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Biomedical subjects

M A Mann

Publications and source records attributed to M A Mann.

6 recordsLinked to original sources

Monoclonal antibodies to reovirus reveal structure/function relationships between capsid proteins and genetics of susceptibility to antibody action.

Thirteen newly isolated monoclonal antibodies (MAbs) were used to study relationships between reovirus outer capsid proteins sigma 3, mu 1c, and lambda 2 (core spike) and the cell attachment protein sigma 1. We focused on sigma 1-associated properties of serotype specificity and hemagglutination (HA). Competition between MAbs revealed two surface epitopes on mu 1c that were highly conserved between reovirus serotype 1 Lang (T1L) and serotype 3 Dearing (T3D). There were several differences between T1L and T3D sigma 3 epitope maps. Studies using T1L x T3D reassortants showed that primary sequence differences between T1L and T3D sigma 3 proteins accounted for differences in sigma 3 epitope maps. Four of 12 non-sigma 1 MAbs showed a serotype-associated pattern of binding to 25 reovirus field isolates. Thus, for reovirus field isolates, different sigma 1 proteins are associated with preferred epitopes on other outer capsid proteins. Further evidence for a close structural and functional interrelationship between sigma 3/mu 1c and sigma 1 included (i) inhibition by sigma 3 and mu 1c MAbs of sigma 1-mediated HA, (ii) enhancement of sigma 1-mediated HA by proteolytic cleavage of sigma 3 and mu 1c, and (iii) genetic studies demonstrating that sigma 1 controlled the capacity of sigma 3 MAbs to inhibit HA. These data suggest that (i) epitopes on sigma 3 and mu 1c lie in close proximity to sigma 1 and that MAbs to these epitopes can modulate sigma 1-mediated functions, (ii) these spatial relationships have functional significance, since removal of sigma 3 and/or cleavage of mu 1c to delta can enhance sigma 1 function, (iii) in nature, the sigma 1 protein places selective constraints on the epitope structure of the other capsid proteins, and (iv) viral susceptibility to antibody action can be determined by genes other than that encoding an antibody's epitope.

Animals

Mice: the initiation and maintenance of pregnancy-induced aggression following thelectomy.

Two experiments were conducted in order to assess the effects of thelectomy (i.e., nipple removal) on the display of pregnancy-induced aggression in Rockland-Swiss (R-S) albino mice. Pregnant animals, thelectomized on Gestation Day (GD) 12, exhibit a high incidence and intensity of aggression toward adult R-S male intruders during tests conducted on GDs 14, 16, and 18 (i.e., during the last third of gestation in this species). Since thelectomized dams display levels of aggression (i.e., 63% incidence) equivalent to those of sham-operated and nonoperated animals (53 and 67% incidence, respectively), it would appear that nipple presence is not a critical factor for the maintenance of pregnancy-induced aggression in mice (Experiment 1). To examine the effects of nipple deprivation on the initiation of pregnancy-induced aggression, virgin animals were thelectomized prior to mating, then repeatedly tested for aggression at 2-day intervals of gestation. Unlike nipple-intact dams, pregnant mice, deprived of nipples prior to conception, rarely exhibit (less than 17% incidence) agonistic behaviors toward intruder males (Experiment 2). These findings suggest that the development and self-stimulation of nipples early in pregnancy may be important conditions for the display of heightened aggression with advancing pregnancy in mice.

Aggression

A role for elevated plasma corticosterone in modulation of host response during infection with Trichinella pseudospiralis.

Suppression of host inflammatory response in mice infected with Trichinella pseudospiralis was associated with host plasma corticosterone levels significantly higher than those seen in uninfected mice or in mice infected with T. spiralis. Increases in the population of mitochondria and depletion of lipid droplets in cells of the zona fasciculata were seen in the adrenals of mice infected with T. pseudospiralis. Elevations in enteritis, myositis and myocarditis accompanied 100% mortality in adrenalectomized mice infected with T. pseudospiralis, while lower levels of inflammation and no mortality were observed in sham operated or intact animals infected with this parasite. The severe myositis normally accompanying infection with T. spiralis was suppressed by concurrent infection with 1000 or 2000 T. pseudospiralis to levels equivalent to those seen in animals receiving 0.15 and 0.41 mg cortisone acetate/25 g mouse/day, respectively.

Adrenal Glands

Pregnancy-induced autogrooming in mice: the effects of nipple removal.

As pregnancy advances, Rockland-Swiss albino mice spend increasingly more time engaged in autogrooming. By gestation day 18 (the day prior to parturition), the total duration of autogrooming (a composite measure) as well as the duration of nipple line grooming is significantly longer than that displayed by virgin and early pregnant females. Nipple excision (i.e., thelectomy) performed prior to pregnancy reduces the time GD 18 dams spend licking nipple line regions without producing a concomitant decrease in the duration of grooming all regions. It is unlikely, therefore, that peripheral stimulation of the nipple line regions via self-licking contributes to the heightened display of grooming by pregnant mice.

Anal Canal

Excretion patterns of cannabinoid metabolites after last use in a group of chronic users.

The urinary excretion patterns of 86 chronic cannabis users were examined after their last cannabis use by two common screening methods, the semiquantitative EMIT-d.a.u. and the qualitative EMIT-st (Syva Company). We demonstrated that under very strictly supervised abstinence, chronic users can have positive results for cannabinoids in urine at 20 ng/ml or above on the EMIT-d.a.u. assay for as many as 46 consecutive days from admission, and can take as many as 77 days to drop below the cutoff calibrator for 10 consecutive days. For all subjects, the mean excretion time was 27 days. Subject excretion patterns were clearly biphasic, with initial higher rates of excretion not sustained. During the subsequent period of leveling off, most subjects had one or more separate sequences of cannabinoid-negative urine test results, lasting a mean of 3 days each and followed by at least one positive result. Demographic, body type, and drug history variables proved to be only moderate predictors of excretion patterns. Findings were discussed in the context of potential clinical and forensic application.

Adolescent