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Biomedical subjects

L Christenson

Publications and source records attributed to L Christenson.

At least 19 recordsLinked to original sources
PubMed1998

Voluntary guidance for the development of tissue-engineered products.

Tissue Engineering is an emerging field of medical research in which there is tremendous activity. Many of these products rely on the use of a cellular component co-formulated with a natural or synthetic biomaterial. At this time, though, there are no consensus safety or efficacy standards for tissue-engineered products. We describe general approaches for assessment of the safety and efficacy of cell-based tissue-engineered products which will lead to reliable medical products for human use. This article provides a general summary of the factors that should be considered in the design and development of cell- and tissue-based products. Seven areas are considered: cell and tissue sourcing; cell and tissue characterization; biomaterials testing; quality assurance; quality control; and nonclinical testing and clinical evaluation. Factors relevant to these areas have been discussed to provide a set of recommendations on which development of products can be standardized. Where relevant, the discussion has been separated in each area to issues that are independent or dependent on cell source. Also, examples are provided of how these guidelines would be applied to two product types that represent somewhat extreme ends of the spectrum for tissue engineering applications. The first example is a product whose mechanism of action is to provide locally-acting structural repair or enhancement in vivo. The second example is a product whose mechanism of action involves systemically distributed physiologically or pharmacologically active products. In general, we have limited the discussion of product types to those that are implanted into the patient for relatively long periods of time. We believe that adoption of these voluntary guidelines would lead to products that are more consistent in quality and performance as well as more rapidly developed.

Animals↗
PubMed1997

Prenatal diagnosis of Klippel-Trénaunay-Weber syndrome as a cause for in utero heart failure and severe postnatal sequelae.

Ultrasound examination led to prenatal diagnosis of Klippel-Trénaunay-Weber syndrome complicated by early fetal congestive heart failure. The postnatal course was complicated by the Kasabach-Merritt syndrome of thrombocytopenia due to platelet consumption within the haemangioma. There was need for neonatal cardiopulmonary resuscitation and limb amputation.

Abdomen↗
PubMed1996

The cyclic GMP-mediated calcium release pathway in sea urchin eggs is not required for the rise in calcium during fertilization.

The mechanisms required for cGMP-induced Ca2+ release in the sea urchin egg were investigated using both egg homogenates and intact eggs. The postulated pathway of cGMP-dependent protein kinase (PKG) activation of ADP-ribosyl cyclase for production of cADPR to activate the ryanodine receptor Ca2+ channel was tested with a variety of activators (cGMP analogs and cIMP) and inhibitors (Rp-8-pCPT-cGMPS, 3-aminopyridine NAD, nicotinamide, and spermine). Our observations are consistent with Ca2+ release by cGMP in the egg being dependent on an isoform of PKG that is distinct from the mammalian enzyme. PKG activity in the sea urchin egg was activated by cIMP, but was insensitive to cGMP analogs, which are potent activators of mammalian isoenzymes. Surprisingly, it appears the activation of the cGMP-dependent Ca2+ release pathway was unnecessary during fertilization. Inhibitors of either PKG or ADP-ribosyl cyclase activities did not prevent the transient rise in intracellular Ca2+ activity in heparin-loaded eggs during fertilization. These results suggest the synthesis of cADPR during fertilization is not necessary for regulating the Ca2+ event.

ADP-ribosyl Cyclase↗
PubMed1992

A novel approach to neural transplantation in Parkinson's disease: use of polymer-encapsulated cell therapy.

Transplantation of dopaminergic neurons derived from fetal or adrenal tissue into the striatum is a potentially useful treatment for Parkinson's disease (PD). Although initially promising, recent clinical studies using adrenal autografts have demonstrated limited efficacy. The use of human fetal cells, despite promising preliminary results, is complicated by tissue availability and ethical concerns. An attractive alternative is based on encapsulating dopamine-producing cells into polymer capsules prior to transplantation. Polymer capsules can be fabricated to surround the cells with a semi-permeable and immunoprotective barrier. The semi-permeable membrane allows nutrients to enter the capsule, so the encapsulated cells will survive and function, and dopamine and other low molecular weight constituents to diffuse out into the host tissue. Thus, the technique allows use of unmatched human tissue (allografts), or even animal tissue (xenografts) without immunosuppression of the recipient. Cell-loaded polymer capsules can also be retrieved if necessary or desired. The demonstration that striatal implants of encapsulated dopamine-producing cells promote behavioral recovery in rodent and primate models of PD further suggests that cellular encapsulation may be a useful strategy for ameliorating the behavioral consequences of PD.

Adrenal Medulla↗
PubMed1991

Mast cells and tissue reaction to intraperitoneally implanted polymer capsules.

The inflammatory reaction to implanted biomaterials often compromises the clinical usefulness of implantable devices. Dexamethasone, an anti-inflammatory agent, acts on macrophages to decrease production of inflammatory mediators, and on mast cells to prevent degranulation. Systemic administration of dexamethasone (dms) in rats decreases the tissue reaction to intraperitoneally implanted vinyl chloride-acrylic copolymer capsules. Local release of even smaller amounts of dms from a polymeric substrate placed inside an acrylic copolymer capsule may control the tissue reaction while avoiding the undesirable side effects of systemic treatment. Such a system also allows investigation of the local effect of soluble molecules on tissue-material interactions without altering the surface properties of the implant or adding the effect of a releasing material. In the present study, we investigated the effect of dms released from ethylene vinyl acetate (EVAc) rods placed in acrylic copolymer capsules and implanted in the peritoneal cavity of rats. In vitro the release of dms from EVAc rods was quasilinear for 5 weeks. When implanted intraperitoneally into rats, polymer capsules containing EVAc/dms rods generated a tissue reaction that was significantly thinner and featured fewer fibroblast and collagen layers than that around capsules containing pure EVAc rods at all time points studied. The tissue reaction layer was also thinner than that previously described in rats treated systemically with dms. The trabeculae of implants with dms-loaded EVAc rods contained significantly more intact mast cells than implants with EVAc alone, suggesting that degranulation of mast cells is involved in the tissue reaction to intraperitoneal polymer implants.

Analysis of Variance↗
PubMed1989

Tissue reaction to intraperitoneal polymer implants: species difference and effects of corticoid and doxorubicin.

The peritoneal cavity is a convenient site for implantation of encapsulated hormone-secreting tissue. However, host tissue organization around such implants may affect solute exchange and viability of the encapsulated tissue. The reaction to polyvinyl chloride acrylic copolymer capsules implanted in the peritoneal cavity of rats and mice was therefore studied. Some animals received a slow release dexamethasone pellet, others were pretreated with doxorubicin, in an attempt to minimize the tissue reaction. The tissue reaction was significantly thicker in rats than in mice at both 2 and 6 weeks after implantation. In rats, corticoids decreased significantly the thickness of the reactive layer as compared to control at all time points studied, but doxorubicin had no effect. The tissue reaction in mice was not significantly affected by corticoid treatment. In both species the thickness of the tissue reaction did not increase significantly between 2 and 6 weeks. At 3 days the tissue reaction consisted of an interrupted single layer of macrophages in mice, whereas in rats the reaction consisted of two or three layers of macrophages and polymorphonuclear cells. At both 2 and 6 weeks, several cell layers surrounded the implants: a single layer of macrophages lying along the polymer, a variable number of layers of fibroblasts interspersed with collagen fibrils (fewer in mice than in rats, and fewer in corticoid treated rats than control rats) and an outer monolayer of mesothelial cells. We conclude that the intensity of tissue reaction to polymer implants in the peritoneal cavity is species dependent and can be decreased by the administration of corticoids but not doxorubicin.

Adrenal Cortex Hormones↗
PubMed1986

Differential expression of T cell differentiation antigens and major histocompatibility antigens on activated T cells during the cell cycle.

In this report we have analyzed cell cycle-related fluctuations of both quantity and density of the T cell differentiation antigens, CD3 (T3), CD4 (T4) and CD8 (T8), as well as the major histocompatibility complex (MHC) antigens on the cell surface of activated T cells. Phytohemagglutinin-activated T cells cultured for 3 days with or without conditioned medium or for 10 days with conditioned medium and mixed lymphocyte culture-derived T cell clones were used for the analysis. Correlated measurements of the surface antigen quantity (immunofluorescence), DNA content (dye Hoechst 33342), and cell size (light scatter), not influenced by synchrony induction methods and cell fixation, were performed by dual-beam flow cytometry. Our results demonstrate that the T cell differentiation antigens, CD3, CD4 and CD8, and class I MHC antigens are increased in density in the G1 phase for all activated T cells tested. In contrast, class II MHC antigens are increased in density in the G2 phase of activated T cells maintained with conditioned medium. Since it is known that the T cell differentiation antigens and class I MHC antigens on activated T cells are necessary for proliferation of T cells, our study suggests that this effect is more significant in the G1 phase. The cell cycle changes in expression of class I and class II MHC antigens, but not of the T cell differentiation antigens, appear to be mediated by soluble factors, probably including interferon-gamma, which could produce a differential increase of class I and class II MHC antigens on G2 phase cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

Investigation of in vivo activated T cells in multiple sclerosis and inflammatory central nervous system diseases.

Monoclonal antibodies have recently been characterized which identify activated T cells at different stages of differentiation. We compared the expression of the late appearing activation antigen defined by monoclonal antibody TS2/7 with the expression of early appearing activation antigens in a group of patients with active multiple sclerosis, encephalitis, non-inflammatory other neurologic diseases, and normal controls. An increase in TS2/7 reactivity of peripheral blood T cells was found in MS patients compared to controls (P less than 0.001), however, there was no increase in the level of early activation antigens. This was in contrast to three patients with viral encephalitis, who had an increase in the early activation antigen 4F2, but minimal, if any, increase in the TS2/7 reactive antigen. This study demonstrates that in vivo, as in vitro, it is possible to identify multiple differentiation stages for activated T cells. Furthermore, the presence of activated T cells in the peripheral blood of multiple sclerosis patients suggests that there is systemic immune activation in MS, and could provide a means to monitor abnormal immunologic activity in MS when these cells are functionally characterized.

Antibodies, Monoclonal↗
PubMed1984

Isolation and culture of a tetraploid subpopulation of smooth muscle cells from the normal rat aorta.

Smooth muscle cells with 4C (double diploid) DNA content have been found in major arteries. The proportion of 4C cells increases with normal aging and with hypertension. These cells may represent a state of arrest at the G2 phase of the cell cycle or may be examples of true tetraploidy. Flow cytometric cell sorting was used to isolate 4C smooth muscle cells from the rat aorta, and the cells were cultured. Flow cytometry, Feulgen microdensitometry, and karyotyping of the progeny of the 4C cells established the presence of true tetraploid cells. These findings demonstrate the presence of reproductively viable tetraploid cells in a normal mammalian tissue.

Animals↗
PubMed1983

Simultaneous flow cytometric analysis of human T cell activation antigen expression and DNA content.

Cell-surface antigens that are induced to appear on T cells activated by the lectin phytohemagglutinin-P (PHA) can be classified both on the basis of the kinetics of their appearance and on their growth-association properties. Seven distinct T cell activation antigens, defined by monoclonal antibodies, were classified as early, intermediate, or late antigens based on their temporal appearance relative to DNA synthesis. Four antigens, the transferrin receptor, the T cell activation antigen Tac, the 4F2 antigen, and the 49.9 antigen were early antigens, whereas the OKT10 antigen appeared at intermediate times and both HLA-DR and antigen 19.2 appeared late. The use of a dye, Hoechst 33342, which stains DNA stoichiometrically, allowed the simultaneous analysis of immunofluorescence and cell cycle position of individual cells. This analysis unexpectedly revealed that essentially all cells in the proliferative phase of the cell cycle expressed each of the four early-activation antigens. The correlation between expression of the four early-activation antigens and T cell proliferation suggests that these molecules are important for the growth of all T cells. The relationship of two of these activation antigens, known to be the receptors for transferrin and interleukin 2, a T cell growth factor, is discussed with special reference to the roles of their ligands in supporting the growth of T cells.

Antibodies, Monoclonal↗
PubMed1983

Immunofluorescence measurement in a flow cytometer using low-power helium-neon laser excitation.

Helium-neon lasers are economical and efficient light sources; their utility in flow cytometry to date has been limited by the lack of fluorescent probes that can be excited at 633 nm. Allophycocyanin (APC), a highly fluorescent phycobiliprotein, can be used as an antibody label and has spectral characteristics suitable for use with He-Ne lasers; we undertook to resolve whether a low-power (7 mW) He-Ne laser could provide sufficient excitation to permit flow cytometric detection of APC-labeled antibodies on cell surfaces. We made an APC conjugate of monoclonal antibody 4F2, which reacts with an antigen abundant on the surfaces of activated human T-lymphocytes; APC-4F2 was used to stain blood mononuclear cells that had been cultured with and without phytohemagglutinin (PHA). Cells so stained were examined in a flow cytometer with orthogonal illumination at 633 nm from a 7 mW He-Ne laser; antibody-bearing cells were detectable by fluorescence emission above 665 nm. Cells from the same cultures were stained with fluorescein-labeled 4F2 antibody and examined in a flow cytometer with argon ion laser excitation at 488 nm. Percentages of antibody-bearing cells determined from APC fluorescence and from fluorescein fluorescence were in good agreement. It thus appears that He-Ne lasers and APC-antibodies are usable for immunofluorescence measurements; the sensitivity attainable with this technique remains to be determined.

Animals↗
PubMedDate not supplied

Effects of frequent and sustained plateletapheresis on peripheral blood mononuclear cell populations and lymphocyte functions of normal volunteer donors.

Per procedure, plateletapheresis may remove 2 X 10(9) to 3 X 10(9) white cells from the peripheral blood of a normal donor. To investigate the effects of frequent and sustained plateletapheresis, multiple peripheral blood tests were performed on 25 volunteer donors undergoing plateletapheresis an average of 72 times over periods of up to 8 years, and results were compared with 25 age- and sex-matched controls who had not undergone apheresis. In donors, significant decreases were observed in: 1) both absolute number and percentage of T4+ cells; 2) absolute number of both T8+ cells and Leu-7+ cells; 3) T4/T8 ratio; 4) responses to both pokeweed mitogen and alloantigens; and 5) IgG levels. Significant increases were observed in percentages of both B cells and monocytes, and responses to both phytohemagglutinin and Concanavalin A. Plateletapheresis removes a large number of T4 and T8 cells, a moderate number of B cells, and a smaller number of monocytes and Leu-7 cells. The results suggest that during vigorous plateletapheresis the replenishment to peripheral blood per month was less than 1.83 X 10(9) and 0.93 X 10(9) for T4 cells and T8 cells, respectively, greater than 0.27 X 10(9) and 0.62 X 10(9) for B cells and monocytes, respectively, and approximately 0.39 X 10(9) for Leu-7 cells. Although no clinical effect was noted, these data suggest that frequent and sustained non-lymphocyte sparing plateletapheresis is associated with changes in laboratory findings related to the immune system.

Adolescent↗