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Biomedical subjects

S A Lloyd

Publications and source records attributed to S A Lloyd.

26 records · Page 2Linked to original sources

Modulation of carbon tetrachloride hepatotoxicity and xenobiotic-metabolizing enzymes by corticosterone pretreatment, adrenalectomy and sham surgery.

These investigations sought to determine the role of physiological concentrations of natural glucocorticoids in modulating chemical toxicity, and to ascertain if effects on toxicity may be due to alterations of chemical metabolizing enzymes by glucocorticoids. The hepatotoxic response to carbon tetrachloride (CCl4) in adrenalectomized or naive Long Evans rats treated with corticosterone was assessed. Alterations of hepatic cytochrome P-450 concentration, mono-oxygenase activities, NADPH-cytochrome (P-450)c reductase activity, and glutathione S-transferase activity were examined. Adrenalectomy and to a lesser extent sham surgery were protective, but corticosterone administration increased CCl4 hepatotoxicity. Corticosterone administration to adrenalectomized or sham-operated rats reduced the protective effect of these treatments. Correlating with the in vivo response, mono-oxygenase activities decreased after adrenalectomy and sham surgery, but increased with glucocorticoid administration. These studies suggest that basal, stress-associated, and pharmacological concentrations of a natural glucocorticoid can modify chemical toxicity and alter hepatic enzymes important to chemical metabolism.

Adrenalectomy↗

Epidermal growth factor messenger RNA production in human lacrimal gland.

Experimental models and clinical investigations have suggested that epidermal growth factor (EGF) may have a role in corneal wound healing. It has been identified as a normal component of human tears. Rabbit and mouse lacrimal glands have recently been shown to synthesize EGF messenger RNA (mRNA). The purpose of the present study was to determine whether the human lacrimal gland synthesizes EGF mRNA. Total cellular RNA was isolated from pathologic specimens of normal human lacrimal glands from two individuals. Reverse transcriptase was used to generate complementary DNA (cDNA) using a human EGF-specific mRNA primer. Amplification of EGF-related cDNA sequences was performed with the polymerase chain reaction (PCR) and human EGF-derived up- and downstream primers. The PCR products from both lacrimal glands contained an amplified product of the expected length of approximately 410 base pairs. The PCR-generated fragment was verified as an EGF-related amplification product with Southern blotting using a synthetic oligonucleotide probe derived from the mature coding sequence of EGF. These results conclusively demonstrate that the human lacrimal gland synthesizes EGF and suggest that the lacrimal gland could have a regulatory role in maintaining the ocular surface and possibly regulating corneal wound healing through the secretion of EGF.

Base Sequence↗

The effect of CCKB/gastrin antagonists on stimulated gastric acid secretion in the anaesthetized rat.

1. The urethane-anaesthetized, vagotomised rat preparation was used to investigate the effects of the histamine H2-antagonist ranitidine, the proton pump inhibitor omeprazole and the CCKB/gastrin antagonists CI-988, PD 136450 and L-365,260 on pentagastrin-, histamine- and bethanechol-induced gastric acid secretion. 2. The novel CCKB/gastrin antagonists CI-988 and PD 136450, and L-365,260 dose-dependently inhibited pentagastrin-induced secretion. The ED50 value for PD 136450 was 0.05 mumol kg-1, the same following intravenous or subcutaneous administration. 3. CI-988 and PD 136450 administered subcutaneously at dose levels highly effective for antagonism of pentagastrin responses had no effect on basal acid secretion. 4. Ranitidine inhibited pentagastrin-, bethanechol-, and histamine-induced acid secretion, whereas the CCKB/gastrin antagonists inhibited only the secretory response to pentagastrin. 5. The selective CCKA antagonist, devazepide, was inactive at up to 300 mumol kg-1 i.p. against the three stimulants of acid secretion. 6. CI-988 and PD 136450 will be useful research tools with which to investigate the role of CCKB/gastrin receptors in gastric acid secretion and the trophic activities of gastrin and cholecystokinin (CCK) on the gastrointestinal tract.

Animals↗

Epidermal growth factor and its receptor, basic fibroblast growth factor, transforming growth factor beta-1, and interleukin-1 alpha messenger RNA production in human corneal endothelial cells.

The authors tried to determine whether human corneal endothelial cells in primary culture synthesize messenger RNA (mRNA) coding for epidermal growth factor (EGF), EGF receptor, basic fibroblast growth factor (FGFb), transforming growth factor beta-1 (TGFb1), and interleukin-1 alpha (IL-1 alpha). Oligodeoxythymidine-primed complementary DNA (cDNA) was generated from total cellular RNA extracted from eight independent primary corneal endothelial cell cultures. Four of these cultures, maintained 18-51 days, had obvious increases in cell numbers and mass over the 2 weeks before RNA extraction and were populated primarily with cells that were small, uniform, and mononuclear (proliferative cultures). The morphology of the cells in other four cultures, maintained 47-78 days, was predominantly large, irregular, vacuolated, and occasionally multinucleated. These cells were identical to senescent cells found in previous studies, and the cell number did not increase in these cultures over the 2 weeks preceding RNA extraction (senescent cultures). The polymerase chain reaction (PCR) was used to amplify the growth factors (EGF, FGFb, TGFb1, and IL-1 alpha), EGF receptor, and beta actin sequences from each of the cDNA samples. The EGF receptor, FGFb, and beta actin mRNAs were present in all eight cDNA samples. The EGF mRNAs were detected by PCR alone in four of the samples from proliferative cultures, TGFb1 mRNAs in three, and IL-1 alpha mRNAs in three. In the samples from senescent cultures, 0, 1, and 0 mRNAs were detected, respectively. Southern blots of the PCR products were probed with oligonucleotides complementary to sequences in each of the amplified products. This technique showed that the appropriately sized amplification products were specific.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Basic fibroblast growth factor (FGFb) and epidermal growth factor (EGF) receptor messenger RNA production in human lacrimal gland.

The polymerase chain reaction (PCR) was used to show that basic fibroblast growth factor (FGFb) and epidermal growth factor (EGF) receptor messenger ribonucleic acids (RNA) are produced in human lacrimal tissue. Transforming growth factor beta-1 (TGF beta-1) messenger RNA was not detected. These results and the previous identification of EGF in the lacrimal gland suggest that EGF could have autocrine or paracrine functions in lacrimal tissue. FGFb could also serve autocrine or paracrine functions in lacrimal gland physiology. It is also plausible that FGFb is released by the lacrimal gland into the tears and that the growth factor may have regulatory effects on the cells of the ocular surface.

Actins↗

Effects of male partners upon proceptivity in ovariectomized estradiol-treated marmosets (Callithrix jacchus).

Effects of male partners upon the expression of female proceptivity were examined in two experiments using 16 ovariectomized marmosets. Experiment 1 showed that the female's proceptive tongue-flicking display (PTF) is triggered specifically by eye contact with the male. Stimulation of PTF by administration of estradiol-17 beta (E2) to ovariectomized females depends in part upon the male's responsiveness to female displays, such as "staring" and "freezing," which may serve to attract his attention and to establish eye contact. Experiment 2 provided evidence that females' proceptivity decreases if their male partners are lesioned in the preoptic area/anterior hypothalamus. Such males are sexually hypoactive and less responsive to the females' visual displays. However, E2 still activates PTF if females succeed in initiating eye contact with males. Results indicate that variability in effects of E2 upon proceptivity in marmosets may be influenced by subtle aspects of facial communication between the sexes as well as by individual differences in hormonal sensitivity. Copulatory activity in males is not essential for E2 to exert its stimulatory action upon proceptivity in female marmosets.

Animals↗

Effects of hypothalamic lesions upon the sexual and social behaviour of the male common marmoset (Callithrix jacchus).

The sexual and associated behaviour of 10 adult male marmosets was recorded during pair tests with ovariectomized females, before and after bilateral thermal lesions of the hypothalamus. Four sham-lesioned males served as controls. Lesions varied in volume from 1.49 to 3.28 mm3 and extended from the ventromedial hypothalamus to the diagonal band of Broca. Precopulatory behaviours (anticipatory erections, tongue flicking and anogenital investigations of the female) as well as frequencies of mounting, intromission and ejaculation decreased in lesioned males. The greatest suppression of sexual behaviour occurred after lesioning the anterior hypothalamus (AH), beneath the anterior commissure, or at the junction of the AH with the preoptic area (POA). Lesions confined to the POA had less profound behavioural effects. Treating ovariectomized females with estradiol stimulated their proceptivity but had no consistent effects upon the males' behaviour. Lesioned males did not exhibit signs of social withdrawal and frequencies of allogrooming or grooming invitations increased post-operatively. Preliminary studies on intermale aggression indicated that lesions which had the greatest effect upon sexual behaviour also tended to decrease aggressive interactions with other males. Hypothalamic lesions did not affect plasma testosterone levels, except in one male and only one animal showed signs of ill health (weight loss and hypothermia) post-operatively. These results show that damage to the AH or AH-POA junction in male marmosets causes a profound suppression of sexual 'arousal' and copulatory behaviour and that such affects are not due to androgen insufficiency or other, non-specific, side effects of neural damage.

Aggression↗

The role of disparity gradient in stereo vision.

Burt and Julesz experimentally demonstrated that, in addition to Panum's fusional area, a quantity defined by them and named disparity gradient also plays a crucial part in deciding whether the human visual system would be able to fuse the images seen by the left and right eyes. The physical meaning of this quantity remains obscure despite attempts to interpret it in terms of depth gradient. Nevertheless, it has been found to be an effective selector of matches in stereo correspondence algorithms. A proof is provided that a disparity gradient limit of less than 2 implies that the matches between the two images preserve the topology of the images. The result, which is invariant under rotations and under relative as well as overall magnifications, holds for pairs of points separated in any direction, not just along epipolar lines. This in turn can be shown to prevent correspondences being established between points which would have to be located in three dimensions on a surface invisible to one eye, assuming opaque surfaces.

Depth Perception↗