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Biomedical subjects

M L Chapman

Publications and source records attributed to M L Chapman.

9 recordsLinked to original sources

Long-term neurochemical and behavioral effects induced by acute chlorpyrifos treatment.

A single dose of the organophosphate insecticide O,O'-diethyl-O-3,5,6- trichloro-2-pyridylphosphorothioate [chlorpyrifos (CPF), 279 mg/kg, SC] caused extensive inhibition of cortical and striatal cholinesterase (ChE) activity in adult rats at 2 (94-96%), 4 (82-83%), and 6 (58-60%) weeks after treatment. These persistent changes in ChE activity were concomitant with reductions in muscarinic receptor binding sites in cortex (34, 33, and 18% reduction in Bmax) and striatum (48, 40, and 23% reduction in Bmax) at 2, 4, and 6 weeks after exposure. Neither ChE activities nor muscarinic receptor densities were different from control levels at 12 weeks after exposure. CPF treatment caused a reduction in locomotor activity for the first 2 days after treatment, after which basal activity levels were not different from controls. CPF-treated rats showed higher activity relative to controls, however, following challenge with scopolamine (1 mg/kg, IP) at 2, 4, 6, 8, and 12 weeks after treatment. These data indicate that acute exposure to CPF in adult rats can cause long-term neurobehavioral changes that may persist following the recovery of neurochemical parameters associated with exposure and tolerance to cholinesterase inhibitors.

Animals

Phenylmethylsulfonyl fluoride alters sensitivity to organophosphorus-induced delayed neurotoxicity in developing animals.

The serine/cysteine hydrolase inhibitor phenylmethylsulfonyl fluoride (PMSF) markedly intensifies the clinical expression of organophosphorus-induced delayed neurotoxicity (OPIDN) in adult chickens when administered after organophosphate exposure. In this study, we have examined the ability of PMSF post-treatment to affect sensitivity to OPIDN in developing animals at ages normally showing resistance. Chickens (35, 49 or 70 days of age) were treated with diisopropylphosphorofluoridate (DFP, 2 mg/kg, sc) and then treated four hours later with PMSF (90 mg/kg, sc) or vehicle only and examined for clinical signs of ataxia and incoordination. Chickens treated with DFP alone showed a marked age-related increase in the severity of motor deficits. Birds treated with DFP followed by PMSF showed more extensive clinical deficits relative to those treated with DFP only, but relatively similar degrees of motor dysfunction among the age groups. Cervical spinal cord samples processed by the Fink-Heimer degeneration method indicated that PMSF post-treatment induced more extensive axonal degeneration in all age groups relative to treatment with DFP only. As the DFP treatment alone caused greater than or equal to 90% inhibition of neurotoxic esterase activity (NTE, the putative molecular target site for OPIDN), interaction with NTE by PMSF does not appear to be involved in potentiation. We hypothesize that PMSF potentiates OPIDN through impairment of a physiological process which normally imparts resistance to young animals and which regresses during development.

Animals

Fractionation on lymphocyte surface antigens. I. Rapid method for eliminating labeled lipid from cell surface antigens iodinated by the lactoperoxidase catalysed reaction.

Fractionation of lactoperoxidase iodinated cell surface material on miniature DEAE-cellulose columns provided a rapid method for separating labeled lipid from cell surface antigens. The procedure also removed poorly solubilized aggregates yielding a labeled preparation which demonstrated stable, reproducible immunoprecipitation results. Using these fractionated antigens components tentatively designated as human 'T' cell specific antigens have been identified.

Antigens

Acid absorption in the canine duodenum.

Alterations in composition of isosmotic acid solutions were studied in exteriorized segments of the proximal (Brunner's gland area) and distal canine duodenum, mounted in lucite chambers. Varying concentrations of HCl (40, 80, 120, 160 mEq/l) made isotonic by the addition of NaCl were instilled into the chamber, removed in 15 minutes and analyzed for volume, electrolytes, protein content and osmolality. Both proximal and distal duodenal mucosa modified the instilled solution with a loss of H+ and a gain in Na+ and K+, which occurred at similar rates independent of the acid concentration of the instilled solution. The rate of ionic movement was twice that for the antrum, and 30-100 times that of the fundus. Calculated H+ loss across the entire duodenal mucosa at these rates could account for 17.5% of the peak acid output from the canine stomach. The loss of H+ could not be accounted for on the basis of neutralization and probably represented transmucosal insorption. In addition to the neutralization of gastric acid by pancreatic juice and bile, duodenal mucosa thus plays an important role in the maintenance of intraluminal pH. Duodenal mucosal permeability to H+ may be related to the vulnerability of the duodenal mucosa to acid-peptic ulceration.

Animals

Isolation of lymphocyte surface antigens. II. Identification of non-beta 2 -microglobulin-associated human T cell-specific antigen.

Iodinated cell surface components from human thymus lymphocytes labeled by the lactoperoxidase method, were solubilized by papain digestion and then 3 M KCl extraction of the residual cell pellet. Antiserum to human thymus bound three components from this material, mol. wt. approximately equal to 40 000, 20 000 and 12 000 daltons. This antiserum was absorbed with cultured human lymphoblasts (CHL) until it no longer bound CHL antigens or the HLA-beta 2-microglobulin complex. It continued to bind labeled antigens from thymus, peripheral blood lymphocytes and "T" cell-enriched fraction of tonsil lymphocytes. The absorbed antiserum bound a component from papain-solubilized thymus antigens which had an estimated molecular weight of approximately 40 000 daltons and which was not associated with beta 2-microglobulin. This component seemed to be a human T cell-specific antigen.

Antigens

Lymphocyte plasma membranes. VI. Surface antigens of lymphocytes in chronic lymphocytic leukemia.

Surface antigens from lymphocytes of patients with chronic lymphocytic leukemia (CLL) and from normal peripheral blood lymphocytes (PBL) were examined by radioimmunoassay; antisera to lymphocytes (ALS) were used to bind the labeled antigens. Cells from patients with CLL, normal PBL, thymus cells (THY), and cultured human lymphoblasts (CHL) were labeled by lactoperoxidase-catalyzed iodination. ALS (prepared against THY and CHL) were used to bind the labeled antigens solubilized in nonionic detergent. PBL resembled THY, but the CLL resembled CHL. Thus ALS(CHL) had greater potency for CLL antigens than for PBL antigens when compared to ALS(THY). Furthermore, the electrophoretic profiles of the immunoprecipitates from CLL cells revealed a peak of approximately 30,000-35,000 mol wt, which was not found for PBL or THY, but was associated with CHL.

Antigens, Neoplasm