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Biomedical subjects

S E Kelly

Publications and source records attributed to S E Kelly.

At least 55 records · Page 3Linked to original sources

Pemphigoid and ulcerative colitis.

We report eight patients with ulcerative colitis who have subsequently developed pemphigoid. Four patients were investigated to determine the pattern of pemphigoid antibody staining on whole and chemically split skin and oral mucosa to distinguish between pemphigoid and epidermolysis bullosa acquisita. The findings were suggestive of pemphigoid with a predominantly epidermal pattern. Three patients were studied for the presence of antibodies against the colon (which were absent). The relationship between pemphigoid and ulcerative colitis is discussed in relation to a case-control study.

Adult↗

The use of chemically split tissue in the detection of circulating anti-basement membrane zone antibodies in bullous pemphigoid and cicatricial pemphigoid.

Human skin and mucous membranes were used to detect circulating auto-antibodies by indirect immunofluorescence in 20 patients with bullous pemphigoid and eight with cicatricial pemphigoid. The tissue substrate was used intact and after chemical separation through the basement membrane zone (BMZ) by incubation with I M NaCl. Chemically split skin and oral mucosa provided a more sensitive assay for demonstrating circulating anti BMZ antibodies. Use of a battery of substrates increased the number of positives in bullous pemphigoid from 30% detected on monkey oesophagus to 100% (tissue battery). In cicatricial pemphigoid there was an increase in the proportion of positive sera from 13% (monkey oesophagus) to 88% (tissue battery). In addition, a different class of antibody was frequently detected on split tissue substrate suggesting that new antigens are exposed by this procedure.

Aged↗

Expression of a pemphigoid gestationis-related antigen by human placenta.

We studied the antigen binding of sera from 25 patients with pemphigoid gestationis (PG) using skin and amnion as substrates in an indirect immunofluorescence technique. In addition, skin was studied after prior incubation with I M NaCl which allows BMZ cleavage through the lamina lucida. Linear BMZ staining was obtained with sera from patients with PG using human amnion as substrate. This was seen with both full-term and second trimester placentae, but not with first trimester placentae. In NaCl incubated skin all sera bound to the epidermal aspect of the separated tissue. The pattern of staining in skin, chemically split skin and amnion was identical to that previously seen with the sera of patients with bullous pemphigoid suggesting that the antigen against which circulating anti-BMZ antigens are directed may be the same in the two conditions.

Amnion↗

The structure of fucosylated blood group substances in fetal rat skin. The combined use of monoclonal antibodies and glycosyl hydrolases.

Cell surface carbohydrates are thought to be important during embryonic development. We have studied a group of defined cell surface carbohydrates during the differentiation of fetal rat skin by the use of immunocytochemical techniques. We used monoclonal antibodies to the LeX and human blood group H type II haptens. The structure of the molecules carrying these haptens has been inferred by the sensitivity of the immune reactions to digestion by glycosyl hydrolases. The primitive ectoderm expressed the LeX hapten. The differentiating epidermis carries the H type II antigen, but this was only detected following cleavage of a terminally modified portion of the carbohydrate containing linear poly-N-acetyl lactosamine chains. These carbohydrates on epidermal cells are carried N linked to glycoproteins.

Animals↗

A clinicopathological study of mucosal involvement in linear IgA disease.

Mucosal involvement in linear IgA disease was assessed clinically and immunologically using direct and indirect immunofluorescence (IF) techniques. There was clinical evidence of oral mucosal involvement in all 10 patients examined and conjunctival diseases in six. Direct IF findings correlated well with clinical oral disease, with all patients demonstrating linear IgA deposits in the basement membrane zone of oral mucosa. However, this was not true of conjunctiva where no linear IgA could be demonstrated. Conjunctiva did provide a good substrate for indirect immunofluorescence using patients' sera, and showed that five of the 10 patients had circulating anti-basement membrane zone IgA.

Adolescent↗

Inhibition of Trypanosoma brucei brucei peptidyl transferase activity by sparsomycin analogs and effects on trypanosome protein synthesis and proliferation.

Peptidyl transferase activity of Trypanosoma brucei brucei polyribosomes was competitively inhibited by analogs of sparsomycin (Ki = 1-100 microM). The analogs were also potent inhibitors of [3H]-leucine and [3H]mannose incorporation into the proteins of intact trypanosomes with little or no effect on overall respiratory rate, suggesting a specific site of action for these analogs on protein synthesis. The peptidyl transferase inhibitors were effective at low concentrations at limiting the proliferation of trypanosomes both in vitro and in vivo. The potency of the compounds as inhibitors of cell proliferation was positively correlated with their efficacy as inhibitors of peptidyl transferase activity. One compound, MDL 20828 (1 mg/kg), increased the survival time of T. b. brucei-infected mice 4-fold in the absence of any overt drug toxicity to the hosts.

Acyltransferases↗

Regulation of growth and macromolecular synthesis by putrescine and spermidine in Pseudomonas aeruginosa.

Growth of P. aeruginosa, slowed by the addition of monofluoromethylornithine, difluoromethylarginine and dicyclohexylammonium sulfate, could be restored by addition of 0.1 mM putrescine plus 0.1 muM spermidine, or 0.1 mM spermidine or 5 mM putrescine by themselves. Lower concentrations of putrescine (0.1 mM - 1 mM) also partially reversed the growth inhibition. Conversion of putrescine to spermidine continued, although at a markedly reduced ratio, in the drug-inhibited cells, but intracellular spermidine concentrations remained depressed suggesting that reversal of inhibition by putrescine may be a direct effect. There was appreciable back-conversion of any added spermidine to putrescine with a demonstrable increase in total intracellular putrescine levels, making conclusions on the effects of spermidine ambiguous. Spermine (0.1 mM), a polyamine not present in bacteria, was also effective in reversing growth inhibition, probably because of its conversion into spermidine and putrescine. The effects of putrescine, spermidine and spermine were specific in that the non-physiological amines, 1,3-diaminopropane, 1,5-diaminopentane (cadaverine), 1,6-diaminohexane, or 1,7-diaminoheptane could not reverse the effects of the three drugs. Rates of total protein, RNA and DNA synthesis were all slowed to the same extent as growth rate and showed similar recovery with the addition of putrescine or spermidine. A role for putrescine in P. aeruginosa growth processes is suggested.

Bacterial Proteins↗

Characterization of spermidine synthase from Trypanosoma brucei brucei.

Spermidine synthase from Trypanosoma brucei brucei was characterized and found to be similar to spermidine synthase from other sources. The Km for putrescine was found to be 0.2 mM and the Km for decarboxylated S-adenosylmethionine 0.1 microM. The approximate molecular weight of the enzyme was 74 000 as determined by a combination of molecular sieve chromatography and sucrose density gradient centrifugation. Spermidine synthase activity was markedly inhibited in vitro by dicyclohexylamine (50% inhibition at 3 microM) and cyclohexylamine (50% inhibition at 15 microM); both being competitive inhibitors with respect to putrescine. S-Adenosyl-1,8-diamino-3-thiooctane, a nucleoside bisubstrate analog, was also a potent inhibitor of enzyme activity (50% inhibition at 25 microM). Administration of dicyclohexylamine to mice with trypanosomiasis resulted in no increase in survival time probably due to the lack of effect on trypanosome spermidine concentrations. Other possible inhibitors remain to be tested in vivo.

Animals↗

Effect of meal composition on calcium absorption: enhancing effect of carbohydrate polymers.

Meal components including fat, fiber, and carbohydrates can influence the intestinal absorption of calcium; such interactions may be of even greater importance in the presence of intestinal disease. This study compares intestinal absorption of 47CaCl2 administered in four ways: in water, within a standard meal, with a liquid formula (Ensure, Ross Laboratories, Columbus, Ohio), or with a glucose polymer solution (Frodex-15, Ross). Studies were carried out in 9 patients with ileal resection, 3 patients with jejunoileal bypass, and 14 controls. Fractional calcium absorption from water was lower in patients than in controls. Absorption was enhanced 1.5- to 5-fold when 47CaCl2 was administered with a liquid formula diet containing a glucose polymer or with the glucose polymer alone. Patients with the lowest calcium absorption from breakfast showed the greatest effect of calcium ingestion with formula or glucose polymer. These findings further emphasize the importance of meal composition on calcium absorption and provide a possible mechanism for enhancing calcium absorption in some patients with chronically impaired absorption.

Adult↗

Comparison of tissue reaction to nylon and prolene sutures in rabbit iris and cornea.

The tissue reaction in rabbit iris and cornea to prolene suture is equivalent to the tissue reaction to nylon suture. The prolene suture retains its tensile strength indefinitely and this may make it particularly useful in situations where a permanent suture is desired, such as in refractive keratoplasty, scleral buckle, or to suture an intraocular lens to the iris. The prolene suture also has a greater elasticity and this property may be advantageous in some clinical applications. We feel that a clinical study on humans is now warranted and we have started such a study.

Animals↗

Drug delivery systems for topical ophthalmic medication.

Two new topical ophthalmic delivery systems are described. The modes of delivery were compared with conventionally administered eyedrops on the basis of intraocular pressure lowering effect, dependability in delivery of prescribed dosage, and patient acceptance of the system. Pilocarpine delivered by each of the systems was found to control IOP as well as conventional pilocarpine drops. Although some patients took a longer time than others to adjust to a new mode of delivery, patient acceptance of the systems was high.

Administration, Topical↗

Intestinal calcium absorption and vitamin D status in chronic cholestatic liver disease.

Metabolic bone disease is common in patients with cholestatic liver disease. The importance of vitamin D status and calcium malabsorption in the pathogenesis of bone disease in these patients remains undefined. We have measured intestinal calcium absorption in relation to vitamin D status in 14 patients with chronic cholestatic liver disease including 11 with primary biliary cirrhosis. Fractional calcium absorption was determined from radioactive counts in the right forearm after separate oral and intravenous doses of 47CaCl2 in the fasting state. Eight of 14 patients (57%) had a decreased calcium absorption compared to controls. A significant correlation was observed between serum 25-hydroxyvitamin D levels and fractional calcium absorption (r = 0.623, p less than 0.02). Treatment with oral 25-hydroxyvitamin D3 in three patients with low serum 25-hydroxyvitamin D levels resulted in correction of serum 25-hydroxyvitamin D levels and improvement in fractional calcium absorption. No correlation was found between serum 1,25-dihydroxyvitamin D levels and fractional calcium absorption (r = 0.221). Calcium malabsorption was common in this series of patients, and serum 25-hydroxyvitamin D levels were useful in predicting fractional calcium absorption. Treatment with oral 25-hydroxyvitamin D3 was accompanied by improved calcium absorption.

Adult↗