Biomedical subjects

S Lackey

Publications and source records attributed to S Lackey.

4 recordsLinked to original sources

PubMed1997

7-alkylidenecephalosporin esters as inhibitors of human leukocyte elastase.

A series of 7-alkylidenecephalosporins and 7-vinylidenecephalosporins, as their benzhydryl esters, have been tested as inhibitors of both porcine pancreatic elastase and human leukocyte elastase. Selected 7-alkylidenecephalosporin esters are found to be potent inhibitors of HLE. One category of new inhibitors is the 7-(haloalkylidene)cephalosporins. In contrast to previously reported cephalosporin-based elastase inhibitors, these haloalkylidene cephems show optimum inhibitory activity as sulfides, rather than as sulfones. They are efficient and irreversible inhibitors. A second class of active compounds is represented by the benzhydryl ester 7-(cyanomethylidene)cephalosporin sulfone. In contrast to the activity of these new inhibitors, the benzhydryl ester of the mechanism-based beta-lactamase inhibitor, 7-[(2'-pyridyl)methylidene]-cephalosporin sulfone showed little inhibitory activity as an elastase inhibitor. 7-Vinylidenecephalosporins were also relatively poor inhibitors, although the terminally unsubstituted allene sulfide showed activity as an inhibitor of PPE. A modeling analysis suggests the 7-alkylidene substituents can be readily accommodated in the S1 pocket. A potential mechanism of inhibition is proposed.

Animals↗

PubMed1993

The amplitude of nocturnal melatonin concentrations is not decreased by oestradiol and does not alter reproductive function in adolescent or adult female rhesus monkeys.

Nocturnal concentrations of melatonin in serum decline significantly with advancing pubertal development in both children and non-human primates and elevated levels may be associated with anovulation in adults. Three studies, using female rhesus monkeys, were performed to determine whether (1) the decline in nocturnal melatonin concentrations in adolescents was due to maturational increases in serum oestradiol, (2) the experimental elevation in nocturnal melatonin would delay the normal progression of puberty in post-menarchial monkeys, and (3) the experimental elevation in nocturnal melatonin would disrupt normal ovulatory function in adults. In experiment 1, juvenile female rhesus monkeys, housed indoors in a fixed photoperiod (12 h light:12 h darkness), were assigned randomly to one of two treatment groups: ovariectomized with no replacement therapy (control; n = 4) or ovariectomized with oestradiol replacement therapy maintaining oestradiol at approximately 90 pmol/l (treated; n = 8). Twenty-four hour as well as daytime serum samples were collected from 19 to 35 months of age. Nocturnal melatonin concentrations declined significantly in all females with advancing chronological age and this change was unaffected by oestradiol treatment. The decline in nocturnal melatonin concentrations occurred, on average, 2.0 +/- 0.2 months after the initial rise in serum LH in control females and 6.0 +/- 0.8 months in treated females. Furthermore, this decline in night-time melatonin was not related to significant developmental changes in body weight. In experiment 2, control (n = 6) and melatonin-treated (treated; n = 6) adolescent female monkeys were studied from -30 to +105 days from menarche. Beginning at 45 days following menarche, treated females received 30 days of nocturnal melatonin infusion to elevate levels to prepubertal values. Developmental changes in perineal swelling and coloration as well as serum oestradiol and insulin-like growth factor-I (IGF-I) were compared with values observed during the 45-day pretreatment and 30-day post-treatment conditions as well as with those observed in control females. Despite a significant elevation in nightly melatonin levels for the 30-day period in treated females, developmental changes in oestradiol, IGF-I, and perineal coloration and swelling were not different compared with the control females. In experiment 3, adult females were given melatonin nightly beginning on the first day of menses following an ovulatory cycle and treatment was continued for 45 days or until the next menstruation occurred. Melatonin was elevated to supraphysiological levels every night throughout the treatment period.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Bizarre imagery, interference, and distinctiveness.

Previous studies have shown that bizarre and common images produce equivalent levels of recall in unmixed-list designs. Using unmixed lists, we tested the view that bizarre images would be less susceptible than common images to common sources of interference. In all experiments, subjects imaged a list of either bizarre or common sentences and then performed some kind of interfering task before recalling the initial list of sentences. Experiment 1 showed that bizarre images were better accessed than common images after imaging an intervening list of common sentences. Also, components of common images tended to be better recalled than those of bizarre images after imaging an intervening list of bizarre sentences. Experiments 2a and 2b showed that interfering tasks consisting of studying lists of common concrete nouns did not differentially affect memory for bizarre and common images. In Experiment 3, labeling and imaging an interfering list of common pictures produced higher recall of bizarre images. Generally, bizarre images appeared to be less susceptible than common images to interference from certain types of common encodings. Importantly, the superior recall of bizarre images was always due to greater image (sentence) access, whereas higher recall of common images was associated with greater recovery of the image (sentence) constituents. Explanation of the precise pattern of results requires consideration of the distinctive properties of bizarre images.

Attention↗

PubMed1985

Failure of cimetidine as an immunomodulator in cancer patients and normal subjects.

Our pilot study of cimetidine as an immunomodulator in cancer patients showed no effect at clinically used doses on total blood, neutrophil, lymphocyte, or monocyte count, quantitative immunoglobulin, percentage of E-rosetting cells, phytohemagglutinin responses or delayed hypersensitivity responsiveness. We concluded that in clinically used doses, cimetidine produces no significant immunomodulation either in vivo or in vitro.

Adenocarcinoma↗