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Biomedical subjects

P S Russell

Publications and source records attributed to P S Russell.

At least 19 recordsLinked to original sources
PubMed2001

Tolerance, mixed chimerism, and chronic transplant arteriopathy.

Much evidence supports the conclusion that immunological responses to donor-specific incompatibilities are a major factor in producing "chronic" transplant rejection, including the arteriopathy (atherosclerosis) commonly present. Our experiments explored the effects of altered immunological responsiveness to these Ags on the formation of arteriopathy in transplanted mouse hearts. Specific immunological nonreactivity, or tolerance, was induced either by neonatal administration of allogeneic spleen cells (from F(1) donors between class I-mismatched donor and recipient strains), resulting in "classical" immunological tolerance, or by bone marrow infusion to suitably prepared adult recipients, either fully MHC mismatched or class I mismatched, yielding "mixed chimerism." Both approaches obviated systemic graft-versus-host effects. In both groups, donor-specific skin grafts survived perfectly and donor cell chimerism persisted. Specific Abs were undetectable in all recipients. Most transplants to either group of tolerant recipients developed striking vasculopathy in their coronary arteries (12 of 15 in neonatal tolerance and 15 of 23 in mixed chimeras). Neointimal infiltrates included CD4 and CD8 T cells and macrophages. Only 2 of 29 contemporary isotransplants showed any evidence of vasculopathy. Recipients essentially incapable of T and B cell responses (C.B-17/SCID and RAG1(-/-)) were also used. Transplants into these animals developed vasculopathy in 16 of 31 instances. Accordingly, in this setting, vasculopathy develops in the presence of H-2 gene-determined incompatibility even with minimal conventional immune reactivity. Perhaps innate responsiveness, that could include NK cell activity, can create such arteriopathic lesions. More evidence is being sought regarding this process.

Animals↗
PubMed2001

Vertical-cavity surface-emitting resonances in photonic crystal films.

It is shown that thin films of dielectric, etched through with a suitably chosen lattice of holes, can support surface-emitting vertical resonances with very-high-cavity Q factors (approximately 10(5) in the case of Al(x)GaAs(1-x) on oxidized AlyGaAs1-y). A Bloch-wave expansion is used to develop a complete vector-field analysis of these resonances and to reveal their underlying physics. Since they do not require multilayer mirrors, such resonators are a practical and simple replacement for conventional vertical-cavity surface-emitting laser structures. Other applications include wavelength-division-multiplexing components and highly sensitive gas detectors.

Journal Article↗
PubMed1999

Determination of human DNA polymerase utilization for the repair of a model ionizing radiation-induced DNA strand break lesion in a defined vector substrate.

Human DNA polymerase and DNA ligase utilization for the repair of a major class of ionizing radiation-induced DNA lesion [DNA single-strand breaks containing 3'-phosphoglycolate (3'-PG)] was examined using a novel, chemically defined vector substrate containing a single, site-specific 3'-PG single-strand break lesion. In addition, the major human AP endonuclease, HAP1 (also known as APE1, APEX, Ref-1), was tested to determine if it was involved in initiating repair of 3'-PG-containing single-strand break lesions. DNA polymerase beta was found to be the primary polymerase responsible for nucleotide incorporation at the lesion site following excision of the 3'-PG blocking group. However, DNA polymerase delta/straightepsilon was also capable of nucleotide incorporation at the lesion site following 3'-PG excision. In addition, repair reactions catalyzed by DNA polymerase beta were found to be most effective in the presence of DNA ligase III, while those catalyzed by DNA polymerase delta/straightepsilon appeared to be more effective in the presence of DNA ligase I. Also, it was demonstrated that the repair initiating 3'-PG excision reaction was not dependent upon HAP1 activity, as judged by inhibition of HAP1 with neutralizing HAP1-specific polyclonal antibody.

Base Sequence↗
PubMed1999

Family intervention for intellectually disabled children. Randomised controlled trial.

BACKGROUND: Resources to address the needs of parents of intellectually disabled children in developing countries are limited. AIMS: The efficacy of interactive group psychoeducation on measures of parental attitude towards intellectual disability was assessed in southern India. METHOD: Fifty-seven parents randomised to 10 weeks of experimental and control therapy were assessed using the Parental Attitude Scale towards the Management of Intellectual Disability. The pre- and post-intervention measurements were done by a single-blinded rater and compared. RESULTS: The intervention group had a statistically significant increase in the outcome scores and clinical improvement in the total parental attitude score, orientation towards child-rearing knowledge towards intellectual disability and attitude towards management of intellectual disability, but no change in attitude towards the intellectual disability subscale. CONCLUSIONS: Interactive group psychoeducation is effective for changing the attitude of parents with intellectually disabled children, and is a viable option to be developed in situations where resources are limited.

Adult↗
PubMed1997

Alloantibody- and T cell-mediated immunity in the pathogenesis of transplant arteriosclerosis: lack of progression to sclerotic lesions in B cell-deficient mice.

BACKGROUND: The relative roles of humoral and cell-mediated immunity in generating chronic allograft arteriopathy have been considered for several years. We have sought definitive evidence regarding these questions using heart transplants between mouse strains selected to isolate the effects of each form of immune responsiveness. METHODS: B10.BR hearts were transplanted to B cell-deficient recipients that are devoid of immunoglobulins (muMT). Their vessels were compared with those of transplants to fully reactive recipients of the same genetic background (C57BL/6). Additional evidence came from comparisons in other strain combinations. RESULTS: Transplants to B cell-deficient and normal recipients developed cellular coronary endothelialitis, with destruction of the arterial media, accompanied by the adherence of T lymphocytes and macrophages to endothelial surfaces. In B cell-deficient recipients, there was no centripetal migration of smooth muscle, alpha-actin-positive myointimal cells and little deposition of collagen or ground substance, compared with lesions in fully reactive C57BL/6 recipients in which these changes are prominent. In two other donor-recipient combinations in which anti-donor antibodies are generally undetectable (B10.BR-->B10.A and 129-->C57BL/6), intimal fibrosis was uncommon. However, B10.A recipients became capable of producing fibrous lesions in B10.BR hearts when given anti-donor, class I antibody by passive transfer, as we have observed previously in scid recipients. CONCLUSIONS: Taken together, these findings indicate that endothelialitis is antibody-independent, whereas antibodies potentiate and can be sufficient for fully developed, fibrous, chronic allograft vasculopathy. Therapeutic strategies for controlling chronic lesions must consider inhibition of the humoral response.

Animals↗
PubMed1996

Accelerated atheromatous lesions in mouse hearts transplanted to apolipoprotein-E-deficient recipients.

Arteriopathy, sometimes termed accelerated atherosclerosis, often impairs transplants. We employed apolipoprotein-E-deficient, hypercholesterolemic mice to determine how the hyperlipidemic environment affected transplanted hearts. Strain 129 hearts transplanted to C57BL/6 normal or C57BL/6 apolipoprotein-E-deficient recipients were evaluated by immunochemical and histological techniques. Analyses were possible both of differences in the coronary lesions that developed in a normolipidemic as compared with a hyperlipidemic environment and of the coronary atherosclerotic process in transplanted hearts compared with native hearts in the same hyperlipidemic environment. Aortas and coronary arteries of transplanted aortas in both recipient groups developed florid intimal thickening by 4 to 10 weeks, with marked lipid deposition, foamy macrophages, and infiltration of smooth muscle alpha-actin-positive cells in apolipoprotein-E-deficient mice. Lipid was layered against the internal elastic lamina as in human transplants. VCAM-1 was increased in various sites in both groups. Allotransplants to apolipoprotein-E-deficient recipients had more severe aortic and coronary lesions with characteristic T cell infiltration than native hearts. In this sense, transplants suffered from accelerated atherosclerosis. The character of coronary vascular changes in transplanted hearts was distinctly affected by their lipid environment, but their severity, in terms of luminal encroachment, was not markedly different.

Animals↗
PubMed1996

The American Academy of Dermatology's response to managed care and capitation.

Managed care is an important part of the health care delivery system; consequently, dermatologists are seeking information about various managed care plans and are joining them. Managed care can encompass a variety of different systems, including preferred provider organizations, health maintenance organizations, and individual practice associations. They all provide health care services to enrolled members through a defined network of providers who are given the responsibility to provide quality medical care while controlling use and access to specialists. Many members of the American Academy of Dermatology (AAD) respond in surveys that education in various aspects of managed care is an area of great importance to them.

Capitation Fee↗
PubMed1995

Coronary atherosclerosis in transplanted mouse hearts. IV Effects of treatment with monoclonal antibodies to intercellular adhesion molecule-1 and leukocyte function-associated antigen-1.

Atherosclerotic lesions in the coronary arteries of transplanted mouse hearts manifest high expression of ICAM-1 (CD54), especially on endothelial surfaces, and of LFA-1 (CD11a) on migratory mononuclear cells. The possible participation of cellular adhesion systems in the evolution of these complex lesions was suggested by the increased expression of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) and also by our previous studies with this experimental system. In our studies, we have found that administration of a monoclonal antibody (mAb) to gamma-interferon will greatly suppress coronary changes, and gamma-interferon is known to stimulate the formation of these adhesion molecules. The present experiments were to evaluate how administration to murine heart transplant recipients of mAbs against ICAM-1, LFA-1, or both affected the development of coronary atherosclerosis. It was found that treatment with either mAb alone did not alter the severity of coronary atherosclerosis, but that both mAbs given together can significantly suppress lesion formation at 30 days compared with controls (P < 0.044). Continuing treatment was even more effective when extended to 60 days (P < 0.003). The mAbs to ICAM-1 and LFA-1 bound their targets in vivo (primarily endothelium and mononuclear cells, respectively), but complete, long-term saturation of combining sites was not attained, even with very high doses. No appreciable reduction in arterial endothelial ICAM-1 expression was evident. It is concluded that the ICAM-1/LFA-1 system is of central importance in the evolution of accelerated coronary atherosclerosis.

Animals↗
PubMed1995

Human cDNA clones that modify radiomimetic sensitivity of ataxia-telangiectasia (group A) cells.

Genes responsible for genetic diseases with increased sensitivity to DNA-damaging agents can be identified using complementation cloning. This strategy is based on in vitro complementation of the cellular sensitivity by gene transfer. Ataxia-telangiectasia (A-T) is a multisystem autosomal recessive disorder involving cellular sensitivity to ionizing radiation and radiomimetic drugs. A-T is genetically heterogeneous, with four complementation groups. We attempted to identify cDNA clones that modify the radiomimetic sensitivity of A-T cells assigned to complementation group [A-T(A)]. The cells were transfected with human cDNA libraries cloned in episomal vectors, and various protocols of radiomimetic selection were applied. Thirteen cDNAs rescued from survivor cells were found to confer various degrees of radiomimetic resistance to A-T(A) cells upon repeated introduction, and one of them also partially influenced another feature of the A-T phenotype, radioresistant DNA synthesis. None of the clones mapped to the A-T locus on chromosome 11q22-23. Nine of the clones were derived from known genes, some of which are involved in cellular stress responses. We concluded that a number of different genes, not necessarily associated with A-T, can influence the response of A-T cells to radiomimetic drugs, and hence the complementation cloning approach may be less applicable to A-T than to other diseases involving abnormal processing of DNA damage.

Antibiotics, Antineoplastic↗
PubMed1995

Radioresistant DNA synthesis in SV40-immortalized ataxia telangiectasia fibroblasts.

Ataxia telangiectasia (AT) is an autosomal recessive disease, characterized by both neurological disorders and a high incidence of early-onset cancers. On a cellular level, cellular radiosensitivity and radioresistant DNA synthesis are the hallmarks of AT. While expression of cellular radiosensitivity varies somewhat among affected individuals, radioresistant DNA synthesis is seen consistently and, in fact, is the only end point used for assigning individuals to genetic complementation groups. For this reason, complementation-group-specific correction of radioresistant DNA synthesis in AT cells has long been thought to be an absolute requirement for confirmation of a bona fide clone of an AT gene. Since primary AT cells grow poorly in culture, SV40-immortalized AT fibroblasts are the usual recipients of transfected DNA in these studies. In experiments reported here, we demonstrate that SV40-immortalized AT fibroblasts have significantly reduced radioresistant DNA synthesis compared to primary AT fibroblasts, and their response to radiation is more like normal cells, in that both the radiosensitive and radioresistant components appear to be present. This suggests that there may be an interaction between SV40 proteins and the AT gene product or its downstream elements. This partial "complementation" of radioresistant DNA synthesis in SV40-immortalized AT cells complicates complementation cloning strategies, and should be considered when terminally screening putative AT gene clones by analysis of radioresistant DNA synthesis.

Ataxia Telangiectasia↗
PubMed1994

Removal of 3'-phosphoglycolate from DNA strand-break damage in an oligonucleotide substrate by recombinant human apurinic/apyrimidinic endonuclease 1.

A recombinant human AP endonuclease, HAP1, was constructed and characterized with respect to its ability to recognize and act upon a model double-stranded 39-mer oligodeoxyribonucleotide substrate containing a strand break site with 3'-phosphoglycolate and 5'-phosphate end-group chemistries. This oligodeoxyribonucleotide substrate exactly duplicates the chemistry and configuration of a major DNA lesion produced by ionizing radiation. HAP1 was found to recognize the strand break, and catalyze the release of the 3'-phosphoglycolate as free phosphoglycolic acid. The enzyme had a Vmax of 0.1 fmole/min/pg of HAP1 protein, and a Km of 0.05 microM for the 3'-phosphoglycolate strand break lesion. The mechanism of catalysis was hydrolysis of the phosphate ester bond between the 3'-phosphoglycolate moiety and the 3'-carbon of the adjacent dGMP moiety within the oligonucleotide. The resulting DNA contained a 3'-hydroxyl which supported nucleotide incorporation by E. coli DNA polymerase I large fragment. AP endonucleolytic activity of HAP1 was examined using an analogous double-stranded 39-mer oligodeoxyribonucleotide substrate, in which the strand break site was replaced by an apyrimidinic site. The Vmax and Km for the AP endonuclease reaction were 68 fmole/min/pg of HAP1 protein and 0.23 microM, respectively.

Amino Acid Sequence↗