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Biomedical subjects

L S Williams

Publications and source records attributed to L S Williams.

At least 73 records · Page 4Linked to original sources
PubMed1993

Further studies on ocular responses to DP receptor stimulation.

Prostaglandin D2 (PGD2) and the selective DP receptor agonist BW 245C have been previously shown to lower intraocular pressure in rabbits, while PGD2, but not BW 245C, caused plasma extravasation, eosinophil infiltration, and goblet cell depletion. In these present studies definition of the ocular pharmacology of prostaglandin D2 (PGD2) has been extended by using a further selective DP receptor agonist SQ 27986 and a potent and selective DP receptor antagonist BW A868C. In cats and rabbits SQ 27986 caused ocular hypotension. The ocular hypotensive effect of PGD2 in rabbits was blocked by pretreatment with the DP receptor antagonist BW A868C, whereas the activities of PGE2 and PGF2 alpha remained unaltered. The singular involvement of the DP receptor in changes in rabbit intraocular pressure evoked by PGD2 was thereby verified by using the antagonist BW A868C. In terms of effects on the ocular surface, SQ 27986 caused no increase in conjunctival microvascular permeability, no eosinophil infiltration, and no depletion of the goblet cell population. These findings reinforce the concept that selective DP receptor agonists may be useful for lowering intraocular pressure without causing ocular surface pathology. PGD2 induced increases in conjunctival microvascular permeability were inhibited by BW A868C, despite the fact that DP receptor agonists failed to evoke a plasma exudation response. This finding was unexpected and suggests a possible subdivision of the DP receptor designation.

Animals↗
PubMed1993

Identification of 19 (R)-OH prostaglandin E2 as a selective prostanoid EP2-receptor agonist.

The physiological significance of the formation of large quantities of 19(R)-hydroxy prostaglandin E's (19-OH PGE) from PGE1 and PGE2 in human seminal plasma is intriguing. The concept that prostaglandins exert their biological effects by interacting with specific receptors, according to the current working classification for prostanoid receptors, was employed as a conceptual framework to re-examine the activity of 19(R)-OH PG's. In contrast to PGE2, which may indiscriminately stimulate a variety of prostanoid receptor subtypes, 19(R)-OH PGE2 exhibited selectivity for the EP2-receptor subtype. In EP1 (guinea pig ileum contraction), EP2 (cat trachea relaxation), and EP3 (chick ileum contraction) preparations where PGE2 is equipotent, 19(R)-OH PGE2 exhibited greater potency in the EP2-receptor population. Moreover, unlike PGE2, 19(R)-OH PGE2 did not stimulate an FP-receptor preparation (cat iris). 19(R)-OH PGE2 was devoid of activity at thromboxane A2-(TP), prostaglandin D2-(DP) and prostacyclin-(IP) sensitive receptors as indicated by its inability to cause human platelet aggregation or inhibit ADP-induced platelet aggregation. 19(R)-OH PGE1 had an entirely converse profile of activity. As a myotropic agent in the guinea pig and chick ileal preparations, 19(R)-OH PGE1 was approximately 1.5 orders of magnitude more potent than 19(R)-OH PGE2 but it appeared devoid of EP2-receptor stimulant properties. 19(R)-OH PGF2 alpha possessed very little biological activity in a diverse variety of isolated tissue preparations, indicating that 19-hydroxylation represents a highly efficient inactivation step for PGF2 alpha. The implications of the formation of receptor selective PGE derivatives in human seminal fluid for human reproductive physiology remains to be established.

Adenosine Diphosphate↗
PubMed1991

Cell cycle dependency of monoclonal antibody production in asynchronous serum-free hybridoma cultures.

The cell cycle kinetics of F3(B6) mouse hybridoma was examined by immunocytochemical staining of bromodeoxyuridine incorporated into the DNA of exponentially growing cells in three different cultures: one supplemented with 10% fetal bovine serum and two adapted to serum-free media, TABIES and BITES. The serum-free cultures, particularly the BITES, had longer cycling times and higher specific antibody production rate. Both observations were correlated to the prolongation of the G1 phase traverse time and substantiated with a starvation blocking experiment.

Animals↗
PubMed1990

Evaluation of immunocytochemical detection methods of incorporated bromodeoxyuridine in hybridomas.

Bivariate distributions obtained from nominal acid hydrolysis or thermal treatment methods used in the cell cycle analysis of incorporated bromodeoxyuridine were shown to be unacceptable with hybridomas. Four different cell treatment and staining methods were compared. These methods are acid hydrolysis, thermal denaturation, nuclei extraction with pepsin digestion, and simultaneous pepsin digestion and acid hydrolysis. The nuclei extraction method was determined to be the most appropriate for the immunocytochemical staining of incorporated bromodeoxyuridine in hybridomas. The resulting bivariate distribution provides a clear distinction between labelled and unlabelled cell fractions. The method based on nuclei extraction with pepsin digestion was optimized for a hybridoma line used in this study.

Animals↗
PubMed1990

Thromboxane A2-mimetics are potent microvascular permeability factors in the conjunctiva.

These studies demonstrate that the thromboxane (Tx) A2 mimetics U-46619, U-44069 and carbocyclic-TxA2 elicit a microvascular permeability response in the conjunctiva. U-46619 and U-44069 are among the most potent microvascular permeability factors described to date for the conjunctiva; their potency is exceeded only by that reported for leukotrienes D4 and E4. The conjunctival microvascular permeability response to U-46619 was inhibited by the TxA2-antagonists daltroban (BM 13505) and SQ 29548. Prostaglandin (PG) D2 also increased conjunctival microvascular permeability, but was less potent than U-46619 and far less susceptible to pretreatment with daltroban or SQ 29548. PGE2, PGF2 alpha and the prostacyclin analog carbocyclin did not increase conjunctival microvascular permeability. It appears that the conjunctiva exhibits a unique microvascular permeability response to TxA2-mimetics: this view is experimentally supported by the absence of a cutaneous microvascular permeability response to U-46619, U-44069 and carbocyclic-TxA2.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1990

Studies on the ocular pharmacology of prostaglandin D2.

Prostaglandin D2 (PGD2) exerts a variety of biologic actions in the eye; these include ocular hypotension and inflammatory effects on the conjunctiva. The profile of activity of PGD2 in ocular tissues was compared to that of BW 245C, a selective agonist for the PGD2-sensitive (DP) receptor, and to that of the biologically active metabolites of PGD2, 9 alpha,11 beta-prostaglandin F2 (9 alpha,11 beta-PGF2) and prostaglandin J2 (PGJ2). PGD2 produced a dose-dependent decrease in intraocular pressure and in the conjunctiva it caused increased conjunctival microvascular permeability, eosinophil infiltration and goblet cell depletion. Although BW 245C was equipotent to PGD2 as an ocular hypotensive agent, it did not cause pathological effects in the conjunctiva. Thus, the ocular hypotensive effect of PGD2 may be separated from inflammatory effects on the conjunctiva by employing a selective DP-receptor agonist such as BW 245C. 9 alpha,11 beta-PGF2 was a weak ocular hypotensive and did not cause conjunctival inflammation. PGJ2 produced no significant effect on intraocular pressure. PGJ2 did not elicit a microvascular permeability response in the conjunctiva, but was inflammatory in other respects and caused eosinophil infiltration and goblet cell depletion similar to PGD2. Thus, both the ocular hypotensive actions and the conjunctival pathology of PGD2 may be replicated individually by employing PGD2 analogues and metabolites.

Animals↗
PubMed1989

Platelet-activating factor causes goblet cell depletion in the conjunctiva.

Platelet-activating factor (PAF) (1-O-hexadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) produced dose-dependent depletion of the goblet cell population associated with the conjunctival epithelium. Reductions in goblet cell numbers did not correspond to leukocyte infiltration and were consistent with a direct effect of PAF. In contrast, LTD4 and LTE4 did not affect the goblet cell population although they caused massive eosinophil infiltration into the conjunctival epithelium. Histamine also produced conjunctival goblet cell depletion, but this appeared secondary to eosinophil degranulation and resultant epithelial desquamation. In addition to goblet cell expulsion, PAF produced an increase in conjunctival microvascular permeability over an identical dose-range. PAF-induced leukocyte emigration was small or absent and comprised a neutrophil infiltrate which exhibited no clear dose-dependent relationship. Lyso-PAF produced effects only at the highest dose employed where pathological changes and a distinct increase in conjunctival microvascular permeability were evident. Lyso-PAF- and PAF-induced increases in conjunctival microvascular permeability were virtually abolished by the PAF antagonist CV-6209. The pronounced inhibitory activity of CV-6209 suggests that high doses of lyso-PAF may either weakly stimulate conjunctival PAF receptors or that there may be sufficient conversion of lyso-PAF to biologically active levels of PAF.

Animals↗