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Biomedical subjects

M A Mann

Publications and source records attributed to M A Mann.

17 recordsLinked to original sources

Gender and intrauterine position influence saccharin preference in mice.

Gender differences in saccharin preference in adult Rockland-Swiss mice were examined in Experiment 1. Separate groups of male and female mice received tap water and one of five concentrations of saccharin solution (either 0.10, 0.25, 0.50, 0.75, or 1.00%). A significantly higher preference score was obtained for females vs. males that received the 0.25% solution. Other concentrations did not yield a significant sex difference. The purpose of Experiment 2 was to examine prenatal influences on preference patterns of adult males. Mice were delivered by cesarean section and classified as having resided between two male (2M), two female (0M), or one male and one female (1M) fetuses. Saccharin preference was then examined in separate groups of adult males that received either a 0.25 or a 0.75% solution. A significantly higher preference score was obtained for 0M vs. 2M males that received the 0.25% concentration; no difference was obtained with the 0.75% solution. Differences between 2M and 0M males may be due to the actions of prenatal steroids.

Animals

Protective antibodies inhibit reovirus internalization and uncoating by intracellular proteases.

We identified in vitro correlates of in vivo protection mediated by nonneutralizing antibodies specific for reovirus capsid proteins. We defined mechanisms of antibody action by analyzing monoclonal antibody (MAb) effects at sequential steps in reovirus serotype 3 strain Dearing (T3D) infection of L cells. Two types of experiments showed that protective MAbs specific for the outer capsid proteins sigma 3 or mu 1 inhibited T3D infection independent of effects on binding. First, MAbs which had no effect on T3D binding inhibited T3D growth. Second, MAb-coated T3D attached to L cells did not replicate as efficiently as T3D without bound antibody. We therefore defined sigma 3-specific MAb effects on postbinding steps in T3D infection. T3D coated with MAb sigma 3-10G10 exhibited prolonged sensitivity to growth inhibition by ammonium chloride. Since ammonium chloride inhibits endosomal acidification and proteolytic processing of the T3D capsid, this suggested that MAbs inhibit early steps in T3D infection. This was confirmed by direct demonstration that several sigma 3-specific MAbs inhibited proteolytic uncoating of virions by fibroblasts. We identified two mechanisms for antibody-mediated inhibition of virion uncoating: (i) inhibition of internalization of T3D-MAb complexes bound to the cell surface, and (ii) inhibition of intracellular proteolysis of the T3D capsid. Studies using a cell-free system confirmed that sigma 3-specific MAbs directly block proteolytic uncoating of the T3D virion. In addition, we found that sigma 3-specific MAbs block (and therefore define) two distinct steps in proteolytic uncoating of the reovirion. We conclude that antibodies which are protective in vivo inhibit postbinding events in reovirus infection of permissive cells. Protective antibodies act by inhibiting internalization and intracellular proteolytic uncoating of the virion. Analysis of postbinding mechanisms of MAb action may identify targets for vaccine development and antiviral therapy.

Ammonium Chloride

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

The role of progesterone in pregnancy-induced aggression in mice.

A series of six experiments was performed in order to explore the potential involvement of progesterone (P) in pregnancy-induced aggression (PIA) displayed by Rockland-Swiss mice toward adult male intruders. In Experiment 1, circulating levels of P and aggression were low on gestation Days 6 and 10 while both the behavior and the steroid reached peak levels by gestation Day 14. By gestation Day 18 (the day prior to parturition), serum P was at its lowest level yet aggressive behavior was still intense. Also, individual differences in the display of fighting behavior by pregnant females were not related to circulating P. Experiments 2 and 3 showed that supplemental P treatment to early pregnant female mice did not advance the onset of aggression. Experiment 4 showed that P treatment promoted the onset and elevated the incidence of aggression in virgin mice, but only in those females with intact ovaries. Experiment 5 showed that the aggressive behavior of P-stimulated virgin females was qualitatively and quantitatively different from that exhibited by pregnant mice in that the former exhibited fewer attacks and lunges than the latter. Finally, Experiment 6 showed that the removal of P from aggressive, P-stimulated virgins dramatically attenuated levels of the behavior. This contrasts sharply with the continued fighting behavior observed in late pregnant P-deficient mice. Thus, although P augments aggression in female mice it apparently is not a sufficient stimulus for producing pregnancy-like aggressive behavior.

Aggression

Infanticide: accounting for genetic variation in mice.

Infanticide, the killing of young, is one of a number of sexually-dimorphic traits in mice that is dependent upon androgen stimulation during perinatal life and during adulthood. Genotype also influences infanticide in that males of some strains of mice (C57BL/6J) exhibit high levels of this behavior while males of other strains (DBA/2J) seldom kill young. The experiments conducted here show that strain differences in pup killing behavior exhibited by males are not related to postweaning social factors nor are they due to differences in perinatal, pubertal, or adult levels of circulating hormones. These results, in combination with those previously reported, suggest that strain differences in the tendency of mice to kill young may instead depend upon the interaction of genotypic features such as prenatal hormone titers and/or sensitivity to these hormones, as well as on extra organismic factors such as intrauterine position. A model for understanding the manner in which genes and hormones may interact to influence infanticide and other hormone dependent sexually-dimorphic behaviors in mice is presented.

Aggression

Infanticide exhibited by female mice: genetic, developmental and hormonal influences.

Approximately 25-40% of 25-45 day old C57BL/6J females killed young (1-3 day old Rockland-Swiss (R-S) albino mouse pups) while similarly aged DBA/2J females were parental or ignored neonates. Beyond 45 days of age C57BL and DBA females seldom killed young. When ovariectomized at weaning and tested for infanticide at 65 days of age, DBA females rarely killed neonates while 40% of C57BL females exhibited the behavior. In contrast to DBA females, significantly more C57BL females killed young in response to the adult administration of testosterone propionate (TP) and estradiol benzoate (EB), but not dihydrotestosterone propionate (DHTP). It is tentatively proposed that strain differences in spontaneous and steroid aroused infanticide in female mice may be related to differences in the prenatal hormone environment.

Animals

Prenatal testosterone exposure elevates maternal aggression in mice.

Pregnant Rockland-Swiss (R-S) female mice were injected with oil, 0.5, 1.0 or 2.0 micrograms of testosterone propionate (TP) on days 12, 14 and 16 of gestation and the maternal aggressive behavior of their resulting female offspring was examined in adulthood. Prenatal exposure to 1 or 2 micrograms of TP, but not 0.5 micrograms of the steroid, significantly increased the number of attacks displayed by parturient mice toward adult male intruders. The behavioral effects on aggression were observed in the absence of effects on external morphology, body weight, or lactational performance. The findings support previous research showing that the development of feminine behavior may be sensitive to prenatal androgens. The possibility that the presence of fetal testosterone augments both male and female aggressive behavior is discussed.

Aggression

Postpartum behavior in the mouse: the contribution of suckling stimulation to water intake, food intake and body weight regulation.

Rockland-Swiss (R-S) Albino female mice that receive suckling stimulation from young consume significantly more water and food and gain significantly more weight than dams without young. Excision of nipples (thelectomy) prevents postpartum increases in these consummatory behaviors and in body weight gain even in dams with extensive prior suckling exposure. Thus, both the initiation and maintenance of postpartum ingestive behaviors depend primarily upon suckling stimulation from young.

Animals

Ergot drugs suppress plasma levels of prolactin (PRL) but not growth hormone (GH), luteinizing hormone (LH) or corticosterone (CORT) in parturient mice.

Plasma levels of prolactin (PRL), growth hormone (GH), luteinizing hormone (LH), and corticosterone (CORT) were measured in parturient Rockland-Swiss (R-S) albino mice following the daily administration for 10 days of 0.5 mg ergocornine (ERGO), 0.5 mg bromocriptine (BROMO), or sesame oil (OIL). The dams were provided with replete foster young on a daily basis so as to prevent the decline in suckling activity that normally occurs in undernourished pups of ergot-treated dams. Circulating PRL levels were significantly reduced by both ergot drugs but plasma levels of the other hormones measured were not altered. Thus, ergot drugs have relatively specific effects on PRL even in parturient animals receiving sustained high levels of suckling stimulation.

Animals

Endoscopic diagnosis of chronic hypertrophic pyloric gastropathy in dogs.

The endoscopic appearance of chronic hypertrophic pyloric gastropathy (CHPG) in five dogs is described. Several patterns of enlarged mucosal folds that surrounded and obstructed the pyloric canal were observed. Initially, endoscopically obtained biopsy samples of mucosa were judged to be histologically normal. Diagnosis of CHPG was confirmed and relief of pyloric obstruction accomplished at exploratory laparotomy (in four dogs). Retrospective evaluation of pyloric tissue samples, obtained during endoscopy, identified subtle histological characteristics of CHPG. Gastric and duodenal neoplasia or antral polyps can mimic the endoscopic appearance of CHPG but can be differentiated based on their endoscopic and histological appearance. These cases show that endoscopic examination is a valuable procedure for the diagnosis of CHPG in dogs that chronically vomit.

Animals