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Biomedical subjects

P A Cox

Publications and source records attributed to P A Cox.

7 recordsLinked to original sources
PubMed1992

Pyrimidine dimers in DNA initiate systemic immunosuppression in UV-irradiated mice.

Exposing the skin of mice to UV radiation interferes with the induction of delayed and contact hypersensitivity immune responses initiated at nonirradiated sites. The identity of the molecular target in the skin for these immunosuppressive effects of UV radiation remains controversial. To test the hypothesis that DNA is the target for UV-induced systemic immunosuppression, we exposed C3H mice to UV radiation and then used liposomes to deliver a dimer-specific excision repair enzyme into the epidermis in situ. The application of T4 endonuclease V encapsulated in liposomes to UV-irradiated mouse skin decreased the number of cyclobutane pyrimidine dimers in the epidermis and prevented suppression of both delayed and contact hypersensitivity responses. Moreover, the formation of suppressor lymphoid cells was inhibited. Control, heat-inactivated endonuclease encapsulated in liposomes had no effect. These studies demonstrate that DNA is the major target of UV radiation in the generation of systemic immunosuppression and suggest that the primary molecular event mediating these types of immunosuppression by UV radiation is the formation of pyrimidine dimers. Furthermore, they illustrate that the delivery of lesion-specific DNA repair enzymes to living skin after UV irradiation is an effective tool for restoring immune function and suggest that this approach may be broadly applicable to preventing other alterations caused by DNA damage.

Analysis of Variance↗
PubMed1991

GABAA receptor subtypes immunopurified from rat brain with alpha subunit-specific antibodies have unique pharmacological properties.

The unique cytoplasmic loop regions of the alpha 1, alpha 2, alpha 3, and alpha 5 subunits of the GABAA receptor were expressed in bacterial and used to produce subunit-specific polyclonal antisera. Antibodies immobilized on protein A-Sepharose were used to isolate naturally occurring alpha-specific populations of GABAA receptors from rat brain that retained the ability to bind [3H]muscimol, [3H]flunitrazepam, [3H]Ro15-1788, and [125I]iodo-clonazepam with high affinity. Pharmacological characterization of these subtypes revealed marked differences between the isolated receptor populations and was generally in agreement with the reported pharmacological profiles of GABAA receptors in cells transiently transfected with alpha 1 beta 1 gamma 2, alpha 2 beta 1 gamma 2, alpha 3 beta 1 gamma 2, and alpha 5 beta 1 gamma 2 combinations of subunits. Additional subtypes were also identified that bind [3H]muscimol but do not bind benzodiazepines with high affinity. The majority of GABAA receptor oligomers contains only a single type of alpha subunit, and we conclude that alpha 1, alpha 2, alpha 3, and alpha 5 subunits exist in vivo in combination with the beta subunit and gamma 2 subunit.

Animals↗
PubMed1990

Ethnopharmacology and the search for new drugs.

Bioactive molecules occur in plants as secondary metabolites and as defence mechanisms against predation, herbivores, fungal attack, microbial invasion and viral infection. Throughout the world indigenous peoples have discovered plants with pharmacological activity; many useful drugs such as vincristine, reserpine, quinine, and even aspirin, have their origins in indigenous ethnopharmacologies. Three features characterize indigenous cultures that are most likely to have discovered useful natural products: (1) possession of a conservative ethnomedical tradition with established cultural mechanisms for accurate transmission of ethnopharmacological knowledge; (2) residence in an area with a diverse flora; and (3) continuity of residence in the area over many generations. Ethnopharmacological data derived from such cultures can be considered as analogues of human bioassay data. Yet indigenous ethnomedical traditions are rapidly disappearing. To preserve indigenous discoveries and make them accessible and useful to Western medicine, collaboration is required between linguistically sophisticated ethnobotanists, pharmacognosists, natural product chemists and pharmacologists. Ethnopharmacologists must be aware of all three components of indigenous medical traditions (a cosmological foundation, a repertoire of crude natural products, and a health care delivery system) to facilitate transfer of useful compounds and information to Western medicine, as well as to protect the interests and cultural integrity of indigenous peoples.

Botany↗
PubMed1987

Defective production of antibody to herpes simplex virus in neonates: defective production of T helper lymphokine and induction of suppression.

Defective production of antibodies to herpes simplex virus (HSV) and low resistance to HSV infection in neonatal mice could be reconstituted by using macrophages from syngeneic adult mice plus concanavalin A-stimulated supernatants prepared from adult mouse spleen cells or adult human peripheral blood lymphocytes. In each supernatant, interleukin-2 (IL-2) produced by T helper cells (positive for Lyt 1.2 or OKT4) was necessary to provide reconstitution. Supernatants from neonatal mice failed to mediate reconstitution because of an age-dependent absence of production of IL-2. Although supernatants from neonatal human cell cultures contained IL-2, they failed to reconstitute production of antibody to HSV and resistance to HSV infection because of a suppressor of IL-2 activity. Early antibody production and antibody-dependent cellular effector function are important defenses against HSV infection and are critically defective in the neonate.

Animals↗
PubMed1985

Clinical efficacy and safety of cefmenoxime in children.

Cefmenoxime, an investigational semisynthetic cephalosporin, was evaluated in 18 pediatric patients with a variety of infections. There were seven patients with urinary tract infections, two with wound infections, two with osteomyelitis, two with abscess infections, one with cervical adenitis, one with hidradenitis, one with pneumonia and sepsis, one with periorbital cellulitis, and one with ventriculitis. A total of 16 (88%) patients had a satisfactory clinical response demonstrated by improvement in clinical signs and symptoms. A total of 12 (67%) patients demonstrated eradication of their infecting organisms. Of the pathogens isolated in these patients, 16 isolates were susceptible to cefmenoxime. One patient developed a generalized urticarial rash that resolved within 24 h after cessation of cefmenoxime therapy. Mean peak level in serum after intravenous infusion was 55 micrograms/ml.

Bacterial Infections↗
PubMed1976

Skeletal extension development: criteria for future designs.

Experience with an intramedullary skeletal extension and a supracortical extension has been reviewed. Criteria for possible use in future developments have been outlined. Tissue interfacing with the material used in fabricating these devices were briefly discussed, stressing the importance of maintaining the skin's integrity. An artificial tendon, which attempts to bring the external mechanical ankle joint under the direct control of existing skeletal muscles, was described. Three animal models were reviewed and our reasons given for selecting the goat. Preoperative preparations, anesthesia, and the surgical procedures were described in some detail. A tabulation of the procedures done on 52 goats (Table 1) shows little difference between the intramedullary rod and the supracortical devices when only the times in place are compared. However, the supracortical devices showed no bone necrosis and produced only one case of osteomyelitis. With the intramedullary rod, five cases of necrosis and/or osteomyelitis were seen. The cone-shaped supracortical devices are somewhat vulnerable to forces in extension.

Animals↗