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Biomedical subjects

T J Simpson

Publications and source records attributed to T J Simpson.

34 records · Page 2Linked to original sources
PubMed1989

Urocanic acid analogues and the suppression of the delayed type hypersensitivity response to Herpes simplex virus.

Ultraviolet irradiated urocanic acid (4-imidazoleacrylic acid) containing a mixture of cis- and trans-isomers has been shown previously to induce suppression of the delayed type hypersensitivity (DTH) response to Herpes simplex virus type 1 (HSV-1) in a murine model of infection. The cis-isomer of urocanic acid was prepared and the cis- and trans-isomers of 2-methylurocanic acid. 2-pyrroleacrylic acid, 2-furanacrylic acid, 2-thiopheneacrylic acid, 3-thiopheneacrylic acid as well as dihydrourocanic acid and histamine. Each was applied at concentrations of 1 and 50 micrograms per mouse to the shaved dorsal skin and the mice were infected subcutaneously with HSV 5 h later. After 8-10 days the DTH response to the virus was measured by an ear swelling test. It was found that cis-urocanic acid was effective in suppressing the DTH response at levels of 1 microgram per mouse or less. The cis- and trans-isomers of 2-furanacrylic acid, 2-pyrroleacrylic acid and 2-thiopheneacrylic acid were also effective, with the cis- form generally being more active than trans, and 2-pyrroleacrylic acid being particularly potent. Cis- and trans-3-thiopheneacrylic acid, on the other hand, were only marginally immunosuppressive while neither isomer of 2-methylurocanic acid had any suppressive ability. Dihydrourocanic acid and histamine were also shown to suppress the DTH response. Thus the structural features necessary for urocanic acid and its analogues to act as mediators of UV-induced immunosuppression could be deduced and implications for their mechanism of action discussed.

Chemical Phenomena↗
PubMed1988

Quantification of urocanic acid isomers in murine skin during development and after irradiation with UVB light.

Urocanic acid has been postulated as the photoreceptor mediator of immunosuppression induced by ultraviolet-B (UVB) irradiation. We have shown previously that transplanted epidermal cells from neonatal mice, irradiated mice or mice skin painted with cis-urocanic acid suppress the immune responses to herpes simplex virus. Dorsal skin from foetal mice at 3 weeks gestation and from neonatal mice within 1 day of birth were assayed for the presence of cis- and trans-urocanic acid and compared with the amounts in the ears of 2, 4, 6 and 8-week old mice. Foetal mice had a low skin urocanic acid content (11.9 ng/mg wet weight), neonatal mice 227 ng/mg, while the other ages had at least 340 ng/mg. Neonatal mice were found to have 11.4% urocanic acid as the cis-isomer, whereas foetal mice had undetectable amounts and all remaining ages had about 4%. Irradiation of 7-week-old mice with 96 mJ/cm2 UVB light resulted in the presence within the ears of 31.1% urocanic acid as the cis-isomer. This level was maintained for at least 16 h, then declined slowly until, after 7 days, 16.2% was in the cis-form. Nonirradiated ears contained 4.7% cis-isomer. It is known that UVB irradiation of mice suppresses the delayed type hypersensitivity response to HSV. The suppression was found to be dependent on the time interval between irradiation and infection with virus; this had to be longer than 5 h and less than 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1987

Ontogeny of fetal liver glucose-6-phosphatase activity.

A reliable and sensitive microassay for the measurement of liver glucose-6-phosphatase is described. Human fetal liver was assayed for glucose-6-phosphatase activity from 7.5 to 24 weeks of gestation and was found to have a mean activity of 2.11 nmol per min per mg of protein. This was approximately 30 per cent of the postnatal controls assayed by the same method, but there was no evidence of a change in activity during the gestational period examined. If fetal liver tissue can be reliably obtained, it may be possible to determine a deficiency of glucose-6-phosphatase in fetuses who are at risk.

Autoradiography↗
PubMed1986

Ultraviolet-irradiated urocanic acid suppresses delayed-type hypersensitivity to herpes simplex virus in mice.

Ultraviolet radiation is known to induce a transient defect in epidermal antigen presentation which leads to the generation of antigen-specific suppression of the delayed-type hypersensitivity (DTH) response. The putative receptor in skin for the primary event in UV-suppression is urocanic acid (UCA) which may then interact locally, or systemically, with antigen presenting cells or initiate a cascade of events resulting in suppression. We present the first direct evidence that UCA, when irradiated with a dose (96 mJ/cm2) of UVB radiation known to suppress the DTH response to herpes simplex virus, type 1 (HSV-1) in mice, can induce suppression following epidermal application or s.c. injection of the irradiated substance. This suppression is transferable with nylon wool-passed spleen cells.

Animals↗
PubMed1985

In utero fetal hematopoietic stem cell transplantation.

The fetus is the preferred candidate for transplantation for a number of reasons. First, the fetal period is the earliest time at which an identified disorder can potentially be treated. If a fetus is identified with a treatable disorder in utero, and if that disorder can affect fetal development, then treatment during fetal life is potentially beneficial. A second advantage of in utero fetal HSC transplantation is the immunotolerance of the fetus, making it both a favorable donor and a favorable recipient. Finding a histocompatible donor and minimizing GVH disease are major concerns in bone marrow HSC transplantation. Fetal immuno-tolerance may eliminate the need for the former and significantly reduce the incidence and severity of the latter. The first hematologic disorders for fetal HSC transplantation may be sickle cell disease and the thalassemias, as recent technologic developments allow diagnosis in the first trimester. However, the potential targets for in utero fetal HSC transplantation are numerous and include a variety of genetic disorders of lymphocyte, platelet, leukocyte, red cell, and enzyme function. Disadvantages of in utero fetal HSC transplantation exist. First, it is necessary to have identified the fetus as being at risk for a genetic disorder, before the prenatal diagnosis can be made. This happens in one of two ways--either a previous pregnancy resulted in an affected fetus, or the parents of the fetus have been identified as being carriers of the genetic disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

The role of histamine-like receptors in immunosuppression of delayed hypersensitivity induced by cis-urocanic acid.

The cis-isomer of urocanic acid (UCA) has been shown previously to mimic the effect of ultraviolet B (UVB) irradiation in suppressing delayed hypersensitivity (DH) responses to virus in a murine model of herpes simplex virus (HSV) infection. Cimetidine, an H2 receptor antagonist, and terfenadine, an H1 receptor antagonist, abrogated the suppression of DH to HSV induced by cis-UCA, leading to the suggestion that histamine-like receptors may be involved in the mechanism of action of cis-UCA on immune responses. In the present study, cis and trans-isomers of 4 UCA analogues (1- and 2-imidazoyl-acrylic acid), and (2- and 3-pyridyl-acrylic acid) were tested for their ability to suppress DH to HSV in infected mice, and only cis-2-pyridyl-acrylic acid was effective. Second, an H2 and H3 agonist were similarly tested: the former was suppressive and the latter had no effect. Third, an H3 receptor antagonist, thioperamide, did not seem to abrogate the suppression of DH induced by cis-UCA. These results substantiate a role for H1 and H2-like receptors, but probably not H3 receptors, in cis-UCA induced immunosuppression.

Animals↗