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Biomedical subjects

C L Wright

Publications and source records attributed to C L Wright.

At least 55 records · Page 3Linked to original sources

Degeneration of the rat and canine adrenal cortex caused by alpha-(1,4-dioxido-3-methylquinoxalin-2-yl)-N-methylnitrone (DMNM).

The antibacterial drug alpha-(1,4-dioxido-3-methylquinoxalin-2-yl) N-methylnitrone (DMNM) given at a dose of 22.5 mg/kg bid to four dogs for 14 days caused diminished adrenal cortical reserves as determined by decreased plasma cortisol (three dogs) and lower aldosterone levels (four dogs) following the intravenous infusion of ACTH. A dose of 100 mg/kg/day of DMNM administered to rats for 31 or 35 days resulted in significant decreases in blood glucose. Histologically, the adrenal glands of both species treated with DMNM for a maximum period of 21 days (dogs) and 35 days (rats) had widespread granular and vacuolar degeneration of the cortex. This degeneration in treated rats began in the zona reticularis and inner regions of the zona fasciculata and eventually involved the entire cortex including the zona glomerulosa. As a result of treatment, significant ultrastructural alterations within cells of the rat and canine adrenal cortex consisted of degeneration of the mitochondria and an increase in the numbers and lipolysis of lipid droplets. The ultrastructure of the zona reticularis and fasciculata was most severely affected.

Adrenal Cortex↗

A 64,000 dalton matrix protein of human cytomegalovirus induces in vitro immune responses similar to those of whole viral antigen.

Human cytomegalovirus contains approximately 30 to 35 structural polypeptides. Although antibodies to several of these proteins are made during natural infection, their relationship to T cell recognition of this virus and subsequent control of infection is poorly understood. We have purified one of these proteins (HCMVgp64) that is found in abundance in infected cell lysates in order to delineate the relationship of single viral proteins to the immune response caused by the virus. HCMVgp64 induced T cell reactivity only in individuals with serologic evidence of past infection. In addition, HCMVgp64 elicited similar in vitro immune reactions as the whole virus including T cell proliferation, interleukin 2 production, and receptor expression as well as interferon production. These studies suggest that single proteins of HCMV such as HCMVgp64 are capable of inducing T cell responses and may be important in the development of immune reactivity to HCMV.

Antigens, Viral↗

Obstetric care in a health maintenance organization and a private fee-for-service practice: a comparative analysis.

This study compares the quality of obstetric care provided for patients in two distinct groups: a federally-qualified health maintenance organization and a private fee-for-service practice. Patients of both groups were delivered in the same hospital with resident coverage equally accessible to both groups. From January, 1979, through December, 1981, the period of the study, the physician group delivered 2385 patients, 57% of them from the health maintenance organization and 43% from the fee-for-service practice. Not only were comparisons of maternal and fetal outcomes available for the two patient groups, but the yearly trends and individual performances of the physicians were available as well. This paper addresses the question, all other things being equal, is the level of care and ultimate outcome the same for both groups of patients? The results in some instances showed surprising differences.

Adult↗

Insecticidal ear tags and sprays for the control of flies on cattle.

Ear tags containing 8.5 per cent w/w cypermethrin gave almost complete control of the biting muscid, Haematobosca stimulans. Protection afforded against nuisance flies was more variable; generally a 70 to 80 per cent reduction of headfly, Hydrotaea irritans, and a 60 to 70 per cent reduction of Morellia simplex. Ear tags containing 8.5 per cent fenvalerate also gave significant protection against biting and nuisance flies. Spraying with 500 ppm cyhalothrin or 1000 ppm cypermethrin afforded complete protection against H stimulans and reduced the burden of H irritans by approximately 90 per cent and M simplex by 80 to 90 per cent. A two week interval between treatments is suggested although this could be extended where weather conditions were favourable to the retention of insecticide on the skin or fly challenge was low. No significant increase in liveweight gain was associated with fly control. Treated animals were less disturbed when grazing and were more easily handled, especially when milking.

Animals↗

Time-dependent inhibition of aromatase in trophoblastic tumor cells in tissue culture.

Human choriocarcinoma trophoblast cells (JAr line) were utilized as whole cell preparations in tissue culture to evaluate the effects of mechanism-based inactivation or "suicide inhibition" of estrogen biosynthesis. A C-19 acetylenic analog (MDL 18,962) of the substrate, androstenedione, was evaluated in competitive and time-dependent assays. Product formation was determined by accumulation of 3H2O resulting from the stereo-specific elimination of 1 beta-tritium from the androgen substrate. Trophoblast cells exhibited initial linear kinetics for at least 3 h following addition of [1-3H]androstenedione. The Km for androstenedione was 35.1 nM with Vmax of 3.7 pmol/h/10(6) trophoblast cells. Kinetic analysis of time-dependent inhibition of aromatase in trophoblast cells revealed an apparent Ki of 0.6 nM for MDL 18,962 and at t 1/2 of inactivation of 26 min at infinite inhibitor concentration. These studies suggest that a suicide aromatase inhibitor can cause irreversible inhibition of estrogen biosynthesis in intact trophoblast cells. In the presence of 1 nM or 10 nM MDL 18,962, trophoblast cells exhibited initial linear kinetics for estrogen biosynthesis during the first hour following co-incubation with inhibitor and 33 nM substrate. During the subsequent 30 min the rate of estrogen biosynthesis precipitously declined from 104 +/- 24 fmol/min/10(6) cells in control cells to 24 +/- 13 and 8 +/- 4 fmol/min/10(6) trophoblasts treated with 1 or 10 nM MDL 18,962, respectively. This significant decrease in aromatase activity (P less than or equal to 0.01) implied irreversible inactivation, which was supported by prolonged inhibition of aromatase activity in trophoblast cells incubated for 6-48 h following removal of medium containing 3 nM or 30 nM MDL 18,962.

Androstenedione↗

Biochemical and endocrine properties of a mechanism-based inhibitor of aromatase.

The conversion of androgens to estrogens by aromatase represents a major alteration in hormonal expression, and its regulation offers a promising method for therapeutic control of disease processes that are hormonally dependent. The design of suicide inhibitors based on enzyme-activated mechanisms provides an attractive approach for regulation of estrogen biosynthesis. MDL 18,962, (10-2(-propynyl)estr-4-ene-3,17-dione), a C-10 substituted analog of the natural substrate androstenedione, was evaluated as a suicide inhibitor of aromatase. Appropriate kinetic evaluations of MLD 18,962 established it to be a highly potent [inhibition constant (Ki) = 4.5 +/- 1.3 nM] irreversible inhibitor of human placental aromatase. The 2-propynyl group was necessary for time-dependent inactivation, as this activity was lost in related compounds. The inactivation process was specific for aromatase, since other P450 enzyme systems are not inactivated by MDL 18,962. This compound exhibited minimal intrinsic hormonal properties, since weak binding affinities were observed for cytosolic androgen, estrogen, or progestin receptors. The stimulation of ovarian aromatase activity by gonadotropins in immature mice was inhibited in animals implanted with 10-mm MDL 18,962 Silastic implants. This inhibition of estrogen biosynthesis suppressed estrogen-dependent uterine growth in these mice.

Androstenedione↗

Flies associated with cattle in south west Scotland during the summer months.

The sheep headfly, Hydrotaea irritans, and Morellia simplex were the species most frequently associated with cattle at pasture and comprised 69.01 per cent and 13.93 per cent, respectively, of the total fly collection made from grazing cattle. The most prevalent biting fly was Haematobosca stimulans which comprised 4.46 per cent of the total catch. A few clegs, Haematopota pluvialis, and horse flies, Hybomitra distinguenda, were also recorded. A few of the headflies swarming around cattle entered milking parlours and byres and made up, at 38.23 per cent, the highest percentage of the total fly collection from these buildings. Headflies congregated on the windows, particularly those in the roof. Lesser numbers of the flies, Hydrotaea albipuncta, Morellia simplex and Trichopticoides decolor, with similar feeding habits to H irritans were also collected from these windows with a number of those species attracted to excrement. The biting muscids, Stomoxys calcitrans and Haematobosca stimulans, were collected mainly from the outside surfaces at the entrance to milking parlours and byres and comprised 23.53 per cent and 11.18 per cent, respectively, of the total fly collection from these buildings. Stomoxys calcitrans, the stable fly was present on every sample taken from calf houses and comprised 63.79 per cent of the total fly collection from these houses. Two other species, Sepsis violacea and the common housefly Musca domestica, were present on occasions in significant numbers and comprised 20.69 per cent and 9.48 per cent, respectively, of the total fly collection from calf houses.

Animals↗

Purification of the hexokinases by affinity chromatography on sepharose-N-aminoacylglucosamine derivates. Design of affinity matrices from free solution kinetics.

The purification is described of rat hepatic hexokinase type III and kidney hexokinase type I on a large scale by using a combination of conventional and affinity techniques similar to those previously used for the purification of rat hepatic glucokinase [Holroyde, Allen, Storer, Warsy, Chesher, Trayer, Cornish-Bowden & Walker (1976) Biochem. J. 153, 363-373] and muscle hexokinase type II [Holroyde & Trayer (1976) FEBS Lett. 62, 215-219]. The key to each purification was the use of a Sepharose-N-aminoacylglucosamine affinity matrix in which a high degree of specificity for a particular hexokinase isoenzyme could be introduced by either varying the length of the aminoacyl spacer and/or varying the ligand concentration coupled to the gel. This was predicted from a study of the free solution kinetic properties of the various N-aminoacylglucosamine derivatives used (N-aminopropionyl, N-aminobutyryl, N-aminohexanoyl and N-aminooctanoyl), synthesized as described by Holroyde, Chesher, Trayer & Walker [(1976) Biochem. J. 153, 351-361]. All derivatives were competitive inhibitors, with respect to glucose, of the hexokinase reaction, and there was a direct correlation between the Ki for a particular derivative and its ability to act as an affinity matrix when immobilized to CNBr-activated Sepharose 4B. Muscle hexokinase type II could be chromatographed on the Sepharose conjugates of all four N-aminoacylglucosamine derivatives, although the N-aminohexanoylglucosamine derivative proved best. This same derivative was readily able to bind hepatic glucokinase and hexokinase type III, but Sepharose-N-amino-octanoyl-glucosamine was better for these enzymes and was the only derivative capable of binding kidney hexokinase type I efficiently. Separate studies with yeast hexokinase showed that again only the Sepharose-N-amino-octanoylglucosamine was capable of acting as an efficient affinity matrix for this enzyme. Implications of these studies in our understanding of affinity-chromatography operation are discussed.

Animals↗

Campylobacter fetus (Vibrio fetus) infection in dairy herds in South-West Scotland.

Infertility and abortion caused by Campylobacter fetus is described in a series of 12 herds in South West Scotland during the period May 1974 to December 1976. Herd studies show that 44 bulls were involved and that there were 34 bull and 18 cow movements for breeding purposes. The need to include C fetus infection in the differential diagnosis of herd infertility is emphasised.

Abortion, Veterinary↗