1 anti-trypsin between direct DNA injection and implantation of transfected myoblast.

Muscle can be used for systemic delivery of non-muscle proteins. In order to investigate the relative effectiveness of direct DNA plasmid injection versus implantation of genetically modified myogenic cell lines, we have used the human alpha 1 anti-trypsin (alpha1AT) cDNA driven by either cytomegalovirus (CMV) or the muscle creatine kinase 3.3 kb (MCK) promoter in immunodeficient mice. We demonstrate that the implantation of transfected myoblasts stably expressing the human alpha1AT cDNA generates a more persistent production of alpha1AT than does direct intramuscular injection of the same construct as plasmid DNA. Moreover, immunohistological labelling of muscle sections implanted with myoblasts show that the newly formed muscle fibres are those containing the human protein.

Animals↗
PubMed1994

Interactions between cardiomyocytes and lymphocytes in tissue culture: an in vitro model of inflammatory heart disease.

Inflammation of heart tissue is a pathological feature of infections and autoimmune diseases, and sometimes also occurs after heart transplantation. In these situations, the invasive infiltration of lymphocytes, most probably cytotoxic (CD8-positive) T cells, is likely to be the cause of cardiac damage, as shown by the results of studies on experimental animal models of myocarditis. However, the cellular and molecular events underlying the interactions between lymphocytes and cardiomyocytes have hitherto not been investigated. In the present study we describe a new procedure for obtaining ventricular heart cells from neonatal mice and for maintaining them in serum-free medium in culture dishes coated with certain matrix components. Such cells adhered, spread, and were functionally active since they started a beating rhythm after 2 days. T and B cells which had been surface-labelled with biotin were added to these cells and lymphocyte adhesion was measured. The number of lymphocytes which became bound to the cardiomyocytes was calculated from the amount of biotin which remained associated with the monolayer after extensive washing to remove non-adherent cells. Colourimetric detection, using a streptavidin-peroxidase reagent, showed that an average of approximately 10 activated lymphocytes bound per heart cell, four times greater than the attachment of resting T cells. The results of this study provide a reproducible basis for using monoclonal antibodies which react against lymphocyte surface receptors and their cognate ligands to identify the specific adhesion molecules involved in heart cell recognition and interaction.

Animals↗
PubMed1993

Collaborative partnering: a new paradigm in materiel management.

Materiel managers have virtually unlimited opportunities to gain support through a measurable quality and service focus. This support can be achieved through organizational strategies, organizational development, customer service, advanced inventory management and purchasing systems, the power and use of information and, ultimately, mutually beneficial partnerships with distributors and manufacturers.

Consumer Behavior↗
PubMed1991

Animal models of muscular dystrophy--what can they teach us?

The discovery and characterization of the X-linked gene which is defective in Duchenne muscular dystrophy (DMD) and of its protein product, dystrophin, has led to the identification of biochemical homologues of this disease in the mouse, the dog and the cat. All three animal models resemble DMD in that they lack dystrophin and that their skeletal muscle fibres undergo spontaneous necrosis and regeneration. In the dog and man, the degenerative and fibrotic aspects predominate, leading to a progressive loss of muscle structure and function, and to severe clinical disability. By contrast, in the mouse and the cat there is little fibrosis and the regenerative process seems to overcompensate, producing a true muscle hypertrophy and little or no clinical deficit. This interspecies variation in pathological response limits the usefulness of these animals as models for therapeutic testing, calling into question the strength of linkage between a given biochemical lesion and a particular pattern of pathology. However, these differences do give a valuable perspective to the pathology of the dystrophin-deficiency diseases, permitting identification of the immediate and secondary consequences of the lack of dystrophin. Moreover, the dystrophic mouse and dog are readily bred as colonies, thus providing consistent material for investigating the function of dystrophin and for testing methods of replacing its function or compensating for the absence of this function in the muscles of DMD patients. The fact that a lack of dystrophin is compatible, in some species, with only minor muscle dysfunction, raises hopes for an effective therapy in man.

Animals↗
PubMed1991

Contact-dependent transfer of a lysosomal enzyme from lymphocytes to fibroblasts.

In this study we have examined the mechanism underlying the contact-mediated transfer of a lysosomal enzyme from lymphocytes to fibroblasts in culture. We found that although antibody against the mannose 6-phosphate lysosomal targetting receptor (MPR) completely inhibited fibroblast uptake of the lysosomal enzyme beta-glucuronidase (Gus) from the culture medium, it had no effect on the transfer of the enzyme from normal lymphocytes. In contrast, the presence of antibody that prevented the adhesion of the lymphocytes to the fibroblasts inhibited Gus acquisition but had no effect on endocytosis. Immunogold electron microscopy of the contact site between the two types of cell showed that the transfer of Gus involved uncoated vesicles localized near the cell surface of the fibroblast at sites of contact with the lymphocytes. The acquired lymphocyte enzyme was shown to be transported to the fibroblast lysosomes.

Animals↗
PubMed1988

Ultrastructural localization of a lysosomal enzyme in resin-embedded lymphocytes.

The intracellular distribution of lysosomal enzymes in lymphocytes has previously been only poorly defined, mainly by cytochemical procedures of low resolution. In the present study we have used a post-embedding immunogold technique to identify the precise ultrastructural localization of a lysosomal enzyme, beta-glucuronidase, in activated lymphocytes embedded in Lowicryl K4M resin. We show that this enzyme is present in the rough endoplasmic reticulum, in the Golgi complex, and in vesicular organelles which probably include lysosomes.

Animals↗
PubMed1988

Ultrastructural studies of a lysosomal enzyme during lymphocyte activation.

A post-embedding immunogold technique has been used for the ultrastructural localization of a lysosomal enzyme, beta-glucuronidase, in resting and activated T- and B-lymphocytes. The results presented here show that mitogen-induced stimulation of T- and B-cells was associated with an increase in the amount of enzyme in the Golgi complex and rough endoplasmic reticulum, organelles which were rarely present in the resting lymphocytes.

Animals↗