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Biomedical subjects

S E Sherman

Publications and source records attributed to S E Sherman.

33 records · Page 2Linked to original sources

Altered leukocyte protein kinase activity in atopic dermatitis.

Previous studies have demonstrated elevated cyclic-AMP-specific phosphodiesterase (PDE) activity in mononuclear leukocytes (MNL) from patients with atopic dermatitis (AD). We questioned whether increased kinase activation could account for this observation. In these studies, we measured abnormally lower basal calcium/phospholipid-dependent protein kinase (PK-C) phosphorylation in MNL from patients with AD. Basal cAMP-dependent protein kinase (PK-A) phosphorylation was concomitantly higher in MNL from patients with AD. These results are in agreement with earlier reports that PK-A activity may have a negative influence on PK-C activity in certain cell systems. Stimulation with the H1-histamine agonist, thiazolylethylamine (TEA), of MNL from normal donors but not patients with AD, resulted in statistically significant increases in PK-C phosphorylation. This implies receptor down regulation or functional desensitization in AD cells. Altered basal protein kinase phosphorylation and abnormal response to selective histamine agonists seen in MNL from patients with AD could explain elevated PDE activity.

Dermatitis, Atopic↗

Tolerance to intrathecal oxymetazoline-induced analgesia, with paradigm-dependent cross-tolerance to intrathecal morphine.

Male, Sprague-Dawley rats, implanted with intrathecal (i.t.) catheters, were given repeated i.t. injections of morphine (40 nmol), oxymetazoline (100 nmol) or saline (10 microliter) at 12-h intervals for 3 days. Antinociception was determined 1 or 1.5 hr after each injection using the tail-flick and paw-pressure tests. Complete tolerance to i.t. morphine and oxymetazoline developed within 72 and 24 hr, respectively. Antinociception after i.t. oxymetazoline (100 nmol) in morphine-tolerant rats, and after i.t. morphine (20 nmol) in oxymetazoline-tolerant rats, was not significantly different from their respective effects in saline-pretreated rats. These data suggest an absence of cross-tolerance between morphine and oxymetazoline in the rat spinal cord. In a separate group of rats, the continuous i.t. infusion of morphine (26 nmol/hr) produced significant antinociception; tolerance to morphine developed within 36 hr. The antinociceptive effect of i.t. oxymetazoline (100 nmol) was significantly attenuated in rats pretreated with continuous i.t. morphine as compared to saline-pretreated rats. In rats pretreated with continuous i.t. oxymetazoline, cross-tolerance to morphine could not be determined due to severe adverse effects during oxymetazoline infusion. The results of this study suggest that functional cross-tolerance between morphine and alpha adrenoceptor agonists in the spinal cord cannot be excluded on the basis of repeated i.t. injection experiments alone.

Analgesia↗

X-ray structure of the major adduct of the anticancer drug cisplatin with DNA: cis-[Pt(NH3)2(d(pGpG))].

Crystals of the adduct of the anticancer drug cis-diamminedichloroplatinum(II), cis-DDP, with d(pGpG), its putative target on DNA in the cancer cell, have been obtained and used in an x-ray crystallographic study to elucidate the molecular structure to atomic resolution. Each of the four crystallographically independent cis-[Pt(NH3)2(d(pGpG))] molecules is comprised of a square-planar platinum atom bonded to two ammonia ligands and two N(7) atoms of guanosine nucleosides from the same chain. Base stacking of the two adjacent guanine rings is completely disrupted by coordination to the cis-(Pt(NH3)2)2+ unit. Comparison of the backbone and deoxyribose ring torsion angles with those found by previous (nuclear magnetic resonance spectroscopy) studies of this adduct in solution demonstrates that the solid state geometry is substantially the same as that in solution. The relevance of these results to the molecular mechanism of action of cis-DDP is discussed.

Cisplatin↗

Evaluation of an improved suture for cataract surgery.

An improved synthetic absorbable suture for ophthalmic surgery, 8-0 Dexon "S" polyglycolic acid, was evaluated in 25 cataract extractions and, in 5 cases, compared with 8-0 Vicryl polyglactin sutures. Dexon "S" sutures caused less tissue drag than Vicryl sutures; Vicryl was more easily knotted. With respect to handling, knotting, tissue drag, absorption, and postoperative complications, the improved Dexon suture was found to be well suited for use in cataract surgery.

Aged↗

Clinical comparison of pilocarpine preparations in heavily pigmented eyes: an evaluation of the influence of polymer vehicles on corneal penetration, drug availability, and duration of hypotensive activity.

Heavily pigmented eyes have been shown to be relatively resistant to pilocarpine, and present special problems in management of open-angle glaucoma. Studies have suggested that the hypotensive effect of pilocarpine may be influenced by the vehicle; therefore, 13 relatively resistant black patients (26 eyes) were selected for a clinical comparison of pilocarpine as delivered in two different polymer vehicles. One vehicle was composed of 1.67% polyvinylpyrrolidone and BP water-soluble polymers (Adsorbobase); the other of hydroxypropyl methylcellulose 0.5%. All patients had been under treatment with the pilocarpine/methylcellulose preparation; 20 of the 26 eyes were judged to be uncontrolled (IOP above 21 mm Hg). Control of intraocular pressure was promptly obtained with the pilocarpine/Adsorbobase solution, and maintained at lower pilocarpine concentrations than with the previous therapy. Often, frequency of instillation could be decreased. This clinical comparison suggests that the Adsorbobase vehicle appreciably enhances corneal penetration and availability of pilocarpine. Three cases are discussed demonstrating the need for titration when instituting a new therapy with as little as one fourth the concentration of the previous pilocarpine therapy.

Aged↗

Evaluation of Dexon suture in ophthalmic surgery.

6-0 Dexon (polyglycolic acid-PGA) suture was used in 30 eyes of 25 patients in surgical procedures which included cataract extraction, strabismus surgery, and ocular plastic surgery. The suture was found to hold the wound firmly, was not absorbed prematurely, was absorbed completely at a predicted time, was relatively easy to use although the knots were large, did not cause any infection or undue tissue reaction, and did not result in any wound dehiscence or vitreous loss.

Adolescent↗